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Pagets disease eosinophilic granulomaheterotopic
ossificationPresented by dr lauay hassan PGY5
Supervised by assistant prof dr omer barawi1032016
Shar hospital
Understand the pathology and the management of paget diseaseeiosinophilic granuloma and heterotopic ossification in relation to orthopedic specialty
objectives
Introduction First Described in 1877 by James Paget Chronic non-metabolic bone disorder Characterized by aggressive bone
resorption and abnormal formation and remodeling rArran unbalanced derangement of normal processes
Results in bone deformity structural weakness altered joint biomechanics
Pagets Disease( OSTEITISDEFORMANS)
Epidemiology A disease of middle to advanced age Rare below age
40 Prevalence in US~1 over age 40 15-3 over age 60
Incidence doubles every decade after age 50
MengtWomen (16 1)Geographic variation Highest prevalence
in Britain Australia New Zealand North America and Western Europe
Etiology Unknown
Proposed Theories Viral Paramyxovirus measles virus RSV canine distemper virus
Viral particles seen in pagetic osteoclasts
Genetic5-40 have 1st degree relative with Pagetrsquos Genetics
inheritance most cases are spontaneous hereditary
familial clusters have been described with ~40 autosomal dominant transmission mutations
at least 4 genes have associated with Pagets disease (amp other disorders of bone turnover) most important is SQSTM1 (p62Sequestosome)
tend to have severe Paget disease
Environmental Arsenic Animals cattle dogs
Pathophysiology Abnormal osteoclastsuarrquantity uarrsize uarractivity uarr of nuclei
Aggressive focal bone resorption makes large cavities in bone
Leads to osteoblast recruitment and overactive osteoblastic activity
Rapid disorganized bone formation
New bone isCoarse disorganized irregular woven
Less resistant to forces there4Prone to deformity and fracture
3 Phases of Disease1) OsteoclasticResorptivePhase Bursts of osteoclastic activity causing bone resorption Lytic lesions trabecular and cortical thinning Osteolytic ldquofrontsrdquoadvance longitudinally from bone
end toward middle ( ldquoVrdquoor ldquoflamerdquoshaped ~1cmyr)
2) OsteoblasticSclerotic or Mixed Phase Mixed osteoclastic and osteoblastic activity Net activity is osteoblastic with deposition of
structurally abnormal bone Bone expansion hyperostosis osteosclerosis
heterogeneous ossification
3-Late ldquoBurn OutrdquoPhasedarrActivity End result widened heterogeneously ossified
but generally sclerotic bones with irregular thickened trabeculae
Phases correlate radiologically and histologically
1048710All 3 Phases may be present simultaneously in the same patient or the same bone
Diseas location Monostotic (25) or polyostotic(75) 1048710Typically affectsPelvis (70) Femur (55) Lumbosacralspine (53) Skull (42) Tibia (32) Rarely in hands feet
1048710No bone-to-bone spread
Clinical Presentation and Complications Usually asymptomatic
Incidental findingAbnormal radiograph or other imaging Abnormal labs (uarrAlkPhos)
Bone pain Constant 1048710Poorly localized 1048710Present at rest
Worse on weight-bearing
pain may be the presenting symptom due to
stress fractures increased vascularity and warmth
new onset intense pain and swelling be suspicious for Pagets secondary sarcoma in a patient with a known history of Pagets who
complains of new onset intense pain and swelling cardiac symptoms
can present with high-output cardiac failure particularly if largemultiple lesions amp pre-existing diminished cardiac function
Bonelimb deformity
Fracture
Arthropathy
uarrincidence of joint disease 1048710Specific pattern of joint diseases in hip uarrfreq of coxa vera protrusio concentric joint space narrowing
uarrSkin temperature
Hypervascularity due to uarrbone turnover activity
uarrbone turnover causes uarrcardiac demands and may lead to high-output heart failure
High-output cardiac failure is caused by the numerous arteriovenous fistulas present in the pagetic bones
Neurologic complaints
Hearing lossvertigotemporal bone involvement with auditory nerve compression
1048710Cranial nerve palsies 1048710Spine involvementMechanical cord compression ldquovascular steal
Hypercalcemia
Rare 1048710Usually inactive or bed-ridden patients 1048710Signs amp SymptomsNausea vomiting MSK aches hyper-reflexia weakness
polyuria headache lethargy altered mental status hellipcoma
Malignant transformation Pagets sarcoma
less than 1 will develop malignant Pagets sarcoma (secondary sarcoma)
osteosarcoma is the most common followed by fibrosarcoma and chondrosarcoma
most common in pelvis femur and humerus Pagets sarcoma has a poor prognosis
5-year survival for non-metastatic Pagets sarcoma is less than 5 appropriate treatment for Pagets sarcoma includes chemotherapy
and wide surgical resection Pagets sarcoma typically presents as a destructive lesion without
periosteal reaction
Diagnosis Clinical assessment Characteristic radiographic appearance Labs (uarrAlkPhos) Bone Scan Usually benign and multiple lesions in old
patients are pagets hyperparathyroidism and bone infarcts
Rarely CT MRI Biopsy
Long bones bend across the trajectories of mechanical stress thus the tibia bows anteriorly and the femur anterolaterally The limb looks bent and feels thick and the skin is unduly warm ndash hence the term lsquoosteitisdeformansrsquo If the skull is affected it enlarges the patient may complain that old hats no longer fit The skull base may become flattened (platybasia) giving the appearance of a short neck In generalized Pagetrsquos disease there may also be considerable kyphosis so the patient becomes shorter and ape-like with bent legs and arms hanging in front of him Cranial nerve compression may lead to impaired vision facial palsy trigeminal neuralgia or deafness Another cause of deafness is otosclerosisVertebral thickening may cause spinal cord or nerve root compression Steal syndromes in which blood is diverted from internal organs to the surrounding skeletal circulationmay cause cerebral impairment and spinal cord ischaemia If there is also spinal stenosis the patient develops typical symptoms of lsquospinal claudicationrsquo and lower limb weakness
Radiographs coarsened trabeculae which give the bone a blastic
appearance both increased and decreased osteodensity may exist
depending on phase of disease lytic phase
lucent areas with expansion and thinned intact cortices blade of grass or flame-shaped lucent advancing edge
mixed phase combination of lysis and sclerosis with coarsened trabeculae
sclerotic phase bone enlargement with cortical thickening sclerotic and lucent
area
remodeled cortices loss of distinction between cortices and medullary cavity
long bone bowing bowing of femur or tibia
fractures hip and knee osteoarthritis osteitis circumscripta
(cotton wool exudates) in skull Pagets secondary sarcoma
shows cortical bone destruction soft tissue mass
MRI may show lumbar spinal stenosis
Bone scan accurately marks site of disease intensely hot in lytic and mixed phase less hot in sclerotic phase
CT scan cortical thickening and coarsened trabeculae
CTMRI Incidental finding Evaluation of atypical presentations
neurological involvement and possible malignant transformation
CT trabecularcortical thinning thickening irregularity
MRI non-specific marrow changes
BiochemistrySerum AlkPhosEnzyme found in osteoblastic membrane Indicator of osteoblastic activity uarrin Pagetrsquos but can be normal Levels correlate with disease extent and activity elevated urinary hydroxyproline (collagen breakdown marker) increased urinary N-telopeptide alpha-C-telopeptide
and deoxypyridinoline normal calcium levels
Other recommended tests ESR -elevation may indicate malignant transformation
CRP Ca -hypercalcemiamay occur in Pagetrsquos PO4 25-hydroxyvitamin D -rule out osteomalacia LFTs-rule out liver disease
Diagnostic Biopsy Diagnosis is usually achieved clinically and by
plain radiographic appearance Biopsy rarely required
Characteristic HistopathologyDisorganized immature trabeculararchitecture with irregular cement lines (ldquomosaicrdquopattern)
Rimming osteoblasts andor multinucleated osteoclasts
Management Options (May require no treatment if asymptomatic)
Supportive Care Pharmacologic Surgical (OrthopedicNeurosurgical
Supportive Care Occupational therapy Physical aides Counseling for fall+fracture prevention
Physical therapy Analgesics Weight control
Pharmacologic ManagementGoals Relieve symptoms and Prevent potential
complications Normalization of serum AlkPhos associated
with better long-term outcomes and disease control
Indications to treat Pain Deformity Neurologic symptoms Asymptomatic but high-risk for complications
(prophylactic) Management of hypercalcemia(rare) Pre-op reduce blood flow and potential
operative blood loss
Calcitonin is the most widely used It reduces bone resorption by decreasing both the activity and the number
of osteoclasts serum alkaline phosphatase and urinaryhydroxyproline levels are lowered Salmon calcitonin is more effective than the porcine variety subcutaneous injections of 50ndash100 MRC units are given daily until pain is relieved and the alkaline phosphatase levels are reduced and stabilized Maintenance injections once or twice weekly may have to be continued indefinitely but some authorities advocate stopping the drug and resuming treatment if symptoms recur Calcitonin can also be administered in a nasal spray Bisphosphonates bind to hydroxyapatite crystals
inhibiting their rate of growth and dissolution It is claimed that the reduction in bone turnover following their use is associated with the formation of lamellar rather than woven bone and that even after treatment is stopped there may be prolonged remission of disease (Bickerstaff et al 1990) Etidronate can be given orally (always on an empty stomach) but dosage should be kept low (eg 5 mgkg per day for up to 6 months) and vitamin D and calcium should also be given lest impaired bone mineralization results inosteomalacia The newer bisphosphonates (eg alendronate or pamidronate) do not have this disadvantage so they should be used as the treatment of choice they produce remissions even with shortcourses of 1 or 2 weeks
BisphosphonatesSynthetic analogues of inorganic phosphate adhere to mineralized surfaces
Ingested selectively by osteoclasts Disrupts enzyme pathways and reduces osteoclastic bone resorption
calcitonin causes osteoclasts to shrink in size and decreases their bone resorptive activity within minutes administered subcutaneously or intramuscularly
teriparatide is contraindicated in Pagets disease due to risk of secondary osteosarcoma
Surgical Management Few require surgery
Common Procedures Corrective osteotomy of long bone deformity indications
fractures through pathologic bowing of long bones impending pathologic fracture of long bone with bowing deformity
Arthroplasty (hip knee) the most common complications include
malalignment with knee arthroplasty bleeding with hip arthroplasty
Combination arthroplasty with osteotomy Fracture fixation
Preoperative Considerations Medical assessment for extraskeletalmanifestations eg high-
output heart failure
Medical treatment of active disease Preoperative autologousblood donation
Thorough planningeg good quality x-rays for templatingand device selection
Intraoperative Considerations Blood salvage system Expansileapproach + soft tissue release Sharp reamersburrsdrills for IM access Extramedullaryguidenavigation systems Concomitant osteotomy
PostoperativeConsiderations Monitoring for cardiac complications Continued medical tx of active disease
uarrHeterotopic ossification Prophylaxis against HO
Possible future excision of HO for painROM
1-Tieg provides a review of Pagets disease of bone and treatment indications In his review he discusses that most patients with Pagets disease are asymptomatic but in those that do present pain is the most common presenting symptom He recommends medical and surgical treatment of asymptomatic patients who have active disease at sites where complications are likely to develop
Altman did a review of 290 patients with Pagets disease of bone His findings showed 83 had one or more rheumatic syndromes He found the rate of osteoarthritis related to Pagets disease was elevated in the hip and knee Rheumatoid arthritis hyperuricemia and gout did not appear increased in this group
Mangham et al looked the rate of secondary sarcomas as a result of Pagets disease of bone They found the rate to be around 03 with male predominance They also found that widespread skeletal involvement by Pagets disease was not a significant risk factor for malignant transformation
Interesting views about pagets
Smith et al reviewed the pathologic complications of Pagets bone disease Pagets bone disease commonly causes osseous weakening (deformity and fracture) and arthritis in the hip joint Management of end stage disease is successful with cemented and cementless total hip arthroplasty Bleeding is the most common intra- and post-operative complication of surgery
Gabel et al retrospectively reviewed thirteen patients who had had sixteen total knee arthroplasties for Pagetic gonarthrosis Unlike total hip arthroplasty surgery Paget disease did not increase the amount of blood lost during the operation or in the postoperative period The most common complication associated with total knee arthroplasty was malalignment
Hansen et al reviewed the incidence of osteosarcomas complicating Pagets Disease Of the typical sites that are usually involved in Pagets disease (eg spine pelvis femur tibia and humerus) secondary osteosarcoma tends to spare the spine
Shaylor et al reported the mortality rates in 26 patient with osteosarcoma secondary to Paget s disease There was a 47 mortality at 1 year and 75 at 2 years from diagnosis In their series no patient survived for 5 years All patients died of metastatic disease
Langston et al conducted a randomized trial that compared the results of symptomatic treatment versus intensive bisphosphonate therapy in patients with Pagets disease Clinical fractures occurred in 46 of 661 patients (70) in the treatment group compared with 49 of 663 patients (74) in the symptomatic treatment group They concluded that bisphosphonates did not show a significant beneficial impact on pain quality of life or fracture incidence
Hadjipavlou et al reviewed Pagets disease of the bone and its management Farmers have been shown to have an increased incidence of Pagets disease Average age at presentation is in the 5th and 6th decade Symptomatic individuals are recommended to be treated initially with medical management They suggest that bisphosphonates are more effective than calcitonin at suppressing the histological and biochemical activity in Pagetrsquos disease
Summary Epid Very common in elderly Path Abnormal osteoclastshellipuarrbone
turnoverhellipdeposition of abnormal bone SampS Pain deformity fracture arthropathy Labs uarrAlkPhos X-ray Characteristic coarse thickened
trabeculae Bone scan Very hot Rx Bisphosphonates Surgery for arthropathy fracture painful
deformity
A 65-year-old male presents with increasing shoulder pain over the past 9 months He is otherwise healthy and has no other complaints Radiograph of his shoulder is shown in Figure A Whole body bone scan and biopsy photograph are shown in Figures B and C What is the most appropriate treatment for this patient
1 Referral to endocrinology 2 Radiation therapy and chemotherapy 3 Wide resection and reconstruction 4 Radiation therapy wide resection and reconstruction 5 Chemotherapy wide resection and reconstruction
Histiocytosis X or Langerhans cell histiocytosis is a spectrum of diseases of the reticuloendothelial system with one of three general presentations Eosinophilic granuloma (EG)
usually a single self-limited lesion found in younger patients
Hand-Schuller-Christian disease (HSC) chronic disseminated form with bone and visceral lesions also known as Langerhans cell histiocytosis with visceral
involvement Letterer-Siwe disease (LSD)
fatal form that occurs in young children
Eosinophilic granuloma
Epidemiology demographics
most commonly occurs in children (80 of afflicted lt 20 years of age)
HSC disease presents in children gt 3 years of age LSD occurs in children lt 3 years of age Male to female ratio of 21
location eosinophilic granuloma
commonly presents in the skull ribs clavicle scapula mandible
isolated lesions of the spine (thoracic most common) can also occur in diaphyseal regions of long bones and the
pelvis HSC
multiple bony sites multiple lytic skull lesions visceral involvement of the lungs spleen liver skin lymph
nodes
Genetics no clear genetic pattern of inheritance or locus has
been determined Prognosis
EG isolated involvement generally treatable with local
management spine lesions can spontaneously resolve
HSC prognosis depends on response to chemotherapy worsening prognosis with increasing extraskeletal
involvement LSD
generally fatal in children lt 3 years of age
Symptoms skeletal involvement
pain and swelling at the region of involvement limping can be seen with pelvic or lower extremity
involvement vertebral involvement
localized or diffuse back pain increasingly kyphotic posture radiculopathy can occur with more aggressive lesions
HSC classic triad of
multiple lytic skull lesions diabetes insipidus
increased thirst and water intake exopthalmos
visceral involvement diffuse or nonspecific abdominal or chest pain
Radiographs general
known as the great mimicker as it appears similar to many lesions radiographic differential includes osteomyelitis leukemia lymphoma
fibrous dysplasia or Ewings sarcoma diaphyseal lesions
well defined intramedullary lytic or punched-out lesion cortex may be thinned expanded or destroyed may have periosteal reaction
metaphyseal lesions extend up to but not through the physis less central location than diaphyseal lesions
spinal lesions vertebra plana (flattened vertebrae) in spine increased kyphosis
cranial involvement multiple punched-out lytic lesions
MRI may show a soft tissue mass adjacent to boney lesions
Bone scan generally shows increased uptake in the region of boney lesion
Histology Langerhans cells
mononuclear histiocyte-like cells with oval nuclei with well-defined round or oval cytoplasm
a prominent nuclear groove (coffee bean nuclei) can be seen in most of the nuclei
eosinophilic cytoplasm (pink generally) stain with CD1A electronmicroscopy
birbeck granules seen inside Langerhans cells mixture of inflammatory cells also present giant cells are present lack of nuclear atypia and atypical mitoses
differentiates this condition from malignant conditions such as Ewings sarcoma lymphoma of bone and metastatic neuroblastoma which may look similar based on the round cells alone
eosinophilic cytoplasm (pink generally)
Treatment
bullNonoperative bull observation alone
bull indications bull a self-limited process and it is reasonable to treat with observation alone
bull bracing bull indications
bull to prevent progressive kyphosis of the spinebull outcomes
bull will correct deformity in 90 of patientsbull vertebral lesions generally regain 50 of their height
bull low dose irradiation (600-800 cGy) bull indications
bull indicated for lesions in the spine that compromise stability neurologic statusbull lesions not amenable to injection or open treatment
bull outcomes bull effective for most lesions
bull chemotherapy bull indications
bull diffuse HSCbull outcomes
bull prognosis is improved with less severe extraskeletal involvementbull corticosteroid injection
bull indications bull isolated lesions bull can be performed after curettage as well
Operative curettage and bone grafting
indications for lesions that endanger the articular surface or are a risk for
impending fractures spinal deformity correction
indications progressive spine deformity refractory to bracing
approximately 10 of patients with spine lesion will need operative intervention for deformity correction
Destructive multiple lesion in young patientsAre eosinophilic granuloma lymphoma and leukemiaLymphoma is unlikely to present with exopthalmos diabetes insipidus or vertebra plana Lymphoma bone lesions are lytic and appear moth eatenpermeative on radiographs
Figure A shows a skin lesion typical of eosinophillic granuloma Figure B shows a lytic lesions without significant surrounding sclerosis as is characteristic of eosinophilic granuloma Figure C shows the characteristic histology of multiple eosinophils with their characteristic oval coffee bean nuclei and staining pattern of purpleredpink cytoplasm (depending on the stain) Importantly the histology slide lacks a malignant appearance (no cellular atypia or mytotic complexes and low nuclearcytoplasmic ratio)
Formation of bone in atypical extraskeletal tissues usually occurs
spontaneously or following trauma within 2 months of neurologic injury (brain or spinal cord)
most common location is between muscle and joint capsule Epidemiology
incidence (see table below)
demographics malefemale = 21 especially men with hypertrophic osteoarthritis and women gt65y
location traumatic brain injury or stroke
hip gt elbow gt shoulder gt knee elbow HO more common following brain trauma
occurs on affected (spastic) side rarely in the knee (TBI)
spinal cord injury hip gt knee gt elbow gt shoulder hip flexors and abductors gt extensors or adductors medial aspect of the knee
Heterotopic Ossification
Risk factors
Pathophysiology exact cause of HO is not known but there appears to be a
genetic pre disposition experimental HO associated with
tissue expression of BMP IT IS SAID TO BE CAUSED BY activation and proliferation of
mesenchymal stem cells Associated conditions
orthopaedic manifestations pathologic fractures
from decreased joint ROM and osteoporotic bone nerve impingement soft tissue contractures contributing to the formation of
decubitus ulcers joint ankylosis HO after THA adversely affects outcome of THA
nonorthopaedic conditions skin maceration and hygiene problems
Pathophysiology Early in the formation of HO oedema with exudative
infiltrate is present followed by fibroblastic proliferation and immature connective tissue formation Posteriorly osteoid formation is seen with the subsequent deposition of bone matrix Primitive osteoid is deposited as small masses in the periphery early (within the first two weeks) and osteoblasts are noted located irregularly Osteoblasts produce tropocollagen which polymerizes to form collagen and secrete alkaline phosphatase which allows calcium to precipitate and the mineralization of bone matrix As mineralization progresses amorphous calcium phosphate is progressively replaced by hydroxyapatite crystals During the following weeks the lesion matures with a centripetal pattern and after 6-12 months an appearance of true bone is noted The new bone is always extra-articular and can be contiguous with the skeleton but generally does not involve the periosteum
IN SUMMARY It has been postulated that three conditions
must be met to achieve heterotopic bone formation ---a stimulating event oestrogenic precursor cells and a proper environment LIKE hypercalcaemia tissue hypoxia pH changes (alkalosis) or prolonged immobilization
ClassificationbullSubtypes
bull neurogenic HO bull Four clinical stages of HO in people with spinal cord injury were
described by Nicholas in 1973
bull traumatic myositis ossificans bull fibrodysplasia ossificans progressiva (Munchmeyers Disease)
Neurogenic HO Symptoms
painless loss of ROM interferes with ADL CRPS symptoms fever
Physical exam inspection
warm painful swollen joint may have effusion skin problems
decubitus ulcers from contractures around skin muscles ligaments
skin maceration and hygiene problems motion
decreased joint ROM joint ankylosis with HO after TKA might develop quad muscle snapping or patella
instability neurovascular
peripheral neuropathy HO often impinges on adjacent NV structures
Imaging
bullRadiographs bull findings
bull ossification usually easy to visualize bull maturity of HO
bull the appearance of a bony cortex suggests mature HObull sharp demarcation from surrounding tissue bull trabecular pattern
bull sensitivity and specificity bull not useful for early diagnosisbull only useful at 1 week after onset of symptoms
bull calcium is deposited 7-10 days later than symptom onsetbullUltrasound
bull indications bull for early diagnosis of hip HO
bull findings bull echogenic surfaces with posterior acoustic shadowing
bullCT bull indications
bull useful for preoperative planning bullTriphasic bone scan
bull indications bull best for early diagnosis bull most commonly used diagnostic study
Radiographs are extremely useful in the staging of heterotopic ossification and will show the development of sharp cortical margins once the lesion has reached maturity
Heterotopic bone is a condition in which lamellar bone forms in non-ossified soft tissues In the early stages studies such as MRI and bone scan are more sensitive for diagnosis as radiographs may appear normal for the first three weeks After the appropriate diagnosis is made sequential radiographs are useful for monitoring the progression of the ossification Once it has reached the mature stage sharp cortical margins will appear and surgical resection may be considered
lab
Labs elevated serum alkaline phosphatase (gt250IUL)
ALP removes inhibitors of mineralization nonspecific may be elevated with skeletal trauma cannot determine maturity of HO elevated 12wks after surgery is predictor
elevated CRP correlates with inflammatory activity of HO better than ESR normalization of CRP may correlate with maturity of HO
elevated ESR (gt35mmh) 12wks after THA is predictor
elevated CK correlates with involvement of muscle extent of muscle
involvement Histology
mature fatty bone marrow mature trabecular bone
Heterotopic ossification (HO) most commonly occurs at the amputation site if the amputation was performed thru the zone of injury especially if the injury was a blast mechanism
Symptomatic heterotopic ossification of the quadriceps may occur following placement of a large-diameter Steinmann pin for the purpose of temporary skeletal traction
TreatmentThe prevention of heterotopic ossification is focused on three basic principles disrupting the inductive signalling pathways altering the osteoprogenitor cells or modifying the environment
bullphysiotherapy should involve an assisted range of movement exercises with gentle stretch and terminal resistance trainingbullProphylaxis
bull bisphosphonates amp NSAIDS bull indications
bull although no literature supports are commonly usedbull technique
bull indomethacin is most commonly used bull dose is 75mgday for 10days to 6 weeks
bull perioperative radiation bull indications
bull although no literature supports commonly usedbull is thought to be effective by blocking osteoblast differentiation
bull technique bull a single perioperative dose of 700cGy can be given either 4
hours preop or within 72 hours postoperatively bull lt550cGy not effective
Nonsteroidal anti-inflammatory drugs (NSAIDs) These drugs have demonstrated good results in
preventing heterotopic ossification after total hip arthroplasty
A direct effect of NSAIDs on the formation of heterotopic ossification has been described due to the inhibition of the differentiation of mesenchymal cells into oestrogenic cells There is also an indirect effect which refers to the inhibition of bone remodelling by suppression of the prostagland unmediated inflammatory response (specifically PGE-2)
Indomethacin has been considered a useful medication for heterotopic ossification prophylaxis following total hip replacement
prescribed for three to six weeks in a dose of 75mgday within two months of the injury may reduce the incidence of heterotopic ossification by two to three times
Biphosphonates inhibits precipitation of calcium phosphate and blocks the aggregation and mineralisation of hydroxyapatite crystals In primary prevention Banovac et al [56] have suggested that the treatment should begin as soon as elevated alkaline phosphatase is diagnosed or positive findings in ultrasonography or bone scans are shown In addition disphosphonates could have long-term effects on prevention when the treatment is finished
Posttraumatic wide exposure and surgical resection
indications severe loss of motion and decreased function
technique wide exposure required to identify all neurovascular
structures that may be involved timing of resection (controversial)
marked decrease in bone scan activity AND normalization of ALP
6 months following general trauma 1 year following SCI 15 years following TBI
some data suggests equivalent results when comparing early versus late resection
postop follow with 5 day course of indomethacin early gentle joint mobilization
The surgery is necessary in patients with symptomatic HO and unsuccessful medical treatment such as
Loss of range of motion and ankylosis with associated functional disability such as sitting difficulties
Complications of immobility such as pressure ulcers
Facilitate rehabilitation and recovery of muscular atrophy secondary to prolonged immobilisation
Difficulties of appropriate hygiene because access to the perineum or bladder care is needed
Severe pain refractory to analgesia Vascular andor nerve compression
Advantages to early excision of heterotopic ossification (vs waiting for maturation) include decreased soft tissue contracture better definition between heterotopic and native bone and decreased waiting time for the patient When the soft tissue envelope is benign one may proceed with operative release While waiting for normalization of alkaline phosphatase levels inactivity on bone scan or radiographic maturity may decrease risk of recurrent heterotopic ossification delaying operative release for these reasons has not been shown to improve results of final elbow range of motion after contracture release
Gartland recommended surgery after six months following traumatic heterotopic ossification one year following spinal cord injury and 18 months after head injury
In the past waiting until maturity in order to minimize the rate of recurrence after the surgical treatment was recommended Nevertheless recent studies do not confirm a higher rate of recurrence when the HO is excised in an earlier phase In addition a long delay before surgery leads to ankylosis a high degree of osteoporosis and more extensive intra-articular injuries These findings are associated with bad functional results and potential complications
Should you wait till lesion maturation
Prevention byHandle tissue carefully Avoid excess bleeding Achieve good hemostasis Beware of lesions that span internervous tissue planes
but if it happens resection of a large enough amount of bone to allow improvement of the range of motion and trying to preserve the joint
Our aim must be
A reactive process that is characterized by a well-circumscribed proliferation of fibroblasts cartilage and bone within muscle
A form of heterotopic ossification that is the result direct trauma intramuscular hematoma
most common location is the diaphysis of long bones Must differentiate from tumors Fibrodysplasia ossificans progressiva (FOP) is a rare subtype of heterotopic ossification
involves mutation of the ACVR1 gene (activin A type I receptor gene a BMP type-1 receptor)
Epidemiology demographics
most common in young active males (15 to 35 years old) body locations
quadriceps brachialis and gluteal muscles Genetics
almost always a posttraumatic condition Prognosis
usually self limiting mass usually begins to decrease in size after 1 yea
Myositis ossificans
PresentationbullSymptoms
bull pain tenderness swelling and decreased range of motion that usually presents within days of the injury
bull pain and size of the mass decrease with timebull mass increases in size over several months(usually 3 to 6 cm)
bull after the mass stops growing it becomes firmbullPhysical exam
bull palpable soft tissue massbull restricted range of motion
ImagingbullRadiographs
bull peripheral bone formation with central lucent areabull may appear as dotted veil pattern
bullMRI with gadolinium bull rim enhancement is seen within the first 3 weeks
bullCT scan bull lesion has an eggshell appearance
bullCharacteristic histology shows zonal pattern bull periphery of lesion
bull mature trabeculae of lamellar and woven bonebull calcification seen on xray
bull center of the lesion bull irregular mass of immature fibroblastsbull cartilage component may be presentbull (no calcification seen on xray) bull no cellular atypia seen
Treatment
bullNonoperative bull rest range of motion exercises and activity modification
bull passive stretching is contraindicated (makes it worse)bull physical therapy
bull utilized to maintain range of motionbull radiographic monitoring
bull obtained to confirm maturation of the lesionbullOperative
bull surgical excision bull indicated only if it remains a problem after it maturesbull do not operate in acute phase wait at least six months
bull excision of the lesion within 6 to 12 months predisposes to local recurrence
A 26-year-old man presents with generalized back and joint stiffness and difficulty opening his mouth His elder sister has similar complaints Since childhood he has had 3 surgeries for excision of recurrent bony prominences around his knees He walks with a stooped over posture seen in Figure A Radiographs of his feet knee hip and spine are seen in Figures B-E respectively
fibrodysplasia ossificans progressiva
Stone Man Disease) which involves a mutation of the ACVR1
There are 2 hallmark characteristics progressive heterotopic ossification (muscles fascia tendons ligaments and joint capsules) and congenital malformation of the great toe (hallux valgus malformed first metatarsal and monophalangism) BMP4 which contributes to the formation of the skeleton in the normal embryo is implicated in this disease
Complications
bullHematoma and intraoperative bleedingbullInfection
bull higher rate of infection following joint arthroplasty if HO is present
bullFractures of osteoporotic bone bull osteopenic from disusebull during surgery or physiotherapy
bullRecurrence bull recurrence rate correlates with neurological injury
bull greater recurrence if severe neurological compromisebullAVN
bull if extensive dissection or stripping is required
HTO AND ISS
When ISS is below 25 the mortality risk is minimal and above 25 it is an almost linear increase
When ISS is 50 the mortality is 50 When above 70 it is close to 100 If an injury is assigned an AIS of 6 (unsurvivable injury) the ISS score is
automatically assigned to 75 Highest ISS score obtainable is 75 For trauma patients of vehicular accidents the scoring system is important
for assessing the effectiveness of medical care in reducing morbidity and mortality
Advantages virtually the only anatomical scoring system in use correlates linearly with
mortality morbidity hospital stay other measures of severity
Weaknesses Any error in AIS scoring increases the ISS error Many different injury patterns can yield the same ISS score Injuries to different body regions are not weighted Not a useful triage tool as a full description of patient injuries is not known
prior to full investigation amp operation
risk factors periosteal stripping off anterior femur male gender obesity post traumatic deformity Anterior and anterolateral approach Cementless
Neurogenic HO around the hip due to SCI occurs more often in the medial region than in the lateral region with ossified tissues extending from the pubic symphysis to the anteromedial femoral shaft posterior to the femoral neurovascular structures Ossification is also seen anteriorly involving the iliopsoas and femoral neurovascular structures laterally within gluteus minimus and posteriorly extending from the ilium to the posterior femur encasing the sciatic nerve
HTO AROUND hip and knee
The Brooker Classification of Heterotopic Ossification around the hip joint Class I has islands of bone within the soft tissues Class II has bone spurs from the pelvis or proximal end of the femur leaving at least 1 cm between opposing surfaces Class III has bone spurs from the pelvis andor proximal end of the femur reducing the space between opposing bone surfaces to less than 1 cm Class IV shows apparent bone ankylosis of the hip
Region I - Heterotopic ossifications are strictly below the tip of the greater trochanter
Region II - Heterotopic ossifications are below and above the tip of the greater trochanter
Region III - Heterotopic ossifications are strictly above the tip of the greater trochanter
Grade A - Single or multiple heterotopic ossifications are less than 10 mm in maximal extent without contact with the pelvis or the femur
Grade B - Heterotopic ossifications are greater than 10 mm without contact with the pelvis but with possible contact with the femur there is no bridging from the femur to the proximal part of the greater trochanter and no evidence of ankylosis
Grade C - Ankylosis by means of firm bridging from the femur to the pelvis is present
Shmidt classification
excision may be performed The results of this procedure are varied Patients may find that their range of movement improves but pain relief is likely to be limited
A patient with heterotopic ossification following total hip arthroplasty is thought to have a 90-100 chance of developing it on the contralateral hip if this hip also undergoes total arthroplasty
it would be prudent to minimize the risk of heterotopic ossification developing after arthroplasty by performing surgery whereby the following are ensured
Exposure is meticulous Retraction is performed carefully and soft tissue
is handled carefully Irrigation is adequate Devitalized tissue is excised Hemostasis is adequate Postoperative drains (when used) are not
retained for longer than necessary Perioperative antibiotic prophylaxis is used Postoperative anticoagulation (when used for
deep vein thrombosis prophylaxis) is carefully controlled
sources of knee stiffness 1-extrinsic severe osteoarthritis of the ipsilateral hip neurologic injury leading to muscle rigidity tight quadriceps or hamstring muscles secondary to muscle injury heterotopic ossification or long-standing juvenile inflammatory conditions limiting knee
range of motion prior to the completion of skeletal growth When extrinsic sources are identified revision total knee arthroplasty is unlikely to be associated with a favorable outcome without correction of the extrinsic problem
2-intrinsic (1) overstuffing of the patellofemoral articulation (2) an
excessively tight flexion andor extension gap (3) a tight posterior cruciate ligament (4) femoral andor tibial malrotation (5) arthrofibrosis and (6) limited bearing excursion in association with a highly conforming mobile-bearing prosthetic design
HTO after TKA
Heterotopic Ossification (HO) following primary Total Knee Replacement (TKR)
Occurs in 3-90 of TKRs 3-grade classification system No correlation between HO and component
alignment or component position
Clinical findings similar to early infection Continuing low-grade fever Warm swollen and erythematous knee Normal blood tests Possibly an association with HLA-A2 and B18 HO patients have worse KSS and function
scores
Patients at HIGH risk for developing HO after TKR (Knee Arthroplasty) (5)
Those with limited postoperative knee flexion
Increased lumbar bone mineral density (BMD) on multivariate analysis (3)
Hypertrophic arthrosis Excessive periosteal trauma Notching of the anterior femur Those who require forced manipulation
after TKA 47 in revision TKR surgery (6) Higher rates in revision TKR cases with
infection (up to 76
DaughertyBell classification of HO of the knee 0 No evidence of HO 1 Bone islands in periarticular soft tissue (no
involvement of femur patella or tibia) or HO within quadriceps expansion measuring lt1 cm
2 Spur formation measuring lt5 cm that involves the femur patella or tibia if more than one bone demonstrates HO separation of HO spurs
measure gt1 cm or HO within quadriceps expansion measuring ge1 cm but lt3 cm
3 Spur formation gt5 cm involving femur patella or tibia if more than one bone demonstrates HO separation of HO spurs measure lt1 cm or HO
within quadriceps expansion measuring ge3 cm 4 Extensive HO of the knee causing ankylosis
class 2 HO begins to involve the major bones of the knee joint with spur formation limited to a size of 5 cm
HO class 2 may be observed in select patients with complete ROM and no reported pain Patients with class 3 HO would likely always benefit from surgical excision
followed by RT prophylaxis Certainly patients in either cohort with a subclass ldquoBrdquo assignment (symptomatic) would
benefit from treatment All patients with class 4 HO require
treatment to alleviate ankylosis
treatment
References Whyte ldquoPagetrsquos Disease of Bonerdquo NEMJ vol 355
2006 Klein and Parvizi ldquoSurgical Manifestations of Pagetrsquos
Diseaserdquo JAAOS vol 14 2006 Orthobullets Campbell Apley Emedicinecom
-Chapter 15 Heterotopic Ossification after Traumatic Brain InjuryBy Jesuacutes Moreta and Joseacute Luis Martiacutenez-de los Mozos DOI 10577257343
Questions
Thank You
Understand the pathology and the management of paget diseaseeiosinophilic granuloma and heterotopic ossification in relation to orthopedic specialty
objectives
Introduction First Described in 1877 by James Paget Chronic non-metabolic bone disorder Characterized by aggressive bone
resorption and abnormal formation and remodeling rArran unbalanced derangement of normal processes
Results in bone deformity structural weakness altered joint biomechanics
Pagets Disease( OSTEITISDEFORMANS)
Epidemiology A disease of middle to advanced age Rare below age
40 Prevalence in US~1 over age 40 15-3 over age 60
Incidence doubles every decade after age 50
MengtWomen (16 1)Geographic variation Highest prevalence
in Britain Australia New Zealand North America and Western Europe
Etiology Unknown
Proposed Theories Viral Paramyxovirus measles virus RSV canine distemper virus
Viral particles seen in pagetic osteoclasts
Genetic5-40 have 1st degree relative with Pagetrsquos Genetics
inheritance most cases are spontaneous hereditary
familial clusters have been described with ~40 autosomal dominant transmission mutations
at least 4 genes have associated with Pagets disease (amp other disorders of bone turnover) most important is SQSTM1 (p62Sequestosome)
tend to have severe Paget disease
Environmental Arsenic Animals cattle dogs
Pathophysiology Abnormal osteoclastsuarrquantity uarrsize uarractivity uarr of nuclei
Aggressive focal bone resorption makes large cavities in bone
Leads to osteoblast recruitment and overactive osteoblastic activity
Rapid disorganized bone formation
New bone isCoarse disorganized irregular woven
Less resistant to forces there4Prone to deformity and fracture
3 Phases of Disease1) OsteoclasticResorptivePhase Bursts of osteoclastic activity causing bone resorption Lytic lesions trabecular and cortical thinning Osteolytic ldquofrontsrdquoadvance longitudinally from bone
end toward middle ( ldquoVrdquoor ldquoflamerdquoshaped ~1cmyr)
2) OsteoblasticSclerotic or Mixed Phase Mixed osteoclastic and osteoblastic activity Net activity is osteoblastic with deposition of
structurally abnormal bone Bone expansion hyperostosis osteosclerosis
heterogeneous ossification
3-Late ldquoBurn OutrdquoPhasedarrActivity End result widened heterogeneously ossified
but generally sclerotic bones with irregular thickened trabeculae
Phases correlate radiologically and histologically
1048710All 3 Phases may be present simultaneously in the same patient or the same bone
Diseas location Monostotic (25) or polyostotic(75) 1048710Typically affectsPelvis (70) Femur (55) Lumbosacralspine (53) Skull (42) Tibia (32) Rarely in hands feet
1048710No bone-to-bone spread
Clinical Presentation and Complications Usually asymptomatic
Incidental findingAbnormal radiograph or other imaging Abnormal labs (uarrAlkPhos)
Bone pain Constant 1048710Poorly localized 1048710Present at rest
Worse on weight-bearing
pain may be the presenting symptom due to
stress fractures increased vascularity and warmth
new onset intense pain and swelling be suspicious for Pagets secondary sarcoma in a patient with a known history of Pagets who
complains of new onset intense pain and swelling cardiac symptoms
can present with high-output cardiac failure particularly if largemultiple lesions amp pre-existing diminished cardiac function
Bonelimb deformity
Fracture
Arthropathy
uarrincidence of joint disease 1048710Specific pattern of joint diseases in hip uarrfreq of coxa vera protrusio concentric joint space narrowing
uarrSkin temperature
Hypervascularity due to uarrbone turnover activity
uarrbone turnover causes uarrcardiac demands and may lead to high-output heart failure
High-output cardiac failure is caused by the numerous arteriovenous fistulas present in the pagetic bones
Neurologic complaints
Hearing lossvertigotemporal bone involvement with auditory nerve compression
1048710Cranial nerve palsies 1048710Spine involvementMechanical cord compression ldquovascular steal
Hypercalcemia
Rare 1048710Usually inactive or bed-ridden patients 1048710Signs amp SymptomsNausea vomiting MSK aches hyper-reflexia weakness
polyuria headache lethargy altered mental status hellipcoma
Malignant transformation Pagets sarcoma
less than 1 will develop malignant Pagets sarcoma (secondary sarcoma)
osteosarcoma is the most common followed by fibrosarcoma and chondrosarcoma
most common in pelvis femur and humerus Pagets sarcoma has a poor prognosis
5-year survival for non-metastatic Pagets sarcoma is less than 5 appropriate treatment for Pagets sarcoma includes chemotherapy
and wide surgical resection Pagets sarcoma typically presents as a destructive lesion without
periosteal reaction
Diagnosis Clinical assessment Characteristic radiographic appearance Labs (uarrAlkPhos) Bone Scan Usually benign and multiple lesions in old
patients are pagets hyperparathyroidism and bone infarcts
Rarely CT MRI Biopsy
Long bones bend across the trajectories of mechanical stress thus the tibia bows anteriorly and the femur anterolaterally The limb looks bent and feels thick and the skin is unduly warm ndash hence the term lsquoosteitisdeformansrsquo If the skull is affected it enlarges the patient may complain that old hats no longer fit The skull base may become flattened (platybasia) giving the appearance of a short neck In generalized Pagetrsquos disease there may also be considerable kyphosis so the patient becomes shorter and ape-like with bent legs and arms hanging in front of him Cranial nerve compression may lead to impaired vision facial palsy trigeminal neuralgia or deafness Another cause of deafness is otosclerosisVertebral thickening may cause spinal cord or nerve root compression Steal syndromes in which blood is diverted from internal organs to the surrounding skeletal circulationmay cause cerebral impairment and spinal cord ischaemia If there is also spinal stenosis the patient develops typical symptoms of lsquospinal claudicationrsquo and lower limb weakness
Radiographs coarsened trabeculae which give the bone a blastic
appearance both increased and decreased osteodensity may exist
depending on phase of disease lytic phase
lucent areas with expansion and thinned intact cortices blade of grass or flame-shaped lucent advancing edge
mixed phase combination of lysis and sclerosis with coarsened trabeculae
sclerotic phase bone enlargement with cortical thickening sclerotic and lucent
area
remodeled cortices loss of distinction between cortices and medullary cavity
long bone bowing bowing of femur or tibia
fractures hip and knee osteoarthritis osteitis circumscripta
(cotton wool exudates) in skull Pagets secondary sarcoma
shows cortical bone destruction soft tissue mass
MRI may show lumbar spinal stenosis
Bone scan accurately marks site of disease intensely hot in lytic and mixed phase less hot in sclerotic phase
CT scan cortical thickening and coarsened trabeculae
CTMRI Incidental finding Evaluation of atypical presentations
neurological involvement and possible malignant transformation
CT trabecularcortical thinning thickening irregularity
MRI non-specific marrow changes
BiochemistrySerum AlkPhosEnzyme found in osteoblastic membrane Indicator of osteoblastic activity uarrin Pagetrsquos but can be normal Levels correlate with disease extent and activity elevated urinary hydroxyproline (collagen breakdown marker) increased urinary N-telopeptide alpha-C-telopeptide
and deoxypyridinoline normal calcium levels
Other recommended tests ESR -elevation may indicate malignant transformation
CRP Ca -hypercalcemiamay occur in Pagetrsquos PO4 25-hydroxyvitamin D -rule out osteomalacia LFTs-rule out liver disease
Diagnostic Biopsy Diagnosis is usually achieved clinically and by
plain radiographic appearance Biopsy rarely required
Characteristic HistopathologyDisorganized immature trabeculararchitecture with irregular cement lines (ldquomosaicrdquopattern)
Rimming osteoblasts andor multinucleated osteoclasts
Management Options (May require no treatment if asymptomatic)
Supportive Care Pharmacologic Surgical (OrthopedicNeurosurgical
Supportive Care Occupational therapy Physical aides Counseling for fall+fracture prevention
Physical therapy Analgesics Weight control
Pharmacologic ManagementGoals Relieve symptoms and Prevent potential
complications Normalization of serum AlkPhos associated
with better long-term outcomes and disease control
Indications to treat Pain Deformity Neurologic symptoms Asymptomatic but high-risk for complications
(prophylactic) Management of hypercalcemia(rare) Pre-op reduce blood flow and potential
operative blood loss
Calcitonin is the most widely used It reduces bone resorption by decreasing both the activity and the number
of osteoclasts serum alkaline phosphatase and urinaryhydroxyproline levels are lowered Salmon calcitonin is more effective than the porcine variety subcutaneous injections of 50ndash100 MRC units are given daily until pain is relieved and the alkaline phosphatase levels are reduced and stabilized Maintenance injections once or twice weekly may have to be continued indefinitely but some authorities advocate stopping the drug and resuming treatment if symptoms recur Calcitonin can also be administered in a nasal spray Bisphosphonates bind to hydroxyapatite crystals
inhibiting their rate of growth and dissolution It is claimed that the reduction in bone turnover following their use is associated with the formation of lamellar rather than woven bone and that even after treatment is stopped there may be prolonged remission of disease (Bickerstaff et al 1990) Etidronate can be given orally (always on an empty stomach) but dosage should be kept low (eg 5 mgkg per day for up to 6 months) and vitamin D and calcium should also be given lest impaired bone mineralization results inosteomalacia The newer bisphosphonates (eg alendronate or pamidronate) do not have this disadvantage so they should be used as the treatment of choice they produce remissions even with shortcourses of 1 or 2 weeks
BisphosphonatesSynthetic analogues of inorganic phosphate adhere to mineralized surfaces
Ingested selectively by osteoclasts Disrupts enzyme pathways and reduces osteoclastic bone resorption
calcitonin causes osteoclasts to shrink in size and decreases their bone resorptive activity within minutes administered subcutaneously or intramuscularly
teriparatide is contraindicated in Pagets disease due to risk of secondary osteosarcoma
Surgical Management Few require surgery
Common Procedures Corrective osteotomy of long bone deformity indications
fractures through pathologic bowing of long bones impending pathologic fracture of long bone with bowing deformity
Arthroplasty (hip knee) the most common complications include
malalignment with knee arthroplasty bleeding with hip arthroplasty
Combination arthroplasty with osteotomy Fracture fixation
Preoperative Considerations Medical assessment for extraskeletalmanifestations eg high-
output heart failure
Medical treatment of active disease Preoperative autologousblood donation
Thorough planningeg good quality x-rays for templatingand device selection
Intraoperative Considerations Blood salvage system Expansileapproach + soft tissue release Sharp reamersburrsdrills for IM access Extramedullaryguidenavigation systems Concomitant osteotomy
PostoperativeConsiderations Monitoring for cardiac complications Continued medical tx of active disease
uarrHeterotopic ossification Prophylaxis against HO
Possible future excision of HO for painROM
1-Tieg provides a review of Pagets disease of bone and treatment indications In his review he discusses that most patients with Pagets disease are asymptomatic but in those that do present pain is the most common presenting symptom He recommends medical and surgical treatment of asymptomatic patients who have active disease at sites where complications are likely to develop
Altman did a review of 290 patients with Pagets disease of bone His findings showed 83 had one or more rheumatic syndromes He found the rate of osteoarthritis related to Pagets disease was elevated in the hip and knee Rheumatoid arthritis hyperuricemia and gout did not appear increased in this group
Mangham et al looked the rate of secondary sarcomas as a result of Pagets disease of bone They found the rate to be around 03 with male predominance They also found that widespread skeletal involvement by Pagets disease was not a significant risk factor for malignant transformation
Interesting views about pagets
Smith et al reviewed the pathologic complications of Pagets bone disease Pagets bone disease commonly causes osseous weakening (deformity and fracture) and arthritis in the hip joint Management of end stage disease is successful with cemented and cementless total hip arthroplasty Bleeding is the most common intra- and post-operative complication of surgery
Gabel et al retrospectively reviewed thirteen patients who had had sixteen total knee arthroplasties for Pagetic gonarthrosis Unlike total hip arthroplasty surgery Paget disease did not increase the amount of blood lost during the operation or in the postoperative period The most common complication associated with total knee arthroplasty was malalignment
Hansen et al reviewed the incidence of osteosarcomas complicating Pagets Disease Of the typical sites that are usually involved in Pagets disease (eg spine pelvis femur tibia and humerus) secondary osteosarcoma tends to spare the spine
Shaylor et al reported the mortality rates in 26 patient with osteosarcoma secondary to Paget s disease There was a 47 mortality at 1 year and 75 at 2 years from diagnosis In their series no patient survived for 5 years All patients died of metastatic disease
Langston et al conducted a randomized trial that compared the results of symptomatic treatment versus intensive bisphosphonate therapy in patients with Pagets disease Clinical fractures occurred in 46 of 661 patients (70) in the treatment group compared with 49 of 663 patients (74) in the symptomatic treatment group They concluded that bisphosphonates did not show a significant beneficial impact on pain quality of life or fracture incidence
Hadjipavlou et al reviewed Pagets disease of the bone and its management Farmers have been shown to have an increased incidence of Pagets disease Average age at presentation is in the 5th and 6th decade Symptomatic individuals are recommended to be treated initially with medical management They suggest that bisphosphonates are more effective than calcitonin at suppressing the histological and biochemical activity in Pagetrsquos disease
Summary Epid Very common in elderly Path Abnormal osteoclastshellipuarrbone
turnoverhellipdeposition of abnormal bone SampS Pain deformity fracture arthropathy Labs uarrAlkPhos X-ray Characteristic coarse thickened
trabeculae Bone scan Very hot Rx Bisphosphonates Surgery for arthropathy fracture painful
deformity
A 65-year-old male presents with increasing shoulder pain over the past 9 months He is otherwise healthy and has no other complaints Radiograph of his shoulder is shown in Figure A Whole body bone scan and biopsy photograph are shown in Figures B and C What is the most appropriate treatment for this patient
1 Referral to endocrinology 2 Radiation therapy and chemotherapy 3 Wide resection and reconstruction 4 Radiation therapy wide resection and reconstruction 5 Chemotherapy wide resection and reconstruction
Histiocytosis X or Langerhans cell histiocytosis is a spectrum of diseases of the reticuloendothelial system with one of three general presentations Eosinophilic granuloma (EG)
usually a single self-limited lesion found in younger patients
Hand-Schuller-Christian disease (HSC) chronic disseminated form with bone and visceral lesions also known as Langerhans cell histiocytosis with visceral
involvement Letterer-Siwe disease (LSD)
fatal form that occurs in young children
Eosinophilic granuloma
Epidemiology demographics
most commonly occurs in children (80 of afflicted lt 20 years of age)
HSC disease presents in children gt 3 years of age LSD occurs in children lt 3 years of age Male to female ratio of 21
location eosinophilic granuloma
commonly presents in the skull ribs clavicle scapula mandible
isolated lesions of the spine (thoracic most common) can also occur in diaphyseal regions of long bones and the
pelvis HSC
multiple bony sites multiple lytic skull lesions visceral involvement of the lungs spleen liver skin lymph
nodes
Genetics no clear genetic pattern of inheritance or locus has
been determined Prognosis
EG isolated involvement generally treatable with local
management spine lesions can spontaneously resolve
HSC prognosis depends on response to chemotherapy worsening prognosis with increasing extraskeletal
involvement LSD
generally fatal in children lt 3 years of age
Symptoms skeletal involvement
pain and swelling at the region of involvement limping can be seen with pelvic or lower extremity
involvement vertebral involvement
localized or diffuse back pain increasingly kyphotic posture radiculopathy can occur with more aggressive lesions
HSC classic triad of
multiple lytic skull lesions diabetes insipidus
increased thirst and water intake exopthalmos
visceral involvement diffuse or nonspecific abdominal or chest pain
Radiographs general
known as the great mimicker as it appears similar to many lesions radiographic differential includes osteomyelitis leukemia lymphoma
fibrous dysplasia or Ewings sarcoma diaphyseal lesions
well defined intramedullary lytic or punched-out lesion cortex may be thinned expanded or destroyed may have periosteal reaction
metaphyseal lesions extend up to but not through the physis less central location than diaphyseal lesions
spinal lesions vertebra plana (flattened vertebrae) in spine increased kyphosis
cranial involvement multiple punched-out lytic lesions
MRI may show a soft tissue mass adjacent to boney lesions
Bone scan generally shows increased uptake in the region of boney lesion
Histology Langerhans cells
mononuclear histiocyte-like cells with oval nuclei with well-defined round or oval cytoplasm
a prominent nuclear groove (coffee bean nuclei) can be seen in most of the nuclei
eosinophilic cytoplasm (pink generally) stain with CD1A electronmicroscopy
birbeck granules seen inside Langerhans cells mixture of inflammatory cells also present giant cells are present lack of nuclear atypia and atypical mitoses
differentiates this condition from malignant conditions such as Ewings sarcoma lymphoma of bone and metastatic neuroblastoma which may look similar based on the round cells alone
eosinophilic cytoplasm (pink generally)
Treatment
bullNonoperative bull observation alone
bull indications bull a self-limited process and it is reasonable to treat with observation alone
bull bracing bull indications
bull to prevent progressive kyphosis of the spinebull outcomes
bull will correct deformity in 90 of patientsbull vertebral lesions generally regain 50 of their height
bull low dose irradiation (600-800 cGy) bull indications
bull indicated for lesions in the spine that compromise stability neurologic statusbull lesions not amenable to injection or open treatment
bull outcomes bull effective for most lesions
bull chemotherapy bull indications
bull diffuse HSCbull outcomes
bull prognosis is improved with less severe extraskeletal involvementbull corticosteroid injection
bull indications bull isolated lesions bull can be performed after curettage as well
Operative curettage and bone grafting
indications for lesions that endanger the articular surface or are a risk for
impending fractures spinal deformity correction
indications progressive spine deformity refractory to bracing
approximately 10 of patients with spine lesion will need operative intervention for deformity correction
Destructive multiple lesion in young patientsAre eosinophilic granuloma lymphoma and leukemiaLymphoma is unlikely to present with exopthalmos diabetes insipidus or vertebra plana Lymphoma bone lesions are lytic and appear moth eatenpermeative on radiographs
Figure A shows a skin lesion typical of eosinophillic granuloma Figure B shows a lytic lesions without significant surrounding sclerosis as is characteristic of eosinophilic granuloma Figure C shows the characteristic histology of multiple eosinophils with their characteristic oval coffee bean nuclei and staining pattern of purpleredpink cytoplasm (depending on the stain) Importantly the histology slide lacks a malignant appearance (no cellular atypia or mytotic complexes and low nuclearcytoplasmic ratio)
Formation of bone in atypical extraskeletal tissues usually occurs
spontaneously or following trauma within 2 months of neurologic injury (brain or spinal cord)
most common location is between muscle and joint capsule Epidemiology
incidence (see table below)
demographics malefemale = 21 especially men with hypertrophic osteoarthritis and women gt65y
location traumatic brain injury or stroke
hip gt elbow gt shoulder gt knee elbow HO more common following brain trauma
occurs on affected (spastic) side rarely in the knee (TBI)
spinal cord injury hip gt knee gt elbow gt shoulder hip flexors and abductors gt extensors or adductors medial aspect of the knee
Heterotopic Ossification
Risk factors
Pathophysiology exact cause of HO is not known but there appears to be a
genetic pre disposition experimental HO associated with
tissue expression of BMP IT IS SAID TO BE CAUSED BY activation and proliferation of
mesenchymal stem cells Associated conditions
orthopaedic manifestations pathologic fractures
from decreased joint ROM and osteoporotic bone nerve impingement soft tissue contractures contributing to the formation of
decubitus ulcers joint ankylosis HO after THA adversely affects outcome of THA
nonorthopaedic conditions skin maceration and hygiene problems
Pathophysiology Early in the formation of HO oedema with exudative
infiltrate is present followed by fibroblastic proliferation and immature connective tissue formation Posteriorly osteoid formation is seen with the subsequent deposition of bone matrix Primitive osteoid is deposited as small masses in the periphery early (within the first two weeks) and osteoblasts are noted located irregularly Osteoblasts produce tropocollagen which polymerizes to form collagen and secrete alkaline phosphatase which allows calcium to precipitate and the mineralization of bone matrix As mineralization progresses amorphous calcium phosphate is progressively replaced by hydroxyapatite crystals During the following weeks the lesion matures with a centripetal pattern and after 6-12 months an appearance of true bone is noted The new bone is always extra-articular and can be contiguous with the skeleton but generally does not involve the periosteum
IN SUMMARY It has been postulated that three conditions
must be met to achieve heterotopic bone formation ---a stimulating event oestrogenic precursor cells and a proper environment LIKE hypercalcaemia tissue hypoxia pH changes (alkalosis) or prolonged immobilization
ClassificationbullSubtypes
bull neurogenic HO bull Four clinical stages of HO in people with spinal cord injury were
described by Nicholas in 1973
bull traumatic myositis ossificans bull fibrodysplasia ossificans progressiva (Munchmeyers Disease)
Neurogenic HO Symptoms
painless loss of ROM interferes with ADL CRPS symptoms fever
Physical exam inspection
warm painful swollen joint may have effusion skin problems
decubitus ulcers from contractures around skin muscles ligaments
skin maceration and hygiene problems motion
decreased joint ROM joint ankylosis with HO after TKA might develop quad muscle snapping or patella
instability neurovascular
peripheral neuropathy HO often impinges on adjacent NV structures
Imaging
bullRadiographs bull findings
bull ossification usually easy to visualize bull maturity of HO
bull the appearance of a bony cortex suggests mature HObull sharp demarcation from surrounding tissue bull trabecular pattern
bull sensitivity and specificity bull not useful for early diagnosisbull only useful at 1 week after onset of symptoms
bull calcium is deposited 7-10 days later than symptom onsetbullUltrasound
bull indications bull for early diagnosis of hip HO
bull findings bull echogenic surfaces with posterior acoustic shadowing
bullCT bull indications
bull useful for preoperative planning bullTriphasic bone scan
bull indications bull best for early diagnosis bull most commonly used diagnostic study
Radiographs are extremely useful in the staging of heterotopic ossification and will show the development of sharp cortical margins once the lesion has reached maturity
Heterotopic bone is a condition in which lamellar bone forms in non-ossified soft tissues In the early stages studies such as MRI and bone scan are more sensitive for diagnosis as radiographs may appear normal for the first three weeks After the appropriate diagnosis is made sequential radiographs are useful for monitoring the progression of the ossification Once it has reached the mature stage sharp cortical margins will appear and surgical resection may be considered
lab
Labs elevated serum alkaline phosphatase (gt250IUL)
ALP removes inhibitors of mineralization nonspecific may be elevated with skeletal trauma cannot determine maturity of HO elevated 12wks after surgery is predictor
elevated CRP correlates with inflammatory activity of HO better than ESR normalization of CRP may correlate with maturity of HO
elevated ESR (gt35mmh) 12wks after THA is predictor
elevated CK correlates with involvement of muscle extent of muscle
involvement Histology
mature fatty bone marrow mature trabecular bone
Heterotopic ossification (HO) most commonly occurs at the amputation site if the amputation was performed thru the zone of injury especially if the injury was a blast mechanism
Symptomatic heterotopic ossification of the quadriceps may occur following placement of a large-diameter Steinmann pin for the purpose of temporary skeletal traction
TreatmentThe prevention of heterotopic ossification is focused on three basic principles disrupting the inductive signalling pathways altering the osteoprogenitor cells or modifying the environment
bullphysiotherapy should involve an assisted range of movement exercises with gentle stretch and terminal resistance trainingbullProphylaxis
bull bisphosphonates amp NSAIDS bull indications
bull although no literature supports are commonly usedbull technique
bull indomethacin is most commonly used bull dose is 75mgday for 10days to 6 weeks
bull perioperative radiation bull indications
bull although no literature supports commonly usedbull is thought to be effective by blocking osteoblast differentiation
bull technique bull a single perioperative dose of 700cGy can be given either 4
hours preop or within 72 hours postoperatively bull lt550cGy not effective
Nonsteroidal anti-inflammatory drugs (NSAIDs) These drugs have demonstrated good results in
preventing heterotopic ossification after total hip arthroplasty
A direct effect of NSAIDs on the formation of heterotopic ossification has been described due to the inhibition of the differentiation of mesenchymal cells into oestrogenic cells There is also an indirect effect which refers to the inhibition of bone remodelling by suppression of the prostagland unmediated inflammatory response (specifically PGE-2)
Indomethacin has been considered a useful medication for heterotopic ossification prophylaxis following total hip replacement
prescribed for three to six weeks in a dose of 75mgday within two months of the injury may reduce the incidence of heterotopic ossification by two to three times
Biphosphonates inhibits precipitation of calcium phosphate and blocks the aggregation and mineralisation of hydroxyapatite crystals In primary prevention Banovac et al [56] have suggested that the treatment should begin as soon as elevated alkaline phosphatase is diagnosed or positive findings in ultrasonography or bone scans are shown In addition disphosphonates could have long-term effects on prevention when the treatment is finished
Posttraumatic wide exposure and surgical resection
indications severe loss of motion and decreased function
technique wide exposure required to identify all neurovascular
structures that may be involved timing of resection (controversial)
marked decrease in bone scan activity AND normalization of ALP
6 months following general trauma 1 year following SCI 15 years following TBI
some data suggests equivalent results when comparing early versus late resection
postop follow with 5 day course of indomethacin early gentle joint mobilization
The surgery is necessary in patients with symptomatic HO and unsuccessful medical treatment such as
Loss of range of motion and ankylosis with associated functional disability such as sitting difficulties
Complications of immobility such as pressure ulcers
Facilitate rehabilitation and recovery of muscular atrophy secondary to prolonged immobilisation
Difficulties of appropriate hygiene because access to the perineum or bladder care is needed
Severe pain refractory to analgesia Vascular andor nerve compression
Advantages to early excision of heterotopic ossification (vs waiting for maturation) include decreased soft tissue contracture better definition between heterotopic and native bone and decreased waiting time for the patient When the soft tissue envelope is benign one may proceed with operative release While waiting for normalization of alkaline phosphatase levels inactivity on bone scan or radiographic maturity may decrease risk of recurrent heterotopic ossification delaying operative release for these reasons has not been shown to improve results of final elbow range of motion after contracture release
Gartland recommended surgery after six months following traumatic heterotopic ossification one year following spinal cord injury and 18 months after head injury
In the past waiting until maturity in order to minimize the rate of recurrence after the surgical treatment was recommended Nevertheless recent studies do not confirm a higher rate of recurrence when the HO is excised in an earlier phase In addition a long delay before surgery leads to ankylosis a high degree of osteoporosis and more extensive intra-articular injuries These findings are associated with bad functional results and potential complications
Should you wait till lesion maturation
Prevention byHandle tissue carefully Avoid excess bleeding Achieve good hemostasis Beware of lesions that span internervous tissue planes
but if it happens resection of a large enough amount of bone to allow improvement of the range of motion and trying to preserve the joint
Our aim must be
A reactive process that is characterized by a well-circumscribed proliferation of fibroblasts cartilage and bone within muscle
A form of heterotopic ossification that is the result direct trauma intramuscular hematoma
most common location is the diaphysis of long bones Must differentiate from tumors Fibrodysplasia ossificans progressiva (FOP) is a rare subtype of heterotopic ossification
involves mutation of the ACVR1 gene (activin A type I receptor gene a BMP type-1 receptor)
Epidemiology demographics
most common in young active males (15 to 35 years old) body locations
quadriceps brachialis and gluteal muscles Genetics
almost always a posttraumatic condition Prognosis
usually self limiting mass usually begins to decrease in size after 1 yea
Myositis ossificans
PresentationbullSymptoms
bull pain tenderness swelling and decreased range of motion that usually presents within days of the injury
bull pain and size of the mass decrease with timebull mass increases in size over several months(usually 3 to 6 cm)
bull after the mass stops growing it becomes firmbullPhysical exam
bull palpable soft tissue massbull restricted range of motion
ImagingbullRadiographs
bull peripheral bone formation with central lucent areabull may appear as dotted veil pattern
bullMRI with gadolinium bull rim enhancement is seen within the first 3 weeks
bullCT scan bull lesion has an eggshell appearance
bullCharacteristic histology shows zonal pattern bull periphery of lesion
bull mature trabeculae of lamellar and woven bonebull calcification seen on xray
bull center of the lesion bull irregular mass of immature fibroblastsbull cartilage component may be presentbull (no calcification seen on xray) bull no cellular atypia seen
Treatment
bullNonoperative bull rest range of motion exercises and activity modification
bull passive stretching is contraindicated (makes it worse)bull physical therapy
bull utilized to maintain range of motionbull radiographic monitoring
bull obtained to confirm maturation of the lesionbullOperative
bull surgical excision bull indicated only if it remains a problem after it maturesbull do not operate in acute phase wait at least six months
bull excision of the lesion within 6 to 12 months predisposes to local recurrence
A 26-year-old man presents with generalized back and joint stiffness and difficulty opening his mouth His elder sister has similar complaints Since childhood he has had 3 surgeries for excision of recurrent bony prominences around his knees He walks with a stooped over posture seen in Figure A Radiographs of his feet knee hip and spine are seen in Figures B-E respectively
fibrodysplasia ossificans progressiva
Stone Man Disease) which involves a mutation of the ACVR1
There are 2 hallmark characteristics progressive heterotopic ossification (muscles fascia tendons ligaments and joint capsules) and congenital malformation of the great toe (hallux valgus malformed first metatarsal and monophalangism) BMP4 which contributes to the formation of the skeleton in the normal embryo is implicated in this disease
Complications
bullHematoma and intraoperative bleedingbullInfection
bull higher rate of infection following joint arthroplasty if HO is present
bullFractures of osteoporotic bone bull osteopenic from disusebull during surgery or physiotherapy
bullRecurrence bull recurrence rate correlates with neurological injury
bull greater recurrence if severe neurological compromisebullAVN
bull if extensive dissection or stripping is required
HTO AND ISS
When ISS is below 25 the mortality risk is minimal and above 25 it is an almost linear increase
When ISS is 50 the mortality is 50 When above 70 it is close to 100 If an injury is assigned an AIS of 6 (unsurvivable injury) the ISS score is
automatically assigned to 75 Highest ISS score obtainable is 75 For trauma patients of vehicular accidents the scoring system is important
for assessing the effectiveness of medical care in reducing morbidity and mortality
Advantages virtually the only anatomical scoring system in use correlates linearly with
mortality morbidity hospital stay other measures of severity
Weaknesses Any error in AIS scoring increases the ISS error Many different injury patterns can yield the same ISS score Injuries to different body regions are not weighted Not a useful triage tool as a full description of patient injuries is not known
prior to full investigation amp operation
risk factors periosteal stripping off anterior femur male gender obesity post traumatic deformity Anterior and anterolateral approach Cementless
Neurogenic HO around the hip due to SCI occurs more often in the medial region than in the lateral region with ossified tissues extending from the pubic symphysis to the anteromedial femoral shaft posterior to the femoral neurovascular structures Ossification is also seen anteriorly involving the iliopsoas and femoral neurovascular structures laterally within gluteus minimus and posteriorly extending from the ilium to the posterior femur encasing the sciatic nerve
HTO AROUND hip and knee
The Brooker Classification of Heterotopic Ossification around the hip joint Class I has islands of bone within the soft tissues Class II has bone spurs from the pelvis or proximal end of the femur leaving at least 1 cm between opposing surfaces Class III has bone spurs from the pelvis andor proximal end of the femur reducing the space between opposing bone surfaces to less than 1 cm Class IV shows apparent bone ankylosis of the hip
Region I - Heterotopic ossifications are strictly below the tip of the greater trochanter
Region II - Heterotopic ossifications are below and above the tip of the greater trochanter
Region III - Heterotopic ossifications are strictly above the tip of the greater trochanter
Grade A - Single or multiple heterotopic ossifications are less than 10 mm in maximal extent without contact with the pelvis or the femur
Grade B - Heterotopic ossifications are greater than 10 mm without contact with the pelvis but with possible contact with the femur there is no bridging from the femur to the proximal part of the greater trochanter and no evidence of ankylosis
Grade C - Ankylosis by means of firm bridging from the femur to the pelvis is present
Shmidt classification
excision may be performed The results of this procedure are varied Patients may find that their range of movement improves but pain relief is likely to be limited
A patient with heterotopic ossification following total hip arthroplasty is thought to have a 90-100 chance of developing it on the contralateral hip if this hip also undergoes total arthroplasty
it would be prudent to minimize the risk of heterotopic ossification developing after arthroplasty by performing surgery whereby the following are ensured
Exposure is meticulous Retraction is performed carefully and soft tissue
is handled carefully Irrigation is adequate Devitalized tissue is excised Hemostasis is adequate Postoperative drains (when used) are not
retained for longer than necessary Perioperative antibiotic prophylaxis is used Postoperative anticoagulation (when used for
deep vein thrombosis prophylaxis) is carefully controlled
sources of knee stiffness 1-extrinsic severe osteoarthritis of the ipsilateral hip neurologic injury leading to muscle rigidity tight quadriceps or hamstring muscles secondary to muscle injury heterotopic ossification or long-standing juvenile inflammatory conditions limiting knee
range of motion prior to the completion of skeletal growth When extrinsic sources are identified revision total knee arthroplasty is unlikely to be associated with a favorable outcome without correction of the extrinsic problem
2-intrinsic (1) overstuffing of the patellofemoral articulation (2) an
excessively tight flexion andor extension gap (3) a tight posterior cruciate ligament (4) femoral andor tibial malrotation (5) arthrofibrosis and (6) limited bearing excursion in association with a highly conforming mobile-bearing prosthetic design
HTO after TKA
Heterotopic Ossification (HO) following primary Total Knee Replacement (TKR)
Occurs in 3-90 of TKRs 3-grade classification system No correlation between HO and component
alignment or component position
Clinical findings similar to early infection Continuing low-grade fever Warm swollen and erythematous knee Normal blood tests Possibly an association with HLA-A2 and B18 HO patients have worse KSS and function
scores
Patients at HIGH risk for developing HO after TKR (Knee Arthroplasty) (5)
Those with limited postoperative knee flexion
Increased lumbar bone mineral density (BMD) on multivariate analysis (3)
Hypertrophic arthrosis Excessive periosteal trauma Notching of the anterior femur Those who require forced manipulation
after TKA 47 in revision TKR surgery (6) Higher rates in revision TKR cases with
infection (up to 76
DaughertyBell classification of HO of the knee 0 No evidence of HO 1 Bone islands in periarticular soft tissue (no
involvement of femur patella or tibia) or HO within quadriceps expansion measuring lt1 cm
2 Spur formation measuring lt5 cm that involves the femur patella or tibia if more than one bone demonstrates HO separation of HO spurs
measure gt1 cm or HO within quadriceps expansion measuring ge1 cm but lt3 cm
3 Spur formation gt5 cm involving femur patella or tibia if more than one bone demonstrates HO separation of HO spurs measure lt1 cm or HO
within quadriceps expansion measuring ge3 cm 4 Extensive HO of the knee causing ankylosis
class 2 HO begins to involve the major bones of the knee joint with spur formation limited to a size of 5 cm
HO class 2 may be observed in select patients with complete ROM and no reported pain Patients with class 3 HO would likely always benefit from surgical excision
followed by RT prophylaxis Certainly patients in either cohort with a subclass ldquoBrdquo assignment (symptomatic) would
benefit from treatment All patients with class 4 HO require
treatment to alleviate ankylosis
treatment
References Whyte ldquoPagetrsquos Disease of Bonerdquo NEMJ vol 355
2006 Klein and Parvizi ldquoSurgical Manifestations of Pagetrsquos
Diseaserdquo JAAOS vol 14 2006 Orthobullets Campbell Apley Emedicinecom
-Chapter 15 Heterotopic Ossification after Traumatic Brain InjuryBy Jesuacutes Moreta and Joseacute Luis Martiacutenez-de los Mozos DOI 10577257343
Questions
Thank You
Introduction First Described in 1877 by James Paget Chronic non-metabolic bone disorder Characterized by aggressive bone
resorption and abnormal formation and remodeling rArran unbalanced derangement of normal processes
Results in bone deformity structural weakness altered joint biomechanics
Pagets Disease( OSTEITISDEFORMANS)
Epidemiology A disease of middle to advanced age Rare below age
40 Prevalence in US~1 over age 40 15-3 over age 60
Incidence doubles every decade after age 50
MengtWomen (16 1)Geographic variation Highest prevalence
in Britain Australia New Zealand North America and Western Europe
Etiology Unknown
Proposed Theories Viral Paramyxovirus measles virus RSV canine distemper virus
Viral particles seen in pagetic osteoclasts
Genetic5-40 have 1st degree relative with Pagetrsquos Genetics
inheritance most cases are spontaneous hereditary
familial clusters have been described with ~40 autosomal dominant transmission mutations
at least 4 genes have associated with Pagets disease (amp other disorders of bone turnover) most important is SQSTM1 (p62Sequestosome)
tend to have severe Paget disease
Environmental Arsenic Animals cattle dogs
Pathophysiology Abnormal osteoclastsuarrquantity uarrsize uarractivity uarr of nuclei
Aggressive focal bone resorption makes large cavities in bone
Leads to osteoblast recruitment and overactive osteoblastic activity
Rapid disorganized bone formation
New bone isCoarse disorganized irregular woven
Less resistant to forces there4Prone to deformity and fracture
3 Phases of Disease1) OsteoclasticResorptivePhase Bursts of osteoclastic activity causing bone resorption Lytic lesions trabecular and cortical thinning Osteolytic ldquofrontsrdquoadvance longitudinally from bone
end toward middle ( ldquoVrdquoor ldquoflamerdquoshaped ~1cmyr)
2) OsteoblasticSclerotic or Mixed Phase Mixed osteoclastic and osteoblastic activity Net activity is osteoblastic with deposition of
structurally abnormal bone Bone expansion hyperostosis osteosclerosis
heterogeneous ossification
3-Late ldquoBurn OutrdquoPhasedarrActivity End result widened heterogeneously ossified
but generally sclerotic bones with irregular thickened trabeculae
Phases correlate radiologically and histologically
1048710All 3 Phases may be present simultaneously in the same patient or the same bone
Diseas location Monostotic (25) or polyostotic(75) 1048710Typically affectsPelvis (70) Femur (55) Lumbosacralspine (53) Skull (42) Tibia (32) Rarely in hands feet
1048710No bone-to-bone spread
Clinical Presentation and Complications Usually asymptomatic
Incidental findingAbnormal radiograph or other imaging Abnormal labs (uarrAlkPhos)
Bone pain Constant 1048710Poorly localized 1048710Present at rest
Worse on weight-bearing
pain may be the presenting symptom due to
stress fractures increased vascularity and warmth
new onset intense pain and swelling be suspicious for Pagets secondary sarcoma in a patient with a known history of Pagets who
complains of new onset intense pain and swelling cardiac symptoms
can present with high-output cardiac failure particularly if largemultiple lesions amp pre-existing diminished cardiac function
Bonelimb deformity
Fracture
Arthropathy
uarrincidence of joint disease 1048710Specific pattern of joint diseases in hip uarrfreq of coxa vera protrusio concentric joint space narrowing
uarrSkin temperature
Hypervascularity due to uarrbone turnover activity
uarrbone turnover causes uarrcardiac demands and may lead to high-output heart failure
High-output cardiac failure is caused by the numerous arteriovenous fistulas present in the pagetic bones
Neurologic complaints
Hearing lossvertigotemporal bone involvement with auditory nerve compression
1048710Cranial nerve palsies 1048710Spine involvementMechanical cord compression ldquovascular steal
Hypercalcemia
Rare 1048710Usually inactive or bed-ridden patients 1048710Signs amp SymptomsNausea vomiting MSK aches hyper-reflexia weakness
polyuria headache lethargy altered mental status hellipcoma
Malignant transformation Pagets sarcoma
less than 1 will develop malignant Pagets sarcoma (secondary sarcoma)
osteosarcoma is the most common followed by fibrosarcoma and chondrosarcoma
most common in pelvis femur and humerus Pagets sarcoma has a poor prognosis
5-year survival for non-metastatic Pagets sarcoma is less than 5 appropriate treatment for Pagets sarcoma includes chemotherapy
and wide surgical resection Pagets sarcoma typically presents as a destructive lesion without
periosteal reaction
Diagnosis Clinical assessment Characteristic radiographic appearance Labs (uarrAlkPhos) Bone Scan Usually benign and multiple lesions in old
patients are pagets hyperparathyroidism and bone infarcts
Rarely CT MRI Biopsy
Long bones bend across the trajectories of mechanical stress thus the tibia bows anteriorly and the femur anterolaterally The limb looks bent and feels thick and the skin is unduly warm ndash hence the term lsquoosteitisdeformansrsquo If the skull is affected it enlarges the patient may complain that old hats no longer fit The skull base may become flattened (platybasia) giving the appearance of a short neck In generalized Pagetrsquos disease there may also be considerable kyphosis so the patient becomes shorter and ape-like with bent legs and arms hanging in front of him Cranial nerve compression may lead to impaired vision facial palsy trigeminal neuralgia or deafness Another cause of deafness is otosclerosisVertebral thickening may cause spinal cord or nerve root compression Steal syndromes in which blood is diverted from internal organs to the surrounding skeletal circulationmay cause cerebral impairment and spinal cord ischaemia If there is also spinal stenosis the patient develops typical symptoms of lsquospinal claudicationrsquo and lower limb weakness
Radiographs coarsened trabeculae which give the bone a blastic
appearance both increased and decreased osteodensity may exist
depending on phase of disease lytic phase
lucent areas with expansion and thinned intact cortices blade of grass or flame-shaped lucent advancing edge
mixed phase combination of lysis and sclerosis with coarsened trabeculae
sclerotic phase bone enlargement with cortical thickening sclerotic and lucent
area
remodeled cortices loss of distinction between cortices and medullary cavity
long bone bowing bowing of femur or tibia
fractures hip and knee osteoarthritis osteitis circumscripta
(cotton wool exudates) in skull Pagets secondary sarcoma
shows cortical bone destruction soft tissue mass
MRI may show lumbar spinal stenosis
Bone scan accurately marks site of disease intensely hot in lytic and mixed phase less hot in sclerotic phase
CT scan cortical thickening and coarsened trabeculae
CTMRI Incidental finding Evaluation of atypical presentations
neurological involvement and possible malignant transformation
CT trabecularcortical thinning thickening irregularity
MRI non-specific marrow changes
BiochemistrySerum AlkPhosEnzyme found in osteoblastic membrane Indicator of osteoblastic activity uarrin Pagetrsquos but can be normal Levels correlate with disease extent and activity elevated urinary hydroxyproline (collagen breakdown marker) increased urinary N-telopeptide alpha-C-telopeptide
and deoxypyridinoline normal calcium levels
Other recommended tests ESR -elevation may indicate malignant transformation
CRP Ca -hypercalcemiamay occur in Pagetrsquos PO4 25-hydroxyvitamin D -rule out osteomalacia LFTs-rule out liver disease
Diagnostic Biopsy Diagnosis is usually achieved clinically and by
plain radiographic appearance Biopsy rarely required
Characteristic HistopathologyDisorganized immature trabeculararchitecture with irregular cement lines (ldquomosaicrdquopattern)
Rimming osteoblasts andor multinucleated osteoclasts
Management Options (May require no treatment if asymptomatic)
Supportive Care Pharmacologic Surgical (OrthopedicNeurosurgical
Supportive Care Occupational therapy Physical aides Counseling for fall+fracture prevention
Physical therapy Analgesics Weight control
Pharmacologic ManagementGoals Relieve symptoms and Prevent potential
complications Normalization of serum AlkPhos associated
with better long-term outcomes and disease control
Indications to treat Pain Deformity Neurologic symptoms Asymptomatic but high-risk for complications
(prophylactic) Management of hypercalcemia(rare) Pre-op reduce blood flow and potential
operative blood loss
Calcitonin is the most widely used It reduces bone resorption by decreasing both the activity and the number
of osteoclasts serum alkaline phosphatase and urinaryhydroxyproline levels are lowered Salmon calcitonin is more effective than the porcine variety subcutaneous injections of 50ndash100 MRC units are given daily until pain is relieved and the alkaline phosphatase levels are reduced and stabilized Maintenance injections once or twice weekly may have to be continued indefinitely but some authorities advocate stopping the drug and resuming treatment if symptoms recur Calcitonin can also be administered in a nasal spray Bisphosphonates bind to hydroxyapatite crystals
inhibiting their rate of growth and dissolution It is claimed that the reduction in bone turnover following their use is associated with the formation of lamellar rather than woven bone and that even after treatment is stopped there may be prolonged remission of disease (Bickerstaff et al 1990) Etidronate can be given orally (always on an empty stomach) but dosage should be kept low (eg 5 mgkg per day for up to 6 months) and vitamin D and calcium should also be given lest impaired bone mineralization results inosteomalacia The newer bisphosphonates (eg alendronate or pamidronate) do not have this disadvantage so they should be used as the treatment of choice they produce remissions even with shortcourses of 1 or 2 weeks
BisphosphonatesSynthetic analogues of inorganic phosphate adhere to mineralized surfaces
Ingested selectively by osteoclasts Disrupts enzyme pathways and reduces osteoclastic bone resorption
calcitonin causes osteoclasts to shrink in size and decreases their bone resorptive activity within minutes administered subcutaneously or intramuscularly
teriparatide is contraindicated in Pagets disease due to risk of secondary osteosarcoma
Surgical Management Few require surgery
Common Procedures Corrective osteotomy of long bone deformity indications
fractures through pathologic bowing of long bones impending pathologic fracture of long bone with bowing deformity
Arthroplasty (hip knee) the most common complications include
malalignment with knee arthroplasty bleeding with hip arthroplasty
Combination arthroplasty with osteotomy Fracture fixation
Preoperative Considerations Medical assessment for extraskeletalmanifestations eg high-
output heart failure
Medical treatment of active disease Preoperative autologousblood donation
Thorough planningeg good quality x-rays for templatingand device selection
Intraoperative Considerations Blood salvage system Expansileapproach + soft tissue release Sharp reamersburrsdrills for IM access Extramedullaryguidenavigation systems Concomitant osteotomy
PostoperativeConsiderations Monitoring for cardiac complications Continued medical tx of active disease
uarrHeterotopic ossification Prophylaxis against HO
Possible future excision of HO for painROM
1-Tieg provides a review of Pagets disease of bone and treatment indications In his review he discusses that most patients with Pagets disease are asymptomatic but in those that do present pain is the most common presenting symptom He recommends medical and surgical treatment of asymptomatic patients who have active disease at sites where complications are likely to develop
Altman did a review of 290 patients with Pagets disease of bone His findings showed 83 had one or more rheumatic syndromes He found the rate of osteoarthritis related to Pagets disease was elevated in the hip and knee Rheumatoid arthritis hyperuricemia and gout did not appear increased in this group
Mangham et al looked the rate of secondary sarcomas as a result of Pagets disease of bone They found the rate to be around 03 with male predominance They also found that widespread skeletal involvement by Pagets disease was not a significant risk factor for malignant transformation
Interesting views about pagets
Smith et al reviewed the pathologic complications of Pagets bone disease Pagets bone disease commonly causes osseous weakening (deformity and fracture) and arthritis in the hip joint Management of end stage disease is successful with cemented and cementless total hip arthroplasty Bleeding is the most common intra- and post-operative complication of surgery
Gabel et al retrospectively reviewed thirteen patients who had had sixteen total knee arthroplasties for Pagetic gonarthrosis Unlike total hip arthroplasty surgery Paget disease did not increase the amount of blood lost during the operation or in the postoperative period The most common complication associated with total knee arthroplasty was malalignment
Hansen et al reviewed the incidence of osteosarcomas complicating Pagets Disease Of the typical sites that are usually involved in Pagets disease (eg spine pelvis femur tibia and humerus) secondary osteosarcoma tends to spare the spine
Shaylor et al reported the mortality rates in 26 patient with osteosarcoma secondary to Paget s disease There was a 47 mortality at 1 year and 75 at 2 years from diagnosis In their series no patient survived for 5 years All patients died of metastatic disease
Langston et al conducted a randomized trial that compared the results of symptomatic treatment versus intensive bisphosphonate therapy in patients with Pagets disease Clinical fractures occurred in 46 of 661 patients (70) in the treatment group compared with 49 of 663 patients (74) in the symptomatic treatment group They concluded that bisphosphonates did not show a significant beneficial impact on pain quality of life or fracture incidence
Hadjipavlou et al reviewed Pagets disease of the bone and its management Farmers have been shown to have an increased incidence of Pagets disease Average age at presentation is in the 5th and 6th decade Symptomatic individuals are recommended to be treated initially with medical management They suggest that bisphosphonates are more effective than calcitonin at suppressing the histological and biochemical activity in Pagetrsquos disease
Summary Epid Very common in elderly Path Abnormal osteoclastshellipuarrbone
turnoverhellipdeposition of abnormal bone SampS Pain deformity fracture arthropathy Labs uarrAlkPhos X-ray Characteristic coarse thickened
trabeculae Bone scan Very hot Rx Bisphosphonates Surgery for arthropathy fracture painful
deformity
A 65-year-old male presents with increasing shoulder pain over the past 9 months He is otherwise healthy and has no other complaints Radiograph of his shoulder is shown in Figure A Whole body bone scan and biopsy photograph are shown in Figures B and C What is the most appropriate treatment for this patient
1 Referral to endocrinology 2 Radiation therapy and chemotherapy 3 Wide resection and reconstruction 4 Radiation therapy wide resection and reconstruction 5 Chemotherapy wide resection and reconstruction
Histiocytosis X or Langerhans cell histiocytosis is a spectrum of diseases of the reticuloendothelial system with one of three general presentations Eosinophilic granuloma (EG)
usually a single self-limited lesion found in younger patients
Hand-Schuller-Christian disease (HSC) chronic disseminated form with bone and visceral lesions also known as Langerhans cell histiocytosis with visceral
involvement Letterer-Siwe disease (LSD)
fatal form that occurs in young children
Eosinophilic granuloma
Epidemiology demographics
most commonly occurs in children (80 of afflicted lt 20 years of age)
HSC disease presents in children gt 3 years of age LSD occurs in children lt 3 years of age Male to female ratio of 21
location eosinophilic granuloma
commonly presents in the skull ribs clavicle scapula mandible
isolated lesions of the spine (thoracic most common) can also occur in diaphyseal regions of long bones and the
pelvis HSC
multiple bony sites multiple lytic skull lesions visceral involvement of the lungs spleen liver skin lymph
nodes
Genetics no clear genetic pattern of inheritance or locus has
been determined Prognosis
EG isolated involvement generally treatable with local
management spine lesions can spontaneously resolve
HSC prognosis depends on response to chemotherapy worsening prognosis with increasing extraskeletal
involvement LSD
generally fatal in children lt 3 years of age
Symptoms skeletal involvement
pain and swelling at the region of involvement limping can be seen with pelvic or lower extremity
involvement vertebral involvement
localized or diffuse back pain increasingly kyphotic posture radiculopathy can occur with more aggressive lesions
HSC classic triad of
multiple lytic skull lesions diabetes insipidus
increased thirst and water intake exopthalmos
visceral involvement diffuse or nonspecific abdominal or chest pain
Radiographs general
known as the great mimicker as it appears similar to many lesions radiographic differential includes osteomyelitis leukemia lymphoma
fibrous dysplasia or Ewings sarcoma diaphyseal lesions
well defined intramedullary lytic or punched-out lesion cortex may be thinned expanded or destroyed may have periosteal reaction
metaphyseal lesions extend up to but not through the physis less central location than diaphyseal lesions
spinal lesions vertebra plana (flattened vertebrae) in spine increased kyphosis
cranial involvement multiple punched-out lytic lesions
MRI may show a soft tissue mass adjacent to boney lesions
Bone scan generally shows increased uptake in the region of boney lesion
Histology Langerhans cells
mononuclear histiocyte-like cells with oval nuclei with well-defined round or oval cytoplasm
a prominent nuclear groove (coffee bean nuclei) can be seen in most of the nuclei
eosinophilic cytoplasm (pink generally) stain with CD1A electronmicroscopy
birbeck granules seen inside Langerhans cells mixture of inflammatory cells also present giant cells are present lack of nuclear atypia and atypical mitoses
differentiates this condition from malignant conditions such as Ewings sarcoma lymphoma of bone and metastatic neuroblastoma which may look similar based on the round cells alone
eosinophilic cytoplasm (pink generally)
Treatment
bullNonoperative bull observation alone
bull indications bull a self-limited process and it is reasonable to treat with observation alone
bull bracing bull indications
bull to prevent progressive kyphosis of the spinebull outcomes
bull will correct deformity in 90 of patientsbull vertebral lesions generally regain 50 of their height
bull low dose irradiation (600-800 cGy) bull indications
bull indicated for lesions in the spine that compromise stability neurologic statusbull lesions not amenable to injection or open treatment
bull outcomes bull effective for most lesions
bull chemotherapy bull indications
bull diffuse HSCbull outcomes
bull prognosis is improved with less severe extraskeletal involvementbull corticosteroid injection
bull indications bull isolated lesions bull can be performed after curettage as well
Operative curettage and bone grafting
indications for lesions that endanger the articular surface or are a risk for
impending fractures spinal deformity correction
indications progressive spine deformity refractory to bracing
approximately 10 of patients with spine lesion will need operative intervention for deformity correction
Destructive multiple lesion in young patientsAre eosinophilic granuloma lymphoma and leukemiaLymphoma is unlikely to present with exopthalmos diabetes insipidus or vertebra plana Lymphoma bone lesions are lytic and appear moth eatenpermeative on radiographs
Figure A shows a skin lesion typical of eosinophillic granuloma Figure B shows a lytic lesions without significant surrounding sclerosis as is characteristic of eosinophilic granuloma Figure C shows the characteristic histology of multiple eosinophils with their characteristic oval coffee bean nuclei and staining pattern of purpleredpink cytoplasm (depending on the stain) Importantly the histology slide lacks a malignant appearance (no cellular atypia or mytotic complexes and low nuclearcytoplasmic ratio)
Formation of bone in atypical extraskeletal tissues usually occurs
spontaneously or following trauma within 2 months of neurologic injury (brain or spinal cord)
most common location is between muscle and joint capsule Epidemiology
incidence (see table below)
demographics malefemale = 21 especially men with hypertrophic osteoarthritis and women gt65y
location traumatic brain injury or stroke
hip gt elbow gt shoulder gt knee elbow HO more common following brain trauma
occurs on affected (spastic) side rarely in the knee (TBI)
spinal cord injury hip gt knee gt elbow gt shoulder hip flexors and abductors gt extensors or adductors medial aspect of the knee
Heterotopic Ossification
Risk factors
Pathophysiology exact cause of HO is not known but there appears to be a
genetic pre disposition experimental HO associated with
tissue expression of BMP IT IS SAID TO BE CAUSED BY activation and proliferation of
mesenchymal stem cells Associated conditions
orthopaedic manifestations pathologic fractures
from decreased joint ROM and osteoporotic bone nerve impingement soft tissue contractures contributing to the formation of
decubitus ulcers joint ankylosis HO after THA adversely affects outcome of THA
nonorthopaedic conditions skin maceration and hygiene problems
Pathophysiology Early in the formation of HO oedema with exudative
infiltrate is present followed by fibroblastic proliferation and immature connective tissue formation Posteriorly osteoid formation is seen with the subsequent deposition of bone matrix Primitive osteoid is deposited as small masses in the periphery early (within the first two weeks) and osteoblasts are noted located irregularly Osteoblasts produce tropocollagen which polymerizes to form collagen and secrete alkaline phosphatase which allows calcium to precipitate and the mineralization of bone matrix As mineralization progresses amorphous calcium phosphate is progressively replaced by hydroxyapatite crystals During the following weeks the lesion matures with a centripetal pattern and after 6-12 months an appearance of true bone is noted The new bone is always extra-articular and can be contiguous with the skeleton but generally does not involve the periosteum
IN SUMMARY It has been postulated that three conditions
must be met to achieve heterotopic bone formation ---a stimulating event oestrogenic precursor cells and a proper environment LIKE hypercalcaemia tissue hypoxia pH changes (alkalosis) or prolonged immobilization
ClassificationbullSubtypes
bull neurogenic HO bull Four clinical stages of HO in people with spinal cord injury were
described by Nicholas in 1973
bull traumatic myositis ossificans bull fibrodysplasia ossificans progressiva (Munchmeyers Disease)
Neurogenic HO Symptoms
painless loss of ROM interferes with ADL CRPS symptoms fever
Physical exam inspection
warm painful swollen joint may have effusion skin problems
decubitus ulcers from contractures around skin muscles ligaments
skin maceration and hygiene problems motion
decreased joint ROM joint ankylosis with HO after TKA might develop quad muscle snapping or patella
instability neurovascular
peripheral neuropathy HO often impinges on adjacent NV structures
Imaging
bullRadiographs bull findings
bull ossification usually easy to visualize bull maturity of HO
bull the appearance of a bony cortex suggests mature HObull sharp demarcation from surrounding tissue bull trabecular pattern
bull sensitivity and specificity bull not useful for early diagnosisbull only useful at 1 week after onset of symptoms
bull calcium is deposited 7-10 days later than symptom onsetbullUltrasound
bull indications bull for early diagnosis of hip HO
bull findings bull echogenic surfaces with posterior acoustic shadowing
bullCT bull indications
bull useful for preoperative planning bullTriphasic bone scan
bull indications bull best for early diagnosis bull most commonly used diagnostic study
Radiographs are extremely useful in the staging of heterotopic ossification and will show the development of sharp cortical margins once the lesion has reached maturity
Heterotopic bone is a condition in which lamellar bone forms in non-ossified soft tissues In the early stages studies such as MRI and bone scan are more sensitive for diagnosis as radiographs may appear normal for the first three weeks After the appropriate diagnosis is made sequential radiographs are useful for monitoring the progression of the ossification Once it has reached the mature stage sharp cortical margins will appear and surgical resection may be considered
lab
Labs elevated serum alkaline phosphatase (gt250IUL)
ALP removes inhibitors of mineralization nonspecific may be elevated with skeletal trauma cannot determine maturity of HO elevated 12wks after surgery is predictor
elevated CRP correlates with inflammatory activity of HO better than ESR normalization of CRP may correlate with maturity of HO
elevated ESR (gt35mmh) 12wks after THA is predictor
elevated CK correlates with involvement of muscle extent of muscle
involvement Histology
mature fatty bone marrow mature trabecular bone
Heterotopic ossification (HO) most commonly occurs at the amputation site if the amputation was performed thru the zone of injury especially if the injury was a blast mechanism
Symptomatic heterotopic ossification of the quadriceps may occur following placement of a large-diameter Steinmann pin for the purpose of temporary skeletal traction
TreatmentThe prevention of heterotopic ossification is focused on three basic principles disrupting the inductive signalling pathways altering the osteoprogenitor cells or modifying the environment
bullphysiotherapy should involve an assisted range of movement exercises with gentle stretch and terminal resistance trainingbullProphylaxis
bull bisphosphonates amp NSAIDS bull indications
bull although no literature supports are commonly usedbull technique
bull indomethacin is most commonly used bull dose is 75mgday for 10days to 6 weeks
bull perioperative radiation bull indications
bull although no literature supports commonly usedbull is thought to be effective by blocking osteoblast differentiation
bull technique bull a single perioperative dose of 700cGy can be given either 4
hours preop or within 72 hours postoperatively bull lt550cGy not effective
Nonsteroidal anti-inflammatory drugs (NSAIDs) These drugs have demonstrated good results in
preventing heterotopic ossification after total hip arthroplasty
A direct effect of NSAIDs on the formation of heterotopic ossification has been described due to the inhibition of the differentiation of mesenchymal cells into oestrogenic cells There is also an indirect effect which refers to the inhibition of bone remodelling by suppression of the prostagland unmediated inflammatory response (specifically PGE-2)
Indomethacin has been considered a useful medication for heterotopic ossification prophylaxis following total hip replacement
prescribed for three to six weeks in a dose of 75mgday within two months of the injury may reduce the incidence of heterotopic ossification by two to three times
Biphosphonates inhibits precipitation of calcium phosphate and blocks the aggregation and mineralisation of hydroxyapatite crystals In primary prevention Banovac et al [56] have suggested that the treatment should begin as soon as elevated alkaline phosphatase is diagnosed or positive findings in ultrasonography or bone scans are shown In addition disphosphonates could have long-term effects on prevention when the treatment is finished
Posttraumatic wide exposure and surgical resection
indications severe loss of motion and decreased function
technique wide exposure required to identify all neurovascular
structures that may be involved timing of resection (controversial)
marked decrease in bone scan activity AND normalization of ALP
6 months following general trauma 1 year following SCI 15 years following TBI
some data suggests equivalent results when comparing early versus late resection
postop follow with 5 day course of indomethacin early gentle joint mobilization
The surgery is necessary in patients with symptomatic HO and unsuccessful medical treatment such as
Loss of range of motion and ankylosis with associated functional disability such as sitting difficulties
Complications of immobility such as pressure ulcers
Facilitate rehabilitation and recovery of muscular atrophy secondary to prolonged immobilisation
Difficulties of appropriate hygiene because access to the perineum or bladder care is needed
Severe pain refractory to analgesia Vascular andor nerve compression
Advantages to early excision of heterotopic ossification (vs waiting for maturation) include decreased soft tissue contracture better definition between heterotopic and native bone and decreased waiting time for the patient When the soft tissue envelope is benign one may proceed with operative release While waiting for normalization of alkaline phosphatase levels inactivity on bone scan or radiographic maturity may decrease risk of recurrent heterotopic ossification delaying operative release for these reasons has not been shown to improve results of final elbow range of motion after contracture release
Gartland recommended surgery after six months following traumatic heterotopic ossification one year following spinal cord injury and 18 months after head injury
In the past waiting until maturity in order to minimize the rate of recurrence after the surgical treatment was recommended Nevertheless recent studies do not confirm a higher rate of recurrence when the HO is excised in an earlier phase In addition a long delay before surgery leads to ankylosis a high degree of osteoporosis and more extensive intra-articular injuries These findings are associated with bad functional results and potential complications
Should you wait till lesion maturation
Prevention byHandle tissue carefully Avoid excess bleeding Achieve good hemostasis Beware of lesions that span internervous tissue planes
but if it happens resection of a large enough amount of bone to allow improvement of the range of motion and trying to preserve the joint
Our aim must be
A reactive process that is characterized by a well-circumscribed proliferation of fibroblasts cartilage and bone within muscle
A form of heterotopic ossification that is the result direct trauma intramuscular hematoma
most common location is the diaphysis of long bones Must differentiate from tumors Fibrodysplasia ossificans progressiva (FOP) is a rare subtype of heterotopic ossification
involves mutation of the ACVR1 gene (activin A type I receptor gene a BMP type-1 receptor)
Epidemiology demographics
most common in young active males (15 to 35 years old) body locations
quadriceps brachialis and gluteal muscles Genetics
almost always a posttraumatic condition Prognosis
usually self limiting mass usually begins to decrease in size after 1 yea
Myositis ossificans
PresentationbullSymptoms
bull pain tenderness swelling and decreased range of motion that usually presents within days of the injury
bull pain and size of the mass decrease with timebull mass increases in size over several months(usually 3 to 6 cm)
bull after the mass stops growing it becomes firmbullPhysical exam
bull palpable soft tissue massbull restricted range of motion
ImagingbullRadiographs
bull peripheral bone formation with central lucent areabull may appear as dotted veil pattern
bullMRI with gadolinium bull rim enhancement is seen within the first 3 weeks
bullCT scan bull lesion has an eggshell appearance
bullCharacteristic histology shows zonal pattern bull periphery of lesion
bull mature trabeculae of lamellar and woven bonebull calcification seen on xray
bull center of the lesion bull irregular mass of immature fibroblastsbull cartilage component may be presentbull (no calcification seen on xray) bull no cellular atypia seen
Treatment
bullNonoperative bull rest range of motion exercises and activity modification
bull passive stretching is contraindicated (makes it worse)bull physical therapy
bull utilized to maintain range of motionbull radiographic monitoring
bull obtained to confirm maturation of the lesionbullOperative
bull surgical excision bull indicated only if it remains a problem after it maturesbull do not operate in acute phase wait at least six months
bull excision of the lesion within 6 to 12 months predisposes to local recurrence
A 26-year-old man presents with generalized back and joint stiffness and difficulty opening his mouth His elder sister has similar complaints Since childhood he has had 3 surgeries for excision of recurrent bony prominences around his knees He walks with a stooped over posture seen in Figure A Radiographs of his feet knee hip and spine are seen in Figures B-E respectively
fibrodysplasia ossificans progressiva
Stone Man Disease) which involves a mutation of the ACVR1
There are 2 hallmark characteristics progressive heterotopic ossification (muscles fascia tendons ligaments and joint capsules) and congenital malformation of the great toe (hallux valgus malformed first metatarsal and monophalangism) BMP4 which contributes to the formation of the skeleton in the normal embryo is implicated in this disease
Complications
bullHematoma and intraoperative bleedingbullInfection
bull higher rate of infection following joint arthroplasty if HO is present
bullFractures of osteoporotic bone bull osteopenic from disusebull during surgery or physiotherapy
bullRecurrence bull recurrence rate correlates with neurological injury
bull greater recurrence if severe neurological compromisebullAVN
bull if extensive dissection or stripping is required
HTO AND ISS
When ISS is below 25 the mortality risk is minimal and above 25 it is an almost linear increase
When ISS is 50 the mortality is 50 When above 70 it is close to 100 If an injury is assigned an AIS of 6 (unsurvivable injury) the ISS score is
automatically assigned to 75 Highest ISS score obtainable is 75 For trauma patients of vehicular accidents the scoring system is important
for assessing the effectiveness of medical care in reducing morbidity and mortality
Advantages virtually the only anatomical scoring system in use correlates linearly with
mortality morbidity hospital stay other measures of severity
Weaknesses Any error in AIS scoring increases the ISS error Many different injury patterns can yield the same ISS score Injuries to different body regions are not weighted Not a useful triage tool as a full description of patient injuries is not known
prior to full investigation amp operation
risk factors periosteal stripping off anterior femur male gender obesity post traumatic deformity Anterior and anterolateral approach Cementless
Neurogenic HO around the hip due to SCI occurs more often in the medial region than in the lateral region with ossified tissues extending from the pubic symphysis to the anteromedial femoral shaft posterior to the femoral neurovascular structures Ossification is also seen anteriorly involving the iliopsoas and femoral neurovascular structures laterally within gluteus minimus and posteriorly extending from the ilium to the posterior femur encasing the sciatic nerve
HTO AROUND hip and knee
The Brooker Classification of Heterotopic Ossification around the hip joint Class I has islands of bone within the soft tissues Class II has bone spurs from the pelvis or proximal end of the femur leaving at least 1 cm between opposing surfaces Class III has bone spurs from the pelvis andor proximal end of the femur reducing the space between opposing bone surfaces to less than 1 cm Class IV shows apparent bone ankylosis of the hip
Region I - Heterotopic ossifications are strictly below the tip of the greater trochanter
Region II - Heterotopic ossifications are below and above the tip of the greater trochanter
Region III - Heterotopic ossifications are strictly above the tip of the greater trochanter
Grade A - Single or multiple heterotopic ossifications are less than 10 mm in maximal extent without contact with the pelvis or the femur
Grade B - Heterotopic ossifications are greater than 10 mm without contact with the pelvis but with possible contact with the femur there is no bridging from the femur to the proximal part of the greater trochanter and no evidence of ankylosis
Grade C - Ankylosis by means of firm bridging from the femur to the pelvis is present
Shmidt classification
excision may be performed The results of this procedure are varied Patients may find that their range of movement improves but pain relief is likely to be limited
A patient with heterotopic ossification following total hip arthroplasty is thought to have a 90-100 chance of developing it on the contralateral hip if this hip also undergoes total arthroplasty
it would be prudent to minimize the risk of heterotopic ossification developing after arthroplasty by performing surgery whereby the following are ensured
Exposure is meticulous Retraction is performed carefully and soft tissue
is handled carefully Irrigation is adequate Devitalized tissue is excised Hemostasis is adequate Postoperative drains (when used) are not
retained for longer than necessary Perioperative antibiotic prophylaxis is used Postoperative anticoagulation (when used for
deep vein thrombosis prophylaxis) is carefully controlled
sources of knee stiffness 1-extrinsic severe osteoarthritis of the ipsilateral hip neurologic injury leading to muscle rigidity tight quadriceps or hamstring muscles secondary to muscle injury heterotopic ossification or long-standing juvenile inflammatory conditions limiting knee
range of motion prior to the completion of skeletal growth When extrinsic sources are identified revision total knee arthroplasty is unlikely to be associated with a favorable outcome without correction of the extrinsic problem
2-intrinsic (1) overstuffing of the patellofemoral articulation (2) an
excessively tight flexion andor extension gap (3) a tight posterior cruciate ligament (4) femoral andor tibial malrotation (5) arthrofibrosis and (6) limited bearing excursion in association with a highly conforming mobile-bearing prosthetic design
HTO after TKA
Heterotopic Ossification (HO) following primary Total Knee Replacement (TKR)
Occurs in 3-90 of TKRs 3-grade classification system No correlation between HO and component
alignment or component position
Clinical findings similar to early infection Continuing low-grade fever Warm swollen and erythematous knee Normal blood tests Possibly an association with HLA-A2 and B18 HO patients have worse KSS and function
scores
Patients at HIGH risk for developing HO after TKR (Knee Arthroplasty) (5)
Those with limited postoperative knee flexion
Increased lumbar bone mineral density (BMD) on multivariate analysis (3)
Hypertrophic arthrosis Excessive periosteal trauma Notching of the anterior femur Those who require forced manipulation
after TKA 47 in revision TKR surgery (6) Higher rates in revision TKR cases with
infection (up to 76
DaughertyBell classification of HO of the knee 0 No evidence of HO 1 Bone islands in periarticular soft tissue (no
involvement of femur patella or tibia) or HO within quadriceps expansion measuring lt1 cm
2 Spur formation measuring lt5 cm that involves the femur patella or tibia if more than one bone demonstrates HO separation of HO spurs
measure gt1 cm or HO within quadriceps expansion measuring ge1 cm but lt3 cm
3 Spur formation gt5 cm involving femur patella or tibia if more than one bone demonstrates HO separation of HO spurs measure lt1 cm or HO
within quadriceps expansion measuring ge3 cm 4 Extensive HO of the knee causing ankylosis
class 2 HO begins to involve the major bones of the knee joint with spur formation limited to a size of 5 cm
HO class 2 may be observed in select patients with complete ROM and no reported pain Patients with class 3 HO would likely always benefit from surgical excision
followed by RT prophylaxis Certainly patients in either cohort with a subclass ldquoBrdquo assignment (symptomatic) would
benefit from treatment All patients with class 4 HO require
treatment to alleviate ankylosis
treatment
References Whyte ldquoPagetrsquos Disease of Bonerdquo NEMJ vol 355
2006 Klein and Parvizi ldquoSurgical Manifestations of Pagetrsquos
Diseaserdquo JAAOS vol 14 2006 Orthobullets Campbell Apley Emedicinecom
-Chapter 15 Heterotopic Ossification after Traumatic Brain InjuryBy Jesuacutes Moreta and Joseacute Luis Martiacutenez-de los Mozos DOI 10577257343
Questions
Thank You
Epidemiology A disease of middle to advanced age Rare below age
40 Prevalence in US~1 over age 40 15-3 over age 60
Incidence doubles every decade after age 50
MengtWomen (16 1)Geographic variation Highest prevalence
in Britain Australia New Zealand North America and Western Europe
Etiology Unknown
Proposed Theories Viral Paramyxovirus measles virus RSV canine distemper virus
Viral particles seen in pagetic osteoclasts
Genetic5-40 have 1st degree relative with Pagetrsquos Genetics
inheritance most cases are spontaneous hereditary
familial clusters have been described with ~40 autosomal dominant transmission mutations
at least 4 genes have associated with Pagets disease (amp other disorders of bone turnover) most important is SQSTM1 (p62Sequestosome)
tend to have severe Paget disease
Environmental Arsenic Animals cattle dogs
Pathophysiology Abnormal osteoclastsuarrquantity uarrsize uarractivity uarr of nuclei
Aggressive focal bone resorption makes large cavities in bone
Leads to osteoblast recruitment and overactive osteoblastic activity
Rapid disorganized bone formation
New bone isCoarse disorganized irregular woven
Less resistant to forces there4Prone to deformity and fracture
3 Phases of Disease1) OsteoclasticResorptivePhase Bursts of osteoclastic activity causing bone resorption Lytic lesions trabecular and cortical thinning Osteolytic ldquofrontsrdquoadvance longitudinally from bone
end toward middle ( ldquoVrdquoor ldquoflamerdquoshaped ~1cmyr)
2) OsteoblasticSclerotic or Mixed Phase Mixed osteoclastic and osteoblastic activity Net activity is osteoblastic with deposition of
structurally abnormal bone Bone expansion hyperostosis osteosclerosis
heterogeneous ossification
3-Late ldquoBurn OutrdquoPhasedarrActivity End result widened heterogeneously ossified
but generally sclerotic bones with irregular thickened trabeculae
Phases correlate radiologically and histologically
1048710All 3 Phases may be present simultaneously in the same patient or the same bone
Diseas location Monostotic (25) or polyostotic(75) 1048710Typically affectsPelvis (70) Femur (55) Lumbosacralspine (53) Skull (42) Tibia (32) Rarely in hands feet
1048710No bone-to-bone spread
Clinical Presentation and Complications Usually asymptomatic
Incidental findingAbnormal radiograph or other imaging Abnormal labs (uarrAlkPhos)
Bone pain Constant 1048710Poorly localized 1048710Present at rest
Worse on weight-bearing
pain may be the presenting symptom due to
stress fractures increased vascularity and warmth
new onset intense pain and swelling be suspicious for Pagets secondary sarcoma in a patient with a known history of Pagets who
complains of new onset intense pain and swelling cardiac symptoms
can present with high-output cardiac failure particularly if largemultiple lesions amp pre-existing diminished cardiac function
Bonelimb deformity
Fracture
Arthropathy
uarrincidence of joint disease 1048710Specific pattern of joint diseases in hip uarrfreq of coxa vera protrusio concentric joint space narrowing
uarrSkin temperature
Hypervascularity due to uarrbone turnover activity
uarrbone turnover causes uarrcardiac demands and may lead to high-output heart failure
High-output cardiac failure is caused by the numerous arteriovenous fistulas present in the pagetic bones
Neurologic complaints
Hearing lossvertigotemporal bone involvement with auditory nerve compression
1048710Cranial nerve palsies 1048710Spine involvementMechanical cord compression ldquovascular steal
Hypercalcemia
Rare 1048710Usually inactive or bed-ridden patients 1048710Signs amp SymptomsNausea vomiting MSK aches hyper-reflexia weakness
polyuria headache lethargy altered mental status hellipcoma
Malignant transformation Pagets sarcoma
less than 1 will develop malignant Pagets sarcoma (secondary sarcoma)
osteosarcoma is the most common followed by fibrosarcoma and chondrosarcoma
most common in pelvis femur and humerus Pagets sarcoma has a poor prognosis
5-year survival for non-metastatic Pagets sarcoma is less than 5 appropriate treatment for Pagets sarcoma includes chemotherapy
and wide surgical resection Pagets sarcoma typically presents as a destructive lesion without
periosteal reaction
Diagnosis Clinical assessment Characteristic radiographic appearance Labs (uarrAlkPhos) Bone Scan Usually benign and multiple lesions in old
patients are pagets hyperparathyroidism and bone infarcts
Rarely CT MRI Biopsy
Long bones bend across the trajectories of mechanical stress thus the tibia bows anteriorly and the femur anterolaterally The limb looks bent and feels thick and the skin is unduly warm ndash hence the term lsquoosteitisdeformansrsquo If the skull is affected it enlarges the patient may complain that old hats no longer fit The skull base may become flattened (platybasia) giving the appearance of a short neck In generalized Pagetrsquos disease there may also be considerable kyphosis so the patient becomes shorter and ape-like with bent legs and arms hanging in front of him Cranial nerve compression may lead to impaired vision facial palsy trigeminal neuralgia or deafness Another cause of deafness is otosclerosisVertebral thickening may cause spinal cord or nerve root compression Steal syndromes in which blood is diverted from internal organs to the surrounding skeletal circulationmay cause cerebral impairment and spinal cord ischaemia If there is also spinal stenosis the patient develops typical symptoms of lsquospinal claudicationrsquo and lower limb weakness
Radiographs coarsened trabeculae which give the bone a blastic
appearance both increased and decreased osteodensity may exist
depending on phase of disease lytic phase
lucent areas with expansion and thinned intact cortices blade of grass or flame-shaped lucent advancing edge
mixed phase combination of lysis and sclerosis with coarsened trabeculae
sclerotic phase bone enlargement with cortical thickening sclerotic and lucent
area
remodeled cortices loss of distinction between cortices and medullary cavity
long bone bowing bowing of femur or tibia
fractures hip and knee osteoarthritis osteitis circumscripta
(cotton wool exudates) in skull Pagets secondary sarcoma
shows cortical bone destruction soft tissue mass
MRI may show lumbar spinal stenosis
Bone scan accurately marks site of disease intensely hot in lytic and mixed phase less hot in sclerotic phase
CT scan cortical thickening and coarsened trabeculae
CTMRI Incidental finding Evaluation of atypical presentations
neurological involvement and possible malignant transformation
CT trabecularcortical thinning thickening irregularity
MRI non-specific marrow changes
BiochemistrySerum AlkPhosEnzyme found in osteoblastic membrane Indicator of osteoblastic activity uarrin Pagetrsquos but can be normal Levels correlate with disease extent and activity elevated urinary hydroxyproline (collagen breakdown marker) increased urinary N-telopeptide alpha-C-telopeptide
and deoxypyridinoline normal calcium levels
Other recommended tests ESR -elevation may indicate malignant transformation
CRP Ca -hypercalcemiamay occur in Pagetrsquos PO4 25-hydroxyvitamin D -rule out osteomalacia LFTs-rule out liver disease
Diagnostic Biopsy Diagnosis is usually achieved clinically and by
plain radiographic appearance Biopsy rarely required
Characteristic HistopathologyDisorganized immature trabeculararchitecture with irregular cement lines (ldquomosaicrdquopattern)
Rimming osteoblasts andor multinucleated osteoclasts
Management Options (May require no treatment if asymptomatic)
Supportive Care Pharmacologic Surgical (OrthopedicNeurosurgical
Supportive Care Occupational therapy Physical aides Counseling for fall+fracture prevention
Physical therapy Analgesics Weight control
Pharmacologic ManagementGoals Relieve symptoms and Prevent potential
complications Normalization of serum AlkPhos associated
with better long-term outcomes and disease control
Indications to treat Pain Deformity Neurologic symptoms Asymptomatic but high-risk for complications
(prophylactic) Management of hypercalcemia(rare) Pre-op reduce blood flow and potential
operative blood loss
Calcitonin is the most widely used It reduces bone resorption by decreasing both the activity and the number
of osteoclasts serum alkaline phosphatase and urinaryhydroxyproline levels are lowered Salmon calcitonin is more effective than the porcine variety subcutaneous injections of 50ndash100 MRC units are given daily until pain is relieved and the alkaline phosphatase levels are reduced and stabilized Maintenance injections once or twice weekly may have to be continued indefinitely but some authorities advocate stopping the drug and resuming treatment if symptoms recur Calcitonin can also be administered in a nasal spray Bisphosphonates bind to hydroxyapatite crystals
inhibiting their rate of growth and dissolution It is claimed that the reduction in bone turnover following their use is associated with the formation of lamellar rather than woven bone and that even after treatment is stopped there may be prolonged remission of disease (Bickerstaff et al 1990) Etidronate can be given orally (always on an empty stomach) but dosage should be kept low (eg 5 mgkg per day for up to 6 months) and vitamin D and calcium should also be given lest impaired bone mineralization results inosteomalacia The newer bisphosphonates (eg alendronate or pamidronate) do not have this disadvantage so they should be used as the treatment of choice they produce remissions even with shortcourses of 1 or 2 weeks
BisphosphonatesSynthetic analogues of inorganic phosphate adhere to mineralized surfaces
Ingested selectively by osteoclasts Disrupts enzyme pathways and reduces osteoclastic bone resorption
calcitonin causes osteoclasts to shrink in size and decreases their bone resorptive activity within minutes administered subcutaneously or intramuscularly
teriparatide is contraindicated in Pagets disease due to risk of secondary osteosarcoma
Surgical Management Few require surgery
Common Procedures Corrective osteotomy of long bone deformity indications
fractures through pathologic bowing of long bones impending pathologic fracture of long bone with bowing deformity
Arthroplasty (hip knee) the most common complications include
malalignment with knee arthroplasty bleeding with hip arthroplasty
Combination arthroplasty with osteotomy Fracture fixation
Preoperative Considerations Medical assessment for extraskeletalmanifestations eg high-
output heart failure
Medical treatment of active disease Preoperative autologousblood donation
Thorough planningeg good quality x-rays for templatingand device selection
Intraoperative Considerations Blood salvage system Expansileapproach + soft tissue release Sharp reamersburrsdrills for IM access Extramedullaryguidenavigation systems Concomitant osteotomy
PostoperativeConsiderations Monitoring for cardiac complications Continued medical tx of active disease
uarrHeterotopic ossification Prophylaxis against HO
Possible future excision of HO for painROM
1-Tieg provides a review of Pagets disease of bone and treatment indications In his review he discusses that most patients with Pagets disease are asymptomatic but in those that do present pain is the most common presenting symptom He recommends medical and surgical treatment of asymptomatic patients who have active disease at sites where complications are likely to develop
Altman did a review of 290 patients with Pagets disease of bone His findings showed 83 had one or more rheumatic syndromes He found the rate of osteoarthritis related to Pagets disease was elevated in the hip and knee Rheumatoid arthritis hyperuricemia and gout did not appear increased in this group
Mangham et al looked the rate of secondary sarcomas as a result of Pagets disease of bone They found the rate to be around 03 with male predominance They also found that widespread skeletal involvement by Pagets disease was not a significant risk factor for malignant transformation
Interesting views about pagets
Smith et al reviewed the pathologic complications of Pagets bone disease Pagets bone disease commonly causes osseous weakening (deformity and fracture) and arthritis in the hip joint Management of end stage disease is successful with cemented and cementless total hip arthroplasty Bleeding is the most common intra- and post-operative complication of surgery
Gabel et al retrospectively reviewed thirteen patients who had had sixteen total knee arthroplasties for Pagetic gonarthrosis Unlike total hip arthroplasty surgery Paget disease did not increase the amount of blood lost during the operation or in the postoperative period The most common complication associated with total knee arthroplasty was malalignment
Hansen et al reviewed the incidence of osteosarcomas complicating Pagets Disease Of the typical sites that are usually involved in Pagets disease (eg spine pelvis femur tibia and humerus) secondary osteosarcoma tends to spare the spine
Shaylor et al reported the mortality rates in 26 patient with osteosarcoma secondary to Paget s disease There was a 47 mortality at 1 year and 75 at 2 years from diagnosis In their series no patient survived for 5 years All patients died of metastatic disease
Langston et al conducted a randomized trial that compared the results of symptomatic treatment versus intensive bisphosphonate therapy in patients with Pagets disease Clinical fractures occurred in 46 of 661 patients (70) in the treatment group compared with 49 of 663 patients (74) in the symptomatic treatment group They concluded that bisphosphonates did not show a significant beneficial impact on pain quality of life or fracture incidence
Hadjipavlou et al reviewed Pagets disease of the bone and its management Farmers have been shown to have an increased incidence of Pagets disease Average age at presentation is in the 5th and 6th decade Symptomatic individuals are recommended to be treated initially with medical management They suggest that bisphosphonates are more effective than calcitonin at suppressing the histological and biochemical activity in Pagetrsquos disease
Summary Epid Very common in elderly Path Abnormal osteoclastshellipuarrbone
turnoverhellipdeposition of abnormal bone SampS Pain deformity fracture arthropathy Labs uarrAlkPhos X-ray Characteristic coarse thickened
trabeculae Bone scan Very hot Rx Bisphosphonates Surgery for arthropathy fracture painful
deformity
A 65-year-old male presents with increasing shoulder pain over the past 9 months He is otherwise healthy and has no other complaints Radiograph of his shoulder is shown in Figure A Whole body bone scan and biopsy photograph are shown in Figures B and C What is the most appropriate treatment for this patient
1 Referral to endocrinology 2 Radiation therapy and chemotherapy 3 Wide resection and reconstruction 4 Radiation therapy wide resection and reconstruction 5 Chemotherapy wide resection and reconstruction
Histiocytosis X or Langerhans cell histiocytosis is a spectrum of diseases of the reticuloendothelial system with one of three general presentations Eosinophilic granuloma (EG)
usually a single self-limited lesion found in younger patients
Hand-Schuller-Christian disease (HSC) chronic disseminated form with bone and visceral lesions also known as Langerhans cell histiocytosis with visceral
involvement Letterer-Siwe disease (LSD)
fatal form that occurs in young children
Eosinophilic granuloma
Epidemiology demographics
most commonly occurs in children (80 of afflicted lt 20 years of age)
HSC disease presents in children gt 3 years of age LSD occurs in children lt 3 years of age Male to female ratio of 21
location eosinophilic granuloma
commonly presents in the skull ribs clavicle scapula mandible
isolated lesions of the spine (thoracic most common) can also occur in diaphyseal regions of long bones and the
pelvis HSC
multiple bony sites multiple lytic skull lesions visceral involvement of the lungs spleen liver skin lymph
nodes
Genetics no clear genetic pattern of inheritance or locus has
been determined Prognosis
EG isolated involvement generally treatable with local
management spine lesions can spontaneously resolve
HSC prognosis depends on response to chemotherapy worsening prognosis with increasing extraskeletal
involvement LSD
generally fatal in children lt 3 years of age
Symptoms skeletal involvement
pain and swelling at the region of involvement limping can be seen with pelvic or lower extremity
involvement vertebral involvement
localized or diffuse back pain increasingly kyphotic posture radiculopathy can occur with more aggressive lesions
HSC classic triad of
multiple lytic skull lesions diabetes insipidus
increased thirst and water intake exopthalmos
visceral involvement diffuse or nonspecific abdominal or chest pain
Radiographs general
known as the great mimicker as it appears similar to many lesions radiographic differential includes osteomyelitis leukemia lymphoma
fibrous dysplasia or Ewings sarcoma diaphyseal lesions
well defined intramedullary lytic or punched-out lesion cortex may be thinned expanded or destroyed may have periosteal reaction
metaphyseal lesions extend up to but not through the physis less central location than diaphyseal lesions
spinal lesions vertebra plana (flattened vertebrae) in spine increased kyphosis
cranial involvement multiple punched-out lytic lesions
MRI may show a soft tissue mass adjacent to boney lesions
Bone scan generally shows increased uptake in the region of boney lesion
Histology Langerhans cells
mononuclear histiocyte-like cells with oval nuclei with well-defined round or oval cytoplasm
a prominent nuclear groove (coffee bean nuclei) can be seen in most of the nuclei
eosinophilic cytoplasm (pink generally) stain with CD1A electronmicroscopy
birbeck granules seen inside Langerhans cells mixture of inflammatory cells also present giant cells are present lack of nuclear atypia and atypical mitoses
differentiates this condition from malignant conditions such as Ewings sarcoma lymphoma of bone and metastatic neuroblastoma which may look similar based on the round cells alone
eosinophilic cytoplasm (pink generally)
Treatment
bullNonoperative bull observation alone
bull indications bull a self-limited process and it is reasonable to treat with observation alone
bull bracing bull indications
bull to prevent progressive kyphosis of the spinebull outcomes
bull will correct deformity in 90 of patientsbull vertebral lesions generally regain 50 of their height
bull low dose irradiation (600-800 cGy) bull indications
bull indicated for lesions in the spine that compromise stability neurologic statusbull lesions not amenable to injection or open treatment
bull outcomes bull effective for most lesions
bull chemotherapy bull indications
bull diffuse HSCbull outcomes
bull prognosis is improved with less severe extraskeletal involvementbull corticosteroid injection
bull indications bull isolated lesions bull can be performed after curettage as well
Operative curettage and bone grafting
indications for lesions that endanger the articular surface or are a risk for
impending fractures spinal deformity correction
indications progressive spine deformity refractory to bracing
approximately 10 of patients with spine lesion will need operative intervention for deformity correction
Destructive multiple lesion in young patientsAre eosinophilic granuloma lymphoma and leukemiaLymphoma is unlikely to present with exopthalmos diabetes insipidus or vertebra plana Lymphoma bone lesions are lytic and appear moth eatenpermeative on radiographs
Figure A shows a skin lesion typical of eosinophillic granuloma Figure B shows a lytic lesions without significant surrounding sclerosis as is characteristic of eosinophilic granuloma Figure C shows the characteristic histology of multiple eosinophils with their characteristic oval coffee bean nuclei and staining pattern of purpleredpink cytoplasm (depending on the stain) Importantly the histology slide lacks a malignant appearance (no cellular atypia or mytotic complexes and low nuclearcytoplasmic ratio)
Formation of bone in atypical extraskeletal tissues usually occurs
spontaneously or following trauma within 2 months of neurologic injury (brain or spinal cord)
most common location is between muscle and joint capsule Epidemiology
incidence (see table below)
demographics malefemale = 21 especially men with hypertrophic osteoarthritis and women gt65y
location traumatic brain injury or stroke
hip gt elbow gt shoulder gt knee elbow HO more common following brain trauma
occurs on affected (spastic) side rarely in the knee (TBI)
spinal cord injury hip gt knee gt elbow gt shoulder hip flexors and abductors gt extensors or adductors medial aspect of the knee
Heterotopic Ossification
Risk factors
Pathophysiology exact cause of HO is not known but there appears to be a
genetic pre disposition experimental HO associated with
tissue expression of BMP IT IS SAID TO BE CAUSED BY activation and proliferation of
mesenchymal stem cells Associated conditions
orthopaedic manifestations pathologic fractures
from decreased joint ROM and osteoporotic bone nerve impingement soft tissue contractures contributing to the formation of
decubitus ulcers joint ankylosis HO after THA adversely affects outcome of THA
nonorthopaedic conditions skin maceration and hygiene problems
Pathophysiology Early in the formation of HO oedema with exudative
infiltrate is present followed by fibroblastic proliferation and immature connective tissue formation Posteriorly osteoid formation is seen with the subsequent deposition of bone matrix Primitive osteoid is deposited as small masses in the periphery early (within the first two weeks) and osteoblasts are noted located irregularly Osteoblasts produce tropocollagen which polymerizes to form collagen and secrete alkaline phosphatase which allows calcium to precipitate and the mineralization of bone matrix As mineralization progresses amorphous calcium phosphate is progressively replaced by hydroxyapatite crystals During the following weeks the lesion matures with a centripetal pattern and after 6-12 months an appearance of true bone is noted The new bone is always extra-articular and can be contiguous with the skeleton but generally does not involve the periosteum
IN SUMMARY It has been postulated that three conditions
must be met to achieve heterotopic bone formation ---a stimulating event oestrogenic precursor cells and a proper environment LIKE hypercalcaemia tissue hypoxia pH changes (alkalosis) or prolonged immobilization
ClassificationbullSubtypes
bull neurogenic HO bull Four clinical stages of HO in people with spinal cord injury were
described by Nicholas in 1973
bull traumatic myositis ossificans bull fibrodysplasia ossificans progressiva (Munchmeyers Disease)
Neurogenic HO Symptoms
painless loss of ROM interferes with ADL CRPS symptoms fever
Physical exam inspection
warm painful swollen joint may have effusion skin problems
decubitus ulcers from contractures around skin muscles ligaments
skin maceration and hygiene problems motion
decreased joint ROM joint ankylosis with HO after TKA might develop quad muscle snapping or patella
instability neurovascular
peripheral neuropathy HO often impinges on adjacent NV structures
Imaging
bullRadiographs bull findings
bull ossification usually easy to visualize bull maturity of HO
bull the appearance of a bony cortex suggests mature HObull sharp demarcation from surrounding tissue bull trabecular pattern
bull sensitivity and specificity bull not useful for early diagnosisbull only useful at 1 week after onset of symptoms
bull calcium is deposited 7-10 days later than symptom onsetbullUltrasound
bull indications bull for early diagnosis of hip HO
bull findings bull echogenic surfaces with posterior acoustic shadowing
bullCT bull indications
bull useful for preoperative planning bullTriphasic bone scan
bull indications bull best for early diagnosis bull most commonly used diagnostic study
Radiographs are extremely useful in the staging of heterotopic ossification and will show the development of sharp cortical margins once the lesion has reached maturity
Heterotopic bone is a condition in which lamellar bone forms in non-ossified soft tissues In the early stages studies such as MRI and bone scan are more sensitive for diagnosis as radiographs may appear normal for the first three weeks After the appropriate diagnosis is made sequential radiographs are useful for monitoring the progression of the ossification Once it has reached the mature stage sharp cortical margins will appear and surgical resection may be considered
lab
Labs elevated serum alkaline phosphatase (gt250IUL)
ALP removes inhibitors of mineralization nonspecific may be elevated with skeletal trauma cannot determine maturity of HO elevated 12wks after surgery is predictor
elevated CRP correlates with inflammatory activity of HO better than ESR normalization of CRP may correlate with maturity of HO
elevated ESR (gt35mmh) 12wks after THA is predictor
elevated CK correlates with involvement of muscle extent of muscle
involvement Histology
mature fatty bone marrow mature trabecular bone
Heterotopic ossification (HO) most commonly occurs at the amputation site if the amputation was performed thru the zone of injury especially if the injury was a blast mechanism
Symptomatic heterotopic ossification of the quadriceps may occur following placement of a large-diameter Steinmann pin for the purpose of temporary skeletal traction
TreatmentThe prevention of heterotopic ossification is focused on three basic principles disrupting the inductive signalling pathways altering the osteoprogenitor cells or modifying the environment
bullphysiotherapy should involve an assisted range of movement exercises with gentle stretch and terminal resistance trainingbullProphylaxis
bull bisphosphonates amp NSAIDS bull indications
bull although no literature supports are commonly usedbull technique
bull indomethacin is most commonly used bull dose is 75mgday for 10days to 6 weeks
bull perioperative radiation bull indications
bull although no literature supports commonly usedbull is thought to be effective by blocking osteoblast differentiation
bull technique bull a single perioperative dose of 700cGy can be given either 4
hours preop or within 72 hours postoperatively bull lt550cGy not effective
Nonsteroidal anti-inflammatory drugs (NSAIDs) These drugs have demonstrated good results in
preventing heterotopic ossification after total hip arthroplasty
A direct effect of NSAIDs on the formation of heterotopic ossification has been described due to the inhibition of the differentiation of mesenchymal cells into oestrogenic cells There is also an indirect effect which refers to the inhibition of bone remodelling by suppression of the prostagland unmediated inflammatory response (specifically PGE-2)
Indomethacin has been considered a useful medication for heterotopic ossification prophylaxis following total hip replacement
prescribed for three to six weeks in a dose of 75mgday within two months of the injury may reduce the incidence of heterotopic ossification by two to three times
Biphosphonates inhibits precipitation of calcium phosphate and blocks the aggregation and mineralisation of hydroxyapatite crystals In primary prevention Banovac et al [56] have suggested that the treatment should begin as soon as elevated alkaline phosphatase is diagnosed or positive findings in ultrasonography or bone scans are shown In addition disphosphonates could have long-term effects on prevention when the treatment is finished
Posttraumatic wide exposure and surgical resection
indications severe loss of motion and decreased function
technique wide exposure required to identify all neurovascular
structures that may be involved timing of resection (controversial)
marked decrease in bone scan activity AND normalization of ALP
6 months following general trauma 1 year following SCI 15 years following TBI
some data suggests equivalent results when comparing early versus late resection
postop follow with 5 day course of indomethacin early gentle joint mobilization
The surgery is necessary in patients with symptomatic HO and unsuccessful medical treatment such as
Loss of range of motion and ankylosis with associated functional disability such as sitting difficulties
Complications of immobility such as pressure ulcers
Facilitate rehabilitation and recovery of muscular atrophy secondary to prolonged immobilisation
Difficulties of appropriate hygiene because access to the perineum or bladder care is needed
Severe pain refractory to analgesia Vascular andor nerve compression
Advantages to early excision of heterotopic ossification (vs waiting for maturation) include decreased soft tissue contracture better definition between heterotopic and native bone and decreased waiting time for the patient When the soft tissue envelope is benign one may proceed with operative release While waiting for normalization of alkaline phosphatase levels inactivity on bone scan or radiographic maturity may decrease risk of recurrent heterotopic ossification delaying operative release for these reasons has not been shown to improve results of final elbow range of motion after contracture release
Gartland recommended surgery after six months following traumatic heterotopic ossification one year following spinal cord injury and 18 months after head injury
In the past waiting until maturity in order to minimize the rate of recurrence after the surgical treatment was recommended Nevertheless recent studies do not confirm a higher rate of recurrence when the HO is excised in an earlier phase In addition a long delay before surgery leads to ankylosis a high degree of osteoporosis and more extensive intra-articular injuries These findings are associated with bad functional results and potential complications
Should you wait till lesion maturation
Prevention byHandle tissue carefully Avoid excess bleeding Achieve good hemostasis Beware of lesions that span internervous tissue planes
but if it happens resection of a large enough amount of bone to allow improvement of the range of motion and trying to preserve the joint
Our aim must be
A reactive process that is characterized by a well-circumscribed proliferation of fibroblasts cartilage and bone within muscle
A form of heterotopic ossification that is the result direct trauma intramuscular hematoma
most common location is the diaphysis of long bones Must differentiate from tumors Fibrodysplasia ossificans progressiva (FOP) is a rare subtype of heterotopic ossification
involves mutation of the ACVR1 gene (activin A type I receptor gene a BMP type-1 receptor)
Epidemiology demographics
most common in young active males (15 to 35 years old) body locations
quadriceps brachialis and gluteal muscles Genetics
almost always a posttraumatic condition Prognosis
usually self limiting mass usually begins to decrease in size after 1 yea
Myositis ossificans
PresentationbullSymptoms
bull pain tenderness swelling and decreased range of motion that usually presents within days of the injury
bull pain and size of the mass decrease with timebull mass increases in size over several months(usually 3 to 6 cm)
bull after the mass stops growing it becomes firmbullPhysical exam
bull palpable soft tissue massbull restricted range of motion
ImagingbullRadiographs
bull peripheral bone formation with central lucent areabull may appear as dotted veil pattern
bullMRI with gadolinium bull rim enhancement is seen within the first 3 weeks
bullCT scan bull lesion has an eggshell appearance
bullCharacteristic histology shows zonal pattern bull periphery of lesion
bull mature trabeculae of lamellar and woven bonebull calcification seen on xray
bull center of the lesion bull irregular mass of immature fibroblastsbull cartilage component may be presentbull (no calcification seen on xray) bull no cellular atypia seen
Treatment
bullNonoperative bull rest range of motion exercises and activity modification
bull passive stretching is contraindicated (makes it worse)bull physical therapy
bull utilized to maintain range of motionbull radiographic monitoring
bull obtained to confirm maturation of the lesionbullOperative
bull surgical excision bull indicated only if it remains a problem after it maturesbull do not operate in acute phase wait at least six months
bull excision of the lesion within 6 to 12 months predisposes to local recurrence
A 26-year-old man presents with generalized back and joint stiffness and difficulty opening his mouth His elder sister has similar complaints Since childhood he has had 3 surgeries for excision of recurrent bony prominences around his knees He walks with a stooped over posture seen in Figure A Radiographs of his feet knee hip and spine are seen in Figures B-E respectively
fibrodysplasia ossificans progressiva
Stone Man Disease) which involves a mutation of the ACVR1
There are 2 hallmark characteristics progressive heterotopic ossification (muscles fascia tendons ligaments and joint capsules) and congenital malformation of the great toe (hallux valgus malformed first metatarsal and monophalangism) BMP4 which contributes to the formation of the skeleton in the normal embryo is implicated in this disease
Complications
bullHematoma and intraoperative bleedingbullInfection
bull higher rate of infection following joint arthroplasty if HO is present
bullFractures of osteoporotic bone bull osteopenic from disusebull during surgery or physiotherapy
bullRecurrence bull recurrence rate correlates with neurological injury
bull greater recurrence if severe neurological compromisebullAVN
bull if extensive dissection or stripping is required
HTO AND ISS
When ISS is below 25 the mortality risk is minimal and above 25 it is an almost linear increase
When ISS is 50 the mortality is 50 When above 70 it is close to 100 If an injury is assigned an AIS of 6 (unsurvivable injury) the ISS score is
automatically assigned to 75 Highest ISS score obtainable is 75 For trauma patients of vehicular accidents the scoring system is important
for assessing the effectiveness of medical care in reducing morbidity and mortality
Advantages virtually the only anatomical scoring system in use correlates linearly with
mortality morbidity hospital stay other measures of severity
Weaknesses Any error in AIS scoring increases the ISS error Many different injury patterns can yield the same ISS score Injuries to different body regions are not weighted Not a useful triage tool as a full description of patient injuries is not known
prior to full investigation amp operation
risk factors periosteal stripping off anterior femur male gender obesity post traumatic deformity Anterior and anterolateral approach Cementless
Neurogenic HO around the hip due to SCI occurs more often in the medial region than in the lateral region with ossified tissues extending from the pubic symphysis to the anteromedial femoral shaft posterior to the femoral neurovascular structures Ossification is also seen anteriorly involving the iliopsoas and femoral neurovascular structures laterally within gluteus minimus and posteriorly extending from the ilium to the posterior femur encasing the sciatic nerve
HTO AROUND hip and knee
The Brooker Classification of Heterotopic Ossification around the hip joint Class I has islands of bone within the soft tissues Class II has bone spurs from the pelvis or proximal end of the femur leaving at least 1 cm between opposing surfaces Class III has bone spurs from the pelvis andor proximal end of the femur reducing the space between opposing bone surfaces to less than 1 cm Class IV shows apparent bone ankylosis of the hip
Region I - Heterotopic ossifications are strictly below the tip of the greater trochanter
Region II - Heterotopic ossifications are below and above the tip of the greater trochanter
Region III - Heterotopic ossifications are strictly above the tip of the greater trochanter
Grade A - Single or multiple heterotopic ossifications are less than 10 mm in maximal extent without contact with the pelvis or the femur
Grade B - Heterotopic ossifications are greater than 10 mm without contact with the pelvis but with possible contact with the femur there is no bridging from the femur to the proximal part of the greater trochanter and no evidence of ankylosis
Grade C - Ankylosis by means of firm bridging from the femur to the pelvis is present
Shmidt classification
excision may be performed The results of this procedure are varied Patients may find that their range of movement improves but pain relief is likely to be limited
A patient with heterotopic ossification following total hip arthroplasty is thought to have a 90-100 chance of developing it on the contralateral hip if this hip also undergoes total arthroplasty
it would be prudent to minimize the risk of heterotopic ossification developing after arthroplasty by performing surgery whereby the following are ensured
Exposure is meticulous Retraction is performed carefully and soft tissue
is handled carefully Irrigation is adequate Devitalized tissue is excised Hemostasis is adequate Postoperative drains (when used) are not
retained for longer than necessary Perioperative antibiotic prophylaxis is used Postoperative anticoagulation (when used for
deep vein thrombosis prophylaxis) is carefully controlled
sources of knee stiffness 1-extrinsic severe osteoarthritis of the ipsilateral hip neurologic injury leading to muscle rigidity tight quadriceps or hamstring muscles secondary to muscle injury heterotopic ossification or long-standing juvenile inflammatory conditions limiting knee
range of motion prior to the completion of skeletal growth When extrinsic sources are identified revision total knee arthroplasty is unlikely to be associated with a favorable outcome without correction of the extrinsic problem
2-intrinsic (1) overstuffing of the patellofemoral articulation (2) an
excessively tight flexion andor extension gap (3) a tight posterior cruciate ligament (4) femoral andor tibial malrotation (5) arthrofibrosis and (6) limited bearing excursion in association with a highly conforming mobile-bearing prosthetic design
HTO after TKA
Heterotopic Ossification (HO) following primary Total Knee Replacement (TKR)
Occurs in 3-90 of TKRs 3-grade classification system No correlation between HO and component
alignment or component position
Clinical findings similar to early infection Continuing low-grade fever Warm swollen and erythematous knee Normal blood tests Possibly an association with HLA-A2 and B18 HO patients have worse KSS and function
scores
Patients at HIGH risk for developing HO after TKR (Knee Arthroplasty) (5)
Those with limited postoperative knee flexion
Increased lumbar bone mineral density (BMD) on multivariate analysis (3)
Hypertrophic arthrosis Excessive periosteal trauma Notching of the anterior femur Those who require forced manipulation
after TKA 47 in revision TKR surgery (6) Higher rates in revision TKR cases with
infection (up to 76
DaughertyBell classification of HO of the knee 0 No evidence of HO 1 Bone islands in periarticular soft tissue (no
involvement of femur patella or tibia) or HO within quadriceps expansion measuring lt1 cm
2 Spur formation measuring lt5 cm that involves the femur patella or tibia if more than one bone demonstrates HO separation of HO spurs
measure gt1 cm or HO within quadriceps expansion measuring ge1 cm but lt3 cm
3 Spur formation gt5 cm involving femur patella or tibia if more than one bone demonstrates HO separation of HO spurs measure lt1 cm or HO
within quadriceps expansion measuring ge3 cm 4 Extensive HO of the knee causing ankylosis
class 2 HO begins to involve the major bones of the knee joint with spur formation limited to a size of 5 cm
HO class 2 may be observed in select patients with complete ROM and no reported pain Patients with class 3 HO would likely always benefit from surgical excision
followed by RT prophylaxis Certainly patients in either cohort with a subclass ldquoBrdquo assignment (symptomatic) would
benefit from treatment All patients with class 4 HO require
treatment to alleviate ankylosis
treatment
References Whyte ldquoPagetrsquos Disease of Bonerdquo NEMJ vol 355
2006 Klein and Parvizi ldquoSurgical Manifestations of Pagetrsquos
Diseaserdquo JAAOS vol 14 2006 Orthobullets Campbell Apley Emedicinecom
-Chapter 15 Heterotopic Ossification after Traumatic Brain InjuryBy Jesuacutes Moreta and Joseacute Luis Martiacutenez-de los Mozos DOI 10577257343
Questions
Thank You
Etiology Unknown
Proposed Theories Viral Paramyxovirus measles virus RSV canine distemper virus
Viral particles seen in pagetic osteoclasts
Genetic5-40 have 1st degree relative with Pagetrsquos Genetics
inheritance most cases are spontaneous hereditary
familial clusters have been described with ~40 autosomal dominant transmission mutations
at least 4 genes have associated with Pagets disease (amp other disorders of bone turnover) most important is SQSTM1 (p62Sequestosome)
tend to have severe Paget disease
Environmental Arsenic Animals cattle dogs
Pathophysiology Abnormal osteoclastsuarrquantity uarrsize uarractivity uarr of nuclei
Aggressive focal bone resorption makes large cavities in bone
Leads to osteoblast recruitment and overactive osteoblastic activity
Rapid disorganized bone formation
New bone isCoarse disorganized irregular woven
Less resistant to forces there4Prone to deformity and fracture
3 Phases of Disease1) OsteoclasticResorptivePhase Bursts of osteoclastic activity causing bone resorption Lytic lesions trabecular and cortical thinning Osteolytic ldquofrontsrdquoadvance longitudinally from bone
end toward middle ( ldquoVrdquoor ldquoflamerdquoshaped ~1cmyr)
2) OsteoblasticSclerotic or Mixed Phase Mixed osteoclastic and osteoblastic activity Net activity is osteoblastic with deposition of
structurally abnormal bone Bone expansion hyperostosis osteosclerosis
heterogeneous ossification
3-Late ldquoBurn OutrdquoPhasedarrActivity End result widened heterogeneously ossified
but generally sclerotic bones with irregular thickened trabeculae
Phases correlate radiologically and histologically
1048710All 3 Phases may be present simultaneously in the same patient or the same bone
Diseas location Monostotic (25) or polyostotic(75) 1048710Typically affectsPelvis (70) Femur (55) Lumbosacralspine (53) Skull (42) Tibia (32) Rarely in hands feet
1048710No bone-to-bone spread
Clinical Presentation and Complications Usually asymptomatic
Incidental findingAbnormal radiograph or other imaging Abnormal labs (uarrAlkPhos)
Bone pain Constant 1048710Poorly localized 1048710Present at rest
Worse on weight-bearing
pain may be the presenting symptom due to
stress fractures increased vascularity and warmth
new onset intense pain and swelling be suspicious for Pagets secondary sarcoma in a patient with a known history of Pagets who
complains of new onset intense pain and swelling cardiac symptoms
can present with high-output cardiac failure particularly if largemultiple lesions amp pre-existing diminished cardiac function
Bonelimb deformity
Fracture
Arthropathy
uarrincidence of joint disease 1048710Specific pattern of joint diseases in hip uarrfreq of coxa vera protrusio concentric joint space narrowing
uarrSkin temperature
Hypervascularity due to uarrbone turnover activity
uarrbone turnover causes uarrcardiac demands and may lead to high-output heart failure
High-output cardiac failure is caused by the numerous arteriovenous fistulas present in the pagetic bones
Neurologic complaints
Hearing lossvertigotemporal bone involvement with auditory nerve compression
1048710Cranial nerve palsies 1048710Spine involvementMechanical cord compression ldquovascular steal
Hypercalcemia
Rare 1048710Usually inactive or bed-ridden patients 1048710Signs amp SymptomsNausea vomiting MSK aches hyper-reflexia weakness
polyuria headache lethargy altered mental status hellipcoma
Malignant transformation Pagets sarcoma
less than 1 will develop malignant Pagets sarcoma (secondary sarcoma)
osteosarcoma is the most common followed by fibrosarcoma and chondrosarcoma
most common in pelvis femur and humerus Pagets sarcoma has a poor prognosis
5-year survival for non-metastatic Pagets sarcoma is less than 5 appropriate treatment for Pagets sarcoma includes chemotherapy
and wide surgical resection Pagets sarcoma typically presents as a destructive lesion without
periosteal reaction
Diagnosis Clinical assessment Characteristic radiographic appearance Labs (uarrAlkPhos) Bone Scan Usually benign and multiple lesions in old
patients are pagets hyperparathyroidism and bone infarcts
Rarely CT MRI Biopsy
Long bones bend across the trajectories of mechanical stress thus the tibia bows anteriorly and the femur anterolaterally The limb looks bent and feels thick and the skin is unduly warm ndash hence the term lsquoosteitisdeformansrsquo If the skull is affected it enlarges the patient may complain that old hats no longer fit The skull base may become flattened (platybasia) giving the appearance of a short neck In generalized Pagetrsquos disease there may also be considerable kyphosis so the patient becomes shorter and ape-like with bent legs and arms hanging in front of him Cranial nerve compression may lead to impaired vision facial palsy trigeminal neuralgia or deafness Another cause of deafness is otosclerosisVertebral thickening may cause spinal cord or nerve root compression Steal syndromes in which blood is diverted from internal organs to the surrounding skeletal circulationmay cause cerebral impairment and spinal cord ischaemia If there is also spinal stenosis the patient develops typical symptoms of lsquospinal claudicationrsquo and lower limb weakness
Radiographs coarsened trabeculae which give the bone a blastic
appearance both increased and decreased osteodensity may exist
depending on phase of disease lytic phase
lucent areas with expansion and thinned intact cortices blade of grass or flame-shaped lucent advancing edge
mixed phase combination of lysis and sclerosis with coarsened trabeculae
sclerotic phase bone enlargement with cortical thickening sclerotic and lucent
area
remodeled cortices loss of distinction between cortices and medullary cavity
long bone bowing bowing of femur or tibia
fractures hip and knee osteoarthritis osteitis circumscripta
(cotton wool exudates) in skull Pagets secondary sarcoma
shows cortical bone destruction soft tissue mass
MRI may show lumbar spinal stenosis
Bone scan accurately marks site of disease intensely hot in lytic and mixed phase less hot in sclerotic phase
CT scan cortical thickening and coarsened trabeculae
CTMRI Incidental finding Evaluation of atypical presentations
neurological involvement and possible malignant transformation
CT trabecularcortical thinning thickening irregularity
MRI non-specific marrow changes
BiochemistrySerum AlkPhosEnzyme found in osteoblastic membrane Indicator of osteoblastic activity uarrin Pagetrsquos but can be normal Levels correlate with disease extent and activity elevated urinary hydroxyproline (collagen breakdown marker) increased urinary N-telopeptide alpha-C-telopeptide
and deoxypyridinoline normal calcium levels
Other recommended tests ESR -elevation may indicate malignant transformation
CRP Ca -hypercalcemiamay occur in Pagetrsquos PO4 25-hydroxyvitamin D -rule out osteomalacia LFTs-rule out liver disease
Diagnostic Biopsy Diagnosis is usually achieved clinically and by
plain radiographic appearance Biopsy rarely required
Characteristic HistopathologyDisorganized immature trabeculararchitecture with irregular cement lines (ldquomosaicrdquopattern)
Rimming osteoblasts andor multinucleated osteoclasts
Management Options (May require no treatment if asymptomatic)
Supportive Care Pharmacologic Surgical (OrthopedicNeurosurgical
Supportive Care Occupational therapy Physical aides Counseling for fall+fracture prevention
Physical therapy Analgesics Weight control
Pharmacologic ManagementGoals Relieve symptoms and Prevent potential
complications Normalization of serum AlkPhos associated
with better long-term outcomes and disease control
Indications to treat Pain Deformity Neurologic symptoms Asymptomatic but high-risk for complications
(prophylactic) Management of hypercalcemia(rare) Pre-op reduce blood flow and potential
operative blood loss
Calcitonin is the most widely used It reduces bone resorption by decreasing both the activity and the number
of osteoclasts serum alkaline phosphatase and urinaryhydroxyproline levels are lowered Salmon calcitonin is more effective than the porcine variety subcutaneous injections of 50ndash100 MRC units are given daily until pain is relieved and the alkaline phosphatase levels are reduced and stabilized Maintenance injections once or twice weekly may have to be continued indefinitely but some authorities advocate stopping the drug and resuming treatment if symptoms recur Calcitonin can also be administered in a nasal spray Bisphosphonates bind to hydroxyapatite crystals
inhibiting their rate of growth and dissolution It is claimed that the reduction in bone turnover following their use is associated with the formation of lamellar rather than woven bone and that even after treatment is stopped there may be prolonged remission of disease (Bickerstaff et al 1990) Etidronate can be given orally (always on an empty stomach) but dosage should be kept low (eg 5 mgkg per day for up to 6 months) and vitamin D and calcium should also be given lest impaired bone mineralization results inosteomalacia The newer bisphosphonates (eg alendronate or pamidronate) do not have this disadvantage so they should be used as the treatment of choice they produce remissions even with shortcourses of 1 or 2 weeks
BisphosphonatesSynthetic analogues of inorganic phosphate adhere to mineralized surfaces
Ingested selectively by osteoclasts Disrupts enzyme pathways and reduces osteoclastic bone resorption
calcitonin causes osteoclasts to shrink in size and decreases their bone resorptive activity within minutes administered subcutaneously or intramuscularly
teriparatide is contraindicated in Pagets disease due to risk of secondary osteosarcoma
Surgical Management Few require surgery
Common Procedures Corrective osteotomy of long bone deformity indications
fractures through pathologic bowing of long bones impending pathologic fracture of long bone with bowing deformity
Arthroplasty (hip knee) the most common complications include
malalignment with knee arthroplasty bleeding with hip arthroplasty
Combination arthroplasty with osteotomy Fracture fixation
Preoperative Considerations Medical assessment for extraskeletalmanifestations eg high-
output heart failure
Medical treatment of active disease Preoperative autologousblood donation
Thorough planningeg good quality x-rays for templatingand device selection
Intraoperative Considerations Blood salvage system Expansileapproach + soft tissue release Sharp reamersburrsdrills for IM access Extramedullaryguidenavigation systems Concomitant osteotomy
PostoperativeConsiderations Monitoring for cardiac complications Continued medical tx of active disease
uarrHeterotopic ossification Prophylaxis against HO
Possible future excision of HO for painROM
1-Tieg provides a review of Pagets disease of bone and treatment indications In his review he discusses that most patients with Pagets disease are asymptomatic but in those that do present pain is the most common presenting symptom He recommends medical and surgical treatment of asymptomatic patients who have active disease at sites where complications are likely to develop
Altman did a review of 290 patients with Pagets disease of bone His findings showed 83 had one or more rheumatic syndromes He found the rate of osteoarthritis related to Pagets disease was elevated in the hip and knee Rheumatoid arthritis hyperuricemia and gout did not appear increased in this group
Mangham et al looked the rate of secondary sarcomas as a result of Pagets disease of bone They found the rate to be around 03 with male predominance They also found that widespread skeletal involvement by Pagets disease was not a significant risk factor for malignant transformation
Interesting views about pagets
Smith et al reviewed the pathologic complications of Pagets bone disease Pagets bone disease commonly causes osseous weakening (deformity and fracture) and arthritis in the hip joint Management of end stage disease is successful with cemented and cementless total hip arthroplasty Bleeding is the most common intra- and post-operative complication of surgery
Gabel et al retrospectively reviewed thirteen patients who had had sixteen total knee arthroplasties for Pagetic gonarthrosis Unlike total hip arthroplasty surgery Paget disease did not increase the amount of blood lost during the operation or in the postoperative period The most common complication associated with total knee arthroplasty was malalignment
Hansen et al reviewed the incidence of osteosarcomas complicating Pagets Disease Of the typical sites that are usually involved in Pagets disease (eg spine pelvis femur tibia and humerus) secondary osteosarcoma tends to spare the spine
Shaylor et al reported the mortality rates in 26 patient with osteosarcoma secondary to Paget s disease There was a 47 mortality at 1 year and 75 at 2 years from diagnosis In their series no patient survived for 5 years All patients died of metastatic disease
Langston et al conducted a randomized trial that compared the results of symptomatic treatment versus intensive bisphosphonate therapy in patients with Pagets disease Clinical fractures occurred in 46 of 661 patients (70) in the treatment group compared with 49 of 663 patients (74) in the symptomatic treatment group They concluded that bisphosphonates did not show a significant beneficial impact on pain quality of life or fracture incidence
Hadjipavlou et al reviewed Pagets disease of the bone and its management Farmers have been shown to have an increased incidence of Pagets disease Average age at presentation is in the 5th and 6th decade Symptomatic individuals are recommended to be treated initially with medical management They suggest that bisphosphonates are more effective than calcitonin at suppressing the histological and biochemical activity in Pagetrsquos disease
Summary Epid Very common in elderly Path Abnormal osteoclastshellipuarrbone
turnoverhellipdeposition of abnormal bone SampS Pain deformity fracture arthropathy Labs uarrAlkPhos X-ray Characteristic coarse thickened
trabeculae Bone scan Very hot Rx Bisphosphonates Surgery for arthropathy fracture painful
deformity
A 65-year-old male presents with increasing shoulder pain over the past 9 months He is otherwise healthy and has no other complaints Radiograph of his shoulder is shown in Figure A Whole body bone scan and biopsy photograph are shown in Figures B and C What is the most appropriate treatment for this patient
1 Referral to endocrinology 2 Radiation therapy and chemotherapy 3 Wide resection and reconstruction 4 Radiation therapy wide resection and reconstruction 5 Chemotherapy wide resection and reconstruction
Histiocytosis X or Langerhans cell histiocytosis is a spectrum of diseases of the reticuloendothelial system with one of three general presentations Eosinophilic granuloma (EG)
usually a single self-limited lesion found in younger patients
Hand-Schuller-Christian disease (HSC) chronic disseminated form with bone and visceral lesions also known as Langerhans cell histiocytosis with visceral
involvement Letterer-Siwe disease (LSD)
fatal form that occurs in young children
Eosinophilic granuloma
Epidemiology demographics
most commonly occurs in children (80 of afflicted lt 20 years of age)
HSC disease presents in children gt 3 years of age LSD occurs in children lt 3 years of age Male to female ratio of 21
location eosinophilic granuloma
commonly presents in the skull ribs clavicle scapula mandible
isolated lesions of the spine (thoracic most common) can also occur in diaphyseal regions of long bones and the
pelvis HSC
multiple bony sites multiple lytic skull lesions visceral involvement of the lungs spleen liver skin lymph
nodes
Genetics no clear genetic pattern of inheritance or locus has
been determined Prognosis
EG isolated involvement generally treatable with local
management spine lesions can spontaneously resolve
HSC prognosis depends on response to chemotherapy worsening prognosis with increasing extraskeletal
involvement LSD
generally fatal in children lt 3 years of age
Symptoms skeletal involvement
pain and swelling at the region of involvement limping can be seen with pelvic or lower extremity
involvement vertebral involvement
localized or diffuse back pain increasingly kyphotic posture radiculopathy can occur with more aggressive lesions
HSC classic triad of
multiple lytic skull lesions diabetes insipidus
increased thirst and water intake exopthalmos
visceral involvement diffuse or nonspecific abdominal or chest pain
Radiographs general
known as the great mimicker as it appears similar to many lesions radiographic differential includes osteomyelitis leukemia lymphoma
fibrous dysplasia or Ewings sarcoma diaphyseal lesions
well defined intramedullary lytic or punched-out lesion cortex may be thinned expanded or destroyed may have periosteal reaction
metaphyseal lesions extend up to but not through the physis less central location than diaphyseal lesions
spinal lesions vertebra plana (flattened vertebrae) in spine increased kyphosis
cranial involvement multiple punched-out lytic lesions
MRI may show a soft tissue mass adjacent to boney lesions
Bone scan generally shows increased uptake in the region of boney lesion
Histology Langerhans cells
mononuclear histiocyte-like cells with oval nuclei with well-defined round or oval cytoplasm
a prominent nuclear groove (coffee bean nuclei) can be seen in most of the nuclei
eosinophilic cytoplasm (pink generally) stain with CD1A electronmicroscopy
birbeck granules seen inside Langerhans cells mixture of inflammatory cells also present giant cells are present lack of nuclear atypia and atypical mitoses
differentiates this condition from malignant conditions such as Ewings sarcoma lymphoma of bone and metastatic neuroblastoma which may look similar based on the round cells alone
eosinophilic cytoplasm (pink generally)
Treatment
bullNonoperative bull observation alone
bull indications bull a self-limited process and it is reasonable to treat with observation alone
bull bracing bull indications
bull to prevent progressive kyphosis of the spinebull outcomes
bull will correct deformity in 90 of patientsbull vertebral lesions generally regain 50 of their height
bull low dose irradiation (600-800 cGy) bull indications
bull indicated for lesions in the spine that compromise stability neurologic statusbull lesions not amenable to injection or open treatment
bull outcomes bull effective for most lesions
bull chemotherapy bull indications
bull diffuse HSCbull outcomes
bull prognosis is improved with less severe extraskeletal involvementbull corticosteroid injection
bull indications bull isolated lesions bull can be performed after curettage as well
Operative curettage and bone grafting
indications for lesions that endanger the articular surface or are a risk for
impending fractures spinal deformity correction
indications progressive spine deformity refractory to bracing
approximately 10 of patients with spine lesion will need operative intervention for deformity correction
Destructive multiple lesion in young patientsAre eosinophilic granuloma lymphoma and leukemiaLymphoma is unlikely to present with exopthalmos diabetes insipidus or vertebra plana Lymphoma bone lesions are lytic and appear moth eatenpermeative on radiographs
Figure A shows a skin lesion typical of eosinophillic granuloma Figure B shows a lytic lesions without significant surrounding sclerosis as is characteristic of eosinophilic granuloma Figure C shows the characteristic histology of multiple eosinophils with their characteristic oval coffee bean nuclei and staining pattern of purpleredpink cytoplasm (depending on the stain) Importantly the histology slide lacks a malignant appearance (no cellular atypia or mytotic complexes and low nuclearcytoplasmic ratio)
Formation of bone in atypical extraskeletal tissues usually occurs
spontaneously or following trauma within 2 months of neurologic injury (brain or spinal cord)
most common location is between muscle and joint capsule Epidemiology
incidence (see table below)
demographics malefemale = 21 especially men with hypertrophic osteoarthritis and women gt65y
location traumatic brain injury or stroke
hip gt elbow gt shoulder gt knee elbow HO more common following brain trauma
occurs on affected (spastic) side rarely in the knee (TBI)
spinal cord injury hip gt knee gt elbow gt shoulder hip flexors and abductors gt extensors or adductors medial aspect of the knee
Heterotopic Ossification
Risk factors
Pathophysiology exact cause of HO is not known but there appears to be a
genetic pre disposition experimental HO associated with
tissue expression of BMP IT IS SAID TO BE CAUSED BY activation and proliferation of
mesenchymal stem cells Associated conditions
orthopaedic manifestations pathologic fractures
from decreased joint ROM and osteoporotic bone nerve impingement soft tissue contractures contributing to the formation of
decubitus ulcers joint ankylosis HO after THA adversely affects outcome of THA
nonorthopaedic conditions skin maceration and hygiene problems
Pathophysiology Early in the formation of HO oedema with exudative
infiltrate is present followed by fibroblastic proliferation and immature connective tissue formation Posteriorly osteoid formation is seen with the subsequent deposition of bone matrix Primitive osteoid is deposited as small masses in the periphery early (within the first two weeks) and osteoblasts are noted located irregularly Osteoblasts produce tropocollagen which polymerizes to form collagen and secrete alkaline phosphatase which allows calcium to precipitate and the mineralization of bone matrix As mineralization progresses amorphous calcium phosphate is progressively replaced by hydroxyapatite crystals During the following weeks the lesion matures with a centripetal pattern and after 6-12 months an appearance of true bone is noted The new bone is always extra-articular and can be contiguous with the skeleton but generally does not involve the periosteum
IN SUMMARY It has been postulated that three conditions
must be met to achieve heterotopic bone formation ---a stimulating event oestrogenic precursor cells and a proper environment LIKE hypercalcaemia tissue hypoxia pH changes (alkalosis) or prolonged immobilization
ClassificationbullSubtypes
bull neurogenic HO bull Four clinical stages of HO in people with spinal cord injury were
described by Nicholas in 1973
bull traumatic myositis ossificans bull fibrodysplasia ossificans progressiva (Munchmeyers Disease)
Neurogenic HO Symptoms
painless loss of ROM interferes with ADL CRPS symptoms fever
Physical exam inspection
warm painful swollen joint may have effusion skin problems
decubitus ulcers from contractures around skin muscles ligaments
skin maceration and hygiene problems motion
decreased joint ROM joint ankylosis with HO after TKA might develop quad muscle snapping or patella
instability neurovascular
peripheral neuropathy HO often impinges on adjacent NV structures
Imaging
bullRadiographs bull findings
bull ossification usually easy to visualize bull maturity of HO
bull the appearance of a bony cortex suggests mature HObull sharp demarcation from surrounding tissue bull trabecular pattern
bull sensitivity and specificity bull not useful for early diagnosisbull only useful at 1 week after onset of symptoms
bull calcium is deposited 7-10 days later than symptom onsetbullUltrasound
bull indications bull for early diagnosis of hip HO
bull findings bull echogenic surfaces with posterior acoustic shadowing
bullCT bull indications
bull useful for preoperative planning bullTriphasic bone scan
bull indications bull best for early diagnosis bull most commonly used diagnostic study
Radiographs are extremely useful in the staging of heterotopic ossification and will show the development of sharp cortical margins once the lesion has reached maturity
Heterotopic bone is a condition in which lamellar bone forms in non-ossified soft tissues In the early stages studies such as MRI and bone scan are more sensitive for diagnosis as radiographs may appear normal for the first three weeks After the appropriate diagnosis is made sequential radiographs are useful for monitoring the progression of the ossification Once it has reached the mature stage sharp cortical margins will appear and surgical resection may be considered
lab
Labs elevated serum alkaline phosphatase (gt250IUL)
ALP removes inhibitors of mineralization nonspecific may be elevated with skeletal trauma cannot determine maturity of HO elevated 12wks after surgery is predictor
elevated CRP correlates with inflammatory activity of HO better than ESR normalization of CRP may correlate with maturity of HO
elevated ESR (gt35mmh) 12wks after THA is predictor
elevated CK correlates with involvement of muscle extent of muscle
involvement Histology
mature fatty bone marrow mature trabecular bone
Heterotopic ossification (HO) most commonly occurs at the amputation site if the amputation was performed thru the zone of injury especially if the injury was a blast mechanism
Symptomatic heterotopic ossification of the quadriceps may occur following placement of a large-diameter Steinmann pin for the purpose of temporary skeletal traction
TreatmentThe prevention of heterotopic ossification is focused on three basic principles disrupting the inductive signalling pathways altering the osteoprogenitor cells or modifying the environment
bullphysiotherapy should involve an assisted range of movement exercises with gentle stretch and terminal resistance trainingbullProphylaxis
bull bisphosphonates amp NSAIDS bull indications
bull although no literature supports are commonly usedbull technique
bull indomethacin is most commonly used bull dose is 75mgday for 10days to 6 weeks
bull perioperative radiation bull indications
bull although no literature supports commonly usedbull is thought to be effective by blocking osteoblast differentiation
bull technique bull a single perioperative dose of 700cGy can be given either 4
hours preop or within 72 hours postoperatively bull lt550cGy not effective
Nonsteroidal anti-inflammatory drugs (NSAIDs) These drugs have demonstrated good results in
preventing heterotopic ossification after total hip arthroplasty
A direct effect of NSAIDs on the formation of heterotopic ossification has been described due to the inhibition of the differentiation of mesenchymal cells into oestrogenic cells There is also an indirect effect which refers to the inhibition of bone remodelling by suppression of the prostagland unmediated inflammatory response (specifically PGE-2)
Indomethacin has been considered a useful medication for heterotopic ossification prophylaxis following total hip replacement
prescribed for three to six weeks in a dose of 75mgday within two months of the injury may reduce the incidence of heterotopic ossification by two to three times
Biphosphonates inhibits precipitation of calcium phosphate and blocks the aggregation and mineralisation of hydroxyapatite crystals In primary prevention Banovac et al [56] have suggested that the treatment should begin as soon as elevated alkaline phosphatase is diagnosed or positive findings in ultrasonography or bone scans are shown In addition disphosphonates could have long-term effects on prevention when the treatment is finished
Posttraumatic wide exposure and surgical resection
indications severe loss of motion and decreased function
technique wide exposure required to identify all neurovascular
structures that may be involved timing of resection (controversial)
marked decrease in bone scan activity AND normalization of ALP
6 months following general trauma 1 year following SCI 15 years following TBI
some data suggests equivalent results when comparing early versus late resection
postop follow with 5 day course of indomethacin early gentle joint mobilization
The surgery is necessary in patients with symptomatic HO and unsuccessful medical treatment such as
Loss of range of motion and ankylosis with associated functional disability such as sitting difficulties
Complications of immobility such as pressure ulcers
Facilitate rehabilitation and recovery of muscular atrophy secondary to prolonged immobilisation
Difficulties of appropriate hygiene because access to the perineum or bladder care is needed
Severe pain refractory to analgesia Vascular andor nerve compression
Advantages to early excision of heterotopic ossification (vs waiting for maturation) include decreased soft tissue contracture better definition between heterotopic and native bone and decreased waiting time for the patient When the soft tissue envelope is benign one may proceed with operative release While waiting for normalization of alkaline phosphatase levels inactivity on bone scan or radiographic maturity may decrease risk of recurrent heterotopic ossification delaying operative release for these reasons has not been shown to improve results of final elbow range of motion after contracture release
Gartland recommended surgery after six months following traumatic heterotopic ossification one year following spinal cord injury and 18 months after head injury
In the past waiting until maturity in order to minimize the rate of recurrence after the surgical treatment was recommended Nevertheless recent studies do not confirm a higher rate of recurrence when the HO is excised in an earlier phase In addition a long delay before surgery leads to ankylosis a high degree of osteoporosis and more extensive intra-articular injuries These findings are associated with bad functional results and potential complications
Should you wait till lesion maturation
Prevention byHandle tissue carefully Avoid excess bleeding Achieve good hemostasis Beware of lesions that span internervous tissue planes
but if it happens resection of a large enough amount of bone to allow improvement of the range of motion and trying to preserve the joint
Our aim must be
A reactive process that is characterized by a well-circumscribed proliferation of fibroblasts cartilage and bone within muscle
A form of heterotopic ossification that is the result direct trauma intramuscular hematoma
most common location is the diaphysis of long bones Must differentiate from tumors Fibrodysplasia ossificans progressiva (FOP) is a rare subtype of heterotopic ossification
involves mutation of the ACVR1 gene (activin A type I receptor gene a BMP type-1 receptor)
Epidemiology demographics
most common in young active males (15 to 35 years old) body locations
quadriceps brachialis and gluteal muscles Genetics
almost always a posttraumatic condition Prognosis
usually self limiting mass usually begins to decrease in size after 1 yea
Myositis ossificans
PresentationbullSymptoms
bull pain tenderness swelling and decreased range of motion that usually presents within days of the injury
bull pain and size of the mass decrease with timebull mass increases in size over several months(usually 3 to 6 cm)
bull after the mass stops growing it becomes firmbullPhysical exam
bull palpable soft tissue massbull restricted range of motion
ImagingbullRadiographs
bull peripheral bone formation with central lucent areabull may appear as dotted veil pattern
bullMRI with gadolinium bull rim enhancement is seen within the first 3 weeks
bullCT scan bull lesion has an eggshell appearance
bullCharacteristic histology shows zonal pattern bull periphery of lesion
bull mature trabeculae of lamellar and woven bonebull calcification seen on xray
bull center of the lesion bull irregular mass of immature fibroblastsbull cartilage component may be presentbull (no calcification seen on xray) bull no cellular atypia seen
Treatment
bullNonoperative bull rest range of motion exercises and activity modification
bull passive stretching is contraindicated (makes it worse)bull physical therapy
bull utilized to maintain range of motionbull radiographic monitoring
bull obtained to confirm maturation of the lesionbullOperative
bull surgical excision bull indicated only if it remains a problem after it maturesbull do not operate in acute phase wait at least six months
bull excision of the lesion within 6 to 12 months predisposes to local recurrence
A 26-year-old man presents with generalized back and joint stiffness and difficulty opening his mouth His elder sister has similar complaints Since childhood he has had 3 surgeries for excision of recurrent bony prominences around his knees He walks with a stooped over posture seen in Figure A Radiographs of his feet knee hip and spine are seen in Figures B-E respectively
fibrodysplasia ossificans progressiva
Stone Man Disease) which involves a mutation of the ACVR1
There are 2 hallmark characteristics progressive heterotopic ossification (muscles fascia tendons ligaments and joint capsules) and congenital malformation of the great toe (hallux valgus malformed first metatarsal and monophalangism) BMP4 which contributes to the formation of the skeleton in the normal embryo is implicated in this disease
Complications
bullHematoma and intraoperative bleedingbullInfection
bull higher rate of infection following joint arthroplasty if HO is present
bullFractures of osteoporotic bone bull osteopenic from disusebull during surgery or physiotherapy
bullRecurrence bull recurrence rate correlates with neurological injury
bull greater recurrence if severe neurological compromisebullAVN
bull if extensive dissection or stripping is required
HTO AND ISS
When ISS is below 25 the mortality risk is minimal and above 25 it is an almost linear increase
When ISS is 50 the mortality is 50 When above 70 it is close to 100 If an injury is assigned an AIS of 6 (unsurvivable injury) the ISS score is
automatically assigned to 75 Highest ISS score obtainable is 75 For trauma patients of vehicular accidents the scoring system is important
for assessing the effectiveness of medical care in reducing morbidity and mortality
Advantages virtually the only anatomical scoring system in use correlates linearly with
mortality morbidity hospital stay other measures of severity
Weaknesses Any error in AIS scoring increases the ISS error Many different injury patterns can yield the same ISS score Injuries to different body regions are not weighted Not a useful triage tool as a full description of patient injuries is not known
prior to full investigation amp operation
risk factors periosteal stripping off anterior femur male gender obesity post traumatic deformity Anterior and anterolateral approach Cementless
Neurogenic HO around the hip due to SCI occurs more often in the medial region than in the lateral region with ossified tissues extending from the pubic symphysis to the anteromedial femoral shaft posterior to the femoral neurovascular structures Ossification is also seen anteriorly involving the iliopsoas and femoral neurovascular structures laterally within gluteus minimus and posteriorly extending from the ilium to the posterior femur encasing the sciatic nerve
HTO AROUND hip and knee
The Brooker Classification of Heterotopic Ossification around the hip joint Class I has islands of bone within the soft tissues Class II has bone spurs from the pelvis or proximal end of the femur leaving at least 1 cm between opposing surfaces Class III has bone spurs from the pelvis andor proximal end of the femur reducing the space between opposing bone surfaces to less than 1 cm Class IV shows apparent bone ankylosis of the hip
Region I - Heterotopic ossifications are strictly below the tip of the greater trochanter
Region II - Heterotopic ossifications are below and above the tip of the greater trochanter
Region III - Heterotopic ossifications are strictly above the tip of the greater trochanter
Grade A - Single or multiple heterotopic ossifications are less than 10 mm in maximal extent without contact with the pelvis or the femur
Grade B - Heterotopic ossifications are greater than 10 mm without contact with the pelvis but with possible contact with the femur there is no bridging from the femur to the proximal part of the greater trochanter and no evidence of ankylosis
Grade C - Ankylosis by means of firm bridging from the femur to the pelvis is present
Shmidt classification
excision may be performed The results of this procedure are varied Patients may find that their range of movement improves but pain relief is likely to be limited
A patient with heterotopic ossification following total hip arthroplasty is thought to have a 90-100 chance of developing it on the contralateral hip if this hip also undergoes total arthroplasty
it would be prudent to minimize the risk of heterotopic ossification developing after arthroplasty by performing surgery whereby the following are ensured
Exposure is meticulous Retraction is performed carefully and soft tissue
is handled carefully Irrigation is adequate Devitalized tissue is excised Hemostasis is adequate Postoperative drains (when used) are not
retained for longer than necessary Perioperative antibiotic prophylaxis is used Postoperative anticoagulation (when used for
deep vein thrombosis prophylaxis) is carefully controlled
sources of knee stiffness 1-extrinsic severe osteoarthritis of the ipsilateral hip neurologic injury leading to muscle rigidity tight quadriceps or hamstring muscles secondary to muscle injury heterotopic ossification or long-standing juvenile inflammatory conditions limiting knee
range of motion prior to the completion of skeletal growth When extrinsic sources are identified revision total knee arthroplasty is unlikely to be associated with a favorable outcome without correction of the extrinsic problem
2-intrinsic (1) overstuffing of the patellofemoral articulation (2) an
excessively tight flexion andor extension gap (3) a tight posterior cruciate ligament (4) femoral andor tibial malrotation (5) arthrofibrosis and (6) limited bearing excursion in association with a highly conforming mobile-bearing prosthetic design
HTO after TKA
Heterotopic Ossification (HO) following primary Total Knee Replacement (TKR)
Occurs in 3-90 of TKRs 3-grade classification system No correlation between HO and component
alignment or component position
Clinical findings similar to early infection Continuing low-grade fever Warm swollen and erythematous knee Normal blood tests Possibly an association with HLA-A2 and B18 HO patients have worse KSS and function
scores
Patients at HIGH risk for developing HO after TKR (Knee Arthroplasty) (5)
Those with limited postoperative knee flexion
Increased lumbar bone mineral density (BMD) on multivariate analysis (3)
Hypertrophic arthrosis Excessive periosteal trauma Notching of the anterior femur Those who require forced manipulation
after TKA 47 in revision TKR surgery (6) Higher rates in revision TKR cases with
infection (up to 76
DaughertyBell classification of HO of the knee 0 No evidence of HO 1 Bone islands in periarticular soft tissue (no
involvement of femur patella or tibia) or HO within quadriceps expansion measuring lt1 cm
2 Spur formation measuring lt5 cm that involves the femur patella or tibia if more than one bone demonstrates HO separation of HO spurs
measure gt1 cm or HO within quadriceps expansion measuring ge1 cm but lt3 cm
3 Spur formation gt5 cm involving femur patella or tibia if more than one bone demonstrates HO separation of HO spurs measure lt1 cm or HO
within quadriceps expansion measuring ge3 cm 4 Extensive HO of the knee causing ankylosis
class 2 HO begins to involve the major bones of the knee joint with spur formation limited to a size of 5 cm
HO class 2 may be observed in select patients with complete ROM and no reported pain Patients with class 3 HO would likely always benefit from surgical excision
followed by RT prophylaxis Certainly patients in either cohort with a subclass ldquoBrdquo assignment (symptomatic) would
benefit from treatment All patients with class 4 HO require
treatment to alleviate ankylosis
treatment
References Whyte ldquoPagetrsquos Disease of Bonerdquo NEMJ vol 355
2006 Klein and Parvizi ldquoSurgical Manifestations of Pagetrsquos
Diseaserdquo JAAOS vol 14 2006 Orthobullets Campbell Apley Emedicinecom
-Chapter 15 Heterotopic Ossification after Traumatic Brain InjuryBy Jesuacutes Moreta and Joseacute Luis Martiacutenez-de los Mozos DOI 10577257343
Questions
Thank You
Pathophysiology Abnormal osteoclastsuarrquantity uarrsize uarractivity uarr of nuclei
Aggressive focal bone resorption makes large cavities in bone
Leads to osteoblast recruitment and overactive osteoblastic activity
Rapid disorganized bone formation
New bone isCoarse disorganized irregular woven
Less resistant to forces there4Prone to deformity and fracture
3 Phases of Disease1) OsteoclasticResorptivePhase Bursts of osteoclastic activity causing bone resorption Lytic lesions trabecular and cortical thinning Osteolytic ldquofrontsrdquoadvance longitudinally from bone
end toward middle ( ldquoVrdquoor ldquoflamerdquoshaped ~1cmyr)
2) OsteoblasticSclerotic or Mixed Phase Mixed osteoclastic and osteoblastic activity Net activity is osteoblastic with deposition of
structurally abnormal bone Bone expansion hyperostosis osteosclerosis
heterogeneous ossification
3-Late ldquoBurn OutrdquoPhasedarrActivity End result widened heterogeneously ossified
but generally sclerotic bones with irregular thickened trabeculae
Phases correlate radiologically and histologically
1048710All 3 Phases may be present simultaneously in the same patient or the same bone
Diseas location Monostotic (25) or polyostotic(75) 1048710Typically affectsPelvis (70) Femur (55) Lumbosacralspine (53) Skull (42) Tibia (32) Rarely in hands feet
1048710No bone-to-bone spread
Clinical Presentation and Complications Usually asymptomatic
Incidental findingAbnormal radiograph or other imaging Abnormal labs (uarrAlkPhos)
Bone pain Constant 1048710Poorly localized 1048710Present at rest
Worse on weight-bearing
pain may be the presenting symptom due to
stress fractures increased vascularity and warmth
new onset intense pain and swelling be suspicious for Pagets secondary sarcoma in a patient with a known history of Pagets who
complains of new onset intense pain and swelling cardiac symptoms
can present with high-output cardiac failure particularly if largemultiple lesions amp pre-existing diminished cardiac function
Bonelimb deformity
Fracture
Arthropathy
uarrincidence of joint disease 1048710Specific pattern of joint diseases in hip uarrfreq of coxa vera protrusio concentric joint space narrowing
uarrSkin temperature
Hypervascularity due to uarrbone turnover activity
uarrbone turnover causes uarrcardiac demands and may lead to high-output heart failure
High-output cardiac failure is caused by the numerous arteriovenous fistulas present in the pagetic bones
Neurologic complaints
Hearing lossvertigotemporal bone involvement with auditory nerve compression
1048710Cranial nerve palsies 1048710Spine involvementMechanical cord compression ldquovascular steal
Hypercalcemia
Rare 1048710Usually inactive or bed-ridden patients 1048710Signs amp SymptomsNausea vomiting MSK aches hyper-reflexia weakness
polyuria headache lethargy altered mental status hellipcoma
Malignant transformation Pagets sarcoma
less than 1 will develop malignant Pagets sarcoma (secondary sarcoma)
osteosarcoma is the most common followed by fibrosarcoma and chondrosarcoma
most common in pelvis femur and humerus Pagets sarcoma has a poor prognosis
5-year survival for non-metastatic Pagets sarcoma is less than 5 appropriate treatment for Pagets sarcoma includes chemotherapy
and wide surgical resection Pagets sarcoma typically presents as a destructive lesion without
periosteal reaction
Diagnosis Clinical assessment Characteristic radiographic appearance Labs (uarrAlkPhos) Bone Scan Usually benign and multiple lesions in old
patients are pagets hyperparathyroidism and bone infarcts
Rarely CT MRI Biopsy
Long bones bend across the trajectories of mechanical stress thus the tibia bows anteriorly and the femur anterolaterally The limb looks bent and feels thick and the skin is unduly warm ndash hence the term lsquoosteitisdeformansrsquo If the skull is affected it enlarges the patient may complain that old hats no longer fit The skull base may become flattened (platybasia) giving the appearance of a short neck In generalized Pagetrsquos disease there may also be considerable kyphosis so the patient becomes shorter and ape-like with bent legs and arms hanging in front of him Cranial nerve compression may lead to impaired vision facial palsy trigeminal neuralgia or deafness Another cause of deafness is otosclerosisVertebral thickening may cause spinal cord or nerve root compression Steal syndromes in which blood is diverted from internal organs to the surrounding skeletal circulationmay cause cerebral impairment and spinal cord ischaemia If there is also spinal stenosis the patient develops typical symptoms of lsquospinal claudicationrsquo and lower limb weakness
Radiographs coarsened trabeculae which give the bone a blastic
appearance both increased and decreased osteodensity may exist
depending on phase of disease lytic phase
lucent areas with expansion and thinned intact cortices blade of grass or flame-shaped lucent advancing edge
mixed phase combination of lysis and sclerosis with coarsened trabeculae
sclerotic phase bone enlargement with cortical thickening sclerotic and lucent
area
remodeled cortices loss of distinction between cortices and medullary cavity
long bone bowing bowing of femur or tibia
fractures hip and knee osteoarthritis osteitis circumscripta
(cotton wool exudates) in skull Pagets secondary sarcoma
shows cortical bone destruction soft tissue mass
MRI may show lumbar spinal stenosis
Bone scan accurately marks site of disease intensely hot in lytic and mixed phase less hot in sclerotic phase
CT scan cortical thickening and coarsened trabeculae
CTMRI Incidental finding Evaluation of atypical presentations
neurological involvement and possible malignant transformation
CT trabecularcortical thinning thickening irregularity
MRI non-specific marrow changes
BiochemistrySerum AlkPhosEnzyme found in osteoblastic membrane Indicator of osteoblastic activity uarrin Pagetrsquos but can be normal Levels correlate with disease extent and activity elevated urinary hydroxyproline (collagen breakdown marker) increased urinary N-telopeptide alpha-C-telopeptide
and deoxypyridinoline normal calcium levels
Other recommended tests ESR -elevation may indicate malignant transformation
CRP Ca -hypercalcemiamay occur in Pagetrsquos PO4 25-hydroxyvitamin D -rule out osteomalacia LFTs-rule out liver disease
Diagnostic Biopsy Diagnosis is usually achieved clinically and by
plain radiographic appearance Biopsy rarely required
Characteristic HistopathologyDisorganized immature trabeculararchitecture with irregular cement lines (ldquomosaicrdquopattern)
Rimming osteoblasts andor multinucleated osteoclasts
Management Options (May require no treatment if asymptomatic)
Supportive Care Pharmacologic Surgical (OrthopedicNeurosurgical
Supportive Care Occupational therapy Physical aides Counseling for fall+fracture prevention
Physical therapy Analgesics Weight control
Pharmacologic ManagementGoals Relieve symptoms and Prevent potential
complications Normalization of serum AlkPhos associated
with better long-term outcomes and disease control
Indications to treat Pain Deformity Neurologic symptoms Asymptomatic but high-risk for complications
(prophylactic) Management of hypercalcemia(rare) Pre-op reduce blood flow and potential
operative blood loss
Calcitonin is the most widely used It reduces bone resorption by decreasing both the activity and the number
of osteoclasts serum alkaline phosphatase and urinaryhydroxyproline levels are lowered Salmon calcitonin is more effective than the porcine variety subcutaneous injections of 50ndash100 MRC units are given daily until pain is relieved and the alkaline phosphatase levels are reduced and stabilized Maintenance injections once or twice weekly may have to be continued indefinitely but some authorities advocate stopping the drug and resuming treatment if symptoms recur Calcitonin can also be administered in a nasal spray Bisphosphonates bind to hydroxyapatite crystals
inhibiting their rate of growth and dissolution It is claimed that the reduction in bone turnover following their use is associated with the formation of lamellar rather than woven bone and that even after treatment is stopped there may be prolonged remission of disease (Bickerstaff et al 1990) Etidronate can be given orally (always on an empty stomach) but dosage should be kept low (eg 5 mgkg per day for up to 6 months) and vitamin D and calcium should also be given lest impaired bone mineralization results inosteomalacia The newer bisphosphonates (eg alendronate or pamidronate) do not have this disadvantage so they should be used as the treatment of choice they produce remissions even with shortcourses of 1 or 2 weeks
BisphosphonatesSynthetic analogues of inorganic phosphate adhere to mineralized surfaces
Ingested selectively by osteoclasts Disrupts enzyme pathways and reduces osteoclastic bone resorption
calcitonin causes osteoclasts to shrink in size and decreases their bone resorptive activity within minutes administered subcutaneously or intramuscularly
teriparatide is contraindicated in Pagets disease due to risk of secondary osteosarcoma
Surgical Management Few require surgery
Common Procedures Corrective osteotomy of long bone deformity indications
fractures through pathologic bowing of long bones impending pathologic fracture of long bone with bowing deformity
Arthroplasty (hip knee) the most common complications include
malalignment with knee arthroplasty bleeding with hip arthroplasty
Combination arthroplasty with osteotomy Fracture fixation
Preoperative Considerations Medical assessment for extraskeletalmanifestations eg high-
output heart failure
Medical treatment of active disease Preoperative autologousblood donation
Thorough planningeg good quality x-rays for templatingand device selection
Intraoperative Considerations Blood salvage system Expansileapproach + soft tissue release Sharp reamersburrsdrills for IM access Extramedullaryguidenavigation systems Concomitant osteotomy
PostoperativeConsiderations Monitoring for cardiac complications Continued medical tx of active disease
uarrHeterotopic ossification Prophylaxis against HO
Possible future excision of HO for painROM
1-Tieg provides a review of Pagets disease of bone and treatment indications In his review he discusses that most patients with Pagets disease are asymptomatic but in those that do present pain is the most common presenting symptom He recommends medical and surgical treatment of asymptomatic patients who have active disease at sites where complications are likely to develop
Altman did a review of 290 patients with Pagets disease of bone His findings showed 83 had one or more rheumatic syndromes He found the rate of osteoarthritis related to Pagets disease was elevated in the hip and knee Rheumatoid arthritis hyperuricemia and gout did not appear increased in this group
Mangham et al looked the rate of secondary sarcomas as a result of Pagets disease of bone They found the rate to be around 03 with male predominance They also found that widespread skeletal involvement by Pagets disease was not a significant risk factor for malignant transformation
Interesting views about pagets
Smith et al reviewed the pathologic complications of Pagets bone disease Pagets bone disease commonly causes osseous weakening (deformity and fracture) and arthritis in the hip joint Management of end stage disease is successful with cemented and cementless total hip arthroplasty Bleeding is the most common intra- and post-operative complication of surgery
Gabel et al retrospectively reviewed thirteen patients who had had sixteen total knee arthroplasties for Pagetic gonarthrosis Unlike total hip arthroplasty surgery Paget disease did not increase the amount of blood lost during the operation or in the postoperative period The most common complication associated with total knee arthroplasty was malalignment
Hansen et al reviewed the incidence of osteosarcomas complicating Pagets Disease Of the typical sites that are usually involved in Pagets disease (eg spine pelvis femur tibia and humerus) secondary osteosarcoma tends to spare the spine
Shaylor et al reported the mortality rates in 26 patient with osteosarcoma secondary to Paget s disease There was a 47 mortality at 1 year and 75 at 2 years from diagnosis In their series no patient survived for 5 years All patients died of metastatic disease
Langston et al conducted a randomized trial that compared the results of symptomatic treatment versus intensive bisphosphonate therapy in patients with Pagets disease Clinical fractures occurred in 46 of 661 patients (70) in the treatment group compared with 49 of 663 patients (74) in the symptomatic treatment group They concluded that bisphosphonates did not show a significant beneficial impact on pain quality of life or fracture incidence
Hadjipavlou et al reviewed Pagets disease of the bone and its management Farmers have been shown to have an increased incidence of Pagets disease Average age at presentation is in the 5th and 6th decade Symptomatic individuals are recommended to be treated initially with medical management They suggest that bisphosphonates are more effective than calcitonin at suppressing the histological and biochemical activity in Pagetrsquos disease
Summary Epid Very common in elderly Path Abnormal osteoclastshellipuarrbone
turnoverhellipdeposition of abnormal bone SampS Pain deformity fracture arthropathy Labs uarrAlkPhos X-ray Characteristic coarse thickened
trabeculae Bone scan Very hot Rx Bisphosphonates Surgery for arthropathy fracture painful
deformity
A 65-year-old male presents with increasing shoulder pain over the past 9 months He is otherwise healthy and has no other complaints Radiograph of his shoulder is shown in Figure A Whole body bone scan and biopsy photograph are shown in Figures B and C What is the most appropriate treatment for this patient
1 Referral to endocrinology 2 Radiation therapy and chemotherapy 3 Wide resection and reconstruction 4 Radiation therapy wide resection and reconstruction 5 Chemotherapy wide resection and reconstruction
Histiocytosis X or Langerhans cell histiocytosis is a spectrum of diseases of the reticuloendothelial system with one of three general presentations Eosinophilic granuloma (EG)
usually a single self-limited lesion found in younger patients
Hand-Schuller-Christian disease (HSC) chronic disseminated form with bone and visceral lesions also known as Langerhans cell histiocytosis with visceral
involvement Letterer-Siwe disease (LSD)
fatal form that occurs in young children
Eosinophilic granuloma
Epidemiology demographics
most commonly occurs in children (80 of afflicted lt 20 years of age)
HSC disease presents in children gt 3 years of age LSD occurs in children lt 3 years of age Male to female ratio of 21
location eosinophilic granuloma
commonly presents in the skull ribs clavicle scapula mandible
isolated lesions of the spine (thoracic most common) can also occur in diaphyseal regions of long bones and the
pelvis HSC
multiple bony sites multiple lytic skull lesions visceral involvement of the lungs spleen liver skin lymph
nodes
Genetics no clear genetic pattern of inheritance or locus has
been determined Prognosis
EG isolated involvement generally treatable with local
management spine lesions can spontaneously resolve
HSC prognosis depends on response to chemotherapy worsening prognosis with increasing extraskeletal
involvement LSD
generally fatal in children lt 3 years of age
Symptoms skeletal involvement
pain and swelling at the region of involvement limping can be seen with pelvic or lower extremity
involvement vertebral involvement
localized or diffuse back pain increasingly kyphotic posture radiculopathy can occur with more aggressive lesions
HSC classic triad of
multiple lytic skull lesions diabetes insipidus
increased thirst and water intake exopthalmos
visceral involvement diffuse or nonspecific abdominal or chest pain
Radiographs general
known as the great mimicker as it appears similar to many lesions radiographic differential includes osteomyelitis leukemia lymphoma
fibrous dysplasia or Ewings sarcoma diaphyseal lesions
well defined intramedullary lytic or punched-out lesion cortex may be thinned expanded or destroyed may have periosteal reaction
metaphyseal lesions extend up to but not through the physis less central location than diaphyseal lesions
spinal lesions vertebra plana (flattened vertebrae) in spine increased kyphosis
cranial involvement multiple punched-out lytic lesions
MRI may show a soft tissue mass adjacent to boney lesions
Bone scan generally shows increased uptake in the region of boney lesion
Histology Langerhans cells
mononuclear histiocyte-like cells with oval nuclei with well-defined round or oval cytoplasm
a prominent nuclear groove (coffee bean nuclei) can be seen in most of the nuclei
eosinophilic cytoplasm (pink generally) stain with CD1A electronmicroscopy
birbeck granules seen inside Langerhans cells mixture of inflammatory cells also present giant cells are present lack of nuclear atypia and atypical mitoses
differentiates this condition from malignant conditions such as Ewings sarcoma lymphoma of bone and metastatic neuroblastoma which may look similar based on the round cells alone
eosinophilic cytoplasm (pink generally)
Treatment
bullNonoperative bull observation alone
bull indications bull a self-limited process and it is reasonable to treat with observation alone
bull bracing bull indications
bull to prevent progressive kyphosis of the spinebull outcomes
bull will correct deformity in 90 of patientsbull vertebral lesions generally regain 50 of their height
bull low dose irradiation (600-800 cGy) bull indications
bull indicated for lesions in the spine that compromise stability neurologic statusbull lesions not amenable to injection or open treatment
bull outcomes bull effective for most lesions
bull chemotherapy bull indications
bull diffuse HSCbull outcomes
bull prognosis is improved with less severe extraskeletal involvementbull corticosteroid injection
bull indications bull isolated lesions bull can be performed after curettage as well
Operative curettage and bone grafting
indications for lesions that endanger the articular surface or are a risk for
impending fractures spinal deformity correction
indications progressive spine deformity refractory to bracing
approximately 10 of patients with spine lesion will need operative intervention for deformity correction
Destructive multiple lesion in young patientsAre eosinophilic granuloma lymphoma and leukemiaLymphoma is unlikely to present with exopthalmos diabetes insipidus or vertebra plana Lymphoma bone lesions are lytic and appear moth eatenpermeative on radiographs
Figure A shows a skin lesion typical of eosinophillic granuloma Figure B shows a lytic lesions without significant surrounding sclerosis as is characteristic of eosinophilic granuloma Figure C shows the characteristic histology of multiple eosinophils with their characteristic oval coffee bean nuclei and staining pattern of purpleredpink cytoplasm (depending on the stain) Importantly the histology slide lacks a malignant appearance (no cellular atypia or mytotic complexes and low nuclearcytoplasmic ratio)
Formation of bone in atypical extraskeletal tissues usually occurs
spontaneously or following trauma within 2 months of neurologic injury (brain or spinal cord)
most common location is between muscle and joint capsule Epidemiology
incidence (see table below)
demographics malefemale = 21 especially men with hypertrophic osteoarthritis and women gt65y
location traumatic brain injury or stroke
hip gt elbow gt shoulder gt knee elbow HO more common following brain trauma
occurs on affected (spastic) side rarely in the knee (TBI)
spinal cord injury hip gt knee gt elbow gt shoulder hip flexors and abductors gt extensors or adductors medial aspect of the knee
Heterotopic Ossification
Risk factors
Pathophysiology exact cause of HO is not known but there appears to be a
genetic pre disposition experimental HO associated with
tissue expression of BMP IT IS SAID TO BE CAUSED BY activation and proliferation of
mesenchymal stem cells Associated conditions
orthopaedic manifestations pathologic fractures
from decreased joint ROM and osteoporotic bone nerve impingement soft tissue contractures contributing to the formation of
decubitus ulcers joint ankylosis HO after THA adversely affects outcome of THA
nonorthopaedic conditions skin maceration and hygiene problems
Pathophysiology Early in the formation of HO oedema with exudative
infiltrate is present followed by fibroblastic proliferation and immature connective tissue formation Posteriorly osteoid formation is seen with the subsequent deposition of bone matrix Primitive osteoid is deposited as small masses in the periphery early (within the first two weeks) and osteoblasts are noted located irregularly Osteoblasts produce tropocollagen which polymerizes to form collagen and secrete alkaline phosphatase which allows calcium to precipitate and the mineralization of bone matrix As mineralization progresses amorphous calcium phosphate is progressively replaced by hydroxyapatite crystals During the following weeks the lesion matures with a centripetal pattern and after 6-12 months an appearance of true bone is noted The new bone is always extra-articular and can be contiguous with the skeleton but generally does not involve the periosteum
IN SUMMARY It has been postulated that three conditions
must be met to achieve heterotopic bone formation ---a stimulating event oestrogenic precursor cells and a proper environment LIKE hypercalcaemia tissue hypoxia pH changes (alkalosis) or prolonged immobilization
ClassificationbullSubtypes
bull neurogenic HO bull Four clinical stages of HO in people with spinal cord injury were
described by Nicholas in 1973
bull traumatic myositis ossificans bull fibrodysplasia ossificans progressiva (Munchmeyers Disease)
Neurogenic HO Symptoms
painless loss of ROM interferes with ADL CRPS symptoms fever
Physical exam inspection
warm painful swollen joint may have effusion skin problems
decubitus ulcers from contractures around skin muscles ligaments
skin maceration and hygiene problems motion
decreased joint ROM joint ankylosis with HO after TKA might develop quad muscle snapping or patella
instability neurovascular
peripheral neuropathy HO often impinges on adjacent NV structures
Imaging
bullRadiographs bull findings
bull ossification usually easy to visualize bull maturity of HO
bull the appearance of a bony cortex suggests mature HObull sharp demarcation from surrounding tissue bull trabecular pattern
bull sensitivity and specificity bull not useful for early diagnosisbull only useful at 1 week after onset of symptoms
bull calcium is deposited 7-10 days later than symptom onsetbullUltrasound
bull indications bull for early diagnosis of hip HO
bull findings bull echogenic surfaces with posterior acoustic shadowing
bullCT bull indications
bull useful for preoperative planning bullTriphasic bone scan
bull indications bull best for early diagnosis bull most commonly used diagnostic study
Radiographs are extremely useful in the staging of heterotopic ossification and will show the development of sharp cortical margins once the lesion has reached maturity
Heterotopic bone is a condition in which lamellar bone forms in non-ossified soft tissues In the early stages studies such as MRI and bone scan are more sensitive for diagnosis as radiographs may appear normal for the first three weeks After the appropriate diagnosis is made sequential radiographs are useful for monitoring the progression of the ossification Once it has reached the mature stage sharp cortical margins will appear and surgical resection may be considered
lab
Labs elevated serum alkaline phosphatase (gt250IUL)
ALP removes inhibitors of mineralization nonspecific may be elevated with skeletal trauma cannot determine maturity of HO elevated 12wks after surgery is predictor
elevated CRP correlates with inflammatory activity of HO better than ESR normalization of CRP may correlate with maturity of HO
elevated ESR (gt35mmh) 12wks after THA is predictor
elevated CK correlates with involvement of muscle extent of muscle
involvement Histology
mature fatty bone marrow mature trabecular bone
Heterotopic ossification (HO) most commonly occurs at the amputation site if the amputation was performed thru the zone of injury especially if the injury was a blast mechanism
Symptomatic heterotopic ossification of the quadriceps may occur following placement of a large-diameter Steinmann pin for the purpose of temporary skeletal traction
TreatmentThe prevention of heterotopic ossification is focused on three basic principles disrupting the inductive signalling pathways altering the osteoprogenitor cells or modifying the environment
bullphysiotherapy should involve an assisted range of movement exercises with gentle stretch and terminal resistance trainingbullProphylaxis
bull bisphosphonates amp NSAIDS bull indications
bull although no literature supports are commonly usedbull technique
bull indomethacin is most commonly used bull dose is 75mgday for 10days to 6 weeks
bull perioperative radiation bull indications
bull although no literature supports commonly usedbull is thought to be effective by blocking osteoblast differentiation
bull technique bull a single perioperative dose of 700cGy can be given either 4
hours preop or within 72 hours postoperatively bull lt550cGy not effective
Nonsteroidal anti-inflammatory drugs (NSAIDs) These drugs have demonstrated good results in
preventing heterotopic ossification after total hip arthroplasty
A direct effect of NSAIDs on the formation of heterotopic ossification has been described due to the inhibition of the differentiation of mesenchymal cells into oestrogenic cells There is also an indirect effect which refers to the inhibition of bone remodelling by suppression of the prostagland unmediated inflammatory response (specifically PGE-2)
Indomethacin has been considered a useful medication for heterotopic ossification prophylaxis following total hip replacement
prescribed for three to six weeks in a dose of 75mgday within two months of the injury may reduce the incidence of heterotopic ossification by two to three times
Biphosphonates inhibits precipitation of calcium phosphate and blocks the aggregation and mineralisation of hydroxyapatite crystals In primary prevention Banovac et al [56] have suggested that the treatment should begin as soon as elevated alkaline phosphatase is diagnosed or positive findings in ultrasonography or bone scans are shown In addition disphosphonates could have long-term effects on prevention when the treatment is finished
Posttraumatic wide exposure and surgical resection
indications severe loss of motion and decreased function
technique wide exposure required to identify all neurovascular
structures that may be involved timing of resection (controversial)
marked decrease in bone scan activity AND normalization of ALP
6 months following general trauma 1 year following SCI 15 years following TBI
some data suggests equivalent results when comparing early versus late resection
postop follow with 5 day course of indomethacin early gentle joint mobilization
The surgery is necessary in patients with symptomatic HO and unsuccessful medical treatment such as
Loss of range of motion and ankylosis with associated functional disability such as sitting difficulties
Complications of immobility such as pressure ulcers
Facilitate rehabilitation and recovery of muscular atrophy secondary to prolonged immobilisation
Difficulties of appropriate hygiene because access to the perineum or bladder care is needed
Severe pain refractory to analgesia Vascular andor nerve compression
Advantages to early excision of heterotopic ossification (vs waiting for maturation) include decreased soft tissue contracture better definition between heterotopic and native bone and decreased waiting time for the patient When the soft tissue envelope is benign one may proceed with operative release While waiting for normalization of alkaline phosphatase levels inactivity on bone scan or radiographic maturity may decrease risk of recurrent heterotopic ossification delaying operative release for these reasons has not been shown to improve results of final elbow range of motion after contracture release
Gartland recommended surgery after six months following traumatic heterotopic ossification one year following spinal cord injury and 18 months after head injury
In the past waiting until maturity in order to minimize the rate of recurrence after the surgical treatment was recommended Nevertheless recent studies do not confirm a higher rate of recurrence when the HO is excised in an earlier phase In addition a long delay before surgery leads to ankylosis a high degree of osteoporosis and more extensive intra-articular injuries These findings are associated with bad functional results and potential complications
Should you wait till lesion maturation
Prevention byHandle tissue carefully Avoid excess bleeding Achieve good hemostasis Beware of lesions that span internervous tissue planes
but if it happens resection of a large enough amount of bone to allow improvement of the range of motion and trying to preserve the joint
Our aim must be
A reactive process that is characterized by a well-circumscribed proliferation of fibroblasts cartilage and bone within muscle
A form of heterotopic ossification that is the result direct trauma intramuscular hematoma
most common location is the diaphysis of long bones Must differentiate from tumors Fibrodysplasia ossificans progressiva (FOP) is a rare subtype of heterotopic ossification
involves mutation of the ACVR1 gene (activin A type I receptor gene a BMP type-1 receptor)
Epidemiology demographics
most common in young active males (15 to 35 years old) body locations
quadriceps brachialis and gluteal muscles Genetics
almost always a posttraumatic condition Prognosis
usually self limiting mass usually begins to decrease in size after 1 yea
Myositis ossificans
PresentationbullSymptoms
bull pain tenderness swelling and decreased range of motion that usually presents within days of the injury
bull pain and size of the mass decrease with timebull mass increases in size over several months(usually 3 to 6 cm)
bull after the mass stops growing it becomes firmbullPhysical exam
bull palpable soft tissue massbull restricted range of motion
ImagingbullRadiographs
bull peripheral bone formation with central lucent areabull may appear as dotted veil pattern
bullMRI with gadolinium bull rim enhancement is seen within the first 3 weeks
bullCT scan bull lesion has an eggshell appearance
bullCharacteristic histology shows zonal pattern bull periphery of lesion
bull mature trabeculae of lamellar and woven bonebull calcification seen on xray
bull center of the lesion bull irregular mass of immature fibroblastsbull cartilage component may be presentbull (no calcification seen on xray) bull no cellular atypia seen
Treatment
bullNonoperative bull rest range of motion exercises and activity modification
bull passive stretching is contraindicated (makes it worse)bull physical therapy
bull utilized to maintain range of motionbull radiographic monitoring
bull obtained to confirm maturation of the lesionbullOperative
bull surgical excision bull indicated only if it remains a problem after it maturesbull do not operate in acute phase wait at least six months
bull excision of the lesion within 6 to 12 months predisposes to local recurrence
A 26-year-old man presents with generalized back and joint stiffness and difficulty opening his mouth His elder sister has similar complaints Since childhood he has had 3 surgeries for excision of recurrent bony prominences around his knees He walks with a stooped over posture seen in Figure A Radiographs of his feet knee hip and spine are seen in Figures B-E respectively
fibrodysplasia ossificans progressiva
Stone Man Disease) which involves a mutation of the ACVR1
There are 2 hallmark characteristics progressive heterotopic ossification (muscles fascia tendons ligaments and joint capsules) and congenital malformation of the great toe (hallux valgus malformed first metatarsal and monophalangism) BMP4 which contributes to the formation of the skeleton in the normal embryo is implicated in this disease
Complications
bullHematoma and intraoperative bleedingbullInfection
bull higher rate of infection following joint arthroplasty if HO is present
bullFractures of osteoporotic bone bull osteopenic from disusebull during surgery or physiotherapy
bullRecurrence bull recurrence rate correlates with neurological injury
bull greater recurrence if severe neurological compromisebullAVN
bull if extensive dissection or stripping is required
HTO AND ISS
When ISS is below 25 the mortality risk is minimal and above 25 it is an almost linear increase
When ISS is 50 the mortality is 50 When above 70 it is close to 100 If an injury is assigned an AIS of 6 (unsurvivable injury) the ISS score is
automatically assigned to 75 Highest ISS score obtainable is 75 For trauma patients of vehicular accidents the scoring system is important
for assessing the effectiveness of medical care in reducing morbidity and mortality
Advantages virtually the only anatomical scoring system in use correlates linearly with
mortality morbidity hospital stay other measures of severity
Weaknesses Any error in AIS scoring increases the ISS error Many different injury patterns can yield the same ISS score Injuries to different body regions are not weighted Not a useful triage tool as a full description of patient injuries is not known
prior to full investigation amp operation
risk factors periosteal stripping off anterior femur male gender obesity post traumatic deformity Anterior and anterolateral approach Cementless
Neurogenic HO around the hip due to SCI occurs more often in the medial region than in the lateral region with ossified tissues extending from the pubic symphysis to the anteromedial femoral shaft posterior to the femoral neurovascular structures Ossification is also seen anteriorly involving the iliopsoas and femoral neurovascular structures laterally within gluteus minimus and posteriorly extending from the ilium to the posterior femur encasing the sciatic nerve
HTO AROUND hip and knee
The Brooker Classification of Heterotopic Ossification around the hip joint Class I has islands of bone within the soft tissues Class II has bone spurs from the pelvis or proximal end of the femur leaving at least 1 cm between opposing surfaces Class III has bone spurs from the pelvis andor proximal end of the femur reducing the space between opposing bone surfaces to less than 1 cm Class IV shows apparent bone ankylosis of the hip
Region I - Heterotopic ossifications are strictly below the tip of the greater trochanter
Region II - Heterotopic ossifications are below and above the tip of the greater trochanter
Region III - Heterotopic ossifications are strictly above the tip of the greater trochanter
Grade A - Single or multiple heterotopic ossifications are less than 10 mm in maximal extent without contact with the pelvis or the femur
Grade B - Heterotopic ossifications are greater than 10 mm without contact with the pelvis but with possible contact with the femur there is no bridging from the femur to the proximal part of the greater trochanter and no evidence of ankylosis
Grade C - Ankylosis by means of firm bridging from the femur to the pelvis is present
Shmidt classification
excision may be performed The results of this procedure are varied Patients may find that their range of movement improves but pain relief is likely to be limited
A patient with heterotopic ossification following total hip arthroplasty is thought to have a 90-100 chance of developing it on the contralateral hip if this hip also undergoes total arthroplasty
it would be prudent to minimize the risk of heterotopic ossification developing after arthroplasty by performing surgery whereby the following are ensured
Exposure is meticulous Retraction is performed carefully and soft tissue
is handled carefully Irrigation is adequate Devitalized tissue is excised Hemostasis is adequate Postoperative drains (when used) are not
retained for longer than necessary Perioperative antibiotic prophylaxis is used Postoperative anticoagulation (when used for
deep vein thrombosis prophylaxis) is carefully controlled
sources of knee stiffness 1-extrinsic severe osteoarthritis of the ipsilateral hip neurologic injury leading to muscle rigidity tight quadriceps or hamstring muscles secondary to muscle injury heterotopic ossification or long-standing juvenile inflammatory conditions limiting knee
range of motion prior to the completion of skeletal growth When extrinsic sources are identified revision total knee arthroplasty is unlikely to be associated with a favorable outcome without correction of the extrinsic problem
2-intrinsic (1) overstuffing of the patellofemoral articulation (2) an
excessively tight flexion andor extension gap (3) a tight posterior cruciate ligament (4) femoral andor tibial malrotation (5) arthrofibrosis and (6) limited bearing excursion in association with a highly conforming mobile-bearing prosthetic design
HTO after TKA
Heterotopic Ossification (HO) following primary Total Knee Replacement (TKR)
Occurs in 3-90 of TKRs 3-grade classification system No correlation between HO and component
alignment or component position
Clinical findings similar to early infection Continuing low-grade fever Warm swollen and erythematous knee Normal blood tests Possibly an association with HLA-A2 and B18 HO patients have worse KSS and function
scores
Patients at HIGH risk for developing HO after TKR (Knee Arthroplasty) (5)
Those with limited postoperative knee flexion
Increased lumbar bone mineral density (BMD) on multivariate analysis (3)
Hypertrophic arthrosis Excessive periosteal trauma Notching of the anterior femur Those who require forced manipulation
after TKA 47 in revision TKR surgery (6) Higher rates in revision TKR cases with
infection (up to 76
DaughertyBell classification of HO of the knee 0 No evidence of HO 1 Bone islands in periarticular soft tissue (no
involvement of femur patella or tibia) or HO within quadriceps expansion measuring lt1 cm
2 Spur formation measuring lt5 cm that involves the femur patella or tibia if more than one bone demonstrates HO separation of HO spurs
measure gt1 cm or HO within quadriceps expansion measuring ge1 cm but lt3 cm
3 Spur formation gt5 cm involving femur patella or tibia if more than one bone demonstrates HO separation of HO spurs measure lt1 cm or HO
within quadriceps expansion measuring ge3 cm 4 Extensive HO of the knee causing ankylosis
class 2 HO begins to involve the major bones of the knee joint with spur formation limited to a size of 5 cm
HO class 2 may be observed in select patients with complete ROM and no reported pain Patients with class 3 HO would likely always benefit from surgical excision
followed by RT prophylaxis Certainly patients in either cohort with a subclass ldquoBrdquo assignment (symptomatic) would
benefit from treatment All patients with class 4 HO require
treatment to alleviate ankylosis
treatment
References Whyte ldquoPagetrsquos Disease of Bonerdquo NEMJ vol 355
2006 Klein and Parvizi ldquoSurgical Manifestations of Pagetrsquos
Diseaserdquo JAAOS vol 14 2006 Orthobullets Campbell Apley Emedicinecom
-Chapter 15 Heterotopic Ossification after Traumatic Brain InjuryBy Jesuacutes Moreta and Joseacute Luis Martiacutenez-de los Mozos DOI 10577257343
Questions
Thank You
3 Phases of Disease1) OsteoclasticResorptivePhase Bursts of osteoclastic activity causing bone resorption Lytic lesions trabecular and cortical thinning Osteolytic ldquofrontsrdquoadvance longitudinally from bone
end toward middle ( ldquoVrdquoor ldquoflamerdquoshaped ~1cmyr)
2) OsteoblasticSclerotic or Mixed Phase Mixed osteoclastic and osteoblastic activity Net activity is osteoblastic with deposition of
structurally abnormal bone Bone expansion hyperostosis osteosclerosis
heterogeneous ossification
3-Late ldquoBurn OutrdquoPhasedarrActivity End result widened heterogeneously ossified
but generally sclerotic bones with irregular thickened trabeculae
Phases correlate radiologically and histologically
1048710All 3 Phases may be present simultaneously in the same patient or the same bone
Diseas location Monostotic (25) or polyostotic(75) 1048710Typically affectsPelvis (70) Femur (55) Lumbosacralspine (53) Skull (42) Tibia (32) Rarely in hands feet
1048710No bone-to-bone spread
Clinical Presentation and Complications Usually asymptomatic
Incidental findingAbnormal radiograph or other imaging Abnormal labs (uarrAlkPhos)
Bone pain Constant 1048710Poorly localized 1048710Present at rest
Worse on weight-bearing
pain may be the presenting symptom due to
stress fractures increased vascularity and warmth
new onset intense pain and swelling be suspicious for Pagets secondary sarcoma in a patient with a known history of Pagets who
complains of new onset intense pain and swelling cardiac symptoms
can present with high-output cardiac failure particularly if largemultiple lesions amp pre-existing diminished cardiac function
Bonelimb deformity
Fracture
Arthropathy
uarrincidence of joint disease 1048710Specific pattern of joint diseases in hip uarrfreq of coxa vera protrusio concentric joint space narrowing
uarrSkin temperature
Hypervascularity due to uarrbone turnover activity
uarrbone turnover causes uarrcardiac demands and may lead to high-output heart failure
High-output cardiac failure is caused by the numerous arteriovenous fistulas present in the pagetic bones
Neurologic complaints
Hearing lossvertigotemporal bone involvement with auditory nerve compression
1048710Cranial nerve palsies 1048710Spine involvementMechanical cord compression ldquovascular steal
Hypercalcemia
Rare 1048710Usually inactive or bed-ridden patients 1048710Signs amp SymptomsNausea vomiting MSK aches hyper-reflexia weakness
polyuria headache lethargy altered mental status hellipcoma
Malignant transformation Pagets sarcoma
less than 1 will develop malignant Pagets sarcoma (secondary sarcoma)
osteosarcoma is the most common followed by fibrosarcoma and chondrosarcoma
most common in pelvis femur and humerus Pagets sarcoma has a poor prognosis
5-year survival for non-metastatic Pagets sarcoma is less than 5 appropriate treatment for Pagets sarcoma includes chemotherapy
and wide surgical resection Pagets sarcoma typically presents as a destructive lesion without
periosteal reaction
Diagnosis Clinical assessment Characteristic radiographic appearance Labs (uarrAlkPhos) Bone Scan Usually benign and multiple lesions in old
patients are pagets hyperparathyroidism and bone infarcts
Rarely CT MRI Biopsy
Long bones bend across the trajectories of mechanical stress thus the tibia bows anteriorly and the femur anterolaterally The limb looks bent and feels thick and the skin is unduly warm ndash hence the term lsquoosteitisdeformansrsquo If the skull is affected it enlarges the patient may complain that old hats no longer fit The skull base may become flattened (platybasia) giving the appearance of a short neck In generalized Pagetrsquos disease there may also be considerable kyphosis so the patient becomes shorter and ape-like with bent legs and arms hanging in front of him Cranial nerve compression may lead to impaired vision facial palsy trigeminal neuralgia or deafness Another cause of deafness is otosclerosisVertebral thickening may cause spinal cord or nerve root compression Steal syndromes in which blood is diverted from internal organs to the surrounding skeletal circulationmay cause cerebral impairment and spinal cord ischaemia If there is also spinal stenosis the patient develops typical symptoms of lsquospinal claudicationrsquo and lower limb weakness
Radiographs coarsened trabeculae which give the bone a blastic
appearance both increased and decreased osteodensity may exist
depending on phase of disease lytic phase
lucent areas with expansion and thinned intact cortices blade of grass or flame-shaped lucent advancing edge
mixed phase combination of lysis and sclerosis with coarsened trabeculae
sclerotic phase bone enlargement with cortical thickening sclerotic and lucent
area
remodeled cortices loss of distinction between cortices and medullary cavity
long bone bowing bowing of femur or tibia
fractures hip and knee osteoarthritis osteitis circumscripta
(cotton wool exudates) in skull Pagets secondary sarcoma
shows cortical bone destruction soft tissue mass
MRI may show lumbar spinal stenosis
Bone scan accurately marks site of disease intensely hot in lytic and mixed phase less hot in sclerotic phase
CT scan cortical thickening and coarsened trabeculae
CTMRI Incidental finding Evaluation of atypical presentations
neurological involvement and possible malignant transformation
CT trabecularcortical thinning thickening irregularity
MRI non-specific marrow changes
BiochemistrySerum AlkPhosEnzyme found in osteoblastic membrane Indicator of osteoblastic activity uarrin Pagetrsquos but can be normal Levels correlate with disease extent and activity elevated urinary hydroxyproline (collagen breakdown marker) increased urinary N-telopeptide alpha-C-telopeptide
and deoxypyridinoline normal calcium levels
Other recommended tests ESR -elevation may indicate malignant transformation
CRP Ca -hypercalcemiamay occur in Pagetrsquos PO4 25-hydroxyvitamin D -rule out osteomalacia LFTs-rule out liver disease
Diagnostic Biopsy Diagnosis is usually achieved clinically and by
plain radiographic appearance Biopsy rarely required
Characteristic HistopathologyDisorganized immature trabeculararchitecture with irregular cement lines (ldquomosaicrdquopattern)
Rimming osteoblasts andor multinucleated osteoclasts
Management Options (May require no treatment if asymptomatic)
Supportive Care Pharmacologic Surgical (OrthopedicNeurosurgical
Supportive Care Occupational therapy Physical aides Counseling for fall+fracture prevention
Physical therapy Analgesics Weight control
Pharmacologic ManagementGoals Relieve symptoms and Prevent potential
complications Normalization of serum AlkPhos associated
with better long-term outcomes and disease control
Indications to treat Pain Deformity Neurologic symptoms Asymptomatic but high-risk for complications
(prophylactic) Management of hypercalcemia(rare) Pre-op reduce blood flow and potential
operative blood loss
Calcitonin is the most widely used It reduces bone resorption by decreasing both the activity and the number
of osteoclasts serum alkaline phosphatase and urinaryhydroxyproline levels are lowered Salmon calcitonin is more effective than the porcine variety subcutaneous injections of 50ndash100 MRC units are given daily until pain is relieved and the alkaline phosphatase levels are reduced and stabilized Maintenance injections once or twice weekly may have to be continued indefinitely but some authorities advocate stopping the drug and resuming treatment if symptoms recur Calcitonin can also be administered in a nasal spray Bisphosphonates bind to hydroxyapatite crystals
inhibiting their rate of growth and dissolution It is claimed that the reduction in bone turnover following their use is associated with the formation of lamellar rather than woven bone and that even after treatment is stopped there may be prolonged remission of disease (Bickerstaff et al 1990) Etidronate can be given orally (always on an empty stomach) but dosage should be kept low (eg 5 mgkg per day for up to 6 months) and vitamin D and calcium should also be given lest impaired bone mineralization results inosteomalacia The newer bisphosphonates (eg alendronate or pamidronate) do not have this disadvantage so they should be used as the treatment of choice they produce remissions even with shortcourses of 1 or 2 weeks
BisphosphonatesSynthetic analogues of inorganic phosphate adhere to mineralized surfaces
Ingested selectively by osteoclasts Disrupts enzyme pathways and reduces osteoclastic bone resorption
calcitonin causes osteoclasts to shrink in size and decreases their bone resorptive activity within minutes administered subcutaneously or intramuscularly
teriparatide is contraindicated in Pagets disease due to risk of secondary osteosarcoma
Surgical Management Few require surgery
Common Procedures Corrective osteotomy of long bone deformity indications
fractures through pathologic bowing of long bones impending pathologic fracture of long bone with bowing deformity
Arthroplasty (hip knee) the most common complications include
malalignment with knee arthroplasty bleeding with hip arthroplasty
Combination arthroplasty with osteotomy Fracture fixation
Preoperative Considerations Medical assessment for extraskeletalmanifestations eg high-
output heart failure
Medical treatment of active disease Preoperative autologousblood donation
Thorough planningeg good quality x-rays for templatingand device selection
Intraoperative Considerations Blood salvage system Expansileapproach + soft tissue release Sharp reamersburrsdrills for IM access Extramedullaryguidenavigation systems Concomitant osteotomy
PostoperativeConsiderations Monitoring for cardiac complications Continued medical tx of active disease
uarrHeterotopic ossification Prophylaxis against HO
Possible future excision of HO for painROM
1-Tieg provides a review of Pagets disease of bone and treatment indications In his review he discusses that most patients with Pagets disease are asymptomatic but in those that do present pain is the most common presenting symptom He recommends medical and surgical treatment of asymptomatic patients who have active disease at sites where complications are likely to develop
Altman did a review of 290 patients with Pagets disease of bone His findings showed 83 had one or more rheumatic syndromes He found the rate of osteoarthritis related to Pagets disease was elevated in the hip and knee Rheumatoid arthritis hyperuricemia and gout did not appear increased in this group
Mangham et al looked the rate of secondary sarcomas as a result of Pagets disease of bone They found the rate to be around 03 with male predominance They also found that widespread skeletal involvement by Pagets disease was not a significant risk factor for malignant transformation
Interesting views about pagets
Smith et al reviewed the pathologic complications of Pagets bone disease Pagets bone disease commonly causes osseous weakening (deformity and fracture) and arthritis in the hip joint Management of end stage disease is successful with cemented and cementless total hip arthroplasty Bleeding is the most common intra- and post-operative complication of surgery
Gabel et al retrospectively reviewed thirteen patients who had had sixteen total knee arthroplasties for Pagetic gonarthrosis Unlike total hip arthroplasty surgery Paget disease did not increase the amount of blood lost during the operation or in the postoperative period The most common complication associated with total knee arthroplasty was malalignment
Hansen et al reviewed the incidence of osteosarcomas complicating Pagets Disease Of the typical sites that are usually involved in Pagets disease (eg spine pelvis femur tibia and humerus) secondary osteosarcoma tends to spare the spine
Shaylor et al reported the mortality rates in 26 patient with osteosarcoma secondary to Paget s disease There was a 47 mortality at 1 year and 75 at 2 years from diagnosis In their series no patient survived for 5 years All patients died of metastatic disease
Langston et al conducted a randomized trial that compared the results of symptomatic treatment versus intensive bisphosphonate therapy in patients with Pagets disease Clinical fractures occurred in 46 of 661 patients (70) in the treatment group compared with 49 of 663 patients (74) in the symptomatic treatment group They concluded that bisphosphonates did not show a significant beneficial impact on pain quality of life or fracture incidence
Hadjipavlou et al reviewed Pagets disease of the bone and its management Farmers have been shown to have an increased incidence of Pagets disease Average age at presentation is in the 5th and 6th decade Symptomatic individuals are recommended to be treated initially with medical management They suggest that bisphosphonates are more effective than calcitonin at suppressing the histological and biochemical activity in Pagetrsquos disease
Summary Epid Very common in elderly Path Abnormal osteoclastshellipuarrbone
turnoverhellipdeposition of abnormal bone SampS Pain deformity fracture arthropathy Labs uarrAlkPhos X-ray Characteristic coarse thickened
trabeculae Bone scan Very hot Rx Bisphosphonates Surgery for arthropathy fracture painful
deformity
A 65-year-old male presents with increasing shoulder pain over the past 9 months He is otherwise healthy and has no other complaints Radiograph of his shoulder is shown in Figure A Whole body bone scan and biopsy photograph are shown in Figures B and C What is the most appropriate treatment for this patient
1 Referral to endocrinology 2 Radiation therapy and chemotherapy 3 Wide resection and reconstruction 4 Radiation therapy wide resection and reconstruction 5 Chemotherapy wide resection and reconstruction
Histiocytosis X or Langerhans cell histiocytosis is a spectrum of diseases of the reticuloendothelial system with one of three general presentations Eosinophilic granuloma (EG)
usually a single self-limited lesion found in younger patients
Hand-Schuller-Christian disease (HSC) chronic disseminated form with bone and visceral lesions also known as Langerhans cell histiocytosis with visceral
involvement Letterer-Siwe disease (LSD)
fatal form that occurs in young children
Eosinophilic granuloma
Epidemiology demographics
most commonly occurs in children (80 of afflicted lt 20 years of age)
HSC disease presents in children gt 3 years of age LSD occurs in children lt 3 years of age Male to female ratio of 21
location eosinophilic granuloma
commonly presents in the skull ribs clavicle scapula mandible
isolated lesions of the spine (thoracic most common) can also occur in diaphyseal regions of long bones and the
pelvis HSC
multiple bony sites multiple lytic skull lesions visceral involvement of the lungs spleen liver skin lymph
nodes
Genetics no clear genetic pattern of inheritance or locus has
been determined Prognosis
EG isolated involvement generally treatable with local
management spine lesions can spontaneously resolve
HSC prognosis depends on response to chemotherapy worsening prognosis with increasing extraskeletal
involvement LSD
generally fatal in children lt 3 years of age
Symptoms skeletal involvement
pain and swelling at the region of involvement limping can be seen with pelvic or lower extremity
involvement vertebral involvement
localized or diffuse back pain increasingly kyphotic posture radiculopathy can occur with more aggressive lesions
HSC classic triad of
multiple lytic skull lesions diabetes insipidus
increased thirst and water intake exopthalmos
visceral involvement diffuse or nonspecific abdominal or chest pain
Radiographs general
known as the great mimicker as it appears similar to many lesions radiographic differential includes osteomyelitis leukemia lymphoma
fibrous dysplasia or Ewings sarcoma diaphyseal lesions
well defined intramedullary lytic or punched-out lesion cortex may be thinned expanded or destroyed may have periosteal reaction
metaphyseal lesions extend up to but not through the physis less central location than diaphyseal lesions
spinal lesions vertebra plana (flattened vertebrae) in spine increased kyphosis
cranial involvement multiple punched-out lytic lesions
MRI may show a soft tissue mass adjacent to boney lesions
Bone scan generally shows increased uptake in the region of boney lesion
Histology Langerhans cells
mononuclear histiocyte-like cells with oval nuclei with well-defined round or oval cytoplasm
a prominent nuclear groove (coffee bean nuclei) can be seen in most of the nuclei
eosinophilic cytoplasm (pink generally) stain with CD1A electronmicroscopy
birbeck granules seen inside Langerhans cells mixture of inflammatory cells also present giant cells are present lack of nuclear atypia and atypical mitoses
differentiates this condition from malignant conditions such as Ewings sarcoma lymphoma of bone and metastatic neuroblastoma which may look similar based on the round cells alone
eosinophilic cytoplasm (pink generally)
Treatment
bullNonoperative bull observation alone
bull indications bull a self-limited process and it is reasonable to treat with observation alone
bull bracing bull indications
bull to prevent progressive kyphosis of the spinebull outcomes
bull will correct deformity in 90 of patientsbull vertebral lesions generally regain 50 of their height
bull low dose irradiation (600-800 cGy) bull indications
bull indicated for lesions in the spine that compromise stability neurologic statusbull lesions not amenable to injection or open treatment
bull outcomes bull effective for most lesions
bull chemotherapy bull indications
bull diffuse HSCbull outcomes
bull prognosis is improved with less severe extraskeletal involvementbull corticosteroid injection
bull indications bull isolated lesions bull can be performed after curettage as well
Operative curettage and bone grafting
indications for lesions that endanger the articular surface or are a risk for
impending fractures spinal deformity correction
indications progressive spine deformity refractory to bracing
approximately 10 of patients with spine lesion will need operative intervention for deformity correction
Destructive multiple lesion in young patientsAre eosinophilic granuloma lymphoma and leukemiaLymphoma is unlikely to present with exopthalmos diabetes insipidus or vertebra plana Lymphoma bone lesions are lytic and appear moth eatenpermeative on radiographs
Figure A shows a skin lesion typical of eosinophillic granuloma Figure B shows a lytic lesions without significant surrounding sclerosis as is characteristic of eosinophilic granuloma Figure C shows the characteristic histology of multiple eosinophils with their characteristic oval coffee bean nuclei and staining pattern of purpleredpink cytoplasm (depending on the stain) Importantly the histology slide lacks a malignant appearance (no cellular atypia or mytotic complexes and low nuclearcytoplasmic ratio)
Formation of bone in atypical extraskeletal tissues usually occurs
spontaneously or following trauma within 2 months of neurologic injury (brain or spinal cord)
most common location is between muscle and joint capsule Epidemiology
incidence (see table below)
demographics malefemale = 21 especially men with hypertrophic osteoarthritis and women gt65y
location traumatic brain injury or stroke
hip gt elbow gt shoulder gt knee elbow HO more common following brain trauma
occurs on affected (spastic) side rarely in the knee (TBI)
spinal cord injury hip gt knee gt elbow gt shoulder hip flexors and abductors gt extensors or adductors medial aspect of the knee
Heterotopic Ossification
Risk factors
Pathophysiology exact cause of HO is not known but there appears to be a
genetic pre disposition experimental HO associated with
tissue expression of BMP IT IS SAID TO BE CAUSED BY activation and proliferation of
mesenchymal stem cells Associated conditions
orthopaedic manifestations pathologic fractures
from decreased joint ROM and osteoporotic bone nerve impingement soft tissue contractures contributing to the formation of
decubitus ulcers joint ankylosis HO after THA adversely affects outcome of THA
nonorthopaedic conditions skin maceration and hygiene problems
Pathophysiology Early in the formation of HO oedema with exudative
infiltrate is present followed by fibroblastic proliferation and immature connective tissue formation Posteriorly osteoid formation is seen with the subsequent deposition of bone matrix Primitive osteoid is deposited as small masses in the periphery early (within the first two weeks) and osteoblasts are noted located irregularly Osteoblasts produce tropocollagen which polymerizes to form collagen and secrete alkaline phosphatase which allows calcium to precipitate and the mineralization of bone matrix As mineralization progresses amorphous calcium phosphate is progressively replaced by hydroxyapatite crystals During the following weeks the lesion matures with a centripetal pattern and after 6-12 months an appearance of true bone is noted The new bone is always extra-articular and can be contiguous with the skeleton but generally does not involve the periosteum
IN SUMMARY It has been postulated that three conditions
must be met to achieve heterotopic bone formation ---a stimulating event oestrogenic precursor cells and a proper environment LIKE hypercalcaemia tissue hypoxia pH changes (alkalosis) or prolonged immobilization
ClassificationbullSubtypes
bull neurogenic HO bull Four clinical stages of HO in people with spinal cord injury were
described by Nicholas in 1973
bull traumatic myositis ossificans bull fibrodysplasia ossificans progressiva (Munchmeyers Disease)
Neurogenic HO Symptoms
painless loss of ROM interferes with ADL CRPS symptoms fever
Physical exam inspection
warm painful swollen joint may have effusion skin problems
decubitus ulcers from contractures around skin muscles ligaments
skin maceration and hygiene problems motion
decreased joint ROM joint ankylosis with HO after TKA might develop quad muscle snapping or patella
instability neurovascular
peripheral neuropathy HO often impinges on adjacent NV structures
Imaging
bullRadiographs bull findings
bull ossification usually easy to visualize bull maturity of HO
bull the appearance of a bony cortex suggests mature HObull sharp demarcation from surrounding tissue bull trabecular pattern
bull sensitivity and specificity bull not useful for early diagnosisbull only useful at 1 week after onset of symptoms
bull calcium is deposited 7-10 days later than symptom onsetbullUltrasound
bull indications bull for early diagnosis of hip HO
bull findings bull echogenic surfaces with posterior acoustic shadowing
bullCT bull indications
bull useful for preoperative planning bullTriphasic bone scan
bull indications bull best for early diagnosis bull most commonly used diagnostic study
Radiographs are extremely useful in the staging of heterotopic ossification and will show the development of sharp cortical margins once the lesion has reached maturity
Heterotopic bone is a condition in which lamellar bone forms in non-ossified soft tissues In the early stages studies such as MRI and bone scan are more sensitive for diagnosis as radiographs may appear normal for the first three weeks After the appropriate diagnosis is made sequential radiographs are useful for monitoring the progression of the ossification Once it has reached the mature stage sharp cortical margins will appear and surgical resection may be considered
lab
Labs elevated serum alkaline phosphatase (gt250IUL)
ALP removes inhibitors of mineralization nonspecific may be elevated with skeletal trauma cannot determine maturity of HO elevated 12wks after surgery is predictor
elevated CRP correlates with inflammatory activity of HO better than ESR normalization of CRP may correlate with maturity of HO
elevated ESR (gt35mmh) 12wks after THA is predictor
elevated CK correlates with involvement of muscle extent of muscle
involvement Histology
mature fatty bone marrow mature trabecular bone
Heterotopic ossification (HO) most commonly occurs at the amputation site if the amputation was performed thru the zone of injury especially if the injury was a blast mechanism
Symptomatic heterotopic ossification of the quadriceps may occur following placement of a large-diameter Steinmann pin for the purpose of temporary skeletal traction
TreatmentThe prevention of heterotopic ossification is focused on three basic principles disrupting the inductive signalling pathways altering the osteoprogenitor cells or modifying the environment
bullphysiotherapy should involve an assisted range of movement exercises with gentle stretch and terminal resistance trainingbullProphylaxis
bull bisphosphonates amp NSAIDS bull indications
bull although no literature supports are commonly usedbull technique
bull indomethacin is most commonly used bull dose is 75mgday for 10days to 6 weeks
bull perioperative radiation bull indications
bull although no literature supports commonly usedbull is thought to be effective by blocking osteoblast differentiation
bull technique bull a single perioperative dose of 700cGy can be given either 4
hours preop or within 72 hours postoperatively bull lt550cGy not effective
Nonsteroidal anti-inflammatory drugs (NSAIDs) These drugs have demonstrated good results in
preventing heterotopic ossification after total hip arthroplasty
A direct effect of NSAIDs on the formation of heterotopic ossification has been described due to the inhibition of the differentiation of mesenchymal cells into oestrogenic cells There is also an indirect effect which refers to the inhibition of bone remodelling by suppression of the prostagland unmediated inflammatory response (specifically PGE-2)
Indomethacin has been considered a useful medication for heterotopic ossification prophylaxis following total hip replacement
prescribed for three to six weeks in a dose of 75mgday within two months of the injury may reduce the incidence of heterotopic ossification by two to three times
Biphosphonates inhibits precipitation of calcium phosphate and blocks the aggregation and mineralisation of hydroxyapatite crystals In primary prevention Banovac et al [56] have suggested that the treatment should begin as soon as elevated alkaline phosphatase is diagnosed or positive findings in ultrasonography or bone scans are shown In addition disphosphonates could have long-term effects on prevention when the treatment is finished
Posttraumatic wide exposure and surgical resection
indications severe loss of motion and decreased function
technique wide exposure required to identify all neurovascular
structures that may be involved timing of resection (controversial)
marked decrease in bone scan activity AND normalization of ALP
6 months following general trauma 1 year following SCI 15 years following TBI
some data suggests equivalent results when comparing early versus late resection
postop follow with 5 day course of indomethacin early gentle joint mobilization
The surgery is necessary in patients with symptomatic HO and unsuccessful medical treatment such as
Loss of range of motion and ankylosis with associated functional disability such as sitting difficulties
Complications of immobility such as pressure ulcers
Facilitate rehabilitation and recovery of muscular atrophy secondary to prolonged immobilisation
Difficulties of appropriate hygiene because access to the perineum or bladder care is needed
Severe pain refractory to analgesia Vascular andor nerve compression
Advantages to early excision of heterotopic ossification (vs waiting for maturation) include decreased soft tissue contracture better definition between heterotopic and native bone and decreased waiting time for the patient When the soft tissue envelope is benign one may proceed with operative release While waiting for normalization of alkaline phosphatase levels inactivity on bone scan or radiographic maturity may decrease risk of recurrent heterotopic ossification delaying operative release for these reasons has not been shown to improve results of final elbow range of motion after contracture release
Gartland recommended surgery after six months following traumatic heterotopic ossification one year following spinal cord injury and 18 months after head injury
In the past waiting until maturity in order to minimize the rate of recurrence after the surgical treatment was recommended Nevertheless recent studies do not confirm a higher rate of recurrence when the HO is excised in an earlier phase In addition a long delay before surgery leads to ankylosis a high degree of osteoporosis and more extensive intra-articular injuries These findings are associated with bad functional results and potential complications
Should you wait till lesion maturation
Prevention byHandle tissue carefully Avoid excess bleeding Achieve good hemostasis Beware of lesions that span internervous tissue planes
but if it happens resection of a large enough amount of bone to allow improvement of the range of motion and trying to preserve the joint
Our aim must be
A reactive process that is characterized by a well-circumscribed proliferation of fibroblasts cartilage and bone within muscle
A form of heterotopic ossification that is the result direct trauma intramuscular hematoma
most common location is the diaphysis of long bones Must differentiate from tumors Fibrodysplasia ossificans progressiva (FOP) is a rare subtype of heterotopic ossification
involves mutation of the ACVR1 gene (activin A type I receptor gene a BMP type-1 receptor)
Epidemiology demographics
most common in young active males (15 to 35 years old) body locations
quadriceps brachialis and gluteal muscles Genetics
almost always a posttraumatic condition Prognosis
usually self limiting mass usually begins to decrease in size after 1 yea
Myositis ossificans
PresentationbullSymptoms
bull pain tenderness swelling and decreased range of motion that usually presents within days of the injury
bull pain and size of the mass decrease with timebull mass increases in size over several months(usually 3 to 6 cm)
bull after the mass stops growing it becomes firmbullPhysical exam
bull palpable soft tissue massbull restricted range of motion
ImagingbullRadiographs
bull peripheral bone formation with central lucent areabull may appear as dotted veil pattern
bullMRI with gadolinium bull rim enhancement is seen within the first 3 weeks
bullCT scan bull lesion has an eggshell appearance
bullCharacteristic histology shows zonal pattern bull periphery of lesion
bull mature trabeculae of lamellar and woven bonebull calcification seen on xray
bull center of the lesion bull irregular mass of immature fibroblastsbull cartilage component may be presentbull (no calcification seen on xray) bull no cellular atypia seen
Treatment
bullNonoperative bull rest range of motion exercises and activity modification
bull passive stretching is contraindicated (makes it worse)bull physical therapy
bull utilized to maintain range of motionbull radiographic monitoring
bull obtained to confirm maturation of the lesionbullOperative
bull surgical excision bull indicated only if it remains a problem after it maturesbull do not operate in acute phase wait at least six months
bull excision of the lesion within 6 to 12 months predisposes to local recurrence
A 26-year-old man presents with generalized back and joint stiffness and difficulty opening his mouth His elder sister has similar complaints Since childhood he has had 3 surgeries for excision of recurrent bony prominences around his knees He walks with a stooped over posture seen in Figure A Radiographs of his feet knee hip and spine are seen in Figures B-E respectively
fibrodysplasia ossificans progressiva
Stone Man Disease) which involves a mutation of the ACVR1
There are 2 hallmark characteristics progressive heterotopic ossification (muscles fascia tendons ligaments and joint capsules) and congenital malformation of the great toe (hallux valgus malformed first metatarsal and monophalangism) BMP4 which contributes to the formation of the skeleton in the normal embryo is implicated in this disease
Complications
bullHematoma and intraoperative bleedingbullInfection
bull higher rate of infection following joint arthroplasty if HO is present
bullFractures of osteoporotic bone bull osteopenic from disusebull during surgery or physiotherapy
bullRecurrence bull recurrence rate correlates with neurological injury
bull greater recurrence if severe neurological compromisebullAVN
bull if extensive dissection or stripping is required
HTO AND ISS
When ISS is below 25 the mortality risk is minimal and above 25 it is an almost linear increase
When ISS is 50 the mortality is 50 When above 70 it is close to 100 If an injury is assigned an AIS of 6 (unsurvivable injury) the ISS score is
automatically assigned to 75 Highest ISS score obtainable is 75 For trauma patients of vehicular accidents the scoring system is important
for assessing the effectiveness of medical care in reducing morbidity and mortality
Advantages virtually the only anatomical scoring system in use correlates linearly with
mortality morbidity hospital stay other measures of severity
Weaknesses Any error in AIS scoring increases the ISS error Many different injury patterns can yield the same ISS score Injuries to different body regions are not weighted Not a useful triage tool as a full description of patient injuries is not known
prior to full investigation amp operation
risk factors periosteal stripping off anterior femur male gender obesity post traumatic deformity Anterior and anterolateral approach Cementless
Neurogenic HO around the hip due to SCI occurs more often in the medial region than in the lateral region with ossified tissues extending from the pubic symphysis to the anteromedial femoral shaft posterior to the femoral neurovascular structures Ossification is also seen anteriorly involving the iliopsoas and femoral neurovascular structures laterally within gluteus minimus and posteriorly extending from the ilium to the posterior femur encasing the sciatic nerve
HTO AROUND hip and knee
The Brooker Classification of Heterotopic Ossification around the hip joint Class I has islands of bone within the soft tissues Class II has bone spurs from the pelvis or proximal end of the femur leaving at least 1 cm between opposing surfaces Class III has bone spurs from the pelvis andor proximal end of the femur reducing the space between opposing bone surfaces to less than 1 cm Class IV shows apparent bone ankylosis of the hip
Region I - Heterotopic ossifications are strictly below the tip of the greater trochanter
Region II - Heterotopic ossifications are below and above the tip of the greater trochanter
Region III - Heterotopic ossifications are strictly above the tip of the greater trochanter
Grade A - Single or multiple heterotopic ossifications are less than 10 mm in maximal extent without contact with the pelvis or the femur
Grade B - Heterotopic ossifications are greater than 10 mm without contact with the pelvis but with possible contact with the femur there is no bridging from the femur to the proximal part of the greater trochanter and no evidence of ankylosis
Grade C - Ankylosis by means of firm bridging from the femur to the pelvis is present
Shmidt classification
excision may be performed The results of this procedure are varied Patients may find that their range of movement improves but pain relief is likely to be limited
A patient with heterotopic ossification following total hip arthroplasty is thought to have a 90-100 chance of developing it on the contralateral hip if this hip also undergoes total arthroplasty
it would be prudent to minimize the risk of heterotopic ossification developing after arthroplasty by performing surgery whereby the following are ensured
Exposure is meticulous Retraction is performed carefully and soft tissue
is handled carefully Irrigation is adequate Devitalized tissue is excised Hemostasis is adequate Postoperative drains (when used) are not
retained for longer than necessary Perioperative antibiotic prophylaxis is used Postoperative anticoagulation (when used for
deep vein thrombosis prophylaxis) is carefully controlled
sources of knee stiffness 1-extrinsic severe osteoarthritis of the ipsilateral hip neurologic injury leading to muscle rigidity tight quadriceps or hamstring muscles secondary to muscle injury heterotopic ossification or long-standing juvenile inflammatory conditions limiting knee
range of motion prior to the completion of skeletal growth When extrinsic sources are identified revision total knee arthroplasty is unlikely to be associated with a favorable outcome without correction of the extrinsic problem
2-intrinsic (1) overstuffing of the patellofemoral articulation (2) an
excessively tight flexion andor extension gap (3) a tight posterior cruciate ligament (4) femoral andor tibial malrotation (5) arthrofibrosis and (6) limited bearing excursion in association with a highly conforming mobile-bearing prosthetic design
HTO after TKA
Heterotopic Ossification (HO) following primary Total Knee Replacement (TKR)
Occurs in 3-90 of TKRs 3-grade classification system No correlation between HO and component
alignment or component position
Clinical findings similar to early infection Continuing low-grade fever Warm swollen and erythematous knee Normal blood tests Possibly an association with HLA-A2 and B18 HO patients have worse KSS and function
scores
Patients at HIGH risk for developing HO after TKR (Knee Arthroplasty) (5)
Those with limited postoperative knee flexion
Increased lumbar bone mineral density (BMD) on multivariate analysis (3)
Hypertrophic arthrosis Excessive periosteal trauma Notching of the anterior femur Those who require forced manipulation
after TKA 47 in revision TKR surgery (6) Higher rates in revision TKR cases with
infection (up to 76
DaughertyBell classification of HO of the knee 0 No evidence of HO 1 Bone islands in periarticular soft tissue (no
involvement of femur patella or tibia) or HO within quadriceps expansion measuring lt1 cm
2 Spur formation measuring lt5 cm that involves the femur patella or tibia if more than one bone demonstrates HO separation of HO spurs
measure gt1 cm or HO within quadriceps expansion measuring ge1 cm but lt3 cm
3 Spur formation gt5 cm involving femur patella or tibia if more than one bone demonstrates HO separation of HO spurs measure lt1 cm or HO
within quadriceps expansion measuring ge3 cm 4 Extensive HO of the knee causing ankylosis
class 2 HO begins to involve the major bones of the knee joint with spur formation limited to a size of 5 cm
HO class 2 may be observed in select patients with complete ROM and no reported pain Patients with class 3 HO would likely always benefit from surgical excision
followed by RT prophylaxis Certainly patients in either cohort with a subclass ldquoBrdquo assignment (symptomatic) would
benefit from treatment All patients with class 4 HO require
treatment to alleviate ankylosis
treatment
References Whyte ldquoPagetrsquos Disease of Bonerdquo NEMJ vol 355
2006 Klein and Parvizi ldquoSurgical Manifestations of Pagetrsquos
Diseaserdquo JAAOS vol 14 2006 Orthobullets Campbell Apley Emedicinecom
-Chapter 15 Heterotopic Ossification after Traumatic Brain InjuryBy Jesuacutes Moreta and Joseacute Luis Martiacutenez-de los Mozos DOI 10577257343
Questions
Thank You
3-Late ldquoBurn OutrdquoPhasedarrActivity End result widened heterogeneously ossified
but generally sclerotic bones with irregular thickened trabeculae
Phases correlate radiologically and histologically
1048710All 3 Phases may be present simultaneously in the same patient or the same bone
Diseas location Monostotic (25) or polyostotic(75) 1048710Typically affectsPelvis (70) Femur (55) Lumbosacralspine (53) Skull (42) Tibia (32) Rarely in hands feet
1048710No bone-to-bone spread
Clinical Presentation and Complications Usually asymptomatic
Incidental findingAbnormal radiograph or other imaging Abnormal labs (uarrAlkPhos)
Bone pain Constant 1048710Poorly localized 1048710Present at rest
Worse on weight-bearing
pain may be the presenting symptom due to
stress fractures increased vascularity and warmth
new onset intense pain and swelling be suspicious for Pagets secondary sarcoma in a patient with a known history of Pagets who
complains of new onset intense pain and swelling cardiac symptoms
can present with high-output cardiac failure particularly if largemultiple lesions amp pre-existing diminished cardiac function
Bonelimb deformity
Fracture
Arthropathy
uarrincidence of joint disease 1048710Specific pattern of joint diseases in hip uarrfreq of coxa vera protrusio concentric joint space narrowing
uarrSkin temperature
Hypervascularity due to uarrbone turnover activity
uarrbone turnover causes uarrcardiac demands and may lead to high-output heart failure
High-output cardiac failure is caused by the numerous arteriovenous fistulas present in the pagetic bones
Neurologic complaints
Hearing lossvertigotemporal bone involvement with auditory nerve compression
1048710Cranial nerve palsies 1048710Spine involvementMechanical cord compression ldquovascular steal
Hypercalcemia
Rare 1048710Usually inactive or bed-ridden patients 1048710Signs amp SymptomsNausea vomiting MSK aches hyper-reflexia weakness
polyuria headache lethargy altered mental status hellipcoma
Malignant transformation Pagets sarcoma
less than 1 will develop malignant Pagets sarcoma (secondary sarcoma)
osteosarcoma is the most common followed by fibrosarcoma and chondrosarcoma
most common in pelvis femur and humerus Pagets sarcoma has a poor prognosis
5-year survival for non-metastatic Pagets sarcoma is less than 5 appropriate treatment for Pagets sarcoma includes chemotherapy
and wide surgical resection Pagets sarcoma typically presents as a destructive lesion without
periosteal reaction
Diagnosis Clinical assessment Characteristic radiographic appearance Labs (uarrAlkPhos) Bone Scan Usually benign and multiple lesions in old
patients are pagets hyperparathyroidism and bone infarcts
Rarely CT MRI Biopsy
Long bones bend across the trajectories of mechanical stress thus the tibia bows anteriorly and the femur anterolaterally The limb looks bent and feels thick and the skin is unduly warm ndash hence the term lsquoosteitisdeformansrsquo If the skull is affected it enlarges the patient may complain that old hats no longer fit The skull base may become flattened (platybasia) giving the appearance of a short neck In generalized Pagetrsquos disease there may also be considerable kyphosis so the patient becomes shorter and ape-like with bent legs and arms hanging in front of him Cranial nerve compression may lead to impaired vision facial palsy trigeminal neuralgia or deafness Another cause of deafness is otosclerosisVertebral thickening may cause spinal cord or nerve root compression Steal syndromes in which blood is diverted from internal organs to the surrounding skeletal circulationmay cause cerebral impairment and spinal cord ischaemia If there is also spinal stenosis the patient develops typical symptoms of lsquospinal claudicationrsquo and lower limb weakness
Radiographs coarsened trabeculae which give the bone a blastic
appearance both increased and decreased osteodensity may exist
depending on phase of disease lytic phase
lucent areas with expansion and thinned intact cortices blade of grass or flame-shaped lucent advancing edge
mixed phase combination of lysis and sclerosis with coarsened trabeculae
sclerotic phase bone enlargement with cortical thickening sclerotic and lucent
area
remodeled cortices loss of distinction between cortices and medullary cavity
long bone bowing bowing of femur or tibia
fractures hip and knee osteoarthritis osteitis circumscripta
(cotton wool exudates) in skull Pagets secondary sarcoma
shows cortical bone destruction soft tissue mass
MRI may show lumbar spinal stenosis
Bone scan accurately marks site of disease intensely hot in lytic and mixed phase less hot in sclerotic phase
CT scan cortical thickening and coarsened trabeculae
CTMRI Incidental finding Evaluation of atypical presentations
neurological involvement and possible malignant transformation
CT trabecularcortical thinning thickening irregularity
MRI non-specific marrow changes
BiochemistrySerum AlkPhosEnzyme found in osteoblastic membrane Indicator of osteoblastic activity uarrin Pagetrsquos but can be normal Levels correlate with disease extent and activity elevated urinary hydroxyproline (collagen breakdown marker) increased urinary N-telopeptide alpha-C-telopeptide
and deoxypyridinoline normal calcium levels
Other recommended tests ESR -elevation may indicate malignant transformation
CRP Ca -hypercalcemiamay occur in Pagetrsquos PO4 25-hydroxyvitamin D -rule out osteomalacia LFTs-rule out liver disease
Diagnostic Biopsy Diagnosis is usually achieved clinically and by
plain radiographic appearance Biopsy rarely required
Characteristic HistopathologyDisorganized immature trabeculararchitecture with irregular cement lines (ldquomosaicrdquopattern)
Rimming osteoblasts andor multinucleated osteoclasts
Management Options (May require no treatment if asymptomatic)
Supportive Care Pharmacologic Surgical (OrthopedicNeurosurgical
Supportive Care Occupational therapy Physical aides Counseling for fall+fracture prevention
Physical therapy Analgesics Weight control
Pharmacologic ManagementGoals Relieve symptoms and Prevent potential
complications Normalization of serum AlkPhos associated
with better long-term outcomes and disease control
Indications to treat Pain Deformity Neurologic symptoms Asymptomatic but high-risk for complications
(prophylactic) Management of hypercalcemia(rare) Pre-op reduce blood flow and potential
operative blood loss
Calcitonin is the most widely used It reduces bone resorption by decreasing both the activity and the number
of osteoclasts serum alkaline phosphatase and urinaryhydroxyproline levels are lowered Salmon calcitonin is more effective than the porcine variety subcutaneous injections of 50ndash100 MRC units are given daily until pain is relieved and the alkaline phosphatase levels are reduced and stabilized Maintenance injections once or twice weekly may have to be continued indefinitely but some authorities advocate stopping the drug and resuming treatment if symptoms recur Calcitonin can also be administered in a nasal spray Bisphosphonates bind to hydroxyapatite crystals
inhibiting their rate of growth and dissolution It is claimed that the reduction in bone turnover following their use is associated with the formation of lamellar rather than woven bone and that even after treatment is stopped there may be prolonged remission of disease (Bickerstaff et al 1990) Etidronate can be given orally (always on an empty stomach) but dosage should be kept low (eg 5 mgkg per day for up to 6 months) and vitamin D and calcium should also be given lest impaired bone mineralization results inosteomalacia The newer bisphosphonates (eg alendronate or pamidronate) do not have this disadvantage so they should be used as the treatment of choice they produce remissions even with shortcourses of 1 or 2 weeks
BisphosphonatesSynthetic analogues of inorganic phosphate adhere to mineralized surfaces
Ingested selectively by osteoclasts Disrupts enzyme pathways and reduces osteoclastic bone resorption
calcitonin causes osteoclasts to shrink in size and decreases their bone resorptive activity within minutes administered subcutaneously or intramuscularly
teriparatide is contraindicated in Pagets disease due to risk of secondary osteosarcoma
Surgical Management Few require surgery
Common Procedures Corrective osteotomy of long bone deformity indications
fractures through pathologic bowing of long bones impending pathologic fracture of long bone with bowing deformity
Arthroplasty (hip knee) the most common complications include
malalignment with knee arthroplasty bleeding with hip arthroplasty
Combination arthroplasty with osteotomy Fracture fixation
Preoperative Considerations Medical assessment for extraskeletalmanifestations eg high-
output heart failure
Medical treatment of active disease Preoperative autologousblood donation
Thorough planningeg good quality x-rays for templatingand device selection
Intraoperative Considerations Blood salvage system Expansileapproach + soft tissue release Sharp reamersburrsdrills for IM access Extramedullaryguidenavigation systems Concomitant osteotomy
PostoperativeConsiderations Monitoring for cardiac complications Continued medical tx of active disease
uarrHeterotopic ossification Prophylaxis against HO
Possible future excision of HO for painROM
1-Tieg provides a review of Pagets disease of bone and treatment indications In his review he discusses that most patients with Pagets disease are asymptomatic but in those that do present pain is the most common presenting symptom He recommends medical and surgical treatment of asymptomatic patients who have active disease at sites where complications are likely to develop
Altman did a review of 290 patients with Pagets disease of bone His findings showed 83 had one or more rheumatic syndromes He found the rate of osteoarthritis related to Pagets disease was elevated in the hip and knee Rheumatoid arthritis hyperuricemia and gout did not appear increased in this group
Mangham et al looked the rate of secondary sarcomas as a result of Pagets disease of bone They found the rate to be around 03 with male predominance They also found that widespread skeletal involvement by Pagets disease was not a significant risk factor for malignant transformation
Interesting views about pagets
Smith et al reviewed the pathologic complications of Pagets bone disease Pagets bone disease commonly causes osseous weakening (deformity and fracture) and arthritis in the hip joint Management of end stage disease is successful with cemented and cementless total hip arthroplasty Bleeding is the most common intra- and post-operative complication of surgery
Gabel et al retrospectively reviewed thirteen patients who had had sixteen total knee arthroplasties for Pagetic gonarthrosis Unlike total hip arthroplasty surgery Paget disease did not increase the amount of blood lost during the operation or in the postoperative period The most common complication associated with total knee arthroplasty was malalignment
Hansen et al reviewed the incidence of osteosarcomas complicating Pagets Disease Of the typical sites that are usually involved in Pagets disease (eg spine pelvis femur tibia and humerus) secondary osteosarcoma tends to spare the spine
Shaylor et al reported the mortality rates in 26 patient with osteosarcoma secondary to Paget s disease There was a 47 mortality at 1 year and 75 at 2 years from diagnosis In their series no patient survived for 5 years All patients died of metastatic disease
Langston et al conducted a randomized trial that compared the results of symptomatic treatment versus intensive bisphosphonate therapy in patients with Pagets disease Clinical fractures occurred in 46 of 661 patients (70) in the treatment group compared with 49 of 663 patients (74) in the symptomatic treatment group They concluded that bisphosphonates did not show a significant beneficial impact on pain quality of life or fracture incidence
Hadjipavlou et al reviewed Pagets disease of the bone and its management Farmers have been shown to have an increased incidence of Pagets disease Average age at presentation is in the 5th and 6th decade Symptomatic individuals are recommended to be treated initially with medical management They suggest that bisphosphonates are more effective than calcitonin at suppressing the histological and biochemical activity in Pagetrsquos disease
Summary Epid Very common in elderly Path Abnormal osteoclastshellipuarrbone
turnoverhellipdeposition of abnormal bone SampS Pain deformity fracture arthropathy Labs uarrAlkPhos X-ray Characteristic coarse thickened
trabeculae Bone scan Very hot Rx Bisphosphonates Surgery for arthropathy fracture painful
deformity
A 65-year-old male presents with increasing shoulder pain over the past 9 months He is otherwise healthy and has no other complaints Radiograph of his shoulder is shown in Figure A Whole body bone scan and biopsy photograph are shown in Figures B and C What is the most appropriate treatment for this patient
1 Referral to endocrinology 2 Radiation therapy and chemotherapy 3 Wide resection and reconstruction 4 Radiation therapy wide resection and reconstruction 5 Chemotherapy wide resection and reconstruction
Histiocytosis X or Langerhans cell histiocytosis is a spectrum of diseases of the reticuloendothelial system with one of three general presentations Eosinophilic granuloma (EG)
usually a single self-limited lesion found in younger patients
Hand-Schuller-Christian disease (HSC) chronic disseminated form with bone and visceral lesions also known as Langerhans cell histiocytosis with visceral
involvement Letterer-Siwe disease (LSD)
fatal form that occurs in young children
Eosinophilic granuloma
Epidemiology demographics
most commonly occurs in children (80 of afflicted lt 20 years of age)
HSC disease presents in children gt 3 years of age LSD occurs in children lt 3 years of age Male to female ratio of 21
location eosinophilic granuloma
commonly presents in the skull ribs clavicle scapula mandible
isolated lesions of the spine (thoracic most common) can also occur in diaphyseal regions of long bones and the
pelvis HSC
multiple bony sites multiple lytic skull lesions visceral involvement of the lungs spleen liver skin lymph
nodes
Genetics no clear genetic pattern of inheritance or locus has
been determined Prognosis
EG isolated involvement generally treatable with local
management spine lesions can spontaneously resolve
HSC prognosis depends on response to chemotherapy worsening prognosis with increasing extraskeletal
involvement LSD
generally fatal in children lt 3 years of age
Symptoms skeletal involvement
pain and swelling at the region of involvement limping can be seen with pelvic or lower extremity
involvement vertebral involvement
localized or diffuse back pain increasingly kyphotic posture radiculopathy can occur with more aggressive lesions
HSC classic triad of
multiple lytic skull lesions diabetes insipidus
increased thirst and water intake exopthalmos
visceral involvement diffuse or nonspecific abdominal or chest pain
Radiographs general
known as the great mimicker as it appears similar to many lesions radiographic differential includes osteomyelitis leukemia lymphoma
fibrous dysplasia or Ewings sarcoma diaphyseal lesions
well defined intramedullary lytic or punched-out lesion cortex may be thinned expanded or destroyed may have periosteal reaction
metaphyseal lesions extend up to but not through the physis less central location than diaphyseal lesions
spinal lesions vertebra plana (flattened vertebrae) in spine increased kyphosis
cranial involvement multiple punched-out lytic lesions
MRI may show a soft tissue mass adjacent to boney lesions
Bone scan generally shows increased uptake in the region of boney lesion
Histology Langerhans cells
mononuclear histiocyte-like cells with oval nuclei with well-defined round or oval cytoplasm
a prominent nuclear groove (coffee bean nuclei) can be seen in most of the nuclei
eosinophilic cytoplasm (pink generally) stain with CD1A electronmicroscopy
birbeck granules seen inside Langerhans cells mixture of inflammatory cells also present giant cells are present lack of nuclear atypia and atypical mitoses
differentiates this condition from malignant conditions such as Ewings sarcoma lymphoma of bone and metastatic neuroblastoma which may look similar based on the round cells alone
eosinophilic cytoplasm (pink generally)
Treatment
bullNonoperative bull observation alone
bull indications bull a self-limited process and it is reasonable to treat with observation alone
bull bracing bull indications
bull to prevent progressive kyphosis of the spinebull outcomes
bull will correct deformity in 90 of patientsbull vertebral lesions generally regain 50 of their height
bull low dose irradiation (600-800 cGy) bull indications
bull indicated for lesions in the spine that compromise stability neurologic statusbull lesions not amenable to injection or open treatment
bull outcomes bull effective for most lesions
bull chemotherapy bull indications
bull diffuse HSCbull outcomes
bull prognosis is improved with less severe extraskeletal involvementbull corticosteroid injection
bull indications bull isolated lesions bull can be performed after curettage as well
Operative curettage and bone grafting
indications for lesions that endanger the articular surface or are a risk for
impending fractures spinal deformity correction
indications progressive spine deformity refractory to bracing
approximately 10 of patients with spine lesion will need operative intervention for deformity correction
Destructive multiple lesion in young patientsAre eosinophilic granuloma lymphoma and leukemiaLymphoma is unlikely to present with exopthalmos diabetes insipidus or vertebra plana Lymphoma bone lesions are lytic and appear moth eatenpermeative on radiographs
Figure A shows a skin lesion typical of eosinophillic granuloma Figure B shows a lytic lesions without significant surrounding sclerosis as is characteristic of eosinophilic granuloma Figure C shows the characteristic histology of multiple eosinophils with their characteristic oval coffee bean nuclei and staining pattern of purpleredpink cytoplasm (depending on the stain) Importantly the histology slide lacks a malignant appearance (no cellular atypia or mytotic complexes and low nuclearcytoplasmic ratio)
Formation of bone in atypical extraskeletal tissues usually occurs
spontaneously or following trauma within 2 months of neurologic injury (brain or spinal cord)
most common location is between muscle and joint capsule Epidemiology
incidence (see table below)
demographics malefemale = 21 especially men with hypertrophic osteoarthritis and women gt65y
location traumatic brain injury or stroke
hip gt elbow gt shoulder gt knee elbow HO more common following brain trauma
occurs on affected (spastic) side rarely in the knee (TBI)
spinal cord injury hip gt knee gt elbow gt shoulder hip flexors and abductors gt extensors or adductors medial aspect of the knee
Heterotopic Ossification
Risk factors
Pathophysiology exact cause of HO is not known but there appears to be a
genetic pre disposition experimental HO associated with
tissue expression of BMP IT IS SAID TO BE CAUSED BY activation and proliferation of
mesenchymal stem cells Associated conditions
orthopaedic manifestations pathologic fractures
from decreased joint ROM and osteoporotic bone nerve impingement soft tissue contractures contributing to the formation of
decubitus ulcers joint ankylosis HO after THA adversely affects outcome of THA
nonorthopaedic conditions skin maceration and hygiene problems
Pathophysiology Early in the formation of HO oedema with exudative
infiltrate is present followed by fibroblastic proliferation and immature connective tissue formation Posteriorly osteoid formation is seen with the subsequent deposition of bone matrix Primitive osteoid is deposited as small masses in the periphery early (within the first two weeks) and osteoblasts are noted located irregularly Osteoblasts produce tropocollagen which polymerizes to form collagen and secrete alkaline phosphatase which allows calcium to precipitate and the mineralization of bone matrix As mineralization progresses amorphous calcium phosphate is progressively replaced by hydroxyapatite crystals During the following weeks the lesion matures with a centripetal pattern and after 6-12 months an appearance of true bone is noted The new bone is always extra-articular and can be contiguous with the skeleton but generally does not involve the periosteum
IN SUMMARY It has been postulated that three conditions
must be met to achieve heterotopic bone formation ---a stimulating event oestrogenic precursor cells and a proper environment LIKE hypercalcaemia tissue hypoxia pH changes (alkalosis) or prolonged immobilization
ClassificationbullSubtypes
bull neurogenic HO bull Four clinical stages of HO in people with spinal cord injury were
described by Nicholas in 1973
bull traumatic myositis ossificans bull fibrodysplasia ossificans progressiva (Munchmeyers Disease)
Neurogenic HO Symptoms
painless loss of ROM interferes with ADL CRPS symptoms fever
Physical exam inspection
warm painful swollen joint may have effusion skin problems
decubitus ulcers from contractures around skin muscles ligaments
skin maceration and hygiene problems motion
decreased joint ROM joint ankylosis with HO after TKA might develop quad muscle snapping or patella
instability neurovascular
peripheral neuropathy HO often impinges on adjacent NV structures
Imaging
bullRadiographs bull findings
bull ossification usually easy to visualize bull maturity of HO
bull the appearance of a bony cortex suggests mature HObull sharp demarcation from surrounding tissue bull trabecular pattern
bull sensitivity and specificity bull not useful for early diagnosisbull only useful at 1 week after onset of symptoms
bull calcium is deposited 7-10 days later than symptom onsetbullUltrasound
bull indications bull for early diagnosis of hip HO
bull findings bull echogenic surfaces with posterior acoustic shadowing
bullCT bull indications
bull useful for preoperative planning bullTriphasic bone scan
bull indications bull best for early diagnosis bull most commonly used diagnostic study
Radiographs are extremely useful in the staging of heterotopic ossification and will show the development of sharp cortical margins once the lesion has reached maturity
Heterotopic bone is a condition in which lamellar bone forms in non-ossified soft tissues In the early stages studies such as MRI and bone scan are more sensitive for diagnosis as radiographs may appear normal for the first three weeks After the appropriate diagnosis is made sequential radiographs are useful for monitoring the progression of the ossification Once it has reached the mature stage sharp cortical margins will appear and surgical resection may be considered
lab
Labs elevated serum alkaline phosphatase (gt250IUL)
ALP removes inhibitors of mineralization nonspecific may be elevated with skeletal trauma cannot determine maturity of HO elevated 12wks after surgery is predictor
elevated CRP correlates with inflammatory activity of HO better than ESR normalization of CRP may correlate with maturity of HO
elevated ESR (gt35mmh) 12wks after THA is predictor
elevated CK correlates with involvement of muscle extent of muscle
involvement Histology
mature fatty bone marrow mature trabecular bone
Heterotopic ossification (HO) most commonly occurs at the amputation site if the amputation was performed thru the zone of injury especially if the injury was a blast mechanism
Symptomatic heterotopic ossification of the quadriceps may occur following placement of a large-diameter Steinmann pin for the purpose of temporary skeletal traction
TreatmentThe prevention of heterotopic ossification is focused on three basic principles disrupting the inductive signalling pathways altering the osteoprogenitor cells or modifying the environment
bullphysiotherapy should involve an assisted range of movement exercises with gentle stretch and terminal resistance trainingbullProphylaxis
bull bisphosphonates amp NSAIDS bull indications
bull although no literature supports are commonly usedbull technique
bull indomethacin is most commonly used bull dose is 75mgday for 10days to 6 weeks
bull perioperative radiation bull indications
bull although no literature supports commonly usedbull is thought to be effective by blocking osteoblast differentiation
bull technique bull a single perioperative dose of 700cGy can be given either 4
hours preop or within 72 hours postoperatively bull lt550cGy not effective
Nonsteroidal anti-inflammatory drugs (NSAIDs) These drugs have demonstrated good results in
preventing heterotopic ossification after total hip arthroplasty
A direct effect of NSAIDs on the formation of heterotopic ossification has been described due to the inhibition of the differentiation of mesenchymal cells into oestrogenic cells There is also an indirect effect which refers to the inhibition of bone remodelling by suppression of the prostagland unmediated inflammatory response (specifically PGE-2)
Indomethacin has been considered a useful medication for heterotopic ossification prophylaxis following total hip replacement
prescribed for three to six weeks in a dose of 75mgday within two months of the injury may reduce the incidence of heterotopic ossification by two to three times
Biphosphonates inhibits precipitation of calcium phosphate and blocks the aggregation and mineralisation of hydroxyapatite crystals In primary prevention Banovac et al [56] have suggested that the treatment should begin as soon as elevated alkaline phosphatase is diagnosed or positive findings in ultrasonography or bone scans are shown In addition disphosphonates could have long-term effects on prevention when the treatment is finished
Posttraumatic wide exposure and surgical resection
indications severe loss of motion and decreased function
technique wide exposure required to identify all neurovascular
structures that may be involved timing of resection (controversial)
marked decrease in bone scan activity AND normalization of ALP
6 months following general trauma 1 year following SCI 15 years following TBI
some data suggests equivalent results when comparing early versus late resection
postop follow with 5 day course of indomethacin early gentle joint mobilization
The surgery is necessary in patients with symptomatic HO and unsuccessful medical treatment such as
Loss of range of motion and ankylosis with associated functional disability such as sitting difficulties
Complications of immobility such as pressure ulcers
Facilitate rehabilitation and recovery of muscular atrophy secondary to prolonged immobilisation
Difficulties of appropriate hygiene because access to the perineum or bladder care is needed
Severe pain refractory to analgesia Vascular andor nerve compression
Advantages to early excision of heterotopic ossification (vs waiting for maturation) include decreased soft tissue contracture better definition between heterotopic and native bone and decreased waiting time for the patient When the soft tissue envelope is benign one may proceed with operative release While waiting for normalization of alkaline phosphatase levels inactivity on bone scan or radiographic maturity may decrease risk of recurrent heterotopic ossification delaying operative release for these reasons has not been shown to improve results of final elbow range of motion after contracture release
Gartland recommended surgery after six months following traumatic heterotopic ossification one year following spinal cord injury and 18 months after head injury
In the past waiting until maturity in order to minimize the rate of recurrence after the surgical treatment was recommended Nevertheless recent studies do not confirm a higher rate of recurrence when the HO is excised in an earlier phase In addition a long delay before surgery leads to ankylosis a high degree of osteoporosis and more extensive intra-articular injuries These findings are associated with bad functional results and potential complications
Should you wait till lesion maturation
Prevention byHandle tissue carefully Avoid excess bleeding Achieve good hemostasis Beware of lesions that span internervous tissue planes
but if it happens resection of a large enough amount of bone to allow improvement of the range of motion and trying to preserve the joint
Our aim must be
A reactive process that is characterized by a well-circumscribed proliferation of fibroblasts cartilage and bone within muscle
A form of heterotopic ossification that is the result direct trauma intramuscular hematoma
most common location is the diaphysis of long bones Must differentiate from tumors Fibrodysplasia ossificans progressiva (FOP) is a rare subtype of heterotopic ossification
involves mutation of the ACVR1 gene (activin A type I receptor gene a BMP type-1 receptor)
Epidemiology demographics
most common in young active males (15 to 35 years old) body locations
quadriceps brachialis and gluteal muscles Genetics
almost always a posttraumatic condition Prognosis
usually self limiting mass usually begins to decrease in size after 1 yea
Myositis ossificans
PresentationbullSymptoms
bull pain tenderness swelling and decreased range of motion that usually presents within days of the injury
bull pain and size of the mass decrease with timebull mass increases in size over several months(usually 3 to 6 cm)
bull after the mass stops growing it becomes firmbullPhysical exam
bull palpable soft tissue massbull restricted range of motion
ImagingbullRadiographs
bull peripheral bone formation with central lucent areabull may appear as dotted veil pattern
bullMRI with gadolinium bull rim enhancement is seen within the first 3 weeks
bullCT scan bull lesion has an eggshell appearance
bullCharacteristic histology shows zonal pattern bull periphery of lesion
bull mature trabeculae of lamellar and woven bonebull calcification seen on xray
bull center of the lesion bull irregular mass of immature fibroblastsbull cartilage component may be presentbull (no calcification seen on xray) bull no cellular atypia seen
Treatment
bullNonoperative bull rest range of motion exercises and activity modification
bull passive stretching is contraindicated (makes it worse)bull physical therapy
bull utilized to maintain range of motionbull radiographic monitoring
bull obtained to confirm maturation of the lesionbullOperative
bull surgical excision bull indicated only if it remains a problem after it maturesbull do not operate in acute phase wait at least six months
bull excision of the lesion within 6 to 12 months predisposes to local recurrence
A 26-year-old man presents with generalized back and joint stiffness and difficulty opening his mouth His elder sister has similar complaints Since childhood he has had 3 surgeries for excision of recurrent bony prominences around his knees He walks with a stooped over posture seen in Figure A Radiographs of his feet knee hip and spine are seen in Figures B-E respectively
fibrodysplasia ossificans progressiva
Stone Man Disease) which involves a mutation of the ACVR1
There are 2 hallmark characteristics progressive heterotopic ossification (muscles fascia tendons ligaments and joint capsules) and congenital malformation of the great toe (hallux valgus malformed first metatarsal and monophalangism) BMP4 which contributes to the formation of the skeleton in the normal embryo is implicated in this disease
Complications
bullHematoma and intraoperative bleedingbullInfection
bull higher rate of infection following joint arthroplasty if HO is present
bullFractures of osteoporotic bone bull osteopenic from disusebull during surgery or physiotherapy
bullRecurrence bull recurrence rate correlates with neurological injury
bull greater recurrence if severe neurological compromisebullAVN
bull if extensive dissection or stripping is required
HTO AND ISS
When ISS is below 25 the mortality risk is minimal and above 25 it is an almost linear increase
When ISS is 50 the mortality is 50 When above 70 it is close to 100 If an injury is assigned an AIS of 6 (unsurvivable injury) the ISS score is
automatically assigned to 75 Highest ISS score obtainable is 75 For trauma patients of vehicular accidents the scoring system is important
for assessing the effectiveness of medical care in reducing morbidity and mortality
Advantages virtually the only anatomical scoring system in use correlates linearly with
mortality morbidity hospital stay other measures of severity
Weaknesses Any error in AIS scoring increases the ISS error Many different injury patterns can yield the same ISS score Injuries to different body regions are not weighted Not a useful triage tool as a full description of patient injuries is not known
prior to full investigation amp operation
risk factors periosteal stripping off anterior femur male gender obesity post traumatic deformity Anterior and anterolateral approach Cementless
Neurogenic HO around the hip due to SCI occurs more often in the medial region than in the lateral region with ossified tissues extending from the pubic symphysis to the anteromedial femoral shaft posterior to the femoral neurovascular structures Ossification is also seen anteriorly involving the iliopsoas and femoral neurovascular structures laterally within gluteus minimus and posteriorly extending from the ilium to the posterior femur encasing the sciatic nerve
HTO AROUND hip and knee
The Brooker Classification of Heterotopic Ossification around the hip joint Class I has islands of bone within the soft tissues Class II has bone spurs from the pelvis or proximal end of the femur leaving at least 1 cm between opposing surfaces Class III has bone spurs from the pelvis andor proximal end of the femur reducing the space between opposing bone surfaces to less than 1 cm Class IV shows apparent bone ankylosis of the hip
Region I - Heterotopic ossifications are strictly below the tip of the greater trochanter
Region II - Heterotopic ossifications are below and above the tip of the greater trochanter
Region III - Heterotopic ossifications are strictly above the tip of the greater trochanter
Grade A - Single or multiple heterotopic ossifications are less than 10 mm in maximal extent without contact with the pelvis or the femur
Grade B - Heterotopic ossifications are greater than 10 mm without contact with the pelvis but with possible contact with the femur there is no bridging from the femur to the proximal part of the greater trochanter and no evidence of ankylosis
Grade C - Ankylosis by means of firm bridging from the femur to the pelvis is present
Shmidt classification
excision may be performed The results of this procedure are varied Patients may find that their range of movement improves but pain relief is likely to be limited
A patient with heterotopic ossification following total hip arthroplasty is thought to have a 90-100 chance of developing it on the contralateral hip if this hip also undergoes total arthroplasty
it would be prudent to minimize the risk of heterotopic ossification developing after arthroplasty by performing surgery whereby the following are ensured
Exposure is meticulous Retraction is performed carefully and soft tissue
is handled carefully Irrigation is adequate Devitalized tissue is excised Hemostasis is adequate Postoperative drains (when used) are not
retained for longer than necessary Perioperative antibiotic prophylaxis is used Postoperative anticoagulation (when used for
deep vein thrombosis prophylaxis) is carefully controlled
sources of knee stiffness 1-extrinsic severe osteoarthritis of the ipsilateral hip neurologic injury leading to muscle rigidity tight quadriceps or hamstring muscles secondary to muscle injury heterotopic ossification or long-standing juvenile inflammatory conditions limiting knee
range of motion prior to the completion of skeletal growth When extrinsic sources are identified revision total knee arthroplasty is unlikely to be associated with a favorable outcome without correction of the extrinsic problem
2-intrinsic (1) overstuffing of the patellofemoral articulation (2) an
excessively tight flexion andor extension gap (3) a tight posterior cruciate ligament (4) femoral andor tibial malrotation (5) arthrofibrosis and (6) limited bearing excursion in association with a highly conforming mobile-bearing prosthetic design
HTO after TKA
Heterotopic Ossification (HO) following primary Total Knee Replacement (TKR)
Occurs in 3-90 of TKRs 3-grade classification system No correlation between HO and component
alignment or component position
Clinical findings similar to early infection Continuing low-grade fever Warm swollen and erythematous knee Normal blood tests Possibly an association with HLA-A2 and B18 HO patients have worse KSS and function
scores
Patients at HIGH risk for developing HO after TKR (Knee Arthroplasty) (5)
Those with limited postoperative knee flexion
Increased lumbar bone mineral density (BMD) on multivariate analysis (3)
Hypertrophic arthrosis Excessive periosteal trauma Notching of the anterior femur Those who require forced manipulation
after TKA 47 in revision TKR surgery (6) Higher rates in revision TKR cases with
infection (up to 76
DaughertyBell classification of HO of the knee 0 No evidence of HO 1 Bone islands in periarticular soft tissue (no
involvement of femur patella or tibia) or HO within quadriceps expansion measuring lt1 cm
2 Spur formation measuring lt5 cm that involves the femur patella or tibia if more than one bone demonstrates HO separation of HO spurs
measure gt1 cm or HO within quadriceps expansion measuring ge1 cm but lt3 cm
3 Spur formation gt5 cm involving femur patella or tibia if more than one bone demonstrates HO separation of HO spurs measure lt1 cm or HO
within quadriceps expansion measuring ge3 cm 4 Extensive HO of the knee causing ankylosis
class 2 HO begins to involve the major bones of the knee joint with spur formation limited to a size of 5 cm
HO class 2 may be observed in select patients with complete ROM and no reported pain Patients with class 3 HO would likely always benefit from surgical excision
followed by RT prophylaxis Certainly patients in either cohort with a subclass ldquoBrdquo assignment (symptomatic) would
benefit from treatment All patients with class 4 HO require
treatment to alleviate ankylosis
treatment
References Whyte ldquoPagetrsquos Disease of Bonerdquo NEMJ vol 355
2006 Klein and Parvizi ldquoSurgical Manifestations of Pagetrsquos
Diseaserdquo JAAOS vol 14 2006 Orthobullets Campbell Apley Emedicinecom
-Chapter 15 Heterotopic Ossification after Traumatic Brain InjuryBy Jesuacutes Moreta and Joseacute Luis Martiacutenez-de los Mozos DOI 10577257343
Questions
Thank You
Diseas location Monostotic (25) or polyostotic(75) 1048710Typically affectsPelvis (70) Femur (55) Lumbosacralspine (53) Skull (42) Tibia (32) Rarely in hands feet
1048710No bone-to-bone spread
Clinical Presentation and Complications Usually asymptomatic
Incidental findingAbnormal radiograph or other imaging Abnormal labs (uarrAlkPhos)
Bone pain Constant 1048710Poorly localized 1048710Present at rest
Worse on weight-bearing
pain may be the presenting symptom due to
stress fractures increased vascularity and warmth
new onset intense pain and swelling be suspicious for Pagets secondary sarcoma in a patient with a known history of Pagets who
complains of new onset intense pain and swelling cardiac symptoms
can present with high-output cardiac failure particularly if largemultiple lesions amp pre-existing diminished cardiac function
Bonelimb deformity
Fracture
Arthropathy
uarrincidence of joint disease 1048710Specific pattern of joint diseases in hip uarrfreq of coxa vera protrusio concentric joint space narrowing
uarrSkin temperature
Hypervascularity due to uarrbone turnover activity
uarrbone turnover causes uarrcardiac demands and may lead to high-output heart failure
High-output cardiac failure is caused by the numerous arteriovenous fistulas present in the pagetic bones
Neurologic complaints
Hearing lossvertigotemporal bone involvement with auditory nerve compression
1048710Cranial nerve palsies 1048710Spine involvementMechanical cord compression ldquovascular steal
Hypercalcemia
Rare 1048710Usually inactive or bed-ridden patients 1048710Signs amp SymptomsNausea vomiting MSK aches hyper-reflexia weakness
polyuria headache lethargy altered mental status hellipcoma
Malignant transformation Pagets sarcoma
less than 1 will develop malignant Pagets sarcoma (secondary sarcoma)
osteosarcoma is the most common followed by fibrosarcoma and chondrosarcoma
most common in pelvis femur and humerus Pagets sarcoma has a poor prognosis
5-year survival for non-metastatic Pagets sarcoma is less than 5 appropriate treatment for Pagets sarcoma includes chemotherapy
and wide surgical resection Pagets sarcoma typically presents as a destructive lesion without
periosteal reaction
Diagnosis Clinical assessment Characteristic radiographic appearance Labs (uarrAlkPhos) Bone Scan Usually benign and multiple lesions in old
patients are pagets hyperparathyroidism and bone infarcts
Rarely CT MRI Biopsy
Long bones bend across the trajectories of mechanical stress thus the tibia bows anteriorly and the femur anterolaterally The limb looks bent and feels thick and the skin is unduly warm ndash hence the term lsquoosteitisdeformansrsquo If the skull is affected it enlarges the patient may complain that old hats no longer fit The skull base may become flattened (platybasia) giving the appearance of a short neck In generalized Pagetrsquos disease there may also be considerable kyphosis so the patient becomes shorter and ape-like with bent legs and arms hanging in front of him Cranial nerve compression may lead to impaired vision facial palsy trigeminal neuralgia or deafness Another cause of deafness is otosclerosisVertebral thickening may cause spinal cord or nerve root compression Steal syndromes in which blood is diverted from internal organs to the surrounding skeletal circulationmay cause cerebral impairment and spinal cord ischaemia If there is also spinal stenosis the patient develops typical symptoms of lsquospinal claudicationrsquo and lower limb weakness
Radiographs coarsened trabeculae which give the bone a blastic
appearance both increased and decreased osteodensity may exist
depending on phase of disease lytic phase
lucent areas with expansion and thinned intact cortices blade of grass or flame-shaped lucent advancing edge
mixed phase combination of lysis and sclerosis with coarsened trabeculae
sclerotic phase bone enlargement with cortical thickening sclerotic and lucent
area
remodeled cortices loss of distinction between cortices and medullary cavity
long bone bowing bowing of femur or tibia
fractures hip and knee osteoarthritis osteitis circumscripta
(cotton wool exudates) in skull Pagets secondary sarcoma
shows cortical bone destruction soft tissue mass
MRI may show lumbar spinal stenosis
Bone scan accurately marks site of disease intensely hot in lytic and mixed phase less hot in sclerotic phase
CT scan cortical thickening and coarsened trabeculae
CTMRI Incidental finding Evaluation of atypical presentations
neurological involvement and possible malignant transformation
CT trabecularcortical thinning thickening irregularity
MRI non-specific marrow changes
BiochemistrySerum AlkPhosEnzyme found in osteoblastic membrane Indicator of osteoblastic activity uarrin Pagetrsquos but can be normal Levels correlate with disease extent and activity elevated urinary hydroxyproline (collagen breakdown marker) increased urinary N-telopeptide alpha-C-telopeptide
and deoxypyridinoline normal calcium levels
Other recommended tests ESR -elevation may indicate malignant transformation
CRP Ca -hypercalcemiamay occur in Pagetrsquos PO4 25-hydroxyvitamin D -rule out osteomalacia LFTs-rule out liver disease
Diagnostic Biopsy Diagnosis is usually achieved clinically and by
plain radiographic appearance Biopsy rarely required
Characteristic HistopathologyDisorganized immature trabeculararchitecture with irregular cement lines (ldquomosaicrdquopattern)
Rimming osteoblasts andor multinucleated osteoclasts
Management Options (May require no treatment if asymptomatic)
Supportive Care Pharmacologic Surgical (OrthopedicNeurosurgical
Supportive Care Occupational therapy Physical aides Counseling for fall+fracture prevention
Physical therapy Analgesics Weight control
Pharmacologic ManagementGoals Relieve symptoms and Prevent potential
complications Normalization of serum AlkPhos associated
with better long-term outcomes and disease control
Indications to treat Pain Deformity Neurologic symptoms Asymptomatic but high-risk for complications
(prophylactic) Management of hypercalcemia(rare) Pre-op reduce blood flow and potential
operative blood loss
Calcitonin is the most widely used It reduces bone resorption by decreasing both the activity and the number
of osteoclasts serum alkaline phosphatase and urinaryhydroxyproline levels are lowered Salmon calcitonin is more effective than the porcine variety subcutaneous injections of 50ndash100 MRC units are given daily until pain is relieved and the alkaline phosphatase levels are reduced and stabilized Maintenance injections once or twice weekly may have to be continued indefinitely but some authorities advocate stopping the drug and resuming treatment if symptoms recur Calcitonin can also be administered in a nasal spray Bisphosphonates bind to hydroxyapatite crystals
inhibiting their rate of growth and dissolution It is claimed that the reduction in bone turnover following their use is associated with the formation of lamellar rather than woven bone and that even after treatment is stopped there may be prolonged remission of disease (Bickerstaff et al 1990) Etidronate can be given orally (always on an empty stomach) but dosage should be kept low (eg 5 mgkg per day for up to 6 months) and vitamin D and calcium should also be given lest impaired bone mineralization results inosteomalacia The newer bisphosphonates (eg alendronate or pamidronate) do not have this disadvantage so they should be used as the treatment of choice they produce remissions even with shortcourses of 1 or 2 weeks
BisphosphonatesSynthetic analogues of inorganic phosphate adhere to mineralized surfaces
Ingested selectively by osteoclasts Disrupts enzyme pathways and reduces osteoclastic bone resorption
calcitonin causes osteoclasts to shrink in size and decreases their bone resorptive activity within minutes administered subcutaneously or intramuscularly
teriparatide is contraindicated in Pagets disease due to risk of secondary osteosarcoma
Surgical Management Few require surgery
Common Procedures Corrective osteotomy of long bone deformity indications
fractures through pathologic bowing of long bones impending pathologic fracture of long bone with bowing deformity
Arthroplasty (hip knee) the most common complications include
malalignment with knee arthroplasty bleeding with hip arthroplasty
Combination arthroplasty with osteotomy Fracture fixation
Preoperative Considerations Medical assessment for extraskeletalmanifestations eg high-
output heart failure
Medical treatment of active disease Preoperative autologousblood donation
Thorough planningeg good quality x-rays for templatingand device selection
Intraoperative Considerations Blood salvage system Expansileapproach + soft tissue release Sharp reamersburrsdrills for IM access Extramedullaryguidenavigation systems Concomitant osteotomy
PostoperativeConsiderations Monitoring for cardiac complications Continued medical tx of active disease
uarrHeterotopic ossification Prophylaxis against HO
Possible future excision of HO for painROM
1-Tieg provides a review of Pagets disease of bone and treatment indications In his review he discusses that most patients with Pagets disease are asymptomatic but in those that do present pain is the most common presenting symptom He recommends medical and surgical treatment of asymptomatic patients who have active disease at sites where complications are likely to develop
Altman did a review of 290 patients with Pagets disease of bone His findings showed 83 had one or more rheumatic syndromes He found the rate of osteoarthritis related to Pagets disease was elevated in the hip and knee Rheumatoid arthritis hyperuricemia and gout did not appear increased in this group
Mangham et al looked the rate of secondary sarcomas as a result of Pagets disease of bone They found the rate to be around 03 with male predominance They also found that widespread skeletal involvement by Pagets disease was not a significant risk factor for malignant transformation
Interesting views about pagets
Smith et al reviewed the pathologic complications of Pagets bone disease Pagets bone disease commonly causes osseous weakening (deformity and fracture) and arthritis in the hip joint Management of end stage disease is successful with cemented and cementless total hip arthroplasty Bleeding is the most common intra- and post-operative complication of surgery
Gabel et al retrospectively reviewed thirteen patients who had had sixteen total knee arthroplasties for Pagetic gonarthrosis Unlike total hip arthroplasty surgery Paget disease did not increase the amount of blood lost during the operation or in the postoperative period The most common complication associated with total knee arthroplasty was malalignment
Hansen et al reviewed the incidence of osteosarcomas complicating Pagets Disease Of the typical sites that are usually involved in Pagets disease (eg spine pelvis femur tibia and humerus) secondary osteosarcoma tends to spare the spine
Shaylor et al reported the mortality rates in 26 patient with osteosarcoma secondary to Paget s disease There was a 47 mortality at 1 year and 75 at 2 years from diagnosis In their series no patient survived for 5 years All patients died of metastatic disease
Langston et al conducted a randomized trial that compared the results of symptomatic treatment versus intensive bisphosphonate therapy in patients with Pagets disease Clinical fractures occurred in 46 of 661 patients (70) in the treatment group compared with 49 of 663 patients (74) in the symptomatic treatment group They concluded that bisphosphonates did not show a significant beneficial impact on pain quality of life or fracture incidence
Hadjipavlou et al reviewed Pagets disease of the bone and its management Farmers have been shown to have an increased incidence of Pagets disease Average age at presentation is in the 5th and 6th decade Symptomatic individuals are recommended to be treated initially with medical management They suggest that bisphosphonates are more effective than calcitonin at suppressing the histological and biochemical activity in Pagetrsquos disease
Summary Epid Very common in elderly Path Abnormal osteoclastshellipuarrbone
turnoverhellipdeposition of abnormal bone SampS Pain deformity fracture arthropathy Labs uarrAlkPhos X-ray Characteristic coarse thickened
trabeculae Bone scan Very hot Rx Bisphosphonates Surgery for arthropathy fracture painful
deformity
A 65-year-old male presents with increasing shoulder pain over the past 9 months He is otherwise healthy and has no other complaints Radiograph of his shoulder is shown in Figure A Whole body bone scan and biopsy photograph are shown in Figures B and C What is the most appropriate treatment for this patient
1 Referral to endocrinology 2 Radiation therapy and chemotherapy 3 Wide resection and reconstruction 4 Radiation therapy wide resection and reconstruction 5 Chemotherapy wide resection and reconstruction
Histiocytosis X or Langerhans cell histiocytosis is a spectrum of diseases of the reticuloendothelial system with one of three general presentations Eosinophilic granuloma (EG)
usually a single self-limited lesion found in younger patients
Hand-Schuller-Christian disease (HSC) chronic disseminated form with bone and visceral lesions also known as Langerhans cell histiocytosis with visceral
involvement Letterer-Siwe disease (LSD)
fatal form that occurs in young children
Eosinophilic granuloma
Epidemiology demographics
most commonly occurs in children (80 of afflicted lt 20 years of age)
HSC disease presents in children gt 3 years of age LSD occurs in children lt 3 years of age Male to female ratio of 21
location eosinophilic granuloma
commonly presents in the skull ribs clavicle scapula mandible
isolated lesions of the spine (thoracic most common) can also occur in diaphyseal regions of long bones and the
pelvis HSC
multiple bony sites multiple lytic skull lesions visceral involvement of the lungs spleen liver skin lymph
nodes
Genetics no clear genetic pattern of inheritance or locus has
been determined Prognosis
EG isolated involvement generally treatable with local
management spine lesions can spontaneously resolve
HSC prognosis depends on response to chemotherapy worsening prognosis with increasing extraskeletal
involvement LSD
generally fatal in children lt 3 years of age
Symptoms skeletal involvement
pain and swelling at the region of involvement limping can be seen with pelvic or lower extremity
involvement vertebral involvement
localized or diffuse back pain increasingly kyphotic posture radiculopathy can occur with more aggressive lesions
HSC classic triad of
multiple lytic skull lesions diabetes insipidus
increased thirst and water intake exopthalmos
visceral involvement diffuse or nonspecific abdominal or chest pain
Radiographs general
known as the great mimicker as it appears similar to many lesions radiographic differential includes osteomyelitis leukemia lymphoma
fibrous dysplasia or Ewings sarcoma diaphyseal lesions
well defined intramedullary lytic or punched-out lesion cortex may be thinned expanded or destroyed may have periosteal reaction
metaphyseal lesions extend up to but not through the physis less central location than diaphyseal lesions
spinal lesions vertebra plana (flattened vertebrae) in spine increased kyphosis
cranial involvement multiple punched-out lytic lesions
MRI may show a soft tissue mass adjacent to boney lesions
Bone scan generally shows increased uptake in the region of boney lesion
Histology Langerhans cells
mononuclear histiocyte-like cells with oval nuclei with well-defined round or oval cytoplasm
a prominent nuclear groove (coffee bean nuclei) can be seen in most of the nuclei
eosinophilic cytoplasm (pink generally) stain with CD1A electronmicroscopy
birbeck granules seen inside Langerhans cells mixture of inflammatory cells also present giant cells are present lack of nuclear atypia and atypical mitoses
differentiates this condition from malignant conditions such as Ewings sarcoma lymphoma of bone and metastatic neuroblastoma which may look similar based on the round cells alone
eosinophilic cytoplasm (pink generally)
Treatment
bullNonoperative bull observation alone
bull indications bull a self-limited process and it is reasonable to treat with observation alone
bull bracing bull indications
bull to prevent progressive kyphosis of the spinebull outcomes
bull will correct deformity in 90 of patientsbull vertebral lesions generally regain 50 of their height
bull low dose irradiation (600-800 cGy) bull indications
bull indicated for lesions in the spine that compromise stability neurologic statusbull lesions not amenable to injection or open treatment
bull outcomes bull effective for most lesions
bull chemotherapy bull indications
bull diffuse HSCbull outcomes
bull prognosis is improved with less severe extraskeletal involvementbull corticosteroid injection
bull indications bull isolated lesions bull can be performed after curettage as well
Operative curettage and bone grafting
indications for lesions that endanger the articular surface or are a risk for
impending fractures spinal deformity correction
indications progressive spine deformity refractory to bracing
approximately 10 of patients with spine lesion will need operative intervention for deformity correction
Destructive multiple lesion in young patientsAre eosinophilic granuloma lymphoma and leukemiaLymphoma is unlikely to present with exopthalmos diabetes insipidus or vertebra plana Lymphoma bone lesions are lytic and appear moth eatenpermeative on radiographs
Figure A shows a skin lesion typical of eosinophillic granuloma Figure B shows a lytic lesions without significant surrounding sclerosis as is characteristic of eosinophilic granuloma Figure C shows the characteristic histology of multiple eosinophils with their characteristic oval coffee bean nuclei and staining pattern of purpleredpink cytoplasm (depending on the stain) Importantly the histology slide lacks a malignant appearance (no cellular atypia or mytotic complexes and low nuclearcytoplasmic ratio)
Formation of bone in atypical extraskeletal tissues usually occurs
spontaneously or following trauma within 2 months of neurologic injury (brain or spinal cord)
most common location is between muscle and joint capsule Epidemiology
incidence (see table below)
demographics malefemale = 21 especially men with hypertrophic osteoarthritis and women gt65y
location traumatic brain injury or stroke
hip gt elbow gt shoulder gt knee elbow HO more common following brain trauma
occurs on affected (spastic) side rarely in the knee (TBI)
spinal cord injury hip gt knee gt elbow gt shoulder hip flexors and abductors gt extensors or adductors medial aspect of the knee
Heterotopic Ossification
Risk factors
Pathophysiology exact cause of HO is not known but there appears to be a
genetic pre disposition experimental HO associated with
tissue expression of BMP IT IS SAID TO BE CAUSED BY activation and proliferation of
mesenchymal stem cells Associated conditions
orthopaedic manifestations pathologic fractures
from decreased joint ROM and osteoporotic bone nerve impingement soft tissue contractures contributing to the formation of
decubitus ulcers joint ankylosis HO after THA adversely affects outcome of THA
nonorthopaedic conditions skin maceration and hygiene problems
Pathophysiology Early in the formation of HO oedema with exudative
infiltrate is present followed by fibroblastic proliferation and immature connective tissue formation Posteriorly osteoid formation is seen with the subsequent deposition of bone matrix Primitive osteoid is deposited as small masses in the periphery early (within the first two weeks) and osteoblasts are noted located irregularly Osteoblasts produce tropocollagen which polymerizes to form collagen and secrete alkaline phosphatase which allows calcium to precipitate and the mineralization of bone matrix As mineralization progresses amorphous calcium phosphate is progressively replaced by hydroxyapatite crystals During the following weeks the lesion matures with a centripetal pattern and after 6-12 months an appearance of true bone is noted The new bone is always extra-articular and can be contiguous with the skeleton but generally does not involve the periosteum
IN SUMMARY It has been postulated that three conditions
must be met to achieve heterotopic bone formation ---a stimulating event oestrogenic precursor cells and a proper environment LIKE hypercalcaemia tissue hypoxia pH changes (alkalosis) or prolonged immobilization
ClassificationbullSubtypes
bull neurogenic HO bull Four clinical stages of HO in people with spinal cord injury were
described by Nicholas in 1973
bull traumatic myositis ossificans bull fibrodysplasia ossificans progressiva (Munchmeyers Disease)
Neurogenic HO Symptoms
painless loss of ROM interferes with ADL CRPS symptoms fever
Physical exam inspection
warm painful swollen joint may have effusion skin problems
decubitus ulcers from contractures around skin muscles ligaments
skin maceration and hygiene problems motion
decreased joint ROM joint ankylosis with HO after TKA might develop quad muscle snapping or patella
instability neurovascular
peripheral neuropathy HO often impinges on adjacent NV structures
Imaging
bullRadiographs bull findings
bull ossification usually easy to visualize bull maturity of HO
bull the appearance of a bony cortex suggests mature HObull sharp demarcation from surrounding tissue bull trabecular pattern
bull sensitivity and specificity bull not useful for early diagnosisbull only useful at 1 week after onset of symptoms
bull calcium is deposited 7-10 days later than symptom onsetbullUltrasound
bull indications bull for early diagnosis of hip HO
bull findings bull echogenic surfaces with posterior acoustic shadowing
bullCT bull indications
bull useful for preoperative planning bullTriphasic bone scan
bull indications bull best for early diagnosis bull most commonly used diagnostic study
Radiographs are extremely useful in the staging of heterotopic ossification and will show the development of sharp cortical margins once the lesion has reached maturity
Heterotopic bone is a condition in which lamellar bone forms in non-ossified soft tissues In the early stages studies such as MRI and bone scan are more sensitive for diagnosis as radiographs may appear normal for the first three weeks After the appropriate diagnosis is made sequential radiographs are useful for monitoring the progression of the ossification Once it has reached the mature stage sharp cortical margins will appear and surgical resection may be considered
lab
Labs elevated serum alkaline phosphatase (gt250IUL)
ALP removes inhibitors of mineralization nonspecific may be elevated with skeletal trauma cannot determine maturity of HO elevated 12wks after surgery is predictor
elevated CRP correlates with inflammatory activity of HO better than ESR normalization of CRP may correlate with maturity of HO
elevated ESR (gt35mmh) 12wks after THA is predictor
elevated CK correlates with involvement of muscle extent of muscle
involvement Histology
mature fatty bone marrow mature trabecular bone
Heterotopic ossification (HO) most commonly occurs at the amputation site if the amputation was performed thru the zone of injury especially if the injury was a blast mechanism
Symptomatic heterotopic ossification of the quadriceps may occur following placement of a large-diameter Steinmann pin for the purpose of temporary skeletal traction
TreatmentThe prevention of heterotopic ossification is focused on three basic principles disrupting the inductive signalling pathways altering the osteoprogenitor cells or modifying the environment
bullphysiotherapy should involve an assisted range of movement exercises with gentle stretch and terminal resistance trainingbullProphylaxis
bull bisphosphonates amp NSAIDS bull indications
bull although no literature supports are commonly usedbull technique
bull indomethacin is most commonly used bull dose is 75mgday for 10days to 6 weeks
bull perioperative radiation bull indications
bull although no literature supports commonly usedbull is thought to be effective by blocking osteoblast differentiation
bull technique bull a single perioperative dose of 700cGy can be given either 4
hours preop or within 72 hours postoperatively bull lt550cGy not effective
Nonsteroidal anti-inflammatory drugs (NSAIDs) These drugs have demonstrated good results in
preventing heterotopic ossification after total hip arthroplasty
A direct effect of NSAIDs on the formation of heterotopic ossification has been described due to the inhibition of the differentiation of mesenchymal cells into oestrogenic cells There is also an indirect effect which refers to the inhibition of bone remodelling by suppression of the prostagland unmediated inflammatory response (specifically PGE-2)
Indomethacin has been considered a useful medication for heterotopic ossification prophylaxis following total hip replacement
prescribed for three to six weeks in a dose of 75mgday within two months of the injury may reduce the incidence of heterotopic ossification by two to three times
Biphosphonates inhibits precipitation of calcium phosphate and blocks the aggregation and mineralisation of hydroxyapatite crystals In primary prevention Banovac et al [56] have suggested that the treatment should begin as soon as elevated alkaline phosphatase is diagnosed or positive findings in ultrasonography or bone scans are shown In addition disphosphonates could have long-term effects on prevention when the treatment is finished
Posttraumatic wide exposure and surgical resection
indications severe loss of motion and decreased function
technique wide exposure required to identify all neurovascular
structures that may be involved timing of resection (controversial)
marked decrease in bone scan activity AND normalization of ALP
6 months following general trauma 1 year following SCI 15 years following TBI
some data suggests equivalent results when comparing early versus late resection
postop follow with 5 day course of indomethacin early gentle joint mobilization
The surgery is necessary in patients with symptomatic HO and unsuccessful medical treatment such as
Loss of range of motion and ankylosis with associated functional disability such as sitting difficulties
Complications of immobility such as pressure ulcers
Facilitate rehabilitation and recovery of muscular atrophy secondary to prolonged immobilisation
Difficulties of appropriate hygiene because access to the perineum or bladder care is needed
Severe pain refractory to analgesia Vascular andor nerve compression
Advantages to early excision of heterotopic ossification (vs waiting for maturation) include decreased soft tissue contracture better definition between heterotopic and native bone and decreased waiting time for the patient When the soft tissue envelope is benign one may proceed with operative release While waiting for normalization of alkaline phosphatase levels inactivity on bone scan or radiographic maturity may decrease risk of recurrent heterotopic ossification delaying operative release for these reasons has not been shown to improve results of final elbow range of motion after contracture release
Gartland recommended surgery after six months following traumatic heterotopic ossification one year following spinal cord injury and 18 months after head injury
In the past waiting until maturity in order to minimize the rate of recurrence after the surgical treatment was recommended Nevertheless recent studies do not confirm a higher rate of recurrence when the HO is excised in an earlier phase In addition a long delay before surgery leads to ankylosis a high degree of osteoporosis and more extensive intra-articular injuries These findings are associated with bad functional results and potential complications
Should you wait till lesion maturation
Prevention byHandle tissue carefully Avoid excess bleeding Achieve good hemostasis Beware of lesions that span internervous tissue planes
but if it happens resection of a large enough amount of bone to allow improvement of the range of motion and trying to preserve the joint
Our aim must be
A reactive process that is characterized by a well-circumscribed proliferation of fibroblasts cartilage and bone within muscle
A form of heterotopic ossification that is the result direct trauma intramuscular hematoma
most common location is the diaphysis of long bones Must differentiate from tumors Fibrodysplasia ossificans progressiva (FOP) is a rare subtype of heterotopic ossification
involves mutation of the ACVR1 gene (activin A type I receptor gene a BMP type-1 receptor)
Epidemiology demographics
most common in young active males (15 to 35 years old) body locations
quadriceps brachialis and gluteal muscles Genetics
almost always a posttraumatic condition Prognosis
usually self limiting mass usually begins to decrease in size after 1 yea
Myositis ossificans
PresentationbullSymptoms
bull pain tenderness swelling and decreased range of motion that usually presents within days of the injury
bull pain and size of the mass decrease with timebull mass increases in size over several months(usually 3 to 6 cm)
bull after the mass stops growing it becomes firmbullPhysical exam
bull palpable soft tissue massbull restricted range of motion
ImagingbullRadiographs
bull peripheral bone formation with central lucent areabull may appear as dotted veil pattern
bullMRI with gadolinium bull rim enhancement is seen within the first 3 weeks
bullCT scan bull lesion has an eggshell appearance
bullCharacteristic histology shows zonal pattern bull periphery of lesion
bull mature trabeculae of lamellar and woven bonebull calcification seen on xray
bull center of the lesion bull irregular mass of immature fibroblastsbull cartilage component may be presentbull (no calcification seen on xray) bull no cellular atypia seen
Treatment
bullNonoperative bull rest range of motion exercises and activity modification
bull passive stretching is contraindicated (makes it worse)bull physical therapy
bull utilized to maintain range of motionbull radiographic monitoring
bull obtained to confirm maturation of the lesionbullOperative
bull surgical excision bull indicated only if it remains a problem after it maturesbull do not operate in acute phase wait at least six months
bull excision of the lesion within 6 to 12 months predisposes to local recurrence
A 26-year-old man presents with generalized back and joint stiffness and difficulty opening his mouth His elder sister has similar complaints Since childhood he has had 3 surgeries for excision of recurrent bony prominences around his knees He walks with a stooped over posture seen in Figure A Radiographs of his feet knee hip and spine are seen in Figures B-E respectively
fibrodysplasia ossificans progressiva
Stone Man Disease) which involves a mutation of the ACVR1
There are 2 hallmark characteristics progressive heterotopic ossification (muscles fascia tendons ligaments and joint capsules) and congenital malformation of the great toe (hallux valgus malformed first metatarsal and monophalangism) BMP4 which contributes to the formation of the skeleton in the normal embryo is implicated in this disease
Complications
bullHematoma and intraoperative bleedingbullInfection
bull higher rate of infection following joint arthroplasty if HO is present
bullFractures of osteoporotic bone bull osteopenic from disusebull during surgery or physiotherapy
bullRecurrence bull recurrence rate correlates with neurological injury
bull greater recurrence if severe neurological compromisebullAVN
bull if extensive dissection or stripping is required
HTO AND ISS
When ISS is below 25 the mortality risk is minimal and above 25 it is an almost linear increase
When ISS is 50 the mortality is 50 When above 70 it is close to 100 If an injury is assigned an AIS of 6 (unsurvivable injury) the ISS score is
automatically assigned to 75 Highest ISS score obtainable is 75 For trauma patients of vehicular accidents the scoring system is important
for assessing the effectiveness of medical care in reducing morbidity and mortality
Advantages virtually the only anatomical scoring system in use correlates linearly with
mortality morbidity hospital stay other measures of severity
Weaknesses Any error in AIS scoring increases the ISS error Many different injury patterns can yield the same ISS score Injuries to different body regions are not weighted Not a useful triage tool as a full description of patient injuries is not known
prior to full investigation amp operation
risk factors periosteal stripping off anterior femur male gender obesity post traumatic deformity Anterior and anterolateral approach Cementless
Neurogenic HO around the hip due to SCI occurs more often in the medial region than in the lateral region with ossified tissues extending from the pubic symphysis to the anteromedial femoral shaft posterior to the femoral neurovascular structures Ossification is also seen anteriorly involving the iliopsoas and femoral neurovascular structures laterally within gluteus minimus and posteriorly extending from the ilium to the posterior femur encasing the sciatic nerve
HTO AROUND hip and knee
The Brooker Classification of Heterotopic Ossification around the hip joint Class I has islands of bone within the soft tissues Class II has bone spurs from the pelvis or proximal end of the femur leaving at least 1 cm between opposing surfaces Class III has bone spurs from the pelvis andor proximal end of the femur reducing the space between opposing bone surfaces to less than 1 cm Class IV shows apparent bone ankylosis of the hip
Region I - Heterotopic ossifications are strictly below the tip of the greater trochanter
Region II - Heterotopic ossifications are below and above the tip of the greater trochanter
Region III - Heterotopic ossifications are strictly above the tip of the greater trochanter
Grade A - Single or multiple heterotopic ossifications are less than 10 mm in maximal extent without contact with the pelvis or the femur
Grade B - Heterotopic ossifications are greater than 10 mm without contact with the pelvis but with possible contact with the femur there is no bridging from the femur to the proximal part of the greater trochanter and no evidence of ankylosis
Grade C - Ankylosis by means of firm bridging from the femur to the pelvis is present
Shmidt classification
excision may be performed The results of this procedure are varied Patients may find that their range of movement improves but pain relief is likely to be limited
A patient with heterotopic ossification following total hip arthroplasty is thought to have a 90-100 chance of developing it on the contralateral hip if this hip also undergoes total arthroplasty
it would be prudent to minimize the risk of heterotopic ossification developing after arthroplasty by performing surgery whereby the following are ensured
Exposure is meticulous Retraction is performed carefully and soft tissue
is handled carefully Irrigation is adequate Devitalized tissue is excised Hemostasis is adequate Postoperative drains (when used) are not
retained for longer than necessary Perioperative antibiotic prophylaxis is used Postoperative anticoagulation (when used for
deep vein thrombosis prophylaxis) is carefully controlled
sources of knee stiffness 1-extrinsic severe osteoarthritis of the ipsilateral hip neurologic injury leading to muscle rigidity tight quadriceps or hamstring muscles secondary to muscle injury heterotopic ossification or long-standing juvenile inflammatory conditions limiting knee
range of motion prior to the completion of skeletal growth When extrinsic sources are identified revision total knee arthroplasty is unlikely to be associated with a favorable outcome without correction of the extrinsic problem
2-intrinsic (1) overstuffing of the patellofemoral articulation (2) an
excessively tight flexion andor extension gap (3) a tight posterior cruciate ligament (4) femoral andor tibial malrotation (5) arthrofibrosis and (6) limited bearing excursion in association with a highly conforming mobile-bearing prosthetic design
HTO after TKA
Heterotopic Ossification (HO) following primary Total Knee Replacement (TKR)
Occurs in 3-90 of TKRs 3-grade classification system No correlation between HO and component
alignment or component position
Clinical findings similar to early infection Continuing low-grade fever Warm swollen and erythematous knee Normal blood tests Possibly an association with HLA-A2 and B18 HO patients have worse KSS and function
scores
Patients at HIGH risk for developing HO after TKR (Knee Arthroplasty) (5)
Those with limited postoperative knee flexion
Increased lumbar bone mineral density (BMD) on multivariate analysis (3)
Hypertrophic arthrosis Excessive periosteal trauma Notching of the anterior femur Those who require forced manipulation
after TKA 47 in revision TKR surgery (6) Higher rates in revision TKR cases with
infection (up to 76
DaughertyBell classification of HO of the knee 0 No evidence of HO 1 Bone islands in periarticular soft tissue (no
involvement of femur patella or tibia) or HO within quadriceps expansion measuring lt1 cm
2 Spur formation measuring lt5 cm that involves the femur patella or tibia if more than one bone demonstrates HO separation of HO spurs
measure gt1 cm or HO within quadriceps expansion measuring ge1 cm but lt3 cm
3 Spur formation gt5 cm involving femur patella or tibia if more than one bone demonstrates HO separation of HO spurs measure lt1 cm or HO
within quadriceps expansion measuring ge3 cm 4 Extensive HO of the knee causing ankylosis
class 2 HO begins to involve the major bones of the knee joint with spur formation limited to a size of 5 cm
HO class 2 may be observed in select patients with complete ROM and no reported pain Patients with class 3 HO would likely always benefit from surgical excision
followed by RT prophylaxis Certainly patients in either cohort with a subclass ldquoBrdquo assignment (symptomatic) would
benefit from treatment All patients with class 4 HO require
treatment to alleviate ankylosis
treatment
References Whyte ldquoPagetrsquos Disease of Bonerdquo NEMJ vol 355
2006 Klein and Parvizi ldquoSurgical Manifestations of Pagetrsquos
Diseaserdquo JAAOS vol 14 2006 Orthobullets Campbell Apley Emedicinecom
-Chapter 15 Heterotopic Ossification after Traumatic Brain InjuryBy Jesuacutes Moreta and Joseacute Luis Martiacutenez-de los Mozos DOI 10577257343
Questions
Thank You
Clinical Presentation and Complications Usually asymptomatic
Incidental findingAbnormal radiograph or other imaging Abnormal labs (uarrAlkPhos)
Bone pain Constant 1048710Poorly localized 1048710Present at rest
Worse on weight-bearing
pain may be the presenting symptom due to
stress fractures increased vascularity and warmth
new onset intense pain and swelling be suspicious for Pagets secondary sarcoma in a patient with a known history of Pagets who
complains of new onset intense pain and swelling cardiac symptoms
can present with high-output cardiac failure particularly if largemultiple lesions amp pre-existing diminished cardiac function
Bonelimb deformity
Fracture
Arthropathy
uarrincidence of joint disease 1048710Specific pattern of joint diseases in hip uarrfreq of coxa vera protrusio concentric joint space narrowing
uarrSkin temperature
Hypervascularity due to uarrbone turnover activity
uarrbone turnover causes uarrcardiac demands and may lead to high-output heart failure
High-output cardiac failure is caused by the numerous arteriovenous fistulas present in the pagetic bones
Neurologic complaints
Hearing lossvertigotemporal bone involvement with auditory nerve compression
1048710Cranial nerve palsies 1048710Spine involvementMechanical cord compression ldquovascular steal
Hypercalcemia
Rare 1048710Usually inactive or bed-ridden patients 1048710Signs amp SymptomsNausea vomiting MSK aches hyper-reflexia weakness
polyuria headache lethargy altered mental status hellipcoma
Malignant transformation Pagets sarcoma
less than 1 will develop malignant Pagets sarcoma (secondary sarcoma)
osteosarcoma is the most common followed by fibrosarcoma and chondrosarcoma
most common in pelvis femur and humerus Pagets sarcoma has a poor prognosis
5-year survival for non-metastatic Pagets sarcoma is less than 5 appropriate treatment for Pagets sarcoma includes chemotherapy
and wide surgical resection Pagets sarcoma typically presents as a destructive lesion without
periosteal reaction
Diagnosis Clinical assessment Characteristic radiographic appearance Labs (uarrAlkPhos) Bone Scan Usually benign and multiple lesions in old
patients are pagets hyperparathyroidism and bone infarcts
Rarely CT MRI Biopsy
Long bones bend across the trajectories of mechanical stress thus the tibia bows anteriorly and the femur anterolaterally The limb looks bent and feels thick and the skin is unduly warm ndash hence the term lsquoosteitisdeformansrsquo If the skull is affected it enlarges the patient may complain that old hats no longer fit The skull base may become flattened (platybasia) giving the appearance of a short neck In generalized Pagetrsquos disease there may also be considerable kyphosis so the patient becomes shorter and ape-like with bent legs and arms hanging in front of him Cranial nerve compression may lead to impaired vision facial palsy trigeminal neuralgia or deafness Another cause of deafness is otosclerosisVertebral thickening may cause spinal cord or nerve root compression Steal syndromes in which blood is diverted from internal organs to the surrounding skeletal circulationmay cause cerebral impairment and spinal cord ischaemia If there is also spinal stenosis the patient develops typical symptoms of lsquospinal claudicationrsquo and lower limb weakness
Radiographs coarsened trabeculae which give the bone a blastic
appearance both increased and decreased osteodensity may exist
depending on phase of disease lytic phase
lucent areas with expansion and thinned intact cortices blade of grass or flame-shaped lucent advancing edge
mixed phase combination of lysis and sclerosis with coarsened trabeculae
sclerotic phase bone enlargement with cortical thickening sclerotic and lucent
area
remodeled cortices loss of distinction between cortices and medullary cavity
long bone bowing bowing of femur or tibia
fractures hip and knee osteoarthritis osteitis circumscripta
(cotton wool exudates) in skull Pagets secondary sarcoma
shows cortical bone destruction soft tissue mass
MRI may show lumbar spinal stenosis
Bone scan accurately marks site of disease intensely hot in lytic and mixed phase less hot in sclerotic phase
CT scan cortical thickening and coarsened trabeculae
CTMRI Incidental finding Evaluation of atypical presentations
neurological involvement and possible malignant transformation
CT trabecularcortical thinning thickening irregularity
MRI non-specific marrow changes
BiochemistrySerum AlkPhosEnzyme found in osteoblastic membrane Indicator of osteoblastic activity uarrin Pagetrsquos but can be normal Levels correlate with disease extent and activity elevated urinary hydroxyproline (collagen breakdown marker) increased urinary N-telopeptide alpha-C-telopeptide
and deoxypyridinoline normal calcium levels
Other recommended tests ESR -elevation may indicate malignant transformation
CRP Ca -hypercalcemiamay occur in Pagetrsquos PO4 25-hydroxyvitamin D -rule out osteomalacia LFTs-rule out liver disease
Diagnostic Biopsy Diagnosis is usually achieved clinically and by
plain radiographic appearance Biopsy rarely required
Characteristic HistopathologyDisorganized immature trabeculararchitecture with irregular cement lines (ldquomosaicrdquopattern)
Rimming osteoblasts andor multinucleated osteoclasts
Management Options (May require no treatment if asymptomatic)
Supportive Care Pharmacologic Surgical (OrthopedicNeurosurgical
Supportive Care Occupational therapy Physical aides Counseling for fall+fracture prevention
Physical therapy Analgesics Weight control
Pharmacologic ManagementGoals Relieve symptoms and Prevent potential
complications Normalization of serum AlkPhos associated
with better long-term outcomes and disease control
Indications to treat Pain Deformity Neurologic symptoms Asymptomatic but high-risk for complications
(prophylactic) Management of hypercalcemia(rare) Pre-op reduce blood flow and potential
operative blood loss
Calcitonin is the most widely used It reduces bone resorption by decreasing both the activity and the number
of osteoclasts serum alkaline phosphatase and urinaryhydroxyproline levels are lowered Salmon calcitonin is more effective than the porcine variety subcutaneous injections of 50ndash100 MRC units are given daily until pain is relieved and the alkaline phosphatase levels are reduced and stabilized Maintenance injections once or twice weekly may have to be continued indefinitely but some authorities advocate stopping the drug and resuming treatment if symptoms recur Calcitonin can also be administered in a nasal spray Bisphosphonates bind to hydroxyapatite crystals
inhibiting their rate of growth and dissolution It is claimed that the reduction in bone turnover following their use is associated with the formation of lamellar rather than woven bone and that even after treatment is stopped there may be prolonged remission of disease (Bickerstaff et al 1990) Etidronate can be given orally (always on an empty stomach) but dosage should be kept low (eg 5 mgkg per day for up to 6 months) and vitamin D and calcium should also be given lest impaired bone mineralization results inosteomalacia The newer bisphosphonates (eg alendronate or pamidronate) do not have this disadvantage so they should be used as the treatment of choice they produce remissions even with shortcourses of 1 or 2 weeks
BisphosphonatesSynthetic analogues of inorganic phosphate adhere to mineralized surfaces
Ingested selectively by osteoclasts Disrupts enzyme pathways and reduces osteoclastic bone resorption
calcitonin causes osteoclasts to shrink in size and decreases their bone resorptive activity within minutes administered subcutaneously or intramuscularly
teriparatide is contraindicated in Pagets disease due to risk of secondary osteosarcoma
Surgical Management Few require surgery
Common Procedures Corrective osteotomy of long bone deformity indications
fractures through pathologic bowing of long bones impending pathologic fracture of long bone with bowing deformity
Arthroplasty (hip knee) the most common complications include
malalignment with knee arthroplasty bleeding with hip arthroplasty
Combination arthroplasty with osteotomy Fracture fixation
Preoperative Considerations Medical assessment for extraskeletalmanifestations eg high-
output heart failure
Medical treatment of active disease Preoperative autologousblood donation
Thorough planningeg good quality x-rays for templatingand device selection
Intraoperative Considerations Blood salvage system Expansileapproach + soft tissue release Sharp reamersburrsdrills for IM access Extramedullaryguidenavigation systems Concomitant osteotomy
PostoperativeConsiderations Monitoring for cardiac complications Continued medical tx of active disease
uarrHeterotopic ossification Prophylaxis against HO
Possible future excision of HO for painROM
1-Tieg provides a review of Pagets disease of bone and treatment indications In his review he discusses that most patients with Pagets disease are asymptomatic but in those that do present pain is the most common presenting symptom He recommends medical and surgical treatment of asymptomatic patients who have active disease at sites where complications are likely to develop
Altman did a review of 290 patients with Pagets disease of bone His findings showed 83 had one or more rheumatic syndromes He found the rate of osteoarthritis related to Pagets disease was elevated in the hip and knee Rheumatoid arthritis hyperuricemia and gout did not appear increased in this group
Mangham et al looked the rate of secondary sarcomas as a result of Pagets disease of bone They found the rate to be around 03 with male predominance They also found that widespread skeletal involvement by Pagets disease was not a significant risk factor for malignant transformation
Interesting views about pagets
Smith et al reviewed the pathologic complications of Pagets bone disease Pagets bone disease commonly causes osseous weakening (deformity and fracture) and arthritis in the hip joint Management of end stage disease is successful with cemented and cementless total hip arthroplasty Bleeding is the most common intra- and post-operative complication of surgery
Gabel et al retrospectively reviewed thirteen patients who had had sixteen total knee arthroplasties for Pagetic gonarthrosis Unlike total hip arthroplasty surgery Paget disease did not increase the amount of blood lost during the operation or in the postoperative period The most common complication associated with total knee arthroplasty was malalignment
Hansen et al reviewed the incidence of osteosarcomas complicating Pagets Disease Of the typical sites that are usually involved in Pagets disease (eg spine pelvis femur tibia and humerus) secondary osteosarcoma tends to spare the spine
Shaylor et al reported the mortality rates in 26 patient with osteosarcoma secondary to Paget s disease There was a 47 mortality at 1 year and 75 at 2 years from diagnosis In their series no patient survived for 5 years All patients died of metastatic disease
Langston et al conducted a randomized trial that compared the results of symptomatic treatment versus intensive bisphosphonate therapy in patients with Pagets disease Clinical fractures occurred in 46 of 661 patients (70) in the treatment group compared with 49 of 663 patients (74) in the symptomatic treatment group They concluded that bisphosphonates did not show a significant beneficial impact on pain quality of life or fracture incidence
Hadjipavlou et al reviewed Pagets disease of the bone and its management Farmers have been shown to have an increased incidence of Pagets disease Average age at presentation is in the 5th and 6th decade Symptomatic individuals are recommended to be treated initially with medical management They suggest that bisphosphonates are more effective than calcitonin at suppressing the histological and biochemical activity in Pagetrsquos disease
Summary Epid Very common in elderly Path Abnormal osteoclastshellipuarrbone
turnoverhellipdeposition of abnormal bone SampS Pain deformity fracture arthropathy Labs uarrAlkPhos X-ray Characteristic coarse thickened
trabeculae Bone scan Very hot Rx Bisphosphonates Surgery for arthropathy fracture painful
deformity
A 65-year-old male presents with increasing shoulder pain over the past 9 months He is otherwise healthy and has no other complaints Radiograph of his shoulder is shown in Figure A Whole body bone scan and biopsy photograph are shown in Figures B and C What is the most appropriate treatment for this patient
1 Referral to endocrinology 2 Radiation therapy and chemotherapy 3 Wide resection and reconstruction 4 Radiation therapy wide resection and reconstruction 5 Chemotherapy wide resection and reconstruction
Histiocytosis X or Langerhans cell histiocytosis is a spectrum of diseases of the reticuloendothelial system with one of three general presentations Eosinophilic granuloma (EG)
usually a single self-limited lesion found in younger patients
Hand-Schuller-Christian disease (HSC) chronic disseminated form with bone and visceral lesions also known as Langerhans cell histiocytosis with visceral
involvement Letterer-Siwe disease (LSD)
fatal form that occurs in young children
Eosinophilic granuloma
Epidemiology demographics
most commonly occurs in children (80 of afflicted lt 20 years of age)
HSC disease presents in children gt 3 years of age LSD occurs in children lt 3 years of age Male to female ratio of 21
location eosinophilic granuloma
commonly presents in the skull ribs clavicle scapula mandible
isolated lesions of the spine (thoracic most common) can also occur in diaphyseal regions of long bones and the
pelvis HSC
multiple bony sites multiple lytic skull lesions visceral involvement of the lungs spleen liver skin lymph
nodes
Genetics no clear genetic pattern of inheritance or locus has
been determined Prognosis
EG isolated involvement generally treatable with local
management spine lesions can spontaneously resolve
HSC prognosis depends on response to chemotherapy worsening prognosis with increasing extraskeletal
involvement LSD
generally fatal in children lt 3 years of age
Symptoms skeletal involvement
pain and swelling at the region of involvement limping can be seen with pelvic or lower extremity
involvement vertebral involvement
localized or diffuse back pain increasingly kyphotic posture radiculopathy can occur with more aggressive lesions
HSC classic triad of
multiple lytic skull lesions diabetes insipidus
increased thirst and water intake exopthalmos
visceral involvement diffuse or nonspecific abdominal or chest pain
Radiographs general
known as the great mimicker as it appears similar to many lesions radiographic differential includes osteomyelitis leukemia lymphoma
fibrous dysplasia or Ewings sarcoma diaphyseal lesions
well defined intramedullary lytic or punched-out lesion cortex may be thinned expanded or destroyed may have periosteal reaction
metaphyseal lesions extend up to but not through the physis less central location than diaphyseal lesions
spinal lesions vertebra plana (flattened vertebrae) in spine increased kyphosis
cranial involvement multiple punched-out lytic lesions
MRI may show a soft tissue mass adjacent to boney lesions
Bone scan generally shows increased uptake in the region of boney lesion
Histology Langerhans cells
mononuclear histiocyte-like cells with oval nuclei with well-defined round or oval cytoplasm
a prominent nuclear groove (coffee bean nuclei) can be seen in most of the nuclei
eosinophilic cytoplasm (pink generally) stain with CD1A electronmicroscopy
birbeck granules seen inside Langerhans cells mixture of inflammatory cells also present giant cells are present lack of nuclear atypia and atypical mitoses
differentiates this condition from malignant conditions such as Ewings sarcoma lymphoma of bone and metastatic neuroblastoma which may look similar based on the round cells alone
eosinophilic cytoplasm (pink generally)
Treatment
bullNonoperative bull observation alone
bull indications bull a self-limited process and it is reasonable to treat with observation alone
bull bracing bull indications
bull to prevent progressive kyphosis of the spinebull outcomes
bull will correct deformity in 90 of patientsbull vertebral lesions generally regain 50 of their height
bull low dose irradiation (600-800 cGy) bull indications
bull indicated for lesions in the spine that compromise stability neurologic statusbull lesions not amenable to injection or open treatment
bull outcomes bull effective for most lesions
bull chemotherapy bull indications
bull diffuse HSCbull outcomes
bull prognosis is improved with less severe extraskeletal involvementbull corticosteroid injection
bull indications bull isolated lesions bull can be performed after curettage as well
Operative curettage and bone grafting
indications for lesions that endanger the articular surface or are a risk for
impending fractures spinal deformity correction
indications progressive spine deformity refractory to bracing
approximately 10 of patients with spine lesion will need operative intervention for deformity correction
Destructive multiple lesion in young patientsAre eosinophilic granuloma lymphoma and leukemiaLymphoma is unlikely to present with exopthalmos diabetes insipidus or vertebra plana Lymphoma bone lesions are lytic and appear moth eatenpermeative on radiographs
Figure A shows a skin lesion typical of eosinophillic granuloma Figure B shows a lytic lesions without significant surrounding sclerosis as is characteristic of eosinophilic granuloma Figure C shows the characteristic histology of multiple eosinophils with their characteristic oval coffee bean nuclei and staining pattern of purpleredpink cytoplasm (depending on the stain) Importantly the histology slide lacks a malignant appearance (no cellular atypia or mytotic complexes and low nuclearcytoplasmic ratio)
Formation of bone in atypical extraskeletal tissues usually occurs
spontaneously or following trauma within 2 months of neurologic injury (brain or spinal cord)
most common location is between muscle and joint capsule Epidemiology
incidence (see table below)
demographics malefemale = 21 especially men with hypertrophic osteoarthritis and women gt65y
location traumatic brain injury or stroke
hip gt elbow gt shoulder gt knee elbow HO more common following brain trauma
occurs on affected (spastic) side rarely in the knee (TBI)
spinal cord injury hip gt knee gt elbow gt shoulder hip flexors and abductors gt extensors or adductors medial aspect of the knee
Heterotopic Ossification
Risk factors
Pathophysiology exact cause of HO is not known but there appears to be a
genetic pre disposition experimental HO associated with
tissue expression of BMP IT IS SAID TO BE CAUSED BY activation and proliferation of
mesenchymal stem cells Associated conditions
orthopaedic manifestations pathologic fractures
from decreased joint ROM and osteoporotic bone nerve impingement soft tissue contractures contributing to the formation of
decubitus ulcers joint ankylosis HO after THA adversely affects outcome of THA
nonorthopaedic conditions skin maceration and hygiene problems
Pathophysiology Early in the formation of HO oedema with exudative
infiltrate is present followed by fibroblastic proliferation and immature connective tissue formation Posteriorly osteoid formation is seen with the subsequent deposition of bone matrix Primitive osteoid is deposited as small masses in the periphery early (within the first two weeks) and osteoblasts are noted located irregularly Osteoblasts produce tropocollagen which polymerizes to form collagen and secrete alkaline phosphatase which allows calcium to precipitate and the mineralization of bone matrix As mineralization progresses amorphous calcium phosphate is progressively replaced by hydroxyapatite crystals During the following weeks the lesion matures with a centripetal pattern and after 6-12 months an appearance of true bone is noted The new bone is always extra-articular and can be contiguous with the skeleton but generally does not involve the periosteum
IN SUMMARY It has been postulated that three conditions
must be met to achieve heterotopic bone formation ---a stimulating event oestrogenic precursor cells and a proper environment LIKE hypercalcaemia tissue hypoxia pH changes (alkalosis) or prolonged immobilization
ClassificationbullSubtypes
bull neurogenic HO bull Four clinical stages of HO in people with spinal cord injury were
described by Nicholas in 1973
bull traumatic myositis ossificans bull fibrodysplasia ossificans progressiva (Munchmeyers Disease)
Neurogenic HO Symptoms
painless loss of ROM interferes with ADL CRPS symptoms fever
Physical exam inspection
warm painful swollen joint may have effusion skin problems
decubitus ulcers from contractures around skin muscles ligaments
skin maceration and hygiene problems motion
decreased joint ROM joint ankylosis with HO after TKA might develop quad muscle snapping or patella
instability neurovascular
peripheral neuropathy HO often impinges on adjacent NV structures
Imaging
bullRadiographs bull findings
bull ossification usually easy to visualize bull maturity of HO
bull the appearance of a bony cortex suggests mature HObull sharp demarcation from surrounding tissue bull trabecular pattern
bull sensitivity and specificity bull not useful for early diagnosisbull only useful at 1 week after onset of symptoms
bull calcium is deposited 7-10 days later than symptom onsetbullUltrasound
bull indications bull for early diagnosis of hip HO
bull findings bull echogenic surfaces with posterior acoustic shadowing
bullCT bull indications
bull useful for preoperative planning bullTriphasic bone scan
bull indications bull best for early diagnosis bull most commonly used diagnostic study
Radiographs are extremely useful in the staging of heterotopic ossification and will show the development of sharp cortical margins once the lesion has reached maturity
Heterotopic bone is a condition in which lamellar bone forms in non-ossified soft tissues In the early stages studies such as MRI and bone scan are more sensitive for diagnosis as radiographs may appear normal for the first three weeks After the appropriate diagnosis is made sequential radiographs are useful for monitoring the progression of the ossification Once it has reached the mature stage sharp cortical margins will appear and surgical resection may be considered
lab
Labs elevated serum alkaline phosphatase (gt250IUL)
ALP removes inhibitors of mineralization nonspecific may be elevated with skeletal trauma cannot determine maturity of HO elevated 12wks after surgery is predictor
elevated CRP correlates with inflammatory activity of HO better than ESR normalization of CRP may correlate with maturity of HO
elevated ESR (gt35mmh) 12wks after THA is predictor
elevated CK correlates with involvement of muscle extent of muscle
involvement Histology
mature fatty bone marrow mature trabecular bone
Heterotopic ossification (HO) most commonly occurs at the amputation site if the amputation was performed thru the zone of injury especially if the injury was a blast mechanism
Symptomatic heterotopic ossification of the quadriceps may occur following placement of a large-diameter Steinmann pin for the purpose of temporary skeletal traction
TreatmentThe prevention of heterotopic ossification is focused on three basic principles disrupting the inductive signalling pathways altering the osteoprogenitor cells or modifying the environment
bullphysiotherapy should involve an assisted range of movement exercises with gentle stretch and terminal resistance trainingbullProphylaxis
bull bisphosphonates amp NSAIDS bull indications
bull although no literature supports are commonly usedbull technique
bull indomethacin is most commonly used bull dose is 75mgday for 10days to 6 weeks
bull perioperative radiation bull indications
bull although no literature supports commonly usedbull is thought to be effective by blocking osteoblast differentiation
bull technique bull a single perioperative dose of 700cGy can be given either 4
hours preop or within 72 hours postoperatively bull lt550cGy not effective
Nonsteroidal anti-inflammatory drugs (NSAIDs) These drugs have demonstrated good results in
preventing heterotopic ossification after total hip arthroplasty
A direct effect of NSAIDs on the formation of heterotopic ossification has been described due to the inhibition of the differentiation of mesenchymal cells into oestrogenic cells There is also an indirect effect which refers to the inhibition of bone remodelling by suppression of the prostagland unmediated inflammatory response (specifically PGE-2)
Indomethacin has been considered a useful medication for heterotopic ossification prophylaxis following total hip replacement
prescribed for three to six weeks in a dose of 75mgday within two months of the injury may reduce the incidence of heterotopic ossification by two to three times
Biphosphonates inhibits precipitation of calcium phosphate and blocks the aggregation and mineralisation of hydroxyapatite crystals In primary prevention Banovac et al [56] have suggested that the treatment should begin as soon as elevated alkaline phosphatase is diagnosed or positive findings in ultrasonography or bone scans are shown In addition disphosphonates could have long-term effects on prevention when the treatment is finished
Posttraumatic wide exposure and surgical resection
indications severe loss of motion and decreased function
technique wide exposure required to identify all neurovascular
structures that may be involved timing of resection (controversial)
marked decrease in bone scan activity AND normalization of ALP
6 months following general trauma 1 year following SCI 15 years following TBI
some data suggests equivalent results when comparing early versus late resection
postop follow with 5 day course of indomethacin early gentle joint mobilization
The surgery is necessary in patients with symptomatic HO and unsuccessful medical treatment such as
Loss of range of motion and ankylosis with associated functional disability such as sitting difficulties
Complications of immobility such as pressure ulcers
Facilitate rehabilitation and recovery of muscular atrophy secondary to prolonged immobilisation
Difficulties of appropriate hygiene because access to the perineum or bladder care is needed
Severe pain refractory to analgesia Vascular andor nerve compression
Advantages to early excision of heterotopic ossification (vs waiting for maturation) include decreased soft tissue contracture better definition between heterotopic and native bone and decreased waiting time for the patient When the soft tissue envelope is benign one may proceed with operative release While waiting for normalization of alkaline phosphatase levels inactivity on bone scan or radiographic maturity may decrease risk of recurrent heterotopic ossification delaying operative release for these reasons has not been shown to improve results of final elbow range of motion after contracture release
Gartland recommended surgery after six months following traumatic heterotopic ossification one year following spinal cord injury and 18 months after head injury
In the past waiting until maturity in order to minimize the rate of recurrence after the surgical treatment was recommended Nevertheless recent studies do not confirm a higher rate of recurrence when the HO is excised in an earlier phase In addition a long delay before surgery leads to ankylosis a high degree of osteoporosis and more extensive intra-articular injuries These findings are associated with bad functional results and potential complications
Should you wait till lesion maturation
Prevention byHandle tissue carefully Avoid excess bleeding Achieve good hemostasis Beware of lesions that span internervous tissue planes
but if it happens resection of a large enough amount of bone to allow improvement of the range of motion and trying to preserve the joint
Our aim must be
A reactive process that is characterized by a well-circumscribed proliferation of fibroblasts cartilage and bone within muscle
A form of heterotopic ossification that is the result direct trauma intramuscular hematoma
most common location is the diaphysis of long bones Must differentiate from tumors Fibrodysplasia ossificans progressiva (FOP) is a rare subtype of heterotopic ossification
involves mutation of the ACVR1 gene (activin A type I receptor gene a BMP type-1 receptor)
Epidemiology demographics
most common in young active males (15 to 35 years old) body locations
quadriceps brachialis and gluteal muscles Genetics
almost always a posttraumatic condition Prognosis
usually self limiting mass usually begins to decrease in size after 1 yea
Myositis ossificans
PresentationbullSymptoms
bull pain tenderness swelling and decreased range of motion that usually presents within days of the injury
bull pain and size of the mass decrease with timebull mass increases in size over several months(usually 3 to 6 cm)
bull after the mass stops growing it becomes firmbullPhysical exam
bull palpable soft tissue massbull restricted range of motion
ImagingbullRadiographs
bull peripheral bone formation with central lucent areabull may appear as dotted veil pattern
bullMRI with gadolinium bull rim enhancement is seen within the first 3 weeks
bullCT scan bull lesion has an eggshell appearance
bullCharacteristic histology shows zonal pattern bull periphery of lesion
bull mature trabeculae of lamellar and woven bonebull calcification seen on xray
bull center of the lesion bull irregular mass of immature fibroblastsbull cartilage component may be presentbull (no calcification seen on xray) bull no cellular atypia seen
Treatment
bullNonoperative bull rest range of motion exercises and activity modification
bull passive stretching is contraindicated (makes it worse)bull physical therapy
bull utilized to maintain range of motionbull radiographic monitoring
bull obtained to confirm maturation of the lesionbullOperative
bull surgical excision bull indicated only if it remains a problem after it maturesbull do not operate in acute phase wait at least six months
bull excision of the lesion within 6 to 12 months predisposes to local recurrence
A 26-year-old man presents with generalized back and joint stiffness and difficulty opening his mouth His elder sister has similar complaints Since childhood he has had 3 surgeries for excision of recurrent bony prominences around his knees He walks with a stooped over posture seen in Figure A Radiographs of his feet knee hip and spine are seen in Figures B-E respectively
fibrodysplasia ossificans progressiva
Stone Man Disease) which involves a mutation of the ACVR1
There are 2 hallmark characteristics progressive heterotopic ossification (muscles fascia tendons ligaments and joint capsules) and congenital malformation of the great toe (hallux valgus malformed first metatarsal and monophalangism) BMP4 which contributes to the formation of the skeleton in the normal embryo is implicated in this disease
Complications
bullHematoma and intraoperative bleedingbullInfection
bull higher rate of infection following joint arthroplasty if HO is present
bullFractures of osteoporotic bone bull osteopenic from disusebull during surgery or physiotherapy
bullRecurrence bull recurrence rate correlates with neurological injury
bull greater recurrence if severe neurological compromisebullAVN
bull if extensive dissection or stripping is required
HTO AND ISS
When ISS is below 25 the mortality risk is minimal and above 25 it is an almost linear increase
When ISS is 50 the mortality is 50 When above 70 it is close to 100 If an injury is assigned an AIS of 6 (unsurvivable injury) the ISS score is
automatically assigned to 75 Highest ISS score obtainable is 75 For trauma patients of vehicular accidents the scoring system is important
for assessing the effectiveness of medical care in reducing morbidity and mortality
Advantages virtually the only anatomical scoring system in use correlates linearly with
mortality morbidity hospital stay other measures of severity
Weaknesses Any error in AIS scoring increases the ISS error Many different injury patterns can yield the same ISS score Injuries to different body regions are not weighted Not a useful triage tool as a full description of patient injuries is not known
prior to full investigation amp operation
risk factors periosteal stripping off anterior femur male gender obesity post traumatic deformity Anterior and anterolateral approach Cementless
Neurogenic HO around the hip due to SCI occurs more often in the medial region than in the lateral region with ossified tissues extending from the pubic symphysis to the anteromedial femoral shaft posterior to the femoral neurovascular structures Ossification is also seen anteriorly involving the iliopsoas and femoral neurovascular structures laterally within gluteus minimus and posteriorly extending from the ilium to the posterior femur encasing the sciatic nerve
HTO AROUND hip and knee
The Brooker Classification of Heterotopic Ossification around the hip joint Class I has islands of bone within the soft tissues Class II has bone spurs from the pelvis or proximal end of the femur leaving at least 1 cm between opposing surfaces Class III has bone spurs from the pelvis andor proximal end of the femur reducing the space between opposing bone surfaces to less than 1 cm Class IV shows apparent bone ankylosis of the hip
Region I - Heterotopic ossifications are strictly below the tip of the greater trochanter
Region II - Heterotopic ossifications are below and above the tip of the greater trochanter
Region III - Heterotopic ossifications are strictly above the tip of the greater trochanter
Grade A - Single or multiple heterotopic ossifications are less than 10 mm in maximal extent without contact with the pelvis or the femur
Grade B - Heterotopic ossifications are greater than 10 mm without contact with the pelvis but with possible contact with the femur there is no bridging from the femur to the proximal part of the greater trochanter and no evidence of ankylosis
Grade C - Ankylosis by means of firm bridging from the femur to the pelvis is present
Shmidt classification
excision may be performed The results of this procedure are varied Patients may find that their range of movement improves but pain relief is likely to be limited
A patient with heterotopic ossification following total hip arthroplasty is thought to have a 90-100 chance of developing it on the contralateral hip if this hip also undergoes total arthroplasty
it would be prudent to minimize the risk of heterotopic ossification developing after arthroplasty by performing surgery whereby the following are ensured
Exposure is meticulous Retraction is performed carefully and soft tissue
is handled carefully Irrigation is adequate Devitalized tissue is excised Hemostasis is adequate Postoperative drains (when used) are not
retained for longer than necessary Perioperative antibiotic prophylaxis is used Postoperative anticoagulation (when used for
deep vein thrombosis prophylaxis) is carefully controlled
sources of knee stiffness 1-extrinsic severe osteoarthritis of the ipsilateral hip neurologic injury leading to muscle rigidity tight quadriceps or hamstring muscles secondary to muscle injury heterotopic ossification or long-standing juvenile inflammatory conditions limiting knee
range of motion prior to the completion of skeletal growth When extrinsic sources are identified revision total knee arthroplasty is unlikely to be associated with a favorable outcome without correction of the extrinsic problem
2-intrinsic (1) overstuffing of the patellofemoral articulation (2) an
excessively tight flexion andor extension gap (3) a tight posterior cruciate ligament (4) femoral andor tibial malrotation (5) arthrofibrosis and (6) limited bearing excursion in association with a highly conforming mobile-bearing prosthetic design
HTO after TKA
Heterotopic Ossification (HO) following primary Total Knee Replacement (TKR)
Occurs in 3-90 of TKRs 3-grade classification system No correlation between HO and component
alignment or component position
Clinical findings similar to early infection Continuing low-grade fever Warm swollen and erythematous knee Normal blood tests Possibly an association with HLA-A2 and B18 HO patients have worse KSS and function
scores
Patients at HIGH risk for developing HO after TKR (Knee Arthroplasty) (5)
Those with limited postoperative knee flexion
Increased lumbar bone mineral density (BMD) on multivariate analysis (3)
Hypertrophic arthrosis Excessive periosteal trauma Notching of the anterior femur Those who require forced manipulation
after TKA 47 in revision TKR surgery (6) Higher rates in revision TKR cases with
infection (up to 76
DaughertyBell classification of HO of the knee 0 No evidence of HO 1 Bone islands in periarticular soft tissue (no
involvement of femur patella or tibia) or HO within quadriceps expansion measuring lt1 cm
2 Spur formation measuring lt5 cm that involves the femur patella or tibia if more than one bone demonstrates HO separation of HO spurs
measure gt1 cm or HO within quadriceps expansion measuring ge1 cm but lt3 cm
3 Spur formation gt5 cm involving femur patella or tibia if more than one bone demonstrates HO separation of HO spurs measure lt1 cm or HO
within quadriceps expansion measuring ge3 cm 4 Extensive HO of the knee causing ankylosis
class 2 HO begins to involve the major bones of the knee joint with spur formation limited to a size of 5 cm
HO class 2 may be observed in select patients with complete ROM and no reported pain Patients with class 3 HO would likely always benefit from surgical excision
followed by RT prophylaxis Certainly patients in either cohort with a subclass ldquoBrdquo assignment (symptomatic) would
benefit from treatment All patients with class 4 HO require
treatment to alleviate ankylosis
treatment
References Whyte ldquoPagetrsquos Disease of Bonerdquo NEMJ vol 355
2006 Klein and Parvizi ldquoSurgical Manifestations of Pagetrsquos
Diseaserdquo JAAOS vol 14 2006 Orthobullets Campbell Apley Emedicinecom
-Chapter 15 Heterotopic Ossification after Traumatic Brain InjuryBy Jesuacutes Moreta and Joseacute Luis Martiacutenez-de los Mozos DOI 10577257343
Questions
Thank You
Fracture
Arthropathy
uarrincidence of joint disease 1048710Specific pattern of joint diseases in hip uarrfreq of coxa vera protrusio concentric joint space narrowing
uarrSkin temperature
Hypervascularity due to uarrbone turnover activity
uarrbone turnover causes uarrcardiac demands and may lead to high-output heart failure
High-output cardiac failure is caused by the numerous arteriovenous fistulas present in the pagetic bones
Neurologic complaints
Hearing lossvertigotemporal bone involvement with auditory nerve compression
1048710Cranial nerve palsies 1048710Spine involvementMechanical cord compression ldquovascular steal
Hypercalcemia
Rare 1048710Usually inactive or bed-ridden patients 1048710Signs amp SymptomsNausea vomiting MSK aches hyper-reflexia weakness
polyuria headache lethargy altered mental status hellipcoma
Malignant transformation Pagets sarcoma
less than 1 will develop malignant Pagets sarcoma (secondary sarcoma)
osteosarcoma is the most common followed by fibrosarcoma and chondrosarcoma
most common in pelvis femur and humerus Pagets sarcoma has a poor prognosis
5-year survival for non-metastatic Pagets sarcoma is less than 5 appropriate treatment for Pagets sarcoma includes chemotherapy
and wide surgical resection Pagets sarcoma typically presents as a destructive lesion without
periosteal reaction
Diagnosis Clinical assessment Characteristic radiographic appearance Labs (uarrAlkPhos) Bone Scan Usually benign and multiple lesions in old
patients are pagets hyperparathyroidism and bone infarcts
Rarely CT MRI Biopsy
Long bones bend across the trajectories of mechanical stress thus the tibia bows anteriorly and the femur anterolaterally The limb looks bent and feels thick and the skin is unduly warm ndash hence the term lsquoosteitisdeformansrsquo If the skull is affected it enlarges the patient may complain that old hats no longer fit The skull base may become flattened (platybasia) giving the appearance of a short neck In generalized Pagetrsquos disease there may also be considerable kyphosis so the patient becomes shorter and ape-like with bent legs and arms hanging in front of him Cranial nerve compression may lead to impaired vision facial palsy trigeminal neuralgia or deafness Another cause of deafness is otosclerosisVertebral thickening may cause spinal cord or nerve root compression Steal syndromes in which blood is diverted from internal organs to the surrounding skeletal circulationmay cause cerebral impairment and spinal cord ischaemia If there is also spinal stenosis the patient develops typical symptoms of lsquospinal claudicationrsquo and lower limb weakness
Radiographs coarsened trabeculae which give the bone a blastic
appearance both increased and decreased osteodensity may exist
depending on phase of disease lytic phase
lucent areas with expansion and thinned intact cortices blade of grass or flame-shaped lucent advancing edge
mixed phase combination of lysis and sclerosis with coarsened trabeculae
sclerotic phase bone enlargement with cortical thickening sclerotic and lucent
area
remodeled cortices loss of distinction between cortices and medullary cavity
long bone bowing bowing of femur or tibia
fractures hip and knee osteoarthritis osteitis circumscripta
(cotton wool exudates) in skull Pagets secondary sarcoma
shows cortical bone destruction soft tissue mass
MRI may show lumbar spinal stenosis
Bone scan accurately marks site of disease intensely hot in lytic and mixed phase less hot in sclerotic phase
CT scan cortical thickening and coarsened trabeculae
CTMRI Incidental finding Evaluation of atypical presentations
neurological involvement and possible malignant transformation
CT trabecularcortical thinning thickening irregularity
MRI non-specific marrow changes
BiochemistrySerum AlkPhosEnzyme found in osteoblastic membrane Indicator of osteoblastic activity uarrin Pagetrsquos but can be normal Levels correlate with disease extent and activity elevated urinary hydroxyproline (collagen breakdown marker) increased urinary N-telopeptide alpha-C-telopeptide
and deoxypyridinoline normal calcium levels
Other recommended tests ESR -elevation may indicate malignant transformation
CRP Ca -hypercalcemiamay occur in Pagetrsquos PO4 25-hydroxyvitamin D -rule out osteomalacia LFTs-rule out liver disease
Diagnostic Biopsy Diagnosis is usually achieved clinically and by
plain radiographic appearance Biopsy rarely required
Characteristic HistopathologyDisorganized immature trabeculararchitecture with irregular cement lines (ldquomosaicrdquopattern)
Rimming osteoblasts andor multinucleated osteoclasts
Management Options (May require no treatment if asymptomatic)
Supportive Care Pharmacologic Surgical (OrthopedicNeurosurgical
Supportive Care Occupational therapy Physical aides Counseling for fall+fracture prevention
Physical therapy Analgesics Weight control
Pharmacologic ManagementGoals Relieve symptoms and Prevent potential
complications Normalization of serum AlkPhos associated
with better long-term outcomes and disease control
Indications to treat Pain Deformity Neurologic symptoms Asymptomatic but high-risk for complications
(prophylactic) Management of hypercalcemia(rare) Pre-op reduce blood flow and potential
operative blood loss
Calcitonin is the most widely used It reduces bone resorption by decreasing both the activity and the number
of osteoclasts serum alkaline phosphatase and urinaryhydroxyproline levels are lowered Salmon calcitonin is more effective than the porcine variety subcutaneous injections of 50ndash100 MRC units are given daily until pain is relieved and the alkaline phosphatase levels are reduced and stabilized Maintenance injections once or twice weekly may have to be continued indefinitely but some authorities advocate stopping the drug and resuming treatment if symptoms recur Calcitonin can also be administered in a nasal spray Bisphosphonates bind to hydroxyapatite crystals
inhibiting their rate of growth and dissolution It is claimed that the reduction in bone turnover following their use is associated with the formation of lamellar rather than woven bone and that even after treatment is stopped there may be prolonged remission of disease (Bickerstaff et al 1990) Etidronate can be given orally (always on an empty stomach) but dosage should be kept low (eg 5 mgkg per day for up to 6 months) and vitamin D and calcium should also be given lest impaired bone mineralization results inosteomalacia The newer bisphosphonates (eg alendronate or pamidronate) do not have this disadvantage so they should be used as the treatment of choice they produce remissions even with shortcourses of 1 or 2 weeks
BisphosphonatesSynthetic analogues of inorganic phosphate adhere to mineralized surfaces
Ingested selectively by osteoclasts Disrupts enzyme pathways and reduces osteoclastic bone resorption
calcitonin causes osteoclasts to shrink in size and decreases their bone resorptive activity within minutes administered subcutaneously or intramuscularly
teriparatide is contraindicated in Pagets disease due to risk of secondary osteosarcoma
Surgical Management Few require surgery
Common Procedures Corrective osteotomy of long bone deformity indications
fractures through pathologic bowing of long bones impending pathologic fracture of long bone with bowing deformity
Arthroplasty (hip knee) the most common complications include
malalignment with knee arthroplasty bleeding with hip arthroplasty
Combination arthroplasty with osteotomy Fracture fixation
Preoperative Considerations Medical assessment for extraskeletalmanifestations eg high-
output heart failure
Medical treatment of active disease Preoperative autologousblood donation
Thorough planningeg good quality x-rays for templatingand device selection
Intraoperative Considerations Blood salvage system Expansileapproach + soft tissue release Sharp reamersburrsdrills for IM access Extramedullaryguidenavigation systems Concomitant osteotomy
PostoperativeConsiderations Monitoring for cardiac complications Continued medical tx of active disease
uarrHeterotopic ossification Prophylaxis against HO
Possible future excision of HO for painROM
1-Tieg provides a review of Pagets disease of bone and treatment indications In his review he discusses that most patients with Pagets disease are asymptomatic but in those that do present pain is the most common presenting symptom He recommends medical and surgical treatment of asymptomatic patients who have active disease at sites where complications are likely to develop
Altman did a review of 290 patients with Pagets disease of bone His findings showed 83 had one or more rheumatic syndromes He found the rate of osteoarthritis related to Pagets disease was elevated in the hip and knee Rheumatoid arthritis hyperuricemia and gout did not appear increased in this group
Mangham et al looked the rate of secondary sarcomas as a result of Pagets disease of bone They found the rate to be around 03 with male predominance They also found that widespread skeletal involvement by Pagets disease was not a significant risk factor for malignant transformation
Interesting views about pagets
Smith et al reviewed the pathologic complications of Pagets bone disease Pagets bone disease commonly causes osseous weakening (deformity and fracture) and arthritis in the hip joint Management of end stage disease is successful with cemented and cementless total hip arthroplasty Bleeding is the most common intra- and post-operative complication of surgery
Gabel et al retrospectively reviewed thirteen patients who had had sixteen total knee arthroplasties for Pagetic gonarthrosis Unlike total hip arthroplasty surgery Paget disease did not increase the amount of blood lost during the operation or in the postoperative period The most common complication associated with total knee arthroplasty was malalignment
Hansen et al reviewed the incidence of osteosarcomas complicating Pagets Disease Of the typical sites that are usually involved in Pagets disease (eg spine pelvis femur tibia and humerus) secondary osteosarcoma tends to spare the spine
Shaylor et al reported the mortality rates in 26 patient with osteosarcoma secondary to Paget s disease There was a 47 mortality at 1 year and 75 at 2 years from diagnosis In their series no patient survived for 5 years All patients died of metastatic disease
Langston et al conducted a randomized trial that compared the results of symptomatic treatment versus intensive bisphosphonate therapy in patients with Pagets disease Clinical fractures occurred in 46 of 661 patients (70) in the treatment group compared with 49 of 663 patients (74) in the symptomatic treatment group They concluded that bisphosphonates did not show a significant beneficial impact on pain quality of life or fracture incidence
Hadjipavlou et al reviewed Pagets disease of the bone and its management Farmers have been shown to have an increased incidence of Pagets disease Average age at presentation is in the 5th and 6th decade Symptomatic individuals are recommended to be treated initially with medical management They suggest that bisphosphonates are more effective than calcitonin at suppressing the histological and biochemical activity in Pagetrsquos disease
Summary Epid Very common in elderly Path Abnormal osteoclastshellipuarrbone
turnoverhellipdeposition of abnormal bone SampS Pain deformity fracture arthropathy Labs uarrAlkPhos X-ray Characteristic coarse thickened
trabeculae Bone scan Very hot Rx Bisphosphonates Surgery for arthropathy fracture painful
deformity
A 65-year-old male presents with increasing shoulder pain over the past 9 months He is otherwise healthy and has no other complaints Radiograph of his shoulder is shown in Figure A Whole body bone scan and biopsy photograph are shown in Figures B and C What is the most appropriate treatment for this patient
1 Referral to endocrinology 2 Radiation therapy and chemotherapy 3 Wide resection and reconstruction 4 Radiation therapy wide resection and reconstruction 5 Chemotherapy wide resection and reconstruction
Histiocytosis X or Langerhans cell histiocytosis is a spectrum of diseases of the reticuloendothelial system with one of three general presentations Eosinophilic granuloma (EG)
usually a single self-limited lesion found in younger patients
Hand-Schuller-Christian disease (HSC) chronic disseminated form with bone and visceral lesions also known as Langerhans cell histiocytosis with visceral
involvement Letterer-Siwe disease (LSD)
fatal form that occurs in young children
Eosinophilic granuloma
Epidemiology demographics
most commonly occurs in children (80 of afflicted lt 20 years of age)
HSC disease presents in children gt 3 years of age LSD occurs in children lt 3 years of age Male to female ratio of 21
location eosinophilic granuloma
commonly presents in the skull ribs clavicle scapula mandible
isolated lesions of the spine (thoracic most common) can also occur in diaphyseal regions of long bones and the
pelvis HSC
multiple bony sites multiple lytic skull lesions visceral involvement of the lungs spleen liver skin lymph
nodes
Genetics no clear genetic pattern of inheritance or locus has
been determined Prognosis
EG isolated involvement generally treatable with local
management spine lesions can spontaneously resolve
HSC prognosis depends on response to chemotherapy worsening prognosis with increasing extraskeletal
involvement LSD
generally fatal in children lt 3 years of age
Symptoms skeletal involvement
pain and swelling at the region of involvement limping can be seen with pelvic or lower extremity
involvement vertebral involvement
localized or diffuse back pain increasingly kyphotic posture radiculopathy can occur with more aggressive lesions
HSC classic triad of
multiple lytic skull lesions diabetes insipidus
increased thirst and water intake exopthalmos
visceral involvement diffuse or nonspecific abdominal or chest pain
Radiographs general
known as the great mimicker as it appears similar to many lesions radiographic differential includes osteomyelitis leukemia lymphoma
fibrous dysplasia or Ewings sarcoma diaphyseal lesions
well defined intramedullary lytic or punched-out lesion cortex may be thinned expanded or destroyed may have periosteal reaction
metaphyseal lesions extend up to but not through the physis less central location than diaphyseal lesions
spinal lesions vertebra plana (flattened vertebrae) in spine increased kyphosis
cranial involvement multiple punched-out lytic lesions
MRI may show a soft tissue mass adjacent to boney lesions
Bone scan generally shows increased uptake in the region of boney lesion
Histology Langerhans cells
mononuclear histiocyte-like cells with oval nuclei with well-defined round or oval cytoplasm
a prominent nuclear groove (coffee bean nuclei) can be seen in most of the nuclei
eosinophilic cytoplasm (pink generally) stain with CD1A electronmicroscopy
birbeck granules seen inside Langerhans cells mixture of inflammatory cells also present giant cells are present lack of nuclear atypia and atypical mitoses
differentiates this condition from malignant conditions such as Ewings sarcoma lymphoma of bone and metastatic neuroblastoma which may look similar based on the round cells alone
eosinophilic cytoplasm (pink generally)
Treatment
bullNonoperative bull observation alone
bull indications bull a self-limited process and it is reasonable to treat with observation alone
bull bracing bull indications
bull to prevent progressive kyphosis of the spinebull outcomes
bull will correct deformity in 90 of patientsbull vertebral lesions generally regain 50 of their height
bull low dose irradiation (600-800 cGy) bull indications
bull indicated for lesions in the spine that compromise stability neurologic statusbull lesions not amenable to injection or open treatment
bull outcomes bull effective for most lesions
bull chemotherapy bull indications
bull diffuse HSCbull outcomes
bull prognosis is improved with less severe extraskeletal involvementbull corticosteroid injection
bull indications bull isolated lesions bull can be performed after curettage as well
Operative curettage and bone grafting
indications for lesions that endanger the articular surface or are a risk for
impending fractures spinal deformity correction
indications progressive spine deformity refractory to bracing
approximately 10 of patients with spine lesion will need operative intervention for deformity correction
Destructive multiple lesion in young patientsAre eosinophilic granuloma lymphoma and leukemiaLymphoma is unlikely to present with exopthalmos diabetes insipidus or vertebra plana Lymphoma bone lesions are lytic and appear moth eatenpermeative on radiographs
Figure A shows a skin lesion typical of eosinophillic granuloma Figure B shows a lytic lesions without significant surrounding sclerosis as is characteristic of eosinophilic granuloma Figure C shows the characteristic histology of multiple eosinophils with their characteristic oval coffee bean nuclei and staining pattern of purpleredpink cytoplasm (depending on the stain) Importantly the histology slide lacks a malignant appearance (no cellular atypia or mytotic complexes and low nuclearcytoplasmic ratio)
Formation of bone in atypical extraskeletal tissues usually occurs
spontaneously or following trauma within 2 months of neurologic injury (brain or spinal cord)
most common location is between muscle and joint capsule Epidemiology
incidence (see table below)
demographics malefemale = 21 especially men with hypertrophic osteoarthritis and women gt65y
location traumatic brain injury or stroke
hip gt elbow gt shoulder gt knee elbow HO more common following brain trauma
occurs on affected (spastic) side rarely in the knee (TBI)
spinal cord injury hip gt knee gt elbow gt shoulder hip flexors and abductors gt extensors or adductors medial aspect of the knee
Heterotopic Ossification
Risk factors
Pathophysiology exact cause of HO is not known but there appears to be a
genetic pre disposition experimental HO associated with
tissue expression of BMP IT IS SAID TO BE CAUSED BY activation and proliferation of
mesenchymal stem cells Associated conditions
orthopaedic manifestations pathologic fractures
from decreased joint ROM and osteoporotic bone nerve impingement soft tissue contractures contributing to the formation of
decubitus ulcers joint ankylosis HO after THA adversely affects outcome of THA
nonorthopaedic conditions skin maceration and hygiene problems
Pathophysiology Early in the formation of HO oedema with exudative
infiltrate is present followed by fibroblastic proliferation and immature connective tissue formation Posteriorly osteoid formation is seen with the subsequent deposition of bone matrix Primitive osteoid is deposited as small masses in the periphery early (within the first two weeks) and osteoblasts are noted located irregularly Osteoblasts produce tropocollagen which polymerizes to form collagen and secrete alkaline phosphatase which allows calcium to precipitate and the mineralization of bone matrix As mineralization progresses amorphous calcium phosphate is progressively replaced by hydroxyapatite crystals During the following weeks the lesion matures with a centripetal pattern and after 6-12 months an appearance of true bone is noted The new bone is always extra-articular and can be contiguous with the skeleton but generally does not involve the periosteum
IN SUMMARY It has been postulated that three conditions
must be met to achieve heterotopic bone formation ---a stimulating event oestrogenic precursor cells and a proper environment LIKE hypercalcaemia tissue hypoxia pH changes (alkalosis) or prolonged immobilization
ClassificationbullSubtypes
bull neurogenic HO bull Four clinical stages of HO in people with spinal cord injury were
described by Nicholas in 1973
bull traumatic myositis ossificans bull fibrodysplasia ossificans progressiva (Munchmeyers Disease)
Neurogenic HO Symptoms
painless loss of ROM interferes with ADL CRPS symptoms fever
Physical exam inspection
warm painful swollen joint may have effusion skin problems
decubitus ulcers from contractures around skin muscles ligaments
skin maceration and hygiene problems motion
decreased joint ROM joint ankylosis with HO after TKA might develop quad muscle snapping or patella
instability neurovascular
peripheral neuropathy HO often impinges on adjacent NV structures
Imaging
bullRadiographs bull findings
bull ossification usually easy to visualize bull maturity of HO
bull the appearance of a bony cortex suggests mature HObull sharp demarcation from surrounding tissue bull trabecular pattern
bull sensitivity and specificity bull not useful for early diagnosisbull only useful at 1 week after onset of symptoms
bull calcium is deposited 7-10 days later than symptom onsetbullUltrasound
bull indications bull for early diagnosis of hip HO
bull findings bull echogenic surfaces with posterior acoustic shadowing
bullCT bull indications
bull useful for preoperative planning bullTriphasic bone scan
bull indications bull best for early diagnosis bull most commonly used diagnostic study
Radiographs are extremely useful in the staging of heterotopic ossification and will show the development of sharp cortical margins once the lesion has reached maturity
Heterotopic bone is a condition in which lamellar bone forms in non-ossified soft tissues In the early stages studies such as MRI and bone scan are more sensitive for diagnosis as radiographs may appear normal for the first three weeks After the appropriate diagnosis is made sequential radiographs are useful for monitoring the progression of the ossification Once it has reached the mature stage sharp cortical margins will appear and surgical resection may be considered
lab
Labs elevated serum alkaline phosphatase (gt250IUL)
ALP removes inhibitors of mineralization nonspecific may be elevated with skeletal trauma cannot determine maturity of HO elevated 12wks after surgery is predictor
elevated CRP correlates with inflammatory activity of HO better than ESR normalization of CRP may correlate with maturity of HO
elevated ESR (gt35mmh) 12wks after THA is predictor
elevated CK correlates with involvement of muscle extent of muscle
involvement Histology
mature fatty bone marrow mature trabecular bone
Heterotopic ossification (HO) most commonly occurs at the amputation site if the amputation was performed thru the zone of injury especially if the injury was a blast mechanism
Symptomatic heterotopic ossification of the quadriceps may occur following placement of a large-diameter Steinmann pin for the purpose of temporary skeletal traction
TreatmentThe prevention of heterotopic ossification is focused on three basic principles disrupting the inductive signalling pathways altering the osteoprogenitor cells or modifying the environment
bullphysiotherapy should involve an assisted range of movement exercises with gentle stretch and terminal resistance trainingbullProphylaxis
bull bisphosphonates amp NSAIDS bull indications
bull although no literature supports are commonly usedbull technique
bull indomethacin is most commonly used bull dose is 75mgday for 10days to 6 weeks
bull perioperative radiation bull indications
bull although no literature supports commonly usedbull is thought to be effective by blocking osteoblast differentiation
bull technique bull a single perioperative dose of 700cGy can be given either 4
hours preop or within 72 hours postoperatively bull lt550cGy not effective
Nonsteroidal anti-inflammatory drugs (NSAIDs) These drugs have demonstrated good results in
preventing heterotopic ossification after total hip arthroplasty
A direct effect of NSAIDs on the formation of heterotopic ossification has been described due to the inhibition of the differentiation of mesenchymal cells into oestrogenic cells There is also an indirect effect which refers to the inhibition of bone remodelling by suppression of the prostagland unmediated inflammatory response (specifically PGE-2)
Indomethacin has been considered a useful medication for heterotopic ossification prophylaxis following total hip replacement
prescribed for three to six weeks in a dose of 75mgday within two months of the injury may reduce the incidence of heterotopic ossification by two to three times
Biphosphonates inhibits precipitation of calcium phosphate and blocks the aggregation and mineralisation of hydroxyapatite crystals In primary prevention Banovac et al [56] have suggested that the treatment should begin as soon as elevated alkaline phosphatase is diagnosed or positive findings in ultrasonography or bone scans are shown In addition disphosphonates could have long-term effects on prevention when the treatment is finished
Posttraumatic wide exposure and surgical resection
indications severe loss of motion and decreased function
technique wide exposure required to identify all neurovascular
structures that may be involved timing of resection (controversial)
marked decrease in bone scan activity AND normalization of ALP
6 months following general trauma 1 year following SCI 15 years following TBI
some data suggests equivalent results when comparing early versus late resection
postop follow with 5 day course of indomethacin early gentle joint mobilization
The surgery is necessary in patients with symptomatic HO and unsuccessful medical treatment such as
Loss of range of motion and ankylosis with associated functional disability such as sitting difficulties
Complications of immobility such as pressure ulcers
Facilitate rehabilitation and recovery of muscular atrophy secondary to prolonged immobilisation
Difficulties of appropriate hygiene because access to the perineum or bladder care is needed
Severe pain refractory to analgesia Vascular andor nerve compression
Advantages to early excision of heterotopic ossification (vs waiting for maturation) include decreased soft tissue contracture better definition between heterotopic and native bone and decreased waiting time for the patient When the soft tissue envelope is benign one may proceed with operative release While waiting for normalization of alkaline phosphatase levels inactivity on bone scan or radiographic maturity may decrease risk of recurrent heterotopic ossification delaying operative release for these reasons has not been shown to improve results of final elbow range of motion after contracture release
Gartland recommended surgery after six months following traumatic heterotopic ossification one year following spinal cord injury and 18 months after head injury
In the past waiting until maturity in order to minimize the rate of recurrence after the surgical treatment was recommended Nevertheless recent studies do not confirm a higher rate of recurrence when the HO is excised in an earlier phase In addition a long delay before surgery leads to ankylosis a high degree of osteoporosis and more extensive intra-articular injuries These findings are associated with bad functional results and potential complications
Should you wait till lesion maturation
Prevention byHandle tissue carefully Avoid excess bleeding Achieve good hemostasis Beware of lesions that span internervous tissue planes
but if it happens resection of a large enough amount of bone to allow improvement of the range of motion and trying to preserve the joint
Our aim must be
A reactive process that is characterized by a well-circumscribed proliferation of fibroblasts cartilage and bone within muscle
A form of heterotopic ossification that is the result direct trauma intramuscular hematoma
most common location is the diaphysis of long bones Must differentiate from tumors Fibrodysplasia ossificans progressiva (FOP) is a rare subtype of heterotopic ossification
involves mutation of the ACVR1 gene (activin A type I receptor gene a BMP type-1 receptor)
Epidemiology demographics
most common in young active males (15 to 35 years old) body locations
quadriceps brachialis and gluteal muscles Genetics
almost always a posttraumatic condition Prognosis
usually self limiting mass usually begins to decrease in size after 1 yea
Myositis ossificans
PresentationbullSymptoms
bull pain tenderness swelling and decreased range of motion that usually presents within days of the injury
bull pain and size of the mass decrease with timebull mass increases in size over several months(usually 3 to 6 cm)
bull after the mass stops growing it becomes firmbullPhysical exam
bull palpable soft tissue massbull restricted range of motion
ImagingbullRadiographs
bull peripheral bone formation with central lucent areabull may appear as dotted veil pattern
bullMRI with gadolinium bull rim enhancement is seen within the first 3 weeks
bullCT scan bull lesion has an eggshell appearance
bullCharacteristic histology shows zonal pattern bull periphery of lesion
bull mature trabeculae of lamellar and woven bonebull calcification seen on xray
bull center of the lesion bull irregular mass of immature fibroblastsbull cartilage component may be presentbull (no calcification seen on xray) bull no cellular atypia seen
Treatment
bullNonoperative bull rest range of motion exercises and activity modification
bull passive stretching is contraindicated (makes it worse)bull physical therapy
bull utilized to maintain range of motionbull radiographic monitoring
bull obtained to confirm maturation of the lesionbullOperative
bull surgical excision bull indicated only if it remains a problem after it maturesbull do not operate in acute phase wait at least six months
bull excision of the lesion within 6 to 12 months predisposes to local recurrence
A 26-year-old man presents with generalized back and joint stiffness and difficulty opening his mouth His elder sister has similar complaints Since childhood he has had 3 surgeries for excision of recurrent bony prominences around his knees He walks with a stooped over posture seen in Figure A Radiographs of his feet knee hip and spine are seen in Figures B-E respectively
fibrodysplasia ossificans progressiva
Stone Man Disease) which involves a mutation of the ACVR1
There are 2 hallmark characteristics progressive heterotopic ossification (muscles fascia tendons ligaments and joint capsules) and congenital malformation of the great toe (hallux valgus malformed first metatarsal and monophalangism) BMP4 which contributes to the formation of the skeleton in the normal embryo is implicated in this disease
Complications
bullHematoma and intraoperative bleedingbullInfection
bull higher rate of infection following joint arthroplasty if HO is present
bullFractures of osteoporotic bone bull osteopenic from disusebull during surgery or physiotherapy
bullRecurrence bull recurrence rate correlates with neurological injury
bull greater recurrence if severe neurological compromisebullAVN
bull if extensive dissection or stripping is required
HTO AND ISS
When ISS is below 25 the mortality risk is minimal and above 25 it is an almost linear increase
When ISS is 50 the mortality is 50 When above 70 it is close to 100 If an injury is assigned an AIS of 6 (unsurvivable injury) the ISS score is
automatically assigned to 75 Highest ISS score obtainable is 75 For trauma patients of vehicular accidents the scoring system is important
for assessing the effectiveness of medical care in reducing morbidity and mortality
Advantages virtually the only anatomical scoring system in use correlates linearly with
mortality morbidity hospital stay other measures of severity
Weaknesses Any error in AIS scoring increases the ISS error Many different injury patterns can yield the same ISS score Injuries to different body regions are not weighted Not a useful triage tool as a full description of patient injuries is not known
prior to full investigation amp operation
risk factors periosteal stripping off anterior femur male gender obesity post traumatic deformity Anterior and anterolateral approach Cementless
Neurogenic HO around the hip due to SCI occurs more often in the medial region than in the lateral region with ossified tissues extending from the pubic symphysis to the anteromedial femoral shaft posterior to the femoral neurovascular structures Ossification is also seen anteriorly involving the iliopsoas and femoral neurovascular structures laterally within gluteus minimus and posteriorly extending from the ilium to the posterior femur encasing the sciatic nerve
HTO AROUND hip and knee
The Brooker Classification of Heterotopic Ossification around the hip joint Class I has islands of bone within the soft tissues Class II has bone spurs from the pelvis or proximal end of the femur leaving at least 1 cm between opposing surfaces Class III has bone spurs from the pelvis andor proximal end of the femur reducing the space between opposing bone surfaces to less than 1 cm Class IV shows apparent bone ankylosis of the hip
Region I - Heterotopic ossifications are strictly below the tip of the greater trochanter
Region II - Heterotopic ossifications are below and above the tip of the greater trochanter
Region III - Heterotopic ossifications are strictly above the tip of the greater trochanter
Grade A - Single or multiple heterotopic ossifications are less than 10 mm in maximal extent without contact with the pelvis or the femur
Grade B - Heterotopic ossifications are greater than 10 mm without contact with the pelvis but with possible contact with the femur there is no bridging from the femur to the proximal part of the greater trochanter and no evidence of ankylosis
Grade C - Ankylosis by means of firm bridging from the femur to the pelvis is present
Shmidt classification
excision may be performed The results of this procedure are varied Patients may find that their range of movement improves but pain relief is likely to be limited
A patient with heterotopic ossification following total hip arthroplasty is thought to have a 90-100 chance of developing it on the contralateral hip if this hip also undergoes total arthroplasty
it would be prudent to minimize the risk of heterotopic ossification developing after arthroplasty by performing surgery whereby the following are ensured
Exposure is meticulous Retraction is performed carefully and soft tissue
is handled carefully Irrigation is adequate Devitalized tissue is excised Hemostasis is adequate Postoperative drains (when used) are not
retained for longer than necessary Perioperative antibiotic prophylaxis is used Postoperative anticoagulation (when used for
deep vein thrombosis prophylaxis) is carefully controlled
sources of knee stiffness 1-extrinsic severe osteoarthritis of the ipsilateral hip neurologic injury leading to muscle rigidity tight quadriceps or hamstring muscles secondary to muscle injury heterotopic ossification or long-standing juvenile inflammatory conditions limiting knee
range of motion prior to the completion of skeletal growth When extrinsic sources are identified revision total knee arthroplasty is unlikely to be associated with a favorable outcome without correction of the extrinsic problem
2-intrinsic (1) overstuffing of the patellofemoral articulation (2) an
excessively tight flexion andor extension gap (3) a tight posterior cruciate ligament (4) femoral andor tibial malrotation (5) arthrofibrosis and (6) limited bearing excursion in association with a highly conforming mobile-bearing prosthetic design
HTO after TKA
Heterotopic Ossification (HO) following primary Total Knee Replacement (TKR)
Occurs in 3-90 of TKRs 3-grade classification system No correlation between HO and component
alignment or component position
Clinical findings similar to early infection Continuing low-grade fever Warm swollen and erythematous knee Normal blood tests Possibly an association with HLA-A2 and B18 HO patients have worse KSS and function
scores
Patients at HIGH risk for developing HO after TKR (Knee Arthroplasty) (5)
Those with limited postoperative knee flexion
Increased lumbar bone mineral density (BMD) on multivariate analysis (3)
Hypertrophic arthrosis Excessive periosteal trauma Notching of the anterior femur Those who require forced manipulation
after TKA 47 in revision TKR surgery (6) Higher rates in revision TKR cases with
infection (up to 76
DaughertyBell classification of HO of the knee 0 No evidence of HO 1 Bone islands in periarticular soft tissue (no
involvement of femur patella or tibia) or HO within quadriceps expansion measuring lt1 cm
2 Spur formation measuring lt5 cm that involves the femur patella or tibia if more than one bone demonstrates HO separation of HO spurs
measure gt1 cm or HO within quadriceps expansion measuring ge1 cm but lt3 cm
3 Spur formation gt5 cm involving femur patella or tibia if more than one bone demonstrates HO separation of HO spurs measure lt1 cm or HO
within quadriceps expansion measuring ge3 cm 4 Extensive HO of the knee causing ankylosis
class 2 HO begins to involve the major bones of the knee joint with spur formation limited to a size of 5 cm
HO class 2 may be observed in select patients with complete ROM and no reported pain Patients with class 3 HO would likely always benefit from surgical excision
followed by RT prophylaxis Certainly patients in either cohort with a subclass ldquoBrdquo assignment (symptomatic) would
benefit from treatment All patients with class 4 HO require
treatment to alleviate ankylosis
treatment
References Whyte ldquoPagetrsquos Disease of Bonerdquo NEMJ vol 355
2006 Klein and Parvizi ldquoSurgical Manifestations of Pagetrsquos
Diseaserdquo JAAOS vol 14 2006 Orthobullets Campbell Apley Emedicinecom
-Chapter 15 Heterotopic Ossification after Traumatic Brain InjuryBy Jesuacutes Moreta and Joseacute Luis Martiacutenez-de los Mozos DOI 10577257343
Questions
Thank You
uarrSkin temperature
Hypervascularity due to uarrbone turnover activity
uarrbone turnover causes uarrcardiac demands and may lead to high-output heart failure
High-output cardiac failure is caused by the numerous arteriovenous fistulas present in the pagetic bones
Neurologic complaints
Hearing lossvertigotemporal bone involvement with auditory nerve compression
1048710Cranial nerve palsies 1048710Spine involvementMechanical cord compression ldquovascular steal
Hypercalcemia
Rare 1048710Usually inactive or bed-ridden patients 1048710Signs amp SymptomsNausea vomiting MSK aches hyper-reflexia weakness
polyuria headache lethargy altered mental status hellipcoma
Malignant transformation Pagets sarcoma
less than 1 will develop malignant Pagets sarcoma (secondary sarcoma)
osteosarcoma is the most common followed by fibrosarcoma and chondrosarcoma
most common in pelvis femur and humerus Pagets sarcoma has a poor prognosis
5-year survival for non-metastatic Pagets sarcoma is less than 5 appropriate treatment for Pagets sarcoma includes chemotherapy
and wide surgical resection Pagets sarcoma typically presents as a destructive lesion without
periosteal reaction
Diagnosis Clinical assessment Characteristic radiographic appearance Labs (uarrAlkPhos) Bone Scan Usually benign and multiple lesions in old
patients are pagets hyperparathyroidism and bone infarcts
Rarely CT MRI Biopsy
Long bones bend across the trajectories of mechanical stress thus the tibia bows anteriorly and the femur anterolaterally The limb looks bent and feels thick and the skin is unduly warm ndash hence the term lsquoosteitisdeformansrsquo If the skull is affected it enlarges the patient may complain that old hats no longer fit The skull base may become flattened (platybasia) giving the appearance of a short neck In generalized Pagetrsquos disease there may also be considerable kyphosis so the patient becomes shorter and ape-like with bent legs and arms hanging in front of him Cranial nerve compression may lead to impaired vision facial palsy trigeminal neuralgia or deafness Another cause of deafness is otosclerosisVertebral thickening may cause spinal cord or nerve root compression Steal syndromes in which blood is diverted from internal organs to the surrounding skeletal circulationmay cause cerebral impairment and spinal cord ischaemia If there is also spinal stenosis the patient develops typical symptoms of lsquospinal claudicationrsquo and lower limb weakness
Radiographs coarsened trabeculae which give the bone a blastic
appearance both increased and decreased osteodensity may exist
depending on phase of disease lytic phase
lucent areas with expansion and thinned intact cortices blade of grass or flame-shaped lucent advancing edge
mixed phase combination of lysis and sclerosis with coarsened trabeculae
sclerotic phase bone enlargement with cortical thickening sclerotic and lucent
area
remodeled cortices loss of distinction between cortices and medullary cavity
long bone bowing bowing of femur or tibia
fractures hip and knee osteoarthritis osteitis circumscripta
(cotton wool exudates) in skull Pagets secondary sarcoma
shows cortical bone destruction soft tissue mass
MRI may show lumbar spinal stenosis
Bone scan accurately marks site of disease intensely hot in lytic and mixed phase less hot in sclerotic phase
CT scan cortical thickening and coarsened trabeculae
CTMRI Incidental finding Evaluation of atypical presentations
neurological involvement and possible malignant transformation
CT trabecularcortical thinning thickening irregularity
MRI non-specific marrow changes
BiochemistrySerum AlkPhosEnzyme found in osteoblastic membrane Indicator of osteoblastic activity uarrin Pagetrsquos but can be normal Levels correlate with disease extent and activity elevated urinary hydroxyproline (collagen breakdown marker) increased urinary N-telopeptide alpha-C-telopeptide
and deoxypyridinoline normal calcium levels
Other recommended tests ESR -elevation may indicate malignant transformation
CRP Ca -hypercalcemiamay occur in Pagetrsquos PO4 25-hydroxyvitamin D -rule out osteomalacia LFTs-rule out liver disease
Diagnostic Biopsy Diagnosis is usually achieved clinically and by
plain radiographic appearance Biopsy rarely required
Characteristic HistopathologyDisorganized immature trabeculararchitecture with irregular cement lines (ldquomosaicrdquopattern)
Rimming osteoblasts andor multinucleated osteoclasts
Management Options (May require no treatment if asymptomatic)
Supportive Care Pharmacologic Surgical (OrthopedicNeurosurgical
Supportive Care Occupational therapy Physical aides Counseling for fall+fracture prevention
Physical therapy Analgesics Weight control
Pharmacologic ManagementGoals Relieve symptoms and Prevent potential
complications Normalization of serum AlkPhos associated
with better long-term outcomes and disease control
Indications to treat Pain Deformity Neurologic symptoms Asymptomatic but high-risk for complications
(prophylactic) Management of hypercalcemia(rare) Pre-op reduce blood flow and potential
operative blood loss
Calcitonin is the most widely used It reduces bone resorption by decreasing both the activity and the number
of osteoclasts serum alkaline phosphatase and urinaryhydroxyproline levels are lowered Salmon calcitonin is more effective than the porcine variety subcutaneous injections of 50ndash100 MRC units are given daily until pain is relieved and the alkaline phosphatase levels are reduced and stabilized Maintenance injections once or twice weekly may have to be continued indefinitely but some authorities advocate stopping the drug and resuming treatment if symptoms recur Calcitonin can also be administered in a nasal spray Bisphosphonates bind to hydroxyapatite crystals
inhibiting their rate of growth and dissolution It is claimed that the reduction in bone turnover following their use is associated with the formation of lamellar rather than woven bone and that even after treatment is stopped there may be prolonged remission of disease (Bickerstaff et al 1990) Etidronate can be given orally (always on an empty stomach) but dosage should be kept low (eg 5 mgkg per day for up to 6 months) and vitamin D and calcium should also be given lest impaired bone mineralization results inosteomalacia The newer bisphosphonates (eg alendronate or pamidronate) do not have this disadvantage so they should be used as the treatment of choice they produce remissions even with shortcourses of 1 or 2 weeks
BisphosphonatesSynthetic analogues of inorganic phosphate adhere to mineralized surfaces
Ingested selectively by osteoclasts Disrupts enzyme pathways and reduces osteoclastic bone resorption
calcitonin causes osteoclasts to shrink in size and decreases their bone resorptive activity within minutes administered subcutaneously or intramuscularly
teriparatide is contraindicated in Pagets disease due to risk of secondary osteosarcoma
Surgical Management Few require surgery
Common Procedures Corrective osteotomy of long bone deformity indications
fractures through pathologic bowing of long bones impending pathologic fracture of long bone with bowing deformity
Arthroplasty (hip knee) the most common complications include
malalignment with knee arthroplasty bleeding with hip arthroplasty
Combination arthroplasty with osteotomy Fracture fixation
Preoperative Considerations Medical assessment for extraskeletalmanifestations eg high-
output heart failure
Medical treatment of active disease Preoperative autologousblood donation
Thorough planningeg good quality x-rays for templatingand device selection
Intraoperative Considerations Blood salvage system Expansileapproach + soft tissue release Sharp reamersburrsdrills for IM access Extramedullaryguidenavigation systems Concomitant osteotomy
PostoperativeConsiderations Monitoring for cardiac complications Continued medical tx of active disease
uarrHeterotopic ossification Prophylaxis against HO
Possible future excision of HO for painROM
1-Tieg provides a review of Pagets disease of bone and treatment indications In his review he discusses that most patients with Pagets disease are asymptomatic but in those that do present pain is the most common presenting symptom He recommends medical and surgical treatment of asymptomatic patients who have active disease at sites where complications are likely to develop
Altman did a review of 290 patients with Pagets disease of bone His findings showed 83 had one or more rheumatic syndromes He found the rate of osteoarthritis related to Pagets disease was elevated in the hip and knee Rheumatoid arthritis hyperuricemia and gout did not appear increased in this group
Mangham et al looked the rate of secondary sarcomas as a result of Pagets disease of bone They found the rate to be around 03 with male predominance They also found that widespread skeletal involvement by Pagets disease was not a significant risk factor for malignant transformation
Interesting views about pagets
Smith et al reviewed the pathologic complications of Pagets bone disease Pagets bone disease commonly causes osseous weakening (deformity and fracture) and arthritis in the hip joint Management of end stage disease is successful with cemented and cementless total hip arthroplasty Bleeding is the most common intra- and post-operative complication of surgery
Gabel et al retrospectively reviewed thirteen patients who had had sixteen total knee arthroplasties for Pagetic gonarthrosis Unlike total hip arthroplasty surgery Paget disease did not increase the amount of blood lost during the operation or in the postoperative period The most common complication associated with total knee arthroplasty was malalignment
Hansen et al reviewed the incidence of osteosarcomas complicating Pagets Disease Of the typical sites that are usually involved in Pagets disease (eg spine pelvis femur tibia and humerus) secondary osteosarcoma tends to spare the spine
Shaylor et al reported the mortality rates in 26 patient with osteosarcoma secondary to Paget s disease There was a 47 mortality at 1 year and 75 at 2 years from diagnosis In their series no patient survived for 5 years All patients died of metastatic disease
Langston et al conducted a randomized trial that compared the results of symptomatic treatment versus intensive bisphosphonate therapy in patients with Pagets disease Clinical fractures occurred in 46 of 661 patients (70) in the treatment group compared with 49 of 663 patients (74) in the symptomatic treatment group They concluded that bisphosphonates did not show a significant beneficial impact on pain quality of life or fracture incidence
Hadjipavlou et al reviewed Pagets disease of the bone and its management Farmers have been shown to have an increased incidence of Pagets disease Average age at presentation is in the 5th and 6th decade Symptomatic individuals are recommended to be treated initially with medical management They suggest that bisphosphonates are more effective than calcitonin at suppressing the histological and biochemical activity in Pagetrsquos disease
Summary Epid Very common in elderly Path Abnormal osteoclastshellipuarrbone
turnoverhellipdeposition of abnormal bone SampS Pain deformity fracture arthropathy Labs uarrAlkPhos X-ray Characteristic coarse thickened
trabeculae Bone scan Very hot Rx Bisphosphonates Surgery for arthropathy fracture painful
deformity
A 65-year-old male presents with increasing shoulder pain over the past 9 months He is otherwise healthy and has no other complaints Radiograph of his shoulder is shown in Figure A Whole body bone scan and biopsy photograph are shown in Figures B and C What is the most appropriate treatment for this patient
1 Referral to endocrinology 2 Radiation therapy and chemotherapy 3 Wide resection and reconstruction 4 Radiation therapy wide resection and reconstruction 5 Chemotherapy wide resection and reconstruction
Histiocytosis X or Langerhans cell histiocytosis is a spectrum of diseases of the reticuloendothelial system with one of three general presentations Eosinophilic granuloma (EG)
usually a single self-limited lesion found in younger patients
Hand-Schuller-Christian disease (HSC) chronic disseminated form with bone and visceral lesions also known as Langerhans cell histiocytosis with visceral
involvement Letterer-Siwe disease (LSD)
fatal form that occurs in young children
Eosinophilic granuloma
Epidemiology demographics
most commonly occurs in children (80 of afflicted lt 20 years of age)
HSC disease presents in children gt 3 years of age LSD occurs in children lt 3 years of age Male to female ratio of 21
location eosinophilic granuloma
commonly presents in the skull ribs clavicle scapula mandible
isolated lesions of the spine (thoracic most common) can also occur in diaphyseal regions of long bones and the
pelvis HSC
multiple bony sites multiple lytic skull lesions visceral involvement of the lungs spleen liver skin lymph
nodes
Genetics no clear genetic pattern of inheritance or locus has
been determined Prognosis
EG isolated involvement generally treatable with local
management spine lesions can spontaneously resolve
HSC prognosis depends on response to chemotherapy worsening prognosis with increasing extraskeletal
involvement LSD
generally fatal in children lt 3 years of age
Symptoms skeletal involvement
pain and swelling at the region of involvement limping can be seen with pelvic or lower extremity
involvement vertebral involvement
localized or diffuse back pain increasingly kyphotic posture radiculopathy can occur with more aggressive lesions
HSC classic triad of
multiple lytic skull lesions diabetes insipidus
increased thirst and water intake exopthalmos
visceral involvement diffuse or nonspecific abdominal or chest pain
Radiographs general
known as the great mimicker as it appears similar to many lesions radiographic differential includes osteomyelitis leukemia lymphoma
fibrous dysplasia or Ewings sarcoma diaphyseal lesions
well defined intramedullary lytic or punched-out lesion cortex may be thinned expanded or destroyed may have periosteal reaction
metaphyseal lesions extend up to but not through the physis less central location than diaphyseal lesions
spinal lesions vertebra plana (flattened vertebrae) in spine increased kyphosis
cranial involvement multiple punched-out lytic lesions
MRI may show a soft tissue mass adjacent to boney lesions
Bone scan generally shows increased uptake in the region of boney lesion
Histology Langerhans cells
mononuclear histiocyte-like cells with oval nuclei with well-defined round or oval cytoplasm
a prominent nuclear groove (coffee bean nuclei) can be seen in most of the nuclei
eosinophilic cytoplasm (pink generally) stain with CD1A electronmicroscopy
birbeck granules seen inside Langerhans cells mixture of inflammatory cells also present giant cells are present lack of nuclear atypia and atypical mitoses
differentiates this condition from malignant conditions such as Ewings sarcoma lymphoma of bone and metastatic neuroblastoma which may look similar based on the round cells alone
eosinophilic cytoplasm (pink generally)
Treatment
bullNonoperative bull observation alone
bull indications bull a self-limited process and it is reasonable to treat with observation alone
bull bracing bull indications
bull to prevent progressive kyphosis of the spinebull outcomes
bull will correct deformity in 90 of patientsbull vertebral lesions generally regain 50 of their height
bull low dose irradiation (600-800 cGy) bull indications
bull indicated for lesions in the spine that compromise stability neurologic statusbull lesions not amenable to injection or open treatment
bull outcomes bull effective for most lesions
bull chemotherapy bull indications
bull diffuse HSCbull outcomes
bull prognosis is improved with less severe extraskeletal involvementbull corticosteroid injection
bull indications bull isolated lesions bull can be performed after curettage as well
Operative curettage and bone grafting
indications for lesions that endanger the articular surface or are a risk for
impending fractures spinal deformity correction
indications progressive spine deformity refractory to bracing
approximately 10 of patients with spine lesion will need operative intervention for deformity correction
Destructive multiple lesion in young patientsAre eosinophilic granuloma lymphoma and leukemiaLymphoma is unlikely to present with exopthalmos diabetes insipidus or vertebra plana Lymphoma bone lesions are lytic and appear moth eatenpermeative on radiographs
Figure A shows a skin lesion typical of eosinophillic granuloma Figure B shows a lytic lesions without significant surrounding sclerosis as is characteristic of eosinophilic granuloma Figure C shows the characteristic histology of multiple eosinophils with their characteristic oval coffee bean nuclei and staining pattern of purpleredpink cytoplasm (depending on the stain) Importantly the histology slide lacks a malignant appearance (no cellular atypia or mytotic complexes and low nuclearcytoplasmic ratio)
Formation of bone in atypical extraskeletal tissues usually occurs
spontaneously or following trauma within 2 months of neurologic injury (brain or spinal cord)
most common location is between muscle and joint capsule Epidemiology
incidence (see table below)
demographics malefemale = 21 especially men with hypertrophic osteoarthritis and women gt65y
location traumatic brain injury or stroke
hip gt elbow gt shoulder gt knee elbow HO more common following brain trauma
occurs on affected (spastic) side rarely in the knee (TBI)
spinal cord injury hip gt knee gt elbow gt shoulder hip flexors and abductors gt extensors or adductors medial aspect of the knee
Heterotopic Ossification
Risk factors
Pathophysiology exact cause of HO is not known but there appears to be a
genetic pre disposition experimental HO associated with
tissue expression of BMP IT IS SAID TO BE CAUSED BY activation and proliferation of
mesenchymal stem cells Associated conditions
orthopaedic manifestations pathologic fractures
from decreased joint ROM and osteoporotic bone nerve impingement soft tissue contractures contributing to the formation of
decubitus ulcers joint ankylosis HO after THA adversely affects outcome of THA
nonorthopaedic conditions skin maceration and hygiene problems
Pathophysiology Early in the formation of HO oedema with exudative
infiltrate is present followed by fibroblastic proliferation and immature connective tissue formation Posteriorly osteoid formation is seen with the subsequent deposition of bone matrix Primitive osteoid is deposited as small masses in the periphery early (within the first two weeks) and osteoblasts are noted located irregularly Osteoblasts produce tropocollagen which polymerizes to form collagen and secrete alkaline phosphatase which allows calcium to precipitate and the mineralization of bone matrix As mineralization progresses amorphous calcium phosphate is progressively replaced by hydroxyapatite crystals During the following weeks the lesion matures with a centripetal pattern and after 6-12 months an appearance of true bone is noted The new bone is always extra-articular and can be contiguous with the skeleton but generally does not involve the periosteum
IN SUMMARY It has been postulated that three conditions
must be met to achieve heterotopic bone formation ---a stimulating event oestrogenic precursor cells and a proper environment LIKE hypercalcaemia tissue hypoxia pH changes (alkalosis) or prolonged immobilization
ClassificationbullSubtypes
bull neurogenic HO bull Four clinical stages of HO in people with spinal cord injury were
described by Nicholas in 1973
bull traumatic myositis ossificans bull fibrodysplasia ossificans progressiva (Munchmeyers Disease)
Neurogenic HO Symptoms
painless loss of ROM interferes with ADL CRPS symptoms fever
Physical exam inspection
warm painful swollen joint may have effusion skin problems
decubitus ulcers from contractures around skin muscles ligaments
skin maceration and hygiene problems motion
decreased joint ROM joint ankylosis with HO after TKA might develop quad muscle snapping or patella
instability neurovascular
peripheral neuropathy HO often impinges on adjacent NV structures
Imaging
bullRadiographs bull findings
bull ossification usually easy to visualize bull maturity of HO
bull the appearance of a bony cortex suggests mature HObull sharp demarcation from surrounding tissue bull trabecular pattern
bull sensitivity and specificity bull not useful for early diagnosisbull only useful at 1 week after onset of symptoms
bull calcium is deposited 7-10 days later than symptom onsetbullUltrasound
bull indications bull for early diagnosis of hip HO
bull findings bull echogenic surfaces with posterior acoustic shadowing
bullCT bull indications
bull useful for preoperative planning bullTriphasic bone scan
bull indications bull best for early diagnosis bull most commonly used diagnostic study
Radiographs are extremely useful in the staging of heterotopic ossification and will show the development of sharp cortical margins once the lesion has reached maturity
Heterotopic bone is a condition in which lamellar bone forms in non-ossified soft tissues In the early stages studies such as MRI and bone scan are more sensitive for diagnosis as radiographs may appear normal for the first three weeks After the appropriate diagnosis is made sequential radiographs are useful for monitoring the progression of the ossification Once it has reached the mature stage sharp cortical margins will appear and surgical resection may be considered
lab
Labs elevated serum alkaline phosphatase (gt250IUL)
ALP removes inhibitors of mineralization nonspecific may be elevated with skeletal trauma cannot determine maturity of HO elevated 12wks after surgery is predictor
elevated CRP correlates with inflammatory activity of HO better than ESR normalization of CRP may correlate with maturity of HO
elevated ESR (gt35mmh) 12wks after THA is predictor
elevated CK correlates with involvement of muscle extent of muscle
involvement Histology
mature fatty bone marrow mature trabecular bone
Heterotopic ossification (HO) most commonly occurs at the amputation site if the amputation was performed thru the zone of injury especially if the injury was a blast mechanism
Symptomatic heterotopic ossification of the quadriceps may occur following placement of a large-diameter Steinmann pin for the purpose of temporary skeletal traction
TreatmentThe prevention of heterotopic ossification is focused on three basic principles disrupting the inductive signalling pathways altering the osteoprogenitor cells or modifying the environment
bullphysiotherapy should involve an assisted range of movement exercises with gentle stretch and terminal resistance trainingbullProphylaxis
bull bisphosphonates amp NSAIDS bull indications
bull although no literature supports are commonly usedbull technique
bull indomethacin is most commonly used bull dose is 75mgday for 10days to 6 weeks
bull perioperative radiation bull indications
bull although no literature supports commonly usedbull is thought to be effective by blocking osteoblast differentiation
bull technique bull a single perioperative dose of 700cGy can be given either 4
hours preop or within 72 hours postoperatively bull lt550cGy not effective
Nonsteroidal anti-inflammatory drugs (NSAIDs) These drugs have demonstrated good results in
preventing heterotopic ossification after total hip arthroplasty
A direct effect of NSAIDs on the formation of heterotopic ossification has been described due to the inhibition of the differentiation of mesenchymal cells into oestrogenic cells There is also an indirect effect which refers to the inhibition of bone remodelling by suppression of the prostagland unmediated inflammatory response (specifically PGE-2)
Indomethacin has been considered a useful medication for heterotopic ossification prophylaxis following total hip replacement
prescribed for three to six weeks in a dose of 75mgday within two months of the injury may reduce the incidence of heterotopic ossification by two to three times
Biphosphonates inhibits precipitation of calcium phosphate and blocks the aggregation and mineralisation of hydroxyapatite crystals In primary prevention Banovac et al [56] have suggested that the treatment should begin as soon as elevated alkaline phosphatase is diagnosed or positive findings in ultrasonography or bone scans are shown In addition disphosphonates could have long-term effects on prevention when the treatment is finished
Posttraumatic wide exposure and surgical resection
indications severe loss of motion and decreased function
technique wide exposure required to identify all neurovascular
structures that may be involved timing of resection (controversial)
marked decrease in bone scan activity AND normalization of ALP
6 months following general trauma 1 year following SCI 15 years following TBI
some data suggests equivalent results when comparing early versus late resection
postop follow with 5 day course of indomethacin early gentle joint mobilization
The surgery is necessary in patients with symptomatic HO and unsuccessful medical treatment such as
Loss of range of motion and ankylosis with associated functional disability such as sitting difficulties
Complications of immobility such as pressure ulcers
Facilitate rehabilitation and recovery of muscular atrophy secondary to prolonged immobilisation
Difficulties of appropriate hygiene because access to the perineum or bladder care is needed
Severe pain refractory to analgesia Vascular andor nerve compression
Advantages to early excision of heterotopic ossification (vs waiting for maturation) include decreased soft tissue contracture better definition between heterotopic and native bone and decreased waiting time for the patient When the soft tissue envelope is benign one may proceed with operative release While waiting for normalization of alkaline phosphatase levels inactivity on bone scan or radiographic maturity may decrease risk of recurrent heterotopic ossification delaying operative release for these reasons has not been shown to improve results of final elbow range of motion after contracture release
Gartland recommended surgery after six months following traumatic heterotopic ossification one year following spinal cord injury and 18 months after head injury
In the past waiting until maturity in order to minimize the rate of recurrence after the surgical treatment was recommended Nevertheless recent studies do not confirm a higher rate of recurrence when the HO is excised in an earlier phase In addition a long delay before surgery leads to ankylosis a high degree of osteoporosis and more extensive intra-articular injuries These findings are associated with bad functional results and potential complications
Should you wait till lesion maturation
Prevention byHandle tissue carefully Avoid excess bleeding Achieve good hemostasis Beware of lesions that span internervous tissue planes
but if it happens resection of a large enough amount of bone to allow improvement of the range of motion and trying to preserve the joint
Our aim must be
A reactive process that is characterized by a well-circumscribed proliferation of fibroblasts cartilage and bone within muscle
A form of heterotopic ossification that is the result direct trauma intramuscular hematoma
most common location is the diaphysis of long bones Must differentiate from tumors Fibrodysplasia ossificans progressiva (FOP) is a rare subtype of heterotopic ossification
involves mutation of the ACVR1 gene (activin A type I receptor gene a BMP type-1 receptor)
Epidemiology demographics
most common in young active males (15 to 35 years old) body locations
quadriceps brachialis and gluteal muscles Genetics
almost always a posttraumatic condition Prognosis
usually self limiting mass usually begins to decrease in size after 1 yea
Myositis ossificans
PresentationbullSymptoms
bull pain tenderness swelling and decreased range of motion that usually presents within days of the injury
bull pain and size of the mass decrease with timebull mass increases in size over several months(usually 3 to 6 cm)
bull after the mass stops growing it becomes firmbullPhysical exam
bull palpable soft tissue massbull restricted range of motion
ImagingbullRadiographs
bull peripheral bone formation with central lucent areabull may appear as dotted veil pattern
bullMRI with gadolinium bull rim enhancement is seen within the first 3 weeks
bullCT scan bull lesion has an eggshell appearance
bullCharacteristic histology shows zonal pattern bull periphery of lesion
bull mature trabeculae of lamellar and woven bonebull calcification seen on xray
bull center of the lesion bull irregular mass of immature fibroblastsbull cartilage component may be presentbull (no calcification seen on xray) bull no cellular atypia seen
Treatment
bullNonoperative bull rest range of motion exercises and activity modification
bull passive stretching is contraindicated (makes it worse)bull physical therapy
bull utilized to maintain range of motionbull radiographic monitoring
bull obtained to confirm maturation of the lesionbullOperative
bull surgical excision bull indicated only if it remains a problem after it maturesbull do not operate in acute phase wait at least six months
bull excision of the lesion within 6 to 12 months predisposes to local recurrence
A 26-year-old man presents with generalized back and joint stiffness and difficulty opening his mouth His elder sister has similar complaints Since childhood he has had 3 surgeries for excision of recurrent bony prominences around his knees He walks with a stooped over posture seen in Figure A Radiographs of his feet knee hip and spine are seen in Figures B-E respectively
fibrodysplasia ossificans progressiva
Stone Man Disease) which involves a mutation of the ACVR1
There are 2 hallmark characteristics progressive heterotopic ossification (muscles fascia tendons ligaments and joint capsules) and congenital malformation of the great toe (hallux valgus malformed first metatarsal and monophalangism) BMP4 which contributes to the formation of the skeleton in the normal embryo is implicated in this disease
Complications
bullHematoma and intraoperative bleedingbullInfection
bull higher rate of infection following joint arthroplasty if HO is present
bullFractures of osteoporotic bone bull osteopenic from disusebull during surgery or physiotherapy
bullRecurrence bull recurrence rate correlates with neurological injury
bull greater recurrence if severe neurological compromisebullAVN
bull if extensive dissection or stripping is required
HTO AND ISS
When ISS is below 25 the mortality risk is minimal and above 25 it is an almost linear increase
When ISS is 50 the mortality is 50 When above 70 it is close to 100 If an injury is assigned an AIS of 6 (unsurvivable injury) the ISS score is
automatically assigned to 75 Highest ISS score obtainable is 75 For trauma patients of vehicular accidents the scoring system is important
for assessing the effectiveness of medical care in reducing morbidity and mortality
Advantages virtually the only anatomical scoring system in use correlates linearly with
mortality morbidity hospital stay other measures of severity
Weaknesses Any error in AIS scoring increases the ISS error Many different injury patterns can yield the same ISS score Injuries to different body regions are not weighted Not a useful triage tool as a full description of patient injuries is not known
prior to full investigation amp operation
risk factors periosteal stripping off anterior femur male gender obesity post traumatic deformity Anterior and anterolateral approach Cementless
Neurogenic HO around the hip due to SCI occurs more often in the medial region than in the lateral region with ossified tissues extending from the pubic symphysis to the anteromedial femoral shaft posterior to the femoral neurovascular structures Ossification is also seen anteriorly involving the iliopsoas and femoral neurovascular structures laterally within gluteus minimus and posteriorly extending from the ilium to the posterior femur encasing the sciatic nerve
HTO AROUND hip and knee
The Brooker Classification of Heterotopic Ossification around the hip joint Class I has islands of bone within the soft tissues Class II has bone spurs from the pelvis or proximal end of the femur leaving at least 1 cm between opposing surfaces Class III has bone spurs from the pelvis andor proximal end of the femur reducing the space between opposing bone surfaces to less than 1 cm Class IV shows apparent bone ankylosis of the hip
Region I - Heterotopic ossifications are strictly below the tip of the greater trochanter
Region II - Heterotopic ossifications are below and above the tip of the greater trochanter
Region III - Heterotopic ossifications are strictly above the tip of the greater trochanter
Grade A - Single or multiple heterotopic ossifications are less than 10 mm in maximal extent without contact with the pelvis or the femur
Grade B - Heterotopic ossifications are greater than 10 mm without contact with the pelvis but with possible contact with the femur there is no bridging from the femur to the proximal part of the greater trochanter and no evidence of ankylosis
Grade C - Ankylosis by means of firm bridging from the femur to the pelvis is present
Shmidt classification
excision may be performed The results of this procedure are varied Patients may find that their range of movement improves but pain relief is likely to be limited
A patient with heterotopic ossification following total hip arthroplasty is thought to have a 90-100 chance of developing it on the contralateral hip if this hip also undergoes total arthroplasty
it would be prudent to minimize the risk of heterotopic ossification developing after arthroplasty by performing surgery whereby the following are ensured
Exposure is meticulous Retraction is performed carefully and soft tissue
is handled carefully Irrigation is adequate Devitalized tissue is excised Hemostasis is adequate Postoperative drains (when used) are not
retained for longer than necessary Perioperative antibiotic prophylaxis is used Postoperative anticoagulation (when used for
deep vein thrombosis prophylaxis) is carefully controlled
sources of knee stiffness 1-extrinsic severe osteoarthritis of the ipsilateral hip neurologic injury leading to muscle rigidity tight quadriceps or hamstring muscles secondary to muscle injury heterotopic ossification or long-standing juvenile inflammatory conditions limiting knee
range of motion prior to the completion of skeletal growth When extrinsic sources are identified revision total knee arthroplasty is unlikely to be associated with a favorable outcome without correction of the extrinsic problem
2-intrinsic (1) overstuffing of the patellofemoral articulation (2) an
excessively tight flexion andor extension gap (3) a tight posterior cruciate ligament (4) femoral andor tibial malrotation (5) arthrofibrosis and (6) limited bearing excursion in association with a highly conforming mobile-bearing prosthetic design
HTO after TKA
Heterotopic Ossification (HO) following primary Total Knee Replacement (TKR)
Occurs in 3-90 of TKRs 3-grade classification system No correlation between HO and component
alignment or component position
Clinical findings similar to early infection Continuing low-grade fever Warm swollen and erythematous knee Normal blood tests Possibly an association with HLA-A2 and B18 HO patients have worse KSS and function
scores
Patients at HIGH risk for developing HO after TKR (Knee Arthroplasty) (5)
Those with limited postoperative knee flexion
Increased lumbar bone mineral density (BMD) on multivariate analysis (3)
Hypertrophic arthrosis Excessive periosteal trauma Notching of the anterior femur Those who require forced manipulation
after TKA 47 in revision TKR surgery (6) Higher rates in revision TKR cases with
infection (up to 76
DaughertyBell classification of HO of the knee 0 No evidence of HO 1 Bone islands in periarticular soft tissue (no
involvement of femur patella or tibia) or HO within quadriceps expansion measuring lt1 cm
2 Spur formation measuring lt5 cm that involves the femur patella or tibia if more than one bone demonstrates HO separation of HO spurs
measure gt1 cm or HO within quadriceps expansion measuring ge1 cm but lt3 cm
3 Spur formation gt5 cm involving femur patella or tibia if more than one bone demonstrates HO separation of HO spurs measure lt1 cm or HO
within quadriceps expansion measuring ge3 cm 4 Extensive HO of the knee causing ankylosis
class 2 HO begins to involve the major bones of the knee joint with spur formation limited to a size of 5 cm
HO class 2 may be observed in select patients with complete ROM and no reported pain Patients with class 3 HO would likely always benefit from surgical excision
followed by RT prophylaxis Certainly patients in either cohort with a subclass ldquoBrdquo assignment (symptomatic) would
benefit from treatment All patients with class 4 HO require
treatment to alleviate ankylosis
treatment
References Whyte ldquoPagetrsquos Disease of Bonerdquo NEMJ vol 355
2006 Klein and Parvizi ldquoSurgical Manifestations of Pagetrsquos
Diseaserdquo JAAOS vol 14 2006 Orthobullets Campbell Apley Emedicinecom
-Chapter 15 Heterotopic Ossification after Traumatic Brain InjuryBy Jesuacutes Moreta and Joseacute Luis Martiacutenez-de los Mozos DOI 10577257343
Questions
Thank You
Malignant transformation Pagets sarcoma
less than 1 will develop malignant Pagets sarcoma (secondary sarcoma)
osteosarcoma is the most common followed by fibrosarcoma and chondrosarcoma
most common in pelvis femur and humerus Pagets sarcoma has a poor prognosis
5-year survival for non-metastatic Pagets sarcoma is less than 5 appropriate treatment for Pagets sarcoma includes chemotherapy
and wide surgical resection Pagets sarcoma typically presents as a destructive lesion without
periosteal reaction
Diagnosis Clinical assessment Characteristic radiographic appearance Labs (uarrAlkPhos) Bone Scan Usually benign and multiple lesions in old
patients are pagets hyperparathyroidism and bone infarcts
Rarely CT MRI Biopsy
Long bones bend across the trajectories of mechanical stress thus the tibia bows anteriorly and the femur anterolaterally The limb looks bent and feels thick and the skin is unduly warm ndash hence the term lsquoosteitisdeformansrsquo If the skull is affected it enlarges the patient may complain that old hats no longer fit The skull base may become flattened (platybasia) giving the appearance of a short neck In generalized Pagetrsquos disease there may also be considerable kyphosis so the patient becomes shorter and ape-like with bent legs and arms hanging in front of him Cranial nerve compression may lead to impaired vision facial palsy trigeminal neuralgia or deafness Another cause of deafness is otosclerosisVertebral thickening may cause spinal cord or nerve root compression Steal syndromes in which blood is diverted from internal organs to the surrounding skeletal circulationmay cause cerebral impairment and spinal cord ischaemia If there is also spinal stenosis the patient develops typical symptoms of lsquospinal claudicationrsquo and lower limb weakness
Radiographs coarsened trabeculae which give the bone a blastic
appearance both increased and decreased osteodensity may exist
depending on phase of disease lytic phase
lucent areas with expansion and thinned intact cortices blade of grass or flame-shaped lucent advancing edge
mixed phase combination of lysis and sclerosis with coarsened trabeculae
sclerotic phase bone enlargement with cortical thickening sclerotic and lucent
area
remodeled cortices loss of distinction between cortices and medullary cavity
long bone bowing bowing of femur or tibia
fractures hip and knee osteoarthritis osteitis circumscripta
(cotton wool exudates) in skull Pagets secondary sarcoma
shows cortical bone destruction soft tissue mass
MRI may show lumbar spinal stenosis
Bone scan accurately marks site of disease intensely hot in lytic and mixed phase less hot in sclerotic phase
CT scan cortical thickening and coarsened trabeculae
CTMRI Incidental finding Evaluation of atypical presentations
neurological involvement and possible malignant transformation
CT trabecularcortical thinning thickening irregularity
MRI non-specific marrow changes
BiochemistrySerum AlkPhosEnzyme found in osteoblastic membrane Indicator of osteoblastic activity uarrin Pagetrsquos but can be normal Levels correlate with disease extent and activity elevated urinary hydroxyproline (collagen breakdown marker) increased urinary N-telopeptide alpha-C-telopeptide
and deoxypyridinoline normal calcium levels
Other recommended tests ESR -elevation may indicate malignant transformation
CRP Ca -hypercalcemiamay occur in Pagetrsquos PO4 25-hydroxyvitamin D -rule out osteomalacia LFTs-rule out liver disease
Diagnostic Biopsy Diagnosis is usually achieved clinically and by
plain radiographic appearance Biopsy rarely required
Characteristic HistopathologyDisorganized immature trabeculararchitecture with irregular cement lines (ldquomosaicrdquopattern)
Rimming osteoblasts andor multinucleated osteoclasts
Management Options (May require no treatment if asymptomatic)
Supportive Care Pharmacologic Surgical (OrthopedicNeurosurgical
Supportive Care Occupational therapy Physical aides Counseling for fall+fracture prevention
Physical therapy Analgesics Weight control
Pharmacologic ManagementGoals Relieve symptoms and Prevent potential
complications Normalization of serum AlkPhos associated
with better long-term outcomes and disease control
Indications to treat Pain Deformity Neurologic symptoms Asymptomatic but high-risk for complications
(prophylactic) Management of hypercalcemia(rare) Pre-op reduce blood flow and potential
operative blood loss
Calcitonin is the most widely used It reduces bone resorption by decreasing both the activity and the number
of osteoclasts serum alkaline phosphatase and urinaryhydroxyproline levels are lowered Salmon calcitonin is more effective than the porcine variety subcutaneous injections of 50ndash100 MRC units are given daily until pain is relieved and the alkaline phosphatase levels are reduced and stabilized Maintenance injections once or twice weekly may have to be continued indefinitely but some authorities advocate stopping the drug and resuming treatment if symptoms recur Calcitonin can also be administered in a nasal spray Bisphosphonates bind to hydroxyapatite crystals
inhibiting their rate of growth and dissolution It is claimed that the reduction in bone turnover following their use is associated with the formation of lamellar rather than woven bone and that even after treatment is stopped there may be prolonged remission of disease (Bickerstaff et al 1990) Etidronate can be given orally (always on an empty stomach) but dosage should be kept low (eg 5 mgkg per day for up to 6 months) and vitamin D and calcium should also be given lest impaired bone mineralization results inosteomalacia The newer bisphosphonates (eg alendronate or pamidronate) do not have this disadvantage so they should be used as the treatment of choice they produce remissions even with shortcourses of 1 or 2 weeks
BisphosphonatesSynthetic analogues of inorganic phosphate adhere to mineralized surfaces
Ingested selectively by osteoclasts Disrupts enzyme pathways and reduces osteoclastic bone resorption
calcitonin causes osteoclasts to shrink in size and decreases their bone resorptive activity within minutes administered subcutaneously or intramuscularly
teriparatide is contraindicated in Pagets disease due to risk of secondary osteosarcoma
Surgical Management Few require surgery
Common Procedures Corrective osteotomy of long bone deformity indications
fractures through pathologic bowing of long bones impending pathologic fracture of long bone with bowing deformity
Arthroplasty (hip knee) the most common complications include
malalignment with knee arthroplasty bleeding with hip arthroplasty
Combination arthroplasty with osteotomy Fracture fixation
Preoperative Considerations Medical assessment for extraskeletalmanifestations eg high-
output heart failure
Medical treatment of active disease Preoperative autologousblood donation
Thorough planningeg good quality x-rays for templatingand device selection
Intraoperative Considerations Blood salvage system Expansileapproach + soft tissue release Sharp reamersburrsdrills for IM access Extramedullaryguidenavigation systems Concomitant osteotomy
PostoperativeConsiderations Monitoring for cardiac complications Continued medical tx of active disease
uarrHeterotopic ossification Prophylaxis against HO
Possible future excision of HO for painROM
1-Tieg provides a review of Pagets disease of bone and treatment indications In his review he discusses that most patients with Pagets disease are asymptomatic but in those that do present pain is the most common presenting symptom He recommends medical and surgical treatment of asymptomatic patients who have active disease at sites where complications are likely to develop
Altman did a review of 290 patients with Pagets disease of bone His findings showed 83 had one or more rheumatic syndromes He found the rate of osteoarthritis related to Pagets disease was elevated in the hip and knee Rheumatoid arthritis hyperuricemia and gout did not appear increased in this group
Mangham et al looked the rate of secondary sarcomas as a result of Pagets disease of bone They found the rate to be around 03 with male predominance They also found that widespread skeletal involvement by Pagets disease was not a significant risk factor for malignant transformation
Interesting views about pagets
Smith et al reviewed the pathologic complications of Pagets bone disease Pagets bone disease commonly causes osseous weakening (deformity and fracture) and arthritis in the hip joint Management of end stage disease is successful with cemented and cementless total hip arthroplasty Bleeding is the most common intra- and post-operative complication of surgery
Gabel et al retrospectively reviewed thirteen patients who had had sixteen total knee arthroplasties for Pagetic gonarthrosis Unlike total hip arthroplasty surgery Paget disease did not increase the amount of blood lost during the operation or in the postoperative period The most common complication associated with total knee arthroplasty was malalignment
Hansen et al reviewed the incidence of osteosarcomas complicating Pagets Disease Of the typical sites that are usually involved in Pagets disease (eg spine pelvis femur tibia and humerus) secondary osteosarcoma tends to spare the spine
Shaylor et al reported the mortality rates in 26 patient with osteosarcoma secondary to Paget s disease There was a 47 mortality at 1 year and 75 at 2 years from diagnosis In their series no patient survived for 5 years All patients died of metastatic disease
Langston et al conducted a randomized trial that compared the results of symptomatic treatment versus intensive bisphosphonate therapy in patients with Pagets disease Clinical fractures occurred in 46 of 661 patients (70) in the treatment group compared with 49 of 663 patients (74) in the symptomatic treatment group They concluded that bisphosphonates did not show a significant beneficial impact on pain quality of life or fracture incidence
Hadjipavlou et al reviewed Pagets disease of the bone and its management Farmers have been shown to have an increased incidence of Pagets disease Average age at presentation is in the 5th and 6th decade Symptomatic individuals are recommended to be treated initially with medical management They suggest that bisphosphonates are more effective than calcitonin at suppressing the histological and biochemical activity in Pagetrsquos disease
Summary Epid Very common in elderly Path Abnormal osteoclastshellipuarrbone
turnoverhellipdeposition of abnormal bone SampS Pain deformity fracture arthropathy Labs uarrAlkPhos X-ray Characteristic coarse thickened
trabeculae Bone scan Very hot Rx Bisphosphonates Surgery for arthropathy fracture painful
deformity
A 65-year-old male presents with increasing shoulder pain over the past 9 months He is otherwise healthy and has no other complaints Radiograph of his shoulder is shown in Figure A Whole body bone scan and biopsy photograph are shown in Figures B and C What is the most appropriate treatment for this patient
1 Referral to endocrinology 2 Radiation therapy and chemotherapy 3 Wide resection and reconstruction 4 Radiation therapy wide resection and reconstruction 5 Chemotherapy wide resection and reconstruction
Histiocytosis X or Langerhans cell histiocytosis is a spectrum of diseases of the reticuloendothelial system with one of three general presentations Eosinophilic granuloma (EG)
usually a single self-limited lesion found in younger patients
Hand-Schuller-Christian disease (HSC) chronic disseminated form with bone and visceral lesions also known as Langerhans cell histiocytosis with visceral
involvement Letterer-Siwe disease (LSD)
fatal form that occurs in young children
Eosinophilic granuloma
Epidemiology demographics
most commonly occurs in children (80 of afflicted lt 20 years of age)
HSC disease presents in children gt 3 years of age LSD occurs in children lt 3 years of age Male to female ratio of 21
location eosinophilic granuloma
commonly presents in the skull ribs clavicle scapula mandible
isolated lesions of the spine (thoracic most common) can also occur in diaphyseal regions of long bones and the
pelvis HSC
multiple bony sites multiple lytic skull lesions visceral involvement of the lungs spleen liver skin lymph
nodes
Genetics no clear genetic pattern of inheritance or locus has
been determined Prognosis
EG isolated involvement generally treatable with local
management spine lesions can spontaneously resolve
HSC prognosis depends on response to chemotherapy worsening prognosis with increasing extraskeletal
involvement LSD
generally fatal in children lt 3 years of age
Symptoms skeletal involvement
pain and swelling at the region of involvement limping can be seen with pelvic or lower extremity
involvement vertebral involvement
localized or diffuse back pain increasingly kyphotic posture radiculopathy can occur with more aggressive lesions
HSC classic triad of
multiple lytic skull lesions diabetes insipidus
increased thirst and water intake exopthalmos
visceral involvement diffuse or nonspecific abdominal or chest pain
Radiographs general
known as the great mimicker as it appears similar to many lesions radiographic differential includes osteomyelitis leukemia lymphoma
fibrous dysplasia or Ewings sarcoma diaphyseal lesions
well defined intramedullary lytic or punched-out lesion cortex may be thinned expanded or destroyed may have periosteal reaction
metaphyseal lesions extend up to but not through the physis less central location than diaphyseal lesions
spinal lesions vertebra plana (flattened vertebrae) in spine increased kyphosis
cranial involvement multiple punched-out lytic lesions
MRI may show a soft tissue mass adjacent to boney lesions
Bone scan generally shows increased uptake in the region of boney lesion
Histology Langerhans cells
mononuclear histiocyte-like cells with oval nuclei with well-defined round or oval cytoplasm
a prominent nuclear groove (coffee bean nuclei) can be seen in most of the nuclei
eosinophilic cytoplasm (pink generally) stain with CD1A electronmicroscopy
birbeck granules seen inside Langerhans cells mixture of inflammatory cells also present giant cells are present lack of nuclear atypia and atypical mitoses
differentiates this condition from malignant conditions such as Ewings sarcoma lymphoma of bone and metastatic neuroblastoma which may look similar based on the round cells alone
eosinophilic cytoplasm (pink generally)
Treatment
bullNonoperative bull observation alone
bull indications bull a self-limited process and it is reasonable to treat with observation alone
bull bracing bull indications
bull to prevent progressive kyphosis of the spinebull outcomes
bull will correct deformity in 90 of patientsbull vertebral lesions generally regain 50 of their height
bull low dose irradiation (600-800 cGy) bull indications
bull indicated for lesions in the spine that compromise stability neurologic statusbull lesions not amenable to injection or open treatment
bull outcomes bull effective for most lesions
bull chemotherapy bull indications
bull diffuse HSCbull outcomes
bull prognosis is improved with less severe extraskeletal involvementbull corticosteroid injection
bull indications bull isolated lesions bull can be performed after curettage as well
Operative curettage and bone grafting
indications for lesions that endanger the articular surface or are a risk for
impending fractures spinal deformity correction
indications progressive spine deformity refractory to bracing
approximately 10 of patients with spine lesion will need operative intervention for deformity correction
Destructive multiple lesion in young patientsAre eosinophilic granuloma lymphoma and leukemiaLymphoma is unlikely to present with exopthalmos diabetes insipidus or vertebra plana Lymphoma bone lesions are lytic and appear moth eatenpermeative on radiographs
Figure A shows a skin lesion typical of eosinophillic granuloma Figure B shows a lytic lesions without significant surrounding sclerosis as is characteristic of eosinophilic granuloma Figure C shows the characteristic histology of multiple eosinophils with their characteristic oval coffee bean nuclei and staining pattern of purpleredpink cytoplasm (depending on the stain) Importantly the histology slide lacks a malignant appearance (no cellular atypia or mytotic complexes and low nuclearcytoplasmic ratio)
Formation of bone in atypical extraskeletal tissues usually occurs
spontaneously or following trauma within 2 months of neurologic injury (brain or spinal cord)
most common location is between muscle and joint capsule Epidemiology
incidence (see table below)
demographics malefemale = 21 especially men with hypertrophic osteoarthritis and women gt65y
location traumatic brain injury or stroke
hip gt elbow gt shoulder gt knee elbow HO more common following brain trauma
occurs on affected (spastic) side rarely in the knee (TBI)
spinal cord injury hip gt knee gt elbow gt shoulder hip flexors and abductors gt extensors or adductors medial aspect of the knee
Heterotopic Ossification
Risk factors
Pathophysiology exact cause of HO is not known but there appears to be a
genetic pre disposition experimental HO associated with
tissue expression of BMP IT IS SAID TO BE CAUSED BY activation and proliferation of
mesenchymal stem cells Associated conditions
orthopaedic manifestations pathologic fractures
from decreased joint ROM and osteoporotic bone nerve impingement soft tissue contractures contributing to the formation of
decubitus ulcers joint ankylosis HO after THA adversely affects outcome of THA
nonorthopaedic conditions skin maceration and hygiene problems
Pathophysiology Early in the formation of HO oedema with exudative
infiltrate is present followed by fibroblastic proliferation and immature connective tissue formation Posteriorly osteoid formation is seen with the subsequent deposition of bone matrix Primitive osteoid is deposited as small masses in the periphery early (within the first two weeks) and osteoblasts are noted located irregularly Osteoblasts produce tropocollagen which polymerizes to form collagen and secrete alkaline phosphatase which allows calcium to precipitate and the mineralization of bone matrix As mineralization progresses amorphous calcium phosphate is progressively replaced by hydroxyapatite crystals During the following weeks the lesion matures with a centripetal pattern and after 6-12 months an appearance of true bone is noted The new bone is always extra-articular and can be contiguous with the skeleton but generally does not involve the periosteum
IN SUMMARY It has been postulated that three conditions
must be met to achieve heterotopic bone formation ---a stimulating event oestrogenic precursor cells and a proper environment LIKE hypercalcaemia tissue hypoxia pH changes (alkalosis) or prolonged immobilization
ClassificationbullSubtypes
bull neurogenic HO bull Four clinical stages of HO in people with spinal cord injury were
described by Nicholas in 1973
bull traumatic myositis ossificans bull fibrodysplasia ossificans progressiva (Munchmeyers Disease)
Neurogenic HO Symptoms
painless loss of ROM interferes with ADL CRPS symptoms fever
Physical exam inspection
warm painful swollen joint may have effusion skin problems
decubitus ulcers from contractures around skin muscles ligaments
skin maceration and hygiene problems motion
decreased joint ROM joint ankylosis with HO after TKA might develop quad muscle snapping or patella
instability neurovascular
peripheral neuropathy HO often impinges on adjacent NV structures
Imaging
bullRadiographs bull findings
bull ossification usually easy to visualize bull maturity of HO
bull the appearance of a bony cortex suggests mature HObull sharp demarcation from surrounding tissue bull trabecular pattern
bull sensitivity and specificity bull not useful for early diagnosisbull only useful at 1 week after onset of symptoms
bull calcium is deposited 7-10 days later than symptom onsetbullUltrasound
bull indications bull for early diagnosis of hip HO
bull findings bull echogenic surfaces with posterior acoustic shadowing
bullCT bull indications
bull useful for preoperative planning bullTriphasic bone scan
bull indications bull best for early diagnosis bull most commonly used diagnostic study
Radiographs are extremely useful in the staging of heterotopic ossification and will show the development of sharp cortical margins once the lesion has reached maturity
Heterotopic bone is a condition in which lamellar bone forms in non-ossified soft tissues In the early stages studies such as MRI and bone scan are more sensitive for diagnosis as radiographs may appear normal for the first three weeks After the appropriate diagnosis is made sequential radiographs are useful for monitoring the progression of the ossification Once it has reached the mature stage sharp cortical margins will appear and surgical resection may be considered
lab
Labs elevated serum alkaline phosphatase (gt250IUL)
ALP removes inhibitors of mineralization nonspecific may be elevated with skeletal trauma cannot determine maturity of HO elevated 12wks after surgery is predictor
elevated CRP correlates with inflammatory activity of HO better than ESR normalization of CRP may correlate with maturity of HO
elevated ESR (gt35mmh) 12wks after THA is predictor
elevated CK correlates with involvement of muscle extent of muscle
involvement Histology
mature fatty bone marrow mature trabecular bone
Heterotopic ossification (HO) most commonly occurs at the amputation site if the amputation was performed thru the zone of injury especially if the injury was a blast mechanism
Symptomatic heterotopic ossification of the quadriceps may occur following placement of a large-diameter Steinmann pin for the purpose of temporary skeletal traction
TreatmentThe prevention of heterotopic ossification is focused on three basic principles disrupting the inductive signalling pathways altering the osteoprogenitor cells or modifying the environment
bullphysiotherapy should involve an assisted range of movement exercises with gentle stretch and terminal resistance trainingbullProphylaxis
bull bisphosphonates amp NSAIDS bull indications
bull although no literature supports are commonly usedbull technique
bull indomethacin is most commonly used bull dose is 75mgday for 10days to 6 weeks
bull perioperative radiation bull indications
bull although no literature supports commonly usedbull is thought to be effective by blocking osteoblast differentiation
bull technique bull a single perioperative dose of 700cGy can be given either 4
hours preop or within 72 hours postoperatively bull lt550cGy not effective
Nonsteroidal anti-inflammatory drugs (NSAIDs) These drugs have demonstrated good results in
preventing heterotopic ossification after total hip arthroplasty
A direct effect of NSAIDs on the formation of heterotopic ossification has been described due to the inhibition of the differentiation of mesenchymal cells into oestrogenic cells There is also an indirect effect which refers to the inhibition of bone remodelling by suppression of the prostagland unmediated inflammatory response (specifically PGE-2)
Indomethacin has been considered a useful medication for heterotopic ossification prophylaxis following total hip replacement
prescribed for three to six weeks in a dose of 75mgday within two months of the injury may reduce the incidence of heterotopic ossification by two to three times
Biphosphonates inhibits precipitation of calcium phosphate and blocks the aggregation and mineralisation of hydroxyapatite crystals In primary prevention Banovac et al [56] have suggested that the treatment should begin as soon as elevated alkaline phosphatase is diagnosed or positive findings in ultrasonography or bone scans are shown In addition disphosphonates could have long-term effects on prevention when the treatment is finished
Posttraumatic wide exposure and surgical resection
indications severe loss of motion and decreased function
technique wide exposure required to identify all neurovascular
structures that may be involved timing of resection (controversial)
marked decrease in bone scan activity AND normalization of ALP
6 months following general trauma 1 year following SCI 15 years following TBI
some data suggests equivalent results when comparing early versus late resection
postop follow with 5 day course of indomethacin early gentle joint mobilization
The surgery is necessary in patients with symptomatic HO and unsuccessful medical treatment such as
Loss of range of motion and ankylosis with associated functional disability such as sitting difficulties
Complications of immobility such as pressure ulcers
Facilitate rehabilitation and recovery of muscular atrophy secondary to prolonged immobilisation
Difficulties of appropriate hygiene because access to the perineum or bladder care is needed
Severe pain refractory to analgesia Vascular andor nerve compression
Advantages to early excision of heterotopic ossification (vs waiting for maturation) include decreased soft tissue contracture better definition between heterotopic and native bone and decreased waiting time for the patient When the soft tissue envelope is benign one may proceed with operative release While waiting for normalization of alkaline phosphatase levels inactivity on bone scan or radiographic maturity may decrease risk of recurrent heterotopic ossification delaying operative release for these reasons has not been shown to improve results of final elbow range of motion after contracture release
Gartland recommended surgery after six months following traumatic heterotopic ossification one year following spinal cord injury and 18 months after head injury
In the past waiting until maturity in order to minimize the rate of recurrence after the surgical treatment was recommended Nevertheless recent studies do not confirm a higher rate of recurrence when the HO is excised in an earlier phase In addition a long delay before surgery leads to ankylosis a high degree of osteoporosis and more extensive intra-articular injuries These findings are associated with bad functional results and potential complications
Should you wait till lesion maturation
Prevention byHandle tissue carefully Avoid excess bleeding Achieve good hemostasis Beware of lesions that span internervous tissue planes
but if it happens resection of a large enough amount of bone to allow improvement of the range of motion and trying to preserve the joint
Our aim must be
A reactive process that is characterized by a well-circumscribed proliferation of fibroblasts cartilage and bone within muscle
A form of heterotopic ossification that is the result direct trauma intramuscular hematoma
most common location is the diaphysis of long bones Must differentiate from tumors Fibrodysplasia ossificans progressiva (FOP) is a rare subtype of heterotopic ossification
involves mutation of the ACVR1 gene (activin A type I receptor gene a BMP type-1 receptor)
Epidemiology demographics
most common in young active males (15 to 35 years old) body locations
quadriceps brachialis and gluteal muscles Genetics
almost always a posttraumatic condition Prognosis
usually self limiting mass usually begins to decrease in size after 1 yea
Myositis ossificans
PresentationbullSymptoms
bull pain tenderness swelling and decreased range of motion that usually presents within days of the injury
bull pain and size of the mass decrease with timebull mass increases in size over several months(usually 3 to 6 cm)
bull after the mass stops growing it becomes firmbullPhysical exam
bull palpable soft tissue massbull restricted range of motion
ImagingbullRadiographs
bull peripheral bone formation with central lucent areabull may appear as dotted veil pattern
bullMRI with gadolinium bull rim enhancement is seen within the first 3 weeks
bullCT scan bull lesion has an eggshell appearance
bullCharacteristic histology shows zonal pattern bull periphery of lesion
bull mature trabeculae of lamellar and woven bonebull calcification seen on xray
bull center of the lesion bull irregular mass of immature fibroblastsbull cartilage component may be presentbull (no calcification seen on xray) bull no cellular atypia seen
Treatment
bullNonoperative bull rest range of motion exercises and activity modification
bull passive stretching is contraindicated (makes it worse)bull physical therapy
bull utilized to maintain range of motionbull radiographic monitoring
bull obtained to confirm maturation of the lesionbullOperative
bull surgical excision bull indicated only if it remains a problem after it maturesbull do not operate in acute phase wait at least six months
bull excision of the lesion within 6 to 12 months predisposes to local recurrence
A 26-year-old man presents with generalized back and joint stiffness and difficulty opening his mouth His elder sister has similar complaints Since childhood he has had 3 surgeries for excision of recurrent bony prominences around his knees He walks with a stooped over posture seen in Figure A Radiographs of his feet knee hip and spine are seen in Figures B-E respectively
fibrodysplasia ossificans progressiva
Stone Man Disease) which involves a mutation of the ACVR1
There are 2 hallmark characteristics progressive heterotopic ossification (muscles fascia tendons ligaments and joint capsules) and congenital malformation of the great toe (hallux valgus malformed first metatarsal and monophalangism) BMP4 which contributes to the formation of the skeleton in the normal embryo is implicated in this disease
Complications
bullHematoma and intraoperative bleedingbullInfection
bull higher rate of infection following joint arthroplasty if HO is present
bullFractures of osteoporotic bone bull osteopenic from disusebull during surgery or physiotherapy
bullRecurrence bull recurrence rate correlates with neurological injury
bull greater recurrence if severe neurological compromisebullAVN
bull if extensive dissection or stripping is required
HTO AND ISS
When ISS is below 25 the mortality risk is minimal and above 25 it is an almost linear increase
When ISS is 50 the mortality is 50 When above 70 it is close to 100 If an injury is assigned an AIS of 6 (unsurvivable injury) the ISS score is
automatically assigned to 75 Highest ISS score obtainable is 75 For trauma patients of vehicular accidents the scoring system is important
for assessing the effectiveness of medical care in reducing morbidity and mortality
Advantages virtually the only anatomical scoring system in use correlates linearly with
mortality morbidity hospital stay other measures of severity
Weaknesses Any error in AIS scoring increases the ISS error Many different injury patterns can yield the same ISS score Injuries to different body regions are not weighted Not a useful triage tool as a full description of patient injuries is not known
prior to full investigation amp operation
risk factors periosteal stripping off anterior femur male gender obesity post traumatic deformity Anterior and anterolateral approach Cementless
Neurogenic HO around the hip due to SCI occurs more often in the medial region than in the lateral region with ossified tissues extending from the pubic symphysis to the anteromedial femoral shaft posterior to the femoral neurovascular structures Ossification is also seen anteriorly involving the iliopsoas and femoral neurovascular structures laterally within gluteus minimus and posteriorly extending from the ilium to the posterior femur encasing the sciatic nerve
HTO AROUND hip and knee
The Brooker Classification of Heterotopic Ossification around the hip joint Class I has islands of bone within the soft tissues Class II has bone spurs from the pelvis or proximal end of the femur leaving at least 1 cm between opposing surfaces Class III has bone spurs from the pelvis andor proximal end of the femur reducing the space between opposing bone surfaces to less than 1 cm Class IV shows apparent bone ankylosis of the hip
Region I - Heterotopic ossifications are strictly below the tip of the greater trochanter
Region II - Heterotopic ossifications are below and above the tip of the greater trochanter
Region III - Heterotopic ossifications are strictly above the tip of the greater trochanter
Grade A - Single or multiple heterotopic ossifications are less than 10 mm in maximal extent without contact with the pelvis or the femur
Grade B - Heterotopic ossifications are greater than 10 mm without contact with the pelvis but with possible contact with the femur there is no bridging from the femur to the proximal part of the greater trochanter and no evidence of ankylosis
Grade C - Ankylosis by means of firm bridging from the femur to the pelvis is present
Shmidt classification
excision may be performed The results of this procedure are varied Patients may find that their range of movement improves but pain relief is likely to be limited
A patient with heterotopic ossification following total hip arthroplasty is thought to have a 90-100 chance of developing it on the contralateral hip if this hip also undergoes total arthroplasty
it would be prudent to minimize the risk of heterotopic ossification developing after arthroplasty by performing surgery whereby the following are ensured
Exposure is meticulous Retraction is performed carefully and soft tissue
is handled carefully Irrigation is adequate Devitalized tissue is excised Hemostasis is adequate Postoperative drains (when used) are not
retained for longer than necessary Perioperative antibiotic prophylaxis is used Postoperative anticoagulation (when used for
deep vein thrombosis prophylaxis) is carefully controlled
sources of knee stiffness 1-extrinsic severe osteoarthritis of the ipsilateral hip neurologic injury leading to muscle rigidity tight quadriceps or hamstring muscles secondary to muscle injury heterotopic ossification or long-standing juvenile inflammatory conditions limiting knee
range of motion prior to the completion of skeletal growth When extrinsic sources are identified revision total knee arthroplasty is unlikely to be associated with a favorable outcome without correction of the extrinsic problem
2-intrinsic (1) overstuffing of the patellofemoral articulation (2) an
excessively tight flexion andor extension gap (3) a tight posterior cruciate ligament (4) femoral andor tibial malrotation (5) arthrofibrosis and (6) limited bearing excursion in association with a highly conforming mobile-bearing prosthetic design
HTO after TKA
Heterotopic Ossification (HO) following primary Total Knee Replacement (TKR)
Occurs in 3-90 of TKRs 3-grade classification system No correlation between HO and component
alignment or component position
Clinical findings similar to early infection Continuing low-grade fever Warm swollen and erythematous knee Normal blood tests Possibly an association with HLA-A2 and B18 HO patients have worse KSS and function
scores
Patients at HIGH risk for developing HO after TKR (Knee Arthroplasty) (5)
Those with limited postoperative knee flexion
Increased lumbar bone mineral density (BMD) on multivariate analysis (3)
Hypertrophic arthrosis Excessive periosteal trauma Notching of the anterior femur Those who require forced manipulation
after TKA 47 in revision TKR surgery (6) Higher rates in revision TKR cases with
infection (up to 76
DaughertyBell classification of HO of the knee 0 No evidence of HO 1 Bone islands in periarticular soft tissue (no
involvement of femur patella or tibia) or HO within quadriceps expansion measuring lt1 cm
2 Spur formation measuring lt5 cm that involves the femur patella or tibia if more than one bone demonstrates HO separation of HO spurs
measure gt1 cm or HO within quadriceps expansion measuring ge1 cm but lt3 cm
3 Spur formation gt5 cm involving femur patella or tibia if more than one bone demonstrates HO separation of HO spurs measure lt1 cm or HO
within quadriceps expansion measuring ge3 cm 4 Extensive HO of the knee causing ankylosis
class 2 HO begins to involve the major bones of the knee joint with spur formation limited to a size of 5 cm
HO class 2 may be observed in select patients with complete ROM and no reported pain Patients with class 3 HO would likely always benefit from surgical excision
followed by RT prophylaxis Certainly patients in either cohort with a subclass ldquoBrdquo assignment (symptomatic) would
benefit from treatment All patients with class 4 HO require
treatment to alleviate ankylosis
treatment
References Whyte ldquoPagetrsquos Disease of Bonerdquo NEMJ vol 355
2006 Klein and Parvizi ldquoSurgical Manifestations of Pagetrsquos
Diseaserdquo JAAOS vol 14 2006 Orthobullets Campbell Apley Emedicinecom
-Chapter 15 Heterotopic Ossification after Traumatic Brain InjuryBy Jesuacutes Moreta and Joseacute Luis Martiacutenez-de los Mozos DOI 10577257343
Questions
Thank You
Diagnosis Clinical assessment Characteristic radiographic appearance Labs (uarrAlkPhos) Bone Scan Usually benign and multiple lesions in old
patients are pagets hyperparathyroidism and bone infarcts
Rarely CT MRI Biopsy
Long bones bend across the trajectories of mechanical stress thus the tibia bows anteriorly and the femur anterolaterally The limb looks bent and feels thick and the skin is unduly warm ndash hence the term lsquoosteitisdeformansrsquo If the skull is affected it enlarges the patient may complain that old hats no longer fit The skull base may become flattened (platybasia) giving the appearance of a short neck In generalized Pagetrsquos disease there may also be considerable kyphosis so the patient becomes shorter and ape-like with bent legs and arms hanging in front of him Cranial nerve compression may lead to impaired vision facial palsy trigeminal neuralgia or deafness Another cause of deafness is otosclerosisVertebral thickening may cause spinal cord or nerve root compression Steal syndromes in which blood is diverted from internal organs to the surrounding skeletal circulationmay cause cerebral impairment and spinal cord ischaemia If there is also spinal stenosis the patient develops typical symptoms of lsquospinal claudicationrsquo and lower limb weakness
Radiographs coarsened trabeculae which give the bone a blastic
appearance both increased and decreased osteodensity may exist
depending on phase of disease lytic phase
lucent areas with expansion and thinned intact cortices blade of grass or flame-shaped lucent advancing edge
mixed phase combination of lysis and sclerosis with coarsened trabeculae
sclerotic phase bone enlargement with cortical thickening sclerotic and lucent
area
remodeled cortices loss of distinction between cortices and medullary cavity
long bone bowing bowing of femur or tibia
fractures hip and knee osteoarthritis osteitis circumscripta
(cotton wool exudates) in skull Pagets secondary sarcoma
shows cortical bone destruction soft tissue mass
MRI may show lumbar spinal stenosis
Bone scan accurately marks site of disease intensely hot in lytic and mixed phase less hot in sclerotic phase
CT scan cortical thickening and coarsened trabeculae
CTMRI Incidental finding Evaluation of atypical presentations
neurological involvement and possible malignant transformation
CT trabecularcortical thinning thickening irregularity
MRI non-specific marrow changes
BiochemistrySerum AlkPhosEnzyme found in osteoblastic membrane Indicator of osteoblastic activity uarrin Pagetrsquos but can be normal Levels correlate with disease extent and activity elevated urinary hydroxyproline (collagen breakdown marker) increased urinary N-telopeptide alpha-C-telopeptide
and deoxypyridinoline normal calcium levels
Other recommended tests ESR -elevation may indicate malignant transformation
CRP Ca -hypercalcemiamay occur in Pagetrsquos PO4 25-hydroxyvitamin D -rule out osteomalacia LFTs-rule out liver disease
Diagnostic Biopsy Diagnosis is usually achieved clinically and by
plain radiographic appearance Biopsy rarely required
Characteristic HistopathologyDisorganized immature trabeculararchitecture with irregular cement lines (ldquomosaicrdquopattern)
Rimming osteoblasts andor multinucleated osteoclasts
Management Options (May require no treatment if asymptomatic)
Supportive Care Pharmacologic Surgical (OrthopedicNeurosurgical
Supportive Care Occupational therapy Physical aides Counseling for fall+fracture prevention
Physical therapy Analgesics Weight control
Pharmacologic ManagementGoals Relieve symptoms and Prevent potential
complications Normalization of serum AlkPhos associated
with better long-term outcomes and disease control
Indications to treat Pain Deformity Neurologic symptoms Asymptomatic but high-risk for complications
(prophylactic) Management of hypercalcemia(rare) Pre-op reduce blood flow and potential
operative blood loss
Calcitonin is the most widely used It reduces bone resorption by decreasing both the activity and the number
of osteoclasts serum alkaline phosphatase and urinaryhydroxyproline levels are lowered Salmon calcitonin is more effective than the porcine variety subcutaneous injections of 50ndash100 MRC units are given daily until pain is relieved and the alkaline phosphatase levels are reduced and stabilized Maintenance injections once or twice weekly may have to be continued indefinitely but some authorities advocate stopping the drug and resuming treatment if symptoms recur Calcitonin can also be administered in a nasal spray Bisphosphonates bind to hydroxyapatite crystals
inhibiting their rate of growth and dissolution It is claimed that the reduction in bone turnover following their use is associated with the formation of lamellar rather than woven bone and that even after treatment is stopped there may be prolonged remission of disease (Bickerstaff et al 1990) Etidronate can be given orally (always on an empty stomach) but dosage should be kept low (eg 5 mgkg per day for up to 6 months) and vitamin D and calcium should also be given lest impaired bone mineralization results inosteomalacia The newer bisphosphonates (eg alendronate or pamidronate) do not have this disadvantage so they should be used as the treatment of choice they produce remissions even with shortcourses of 1 or 2 weeks
BisphosphonatesSynthetic analogues of inorganic phosphate adhere to mineralized surfaces
Ingested selectively by osteoclasts Disrupts enzyme pathways and reduces osteoclastic bone resorption
calcitonin causes osteoclasts to shrink in size and decreases their bone resorptive activity within minutes administered subcutaneously or intramuscularly
teriparatide is contraindicated in Pagets disease due to risk of secondary osteosarcoma
Surgical Management Few require surgery
Common Procedures Corrective osteotomy of long bone deformity indications
fractures through pathologic bowing of long bones impending pathologic fracture of long bone with bowing deformity
Arthroplasty (hip knee) the most common complications include
malalignment with knee arthroplasty bleeding with hip arthroplasty
Combination arthroplasty with osteotomy Fracture fixation
Preoperative Considerations Medical assessment for extraskeletalmanifestations eg high-
output heart failure
Medical treatment of active disease Preoperative autologousblood donation
Thorough planningeg good quality x-rays for templatingand device selection
Intraoperative Considerations Blood salvage system Expansileapproach + soft tissue release Sharp reamersburrsdrills for IM access Extramedullaryguidenavigation systems Concomitant osteotomy
PostoperativeConsiderations Monitoring for cardiac complications Continued medical tx of active disease
uarrHeterotopic ossification Prophylaxis against HO
Possible future excision of HO for painROM
1-Tieg provides a review of Pagets disease of bone and treatment indications In his review he discusses that most patients with Pagets disease are asymptomatic but in those that do present pain is the most common presenting symptom He recommends medical and surgical treatment of asymptomatic patients who have active disease at sites where complications are likely to develop
Altman did a review of 290 patients with Pagets disease of bone His findings showed 83 had one or more rheumatic syndromes He found the rate of osteoarthritis related to Pagets disease was elevated in the hip and knee Rheumatoid arthritis hyperuricemia and gout did not appear increased in this group
Mangham et al looked the rate of secondary sarcomas as a result of Pagets disease of bone They found the rate to be around 03 with male predominance They also found that widespread skeletal involvement by Pagets disease was not a significant risk factor for malignant transformation
Interesting views about pagets
Smith et al reviewed the pathologic complications of Pagets bone disease Pagets bone disease commonly causes osseous weakening (deformity and fracture) and arthritis in the hip joint Management of end stage disease is successful with cemented and cementless total hip arthroplasty Bleeding is the most common intra- and post-operative complication of surgery
Gabel et al retrospectively reviewed thirteen patients who had had sixteen total knee arthroplasties for Pagetic gonarthrosis Unlike total hip arthroplasty surgery Paget disease did not increase the amount of blood lost during the operation or in the postoperative period The most common complication associated with total knee arthroplasty was malalignment
Hansen et al reviewed the incidence of osteosarcomas complicating Pagets Disease Of the typical sites that are usually involved in Pagets disease (eg spine pelvis femur tibia and humerus) secondary osteosarcoma tends to spare the spine
Shaylor et al reported the mortality rates in 26 patient with osteosarcoma secondary to Paget s disease There was a 47 mortality at 1 year and 75 at 2 years from diagnosis In their series no patient survived for 5 years All patients died of metastatic disease
Langston et al conducted a randomized trial that compared the results of symptomatic treatment versus intensive bisphosphonate therapy in patients with Pagets disease Clinical fractures occurred in 46 of 661 patients (70) in the treatment group compared with 49 of 663 patients (74) in the symptomatic treatment group They concluded that bisphosphonates did not show a significant beneficial impact on pain quality of life or fracture incidence
Hadjipavlou et al reviewed Pagets disease of the bone and its management Farmers have been shown to have an increased incidence of Pagets disease Average age at presentation is in the 5th and 6th decade Symptomatic individuals are recommended to be treated initially with medical management They suggest that bisphosphonates are more effective than calcitonin at suppressing the histological and biochemical activity in Pagetrsquos disease
Summary Epid Very common in elderly Path Abnormal osteoclastshellipuarrbone
turnoverhellipdeposition of abnormal bone SampS Pain deformity fracture arthropathy Labs uarrAlkPhos X-ray Characteristic coarse thickened
trabeculae Bone scan Very hot Rx Bisphosphonates Surgery for arthropathy fracture painful
deformity
A 65-year-old male presents with increasing shoulder pain over the past 9 months He is otherwise healthy and has no other complaints Radiograph of his shoulder is shown in Figure A Whole body bone scan and biopsy photograph are shown in Figures B and C What is the most appropriate treatment for this patient
1 Referral to endocrinology 2 Radiation therapy and chemotherapy 3 Wide resection and reconstruction 4 Radiation therapy wide resection and reconstruction 5 Chemotherapy wide resection and reconstruction
Histiocytosis X or Langerhans cell histiocytosis is a spectrum of diseases of the reticuloendothelial system with one of three general presentations Eosinophilic granuloma (EG)
usually a single self-limited lesion found in younger patients
Hand-Schuller-Christian disease (HSC) chronic disseminated form with bone and visceral lesions also known as Langerhans cell histiocytosis with visceral
involvement Letterer-Siwe disease (LSD)
fatal form that occurs in young children
Eosinophilic granuloma
Epidemiology demographics
most commonly occurs in children (80 of afflicted lt 20 years of age)
HSC disease presents in children gt 3 years of age LSD occurs in children lt 3 years of age Male to female ratio of 21
location eosinophilic granuloma
commonly presents in the skull ribs clavicle scapula mandible
isolated lesions of the spine (thoracic most common) can also occur in diaphyseal regions of long bones and the
pelvis HSC
multiple bony sites multiple lytic skull lesions visceral involvement of the lungs spleen liver skin lymph
nodes
Genetics no clear genetic pattern of inheritance or locus has
been determined Prognosis
EG isolated involvement generally treatable with local
management spine lesions can spontaneously resolve
HSC prognosis depends on response to chemotherapy worsening prognosis with increasing extraskeletal
involvement LSD
generally fatal in children lt 3 years of age
Symptoms skeletal involvement
pain and swelling at the region of involvement limping can be seen with pelvic or lower extremity
involvement vertebral involvement
localized or diffuse back pain increasingly kyphotic posture radiculopathy can occur with more aggressive lesions
HSC classic triad of
multiple lytic skull lesions diabetes insipidus
increased thirst and water intake exopthalmos
visceral involvement diffuse or nonspecific abdominal or chest pain
Radiographs general
known as the great mimicker as it appears similar to many lesions radiographic differential includes osteomyelitis leukemia lymphoma
fibrous dysplasia or Ewings sarcoma diaphyseal lesions
well defined intramedullary lytic or punched-out lesion cortex may be thinned expanded or destroyed may have periosteal reaction
metaphyseal lesions extend up to but not through the physis less central location than diaphyseal lesions
spinal lesions vertebra plana (flattened vertebrae) in spine increased kyphosis
cranial involvement multiple punched-out lytic lesions
MRI may show a soft tissue mass adjacent to boney lesions
Bone scan generally shows increased uptake in the region of boney lesion
Histology Langerhans cells
mononuclear histiocyte-like cells with oval nuclei with well-defined round or oval cytoplasm
a prominent nuclear groove (coffee bean nuclei) can be seen in most of the nuclei
eosinophilic cytoplasm (pink generally) stain with CD1A electronmicroscopy
birbeck granules seen inside Langerhans cells mixture of inflammatory cells also present giant cells are present lack of nuclear atypia and atypical mitoses
differentiates this condition from malignant conditions such as Ewings sarcoma lymphoma of bone and metastatic neuroblastoma which may look similar based on the round cells alone
eosinophilic cytoplasm (pink generally)
Treatment
bullNonoperative bull observation alone
bull indications bull a self-limited process and it is reasonable to treat with observation alone
bull bracing bull indications
bull to prevent progressive kyphosis of the spinebull outcomes
bull will correct deformity in 90 of patientsbull vertebral lesions generally regain 50 of their height
bull low dose irradiation (600-800 cGy) bull indications
bull indicated for lesions in the spine that compromise stability neurologic statusbull lesions not amenable to injection or open treatment
bull outcomes bull effective for most lesions
bull chemotherapy bull indications
bull diffuse HSCbull outcomes
bull prognosis is improved with less severe extraskeletal involvementbull corticosteroid injection
bull indications bull isolated lesions bull can be performed after curettage as well
Operative curettage and bone grafting
indications for lesions that endanger the articular surface or are a risk for
impending fractures spinal deformity correction
indications progressive spine deformity refractory to bracing
approximately 10 of patients with spine lesion will need operative intervention for deformity correction
Destructive multiple lesion in young patientsAre eosinophilic granuloma lymphoma and leukemiaLymphoma is unlikely to present with exopthalmos diabetes insipidus or vertebra plana Lymphoma bone lesions are lytic and appear moth eatenpermeative on radiographs
Figure A shows a skin lesion typical of eosinophillic granuloma Figure B shows a lytic lesions without significant surrounding sclerosis as is characteristic of eosinophilic granuloma Figure C shows the characteristic histology of multiple eosinophils with their characteristic oval coffee bean nuclei and staining pattern of purpleredpink cytoplasm (depending on the stain) Importantly the histology slide lacks a malignant appearance (no cellular atypia or mytotic complexes and low nuclearcytoplasmic ratio)
Formation of bone in atypical extraskeletal tissues usually occurs
spontaneously or following trauma within 2 months of neurologic injury (brain or spinal cord)
most common location is between muscle and joint capsule Epidemiology
incidence (see table below)
demographics malefemale = 21 especially men with hypertrophic osteoarthritis and women gt65y
location traumatic brain injury or stroke
hip gt elbow gt shoulder gt knee elbow HO more common following brain trauma
occurs on affected (spastic) side rarely in the knee (TBI)
spinal cord injury hip gt knee gt elbow gt shoulder hip flexors and abductors gt extensors or adductors medial aspect of the knee
Heterotopic Ossification
Risk factors
Pathophysiology exact cause of HO is not known but there appears to be a
genetic pre disposition experimental HO associated with
tissue expression of BMP IT IS SAID TO BE CAUSED BY activation and proliferation of
mesenchymal stem cells Associated conditions
orthopaedic manifestations pathologic fractures
from decreased joint ROM and osteoporotic bone nerve impingement soft tissue contractures contributing to the formation of
decubitus ulcers joint ankylosis HO after THA adversely affects outcome of THA
nonorthopaedic conditions skin maceration and hygiene problems
Pathophysiology Early in the formation of HO oedema with exudative
infiltrate is present followed by fibroblastic proliferation and immature connective tissue formation Posteriorly osteoid formation is seen with the subsequent deposition of bone matrix Primitive osteoid is deposited as small masses in the periphery early (within the first two weeks) and osteoblasts are noted located irregularly Osteoblasts produce tropocollagen which polymerizes to form collagen and secrete alkaline phosphatase which allows calcium to precipitate and the mineralization of bone matrix As mineralization progresses amorphous calcium phosphate is progressively replaced by hydroxyapatite crystals During the following weeks the lesion matures with a centripetal pattern and after 6-12 months an appearance of true bone is noted The new bone is always extra-articular and can be contiguous with the skeleton but generally does not involve the periosteum
IN SUMMARY It has been postulated that three conditions
must be met to achieve heterotopic bone formation ---a stimulating event oestrogenic precursor cells and a proper environment LIKE hypercalcaemia tissue hypoxia pH changes (alkalosis) or prolonged immobilization
ClassificationbullSubtypes
bull neurogenic HO bull Four clinical stages of HO in people with spinal cord injury were
described by Nicholas in 1973
bull traumatic myositis ossificans bull fibrodysplasia ossificans progressiva (Munchmeyers Disease)
Neurogenic HO Symptoms
painless loss of ROM interferes with ADL CRPS symptoms fever
Physical exam inspection
warm painful swollen joint may have effusion skin problems
decubitus ulcers from contractures around skin muscles ligaments
skin maceration and hygiene problems motion
decreased joint ROM joint ankylosis with HO after TKA might develop quad muscle snapping or patella
instability neurovascular
peripheral neuropathy HO often impinges on adjacent NV structures
Imaging
bullRadiographs bull findings
bull ossification usually easy to visualize bull maturity of HO
bull the appearance of a bony cortex suggests mature HObull sharp demarcation from surrounding tissue bull trabecular pattern
bull sensitivity and specificity bull not useful for early diagnosisbull only useful at 1 week after onset of symptoms
bull calcium is deposited 7-10 days later than symptom onsetbullUltrasound
bull indications bull for early diagnosis of hip HO
bull findings bull echogenic surfaces with posterior acoustic shadowing
bullCT bull indications
bull useful for preoperative planning bullTriphasic bone scan
bull indications bull best for early diagnosis bull most commonly used diagnostic study
Radiographs are extremely useful in the staging of heterotopic ossification and will show the development of sharp cortical margins once the lesion has reached maturity
Heterotopic bone is a condition in which lamellar bone forms in non-ossified soft tissues In the early stages studies such as MRI and bone scan are more sensitive for diagnosis as radiographs may appear normal for the first three weeks After the appropriate diagnosis is made sequential radiographs are useful for monitoring the progression of the ossification Once it has reached the mature stage sharp cortical margins will appear and surgical resection may be considered
lab
Labs elevated serum alkaline phosphatase (gt250IUL)
ALP removes inhibitors of mineralization nonspecific may be elevated with skeletal trauma cannot determine maturity of HO elevated 12wks after surgery is predictor
elevated CRP correlates with inflammatory activity of HO better than ESR normalization of CRP may correlate with maturity of HO
elevated ESR (gt35mmh) 12wks after THA is predictor
elevated CK correlates with involvement of muscle extent of muscle
involvement Histology
mature fatty bone marrow mature trabecular bone
Heterotopic ossification (HO) most commonly occurs at the amputation site if the amputation was performed thru the zone of injury especially if the injury was a blast mechanism
Symptomatic heterotopic ossification of the quadriceps may occur following placement of a large-diameter Steinmann pin for the purpose of temporary skeletal traction
TreatmentThe prevention of heterotopic ossification is focused on three basic principles disrupting the inductive signalling pathways altering the osteoprogenitor cells or modifying the environment
bullphysiotherapy should involve an assisted range of movement exercises with gentle stretch and terminal resistance trainingbullProphylaxis
bull bisphosphonates amp NSAIDS bull indications
bull although no literature supports are commonly usedbull technique
bull indomethacin is most commonly used bull dose is 75mgday for 10days to 6 weeks
bull perioperative radiation bull indications
bull although no literature supports commonly usedbull is thought to be effective by blocking osteoblast differentiation
bull technique bull a single perioperative dose of 700cGy can be given either 4
hours preop or within 72 hours postoperatively bull lt550cGy not effective
Nonsteroidal anti-inflammatory drugs (NSAIDs) These drugs have demonstrated good results in
preventing heterotopic ossification after total hip arthroplasty
A direct effect of NSAIDs on the formation of heterotopic ossification has been described due to the inhibition of the differentiation of mesenchymal cells into oestrogenic cells There is also an indirect effect which refers to the inhibition of bone remodelling by suppression of the prostagland unmediated inflammatory response (specifically PGE-2)
Indomethacin has been considered a useful medication for heterotopic ossification prophylaxis following total hip replacement
prescribed for three to six weeks in a dose of 75mgday within two months of the injury may reduce the incidence of heterotopic ossification by two to three times
Biphosphonates inhibits precipitation of calcium phosphate and blocks the aggregation and mineralisation of hydroxyapatite crystals In primary prevention Banovac et al [56] have suggested that the treatment should begin as soon as elevated alkaline phosphatase is diagnosed or positive findings in ultrasonography or bone scans are shown In addition disphosphonates could have long-term effects on prevention when the treatment is finished
Posttraumatic wide exposure and surgical resection
indications severe loss of motion and decreased function
technique wide exposure required to identify all neurovascular
structures that may be involved timing of resection (controversial)
marked decrease in bone scan activity AND normalization of ALP
6 months following general trauma 1 year following SCI 15 years following TBI
some data suggests equivalent results when comparing early versus late resection
postop follow with 5 day course of indomethacin early gentle joint mobilization
The surgery is necessary in patients with symptomatic HO and unsuccessful medical treatment such as
Loss of range of motion and ankylosis with associated functional disability such as sitting difficulties
Complications of immobility such as pressure ulcers
Facilitate rehabilitation and recovery of muscular atrophy secondary to prolonged immobilisation
Difficulties of appropriate hygiene because access to the perineum or bladder care is needed
Severe pain refractory to analgesia Vascular andor nerve compression
Advantages to early excision of heterotopic ossification (vs waiting for maturation) include decreased soft tissue contracture better definition between heterotopic and native bone and decreased waiting time for the patient When the soft tissue envelope is benign one may proceed with operative release While waiting for normalization of alkaline phosphatase levels inactivity on bone scan or radiographic maturity may decrease risk of recurrent heterotopic ossification delaying operative release for these reasons has not been shown to improve results of final elbow range of motion after contracture release
Gartland recommended surgery after six months following traumatic heterotopic ossification one year following spinal cord injury and 18 months after head injury
In the past waiting until maturity in order to minimize the rate of recurrence after the surgical treatment was recommended Nevertheless recent studies do not confirm a higher rate of recurrence when the HO is excised in an earlier phase In addition a long delay before surgery leads to ankylosis a high degree of osteoporosis and more extensive intra-articular injuries These findings are associated with bad functional results and potential complications
Should you wait till lesion maturation
Prevention byHandle tissue carefully Avoid excess bleeding Achieve good hemostasis Beware of lesions that span internervous tissue planes
but if it happens resection of a large enough amount of bone to allow improvement of the range of motion and trying to preserve the joint
Our aim must be
A reactive process that is characterized by a well-circumscribed proliferation of fibroblasts cartilage and bone within muscle
A form of heterotopic ossification that is the result direct trauma intramuscular hematoma
most common location is the diaphysis of long bones Must differentiate from tumors Fibrodysplasia ossificans progressiva (FOP) is a rare subtype of heterotopic ossification
involves mutation of the ACVR1 gene (activin A type I receptor gene a BMP type-1 receptor)
Epidemiology demographics
most common in young active males (15 to 35 years old) body locations
quadriceps brachialis and gluteal muscles Genetics
almost always a posttraumatic condition Prognosis
usually self limiting mass usually begins to decrease in size after 1 yea
Myositis ossificans
PresentationbullSymptoms
bull pain tenderness swelling and decreased range of motion that usually presents within days of the injury
bull pain and size of the mass decrease with timebull mass increases in size over several months(usually 3 to 6 cm)
bull after the mass stops growing it becomes firmbullPhysical exam
bull palpable soft tissue massbull restricted range of motion
ImagingbullRadiographs
bull peripheral bone formation with central lucent areabull may appear as dotted veil pattern
bullMRI with gadolinium bull rim enhancement is seen within the first 3 weeks
bullCT scan bull lesion has an eggshell appearance
bullCharacteristic histology shows zonal pattern bull periphery of lesion
bull mature trabeculae of lamellar and woven bonebull calcification seen on xray
bull center of the lesion bull irregular mass of immature fibroblastsbull cartilage component may be presentbull (no calcification seen on xray) bull no cellular atypia seen
Treatment
bullNonoperative bull rest range of motion exercises and activity modification
bull passive stretching is contraindicated (makes it worse)bull physical therapy
bull utilized to maintain range of motionbull radiographic monitoring
bull obtained to confirm maturation of the lesionbullOperative
bull surgical excision bull indicated only if it remains a problem after it maturesbull do not operate in acute phase wait at least six months
bull excision of the lesion within 6 to 12 months predisposes to local recurrence
A 26-year-old man presents with generalized back and joint stiffness and difficulty opening his mouth His elder sister has similar complaints Since childhood he has had 3 surgeries for excision of recurrent bony prominences around his knees He walks with a stooped over posture seen in Figure A Radiographs of his feet knee hip and spine are seen in Figures B-E respectively
fibrodysplasia ossificans progressiva
Stone Man Disease) which involves a mutation of the ACVR1
There are 2 hallmark characteristics progressive heterotopic ossification (muscles fascia tendons ligaments and joint capsules) and congenital malformation of the great toe (hallux valgus malformed first metatarsal and monophalangism) BMP4 which contributes to the formation of the skeleton in the normal embryo is implicated in this disease
Complications
bullHematoma and intraoperative bleedingbullInfection
bull higher rate of infection following joint arthroplasty if HO is present
bullFractures of osteoporotic bone bull osteopenic from disusebull during surgery or physiotherapy
bullRecurrence bull recurrence rate correlates with neurological injury
bull greater recurrence if severe neurological compromisebullAVN
bull if extensive dissection or stripping is required
HTO AND ISS
When ISS is below 25 the mortality risk is minimal and above 25 it is an almost linear increase
When ISS is 50 the mortality is 50 When above 70 it is close to 100 If an injury is assigned an AIS of 6 (unsurvivable injury) the ISS score is
automatically assigned to 75 Highest ISS score obtainable is 75 For trauma patients of vehicular accidents the scoring system is important
for assessing the effectiveness of medical care in reducing morbidity and mortality
Advantages virtually the only anatomical scoring system in use correlates linearly with
mortality morbidity hospital stay other measures of severity
Weaknesses Any error in AIS scoring increases the ISS error Many different injury patterns can yield the same ISS score Injuries to different body regions are not weighted Not a useful triage tool as a full description of patient injuries is not known
prior to full investigation amp operation
risk factors periosteal stripping off anterior femur male gender obesity post traumatic deformity Anterior and anterolateral approach Cementless
Neurogenic HO around the hip due to SCI occurs more often in the medial region than in the lateral region with ossified tissues extending from the pubic symphysis to the anteromedial femoral shaft posterior to the femoral neurovascular structures Ossification is also seen anteriorly involving the iliopsoas and femoral neurovascular structures laterally within gluteus minimus and posteriorly extending from the ilium to the posterior femur encasing the sciatic nerve
HTO AROUND hip and knee
The Brooker Classification of Heterotopic Ossification around the hip joint Class I has islands of bone within the soft tissues Class II has bone spurs from the pelvis or proximal end of the femur leaving at least 1 cm between opposing surfaces Class III has bone spurs from the pelvis andor proximal end of the femur reducing the space between opposing bone surfaces to less than 1 cm Class IV shows apparent bone ankylosis of the hip
Region I - Heterotopic ossifications are strictly below the tip of the greater trochanter
Region II - Heterotopic ossifications are below and above the tip of the greater trochanter
Region III - Heterotopic ossifications are strictly above the tip of the greater trochanter
Grade A - Single or multiple heterotopic ossifications are less than 10 mm in maximal extent without contact with the pelvis or the femur
Grade B - Heterotopic ossifications are greater than 10 mm without contact with the pelvis but with possible contact with the femur there is no bridging from the femur to the proximal part of the greater trochanter and no evidence of ankylosis
Grade C - Ankylosis by means of firm bridging from the femur to the pelvis is present
Shmidt classification
excision may be performed The results of this procedure are varied Patients may find that their range of movement improves but pain relief is likely to be limited
A patient with heterotopic ossification following total hip arthroplasty is thought to have a 90-100 chance of developing it on the contralateral hip if this hip also undergoes total arthroplasty
it would be prudent to minimize the risk of heterotopic ossification developing after arthroplasty by performing surgery whereby the following are ensured
Exposure is meticulous Retraction is performed carefully and soft tissue
is handled carefully Irrigation is adequate Devitalized tissue is excised Hemostasis is adequate Postoperative drains (when used) are not
retained for longer than necessary Perioperative antibiotic prophylaxis is used Postoperative anticoagulation (when used for
deep vein thrombosis prophylaxis) is carefully controlled
sources of knee stiffness 1-extrinsic severe osteoarthritis of the ipsilateral hip neurologic injury leading to muscle rigidity tight quadriceps or hamstring muscles secondary to muscle injury heterotopic ossification or long-standing juvenile inflammatory conditions limiting knee
range of motion prior to the completion of skeletal growth When extrinsic sources are identified revision total knee arthroplasty is unlikely to be associated with a favorable outcome without correction of the extrinsic problem
2-intrinsic (1) overstuffing of the patellofemoral articulation (2) an
excessively tight flexion andor extension gap (3) a tight posterior cruciate ligament (4) femoral andor tibial malrotation (5) arthrofibrosis and (6) limited bearing excursion in association with a highly conforming mobile-bearing prosthetic design
HTO after TKA
Heterotopic Ossification (HO) following primary Total Knee Replacement (TKR)
Occurs in 3-90 of TKRs 3-grade classification system No correlation between HO and component
alignment or component position
Clinical findings similar to early infection Continuing low-grade fever Warm swollen and erythematous knee Normal blood tests Possibly an association with HLA-A2 and B18 HO patients have worse KSS and function
scores
Patients at HIGH risk for developing HO after TKR (Knee Arthroplasty) (5)
Those with limited postoperative knee flexion
Increased lumbar bone mineral density (BMD) on multivariate analysis (3)
Hypertrophic arthrosis Excessive periosteal trauma Notching of the anterior femur Those who require forced manipulation
after TKA 47 in revision TKR surgery (6) Higher rates in revision TKR cases with
infection (up to 76
DaughertyBell classification of HO of the knee 0 No evidence of HO 1 Bone islands in periarticular soft tissue (no
involvement of femur patella or tibia) or HO within quadriceps expansion measuring lt1 cm
2 Spur formation measuring lt5 cm that involves the femur patella or tibia if more than one bone demonstrates HO separation of HO spurs
measure gt1 cm or HO within quadriceps expansion measuring ge1 cm but lt3 cm
3 Spur formation gt5 cm involving femur patella or tibia if more than one bone demonstrates HO separation of HO spurs measure lt1 cm or HO
within quadriceps expansion measuring ge3 cm 4 Extensive HO of the knee causing ankylosis
class 2 HO begins to involve the major bones of the knee joint with spur formation limited to a size of 5 cm
HO class 2 may be observed in select patients with complete ROM and no reported pain Patients with class 3 HO would likely always benefit from surgical excision
followed by RT prophylaxis Certainly patients in either cohort with a subclass ldquoBrdquo assignment (symptomatic) would
benefit from treatment All patients with class 4 HO require
treatment to alleviate ankylosis
treatment
References Whyte ldquoPagetrsquos Disease of Bonerdquo NEMJ vol 355
2006 Klein and Parvizi ldquoSurgical Manifestations of Pagetrsquos
Diseaserdquo JAAOS vol 14 2006 Orthobullets Campbell Apley Emedicinecom
-Chapter 15 Heterotopic Ossification after Traumatic Brain InjuryBy Jesuacutes Moreta and Joseacute Luis Martiacutenez-de los Mozos DOI 10577257343
Questions
Thank You
Long bones bend across the trajectories of mechanical stress thus the tibia bows anteriorly and the femur anterolaterally The limb looks bent and feels thick and the skin is unduly warm ndash hence the term lsquoosteitisdeformansrsquo If the skull is affected it enlarges the patient may complain that old hats no longer fit The skull base may become flattened (platybasia) giving the appearance of a short neck In generalized Pagetrsquos disease there may also be considerable kyphosis so the patient becomes shorter and ape-like with bent legs and arms hanging in front of him Cranial nerve compression may lead to impaired vision facial palsy trigeminal neuralgia or deafness Another cause of deafness is otosclerosisVertebral thickening may cause spinal cord or nerve root compression Steal syndromes in which blood is diverted from internal organs to the surrounding skeletal circulationmay cause cerebral impairment and spinal cord ischaemia If there is also spinal stenosis the patient develops typical symptoms of lsquospinal claudicationrsquo and lower limb weakness
Radiographs coarsened trabeculae which give the bone a blastic
appearance both increased and decreased osteodensity may exist
depending on phase of disease lytic phase
lucent areas with expansion and thinned intact cortices blade of grass or flame-shaped lucent advancing edge
mixed phase combination of lysis and sclerosis with coarsened trabeculae
sclerotic phase bone enlargement with cortical thickening sclerotic and lucent
area
remodeled cortices loss of distinction between cortices and medullary cavity
long bone bowing bowing of femur or tibia
fractures hip and knee osteoarthritis osteitis circumscripta
(cotton wool exudates) in skull Pagets secondary sarcoma
shows cortical bone destruction soft tissue mass
MRI may show lumbar spinal stenosis
Bone scan accurately marks site of disease intensely hot in lytic and mixed phase less hot in sclerotic phase
CT scan cortical thickening and coarsened trabeculae
CTMRI Incidental finding Evaluation of atypical presentations
neurological involvement and possible malignant transformation
CT trabecularcortical thinning thickening irregularity
MRI non-specific marrow changes
BiochemistrySerum AlkPhosEnzyme found in osteoblastic membrane Indicator of osteoblastic activity uarrin Pagetrsquos but can be normal Levels correlate with disease extent and activity elevated urinary hydroxyproline (collagen breakdown marker) increased urinary N-telopeptide alpha-C-telopeptide
and deoxypyridinoline normal calcium levels
Other recommended tests ESR -elevation may indicate malignant transformation
CRP Ca -hypercalcemiamay occur in Pagetrsquos PO4 25-hydroxyvitamin D -rule out osteomalacia LFTs-rule out liver disease
Diagnostic Biopsy Diagnosis is usually achieved clinically and by
plain radiographic appearance Biopsy rarely required
Characteristic HistopathologyDisorganized immature trabeculararchitecture with irregular cement lines (ldquomosaicrdquopattern)
Rimming osteoblasts andor multinucleated osteoclasts
Management Options (May require no treatment if asymptomatic)
Supportive Care Pharmacologic Surgical (OrthopedicNeurosurgical
Supportive Care Occupational therapy Physical aides Counseling for fall+fracture prevention
Physical therapy Analgesics Weight control
Pharmacologic ManagementGoals Relieve symptoms and Prevent potential
complications Normalization of serum AlkPhos associated
with better long-term outcomes and disease control
Indications to treat Pain Deformity Neurologic symptoms Asymptomatic but high-risk for complications
(prophylactic) Management of hypercalcemia(rare) Pre-op reduce blood flow and potential
operative blood loss
Calcitonin is the most widely used It reduces bone resorption by decreasing both the activity and the number
of osteoclasts serum alkaline phosphatase and urinaryhydroxyproline levels are lowered Salmon calcitonin is more effective than the porcine variety subcutaneous injections of 50ndash100 MRC units are given daily until pain is relieved and the alkaline phosphatase levels are reduced and stabilized Maintenance injections once or twice weekly may have to be continued indefinitely but some authorities advocate stopping the drug and resuming treatment if symptoms recur Calcitonin can also be administered in a nasal spray Bisphosphonates bind to hydroxyapatite crystals
inhibiting their rate of growth and dissolution It is claimed that the reduction in bone turnover following their use is associated with the formation of lamellar rather than woven bone and that even after treatment is stopped there may be prolonged remission of disease (Bickerstaff et al 1990) Etidronate can be given orally (always on an empty stomach) but dosage should be kept low (eg 5 mgkg per day for up to 6 months) and vitamin D and calcium should also be given lest impaired bone mineralization results inosteomalacia The newer bisphosphonates (eg alendronate or pamidronate) do not have this disadvantage so they should be used as the treatment of choice they produce remissions even with shortcourses of 1 or 2 weeks
BisphosphonatesSynthetic analogues of inorganic phosphate adhere to mineralized surfaces
Ingested selectively by osteoclasts Disrupts enzyme pathways and reduces osteoclastic bone resorption
calcitonin causes osteoclasts to shrink in size and decreases their bone resorptive activity within minutes administered subcutaneously or intramuscularly
teriparatide is contraindicated in Pagets disease due to risk of secondary osteosarcoma
Surgical Management Few require surgery
Common Procedures Corrective osteotomy of long bone deformity indications
fractures through pathologic bowing of long bones impending pathologic fracture of long bone with bowing deformity
Arthroplasty (hip knee) the most common complications include
malalignment with knee arthroplasty bleeding with hip arthroplasty
Combination arthroplasty with osteotomy Fracture fixation
Preoperative Considerations Medical assessment for extraskeletalmanifestations eg high-
output heart failure
Medical treatment of active disease Preoperative autologousblood donation
Thorough planningeg good quality x-rays for templatingand device selection
Intraoperative Considerations Blood salvage system Expansileapproach + soft tissue release Sharp reamersburrsdrills for IM access Extramedullaryguidenavigation systems Concomitant osteotomy
PostoperativeConsiderations Monitoring for cardiac complications Continued medical tx of active disease
uarrHeterotopic ossification Prophylaxis against HO
Possible future excision of HO for painROM
1-Tieg provides a review of Pagets disease of bone and treatment indications In his review he discusses that most patients with Pagets disease are asymptomatic but in those that do present pain is the most common presenting symptom He recommends medical and surgical treatment of asymptomatic patients who have active disease at sites where complications are likely to develop
Altman did a review of 290 patients with Pagets disease of bone His findings showed 83 had one or more rheumatic syndromes He found the rate of osteoarthritis related to Pagets disease was elevated in the hip and knee Rheumatoid arthritis hyperuricemia and gout did not appear increased in this group
Mangham et al looked the rate of secondary sarcomas as a result of Pagets disease of bone They found the rate to be around 03 with male predominance They also found that widespread skeletal involvement by Pagets disease was not a significant risk factor for malignant transformation
Interesting views about pagets
Smith et al reviewed the pathologic complications of Pagets bone disease Pagets bone disease commonly causes osseous weakening (deformity and fracture) and arthritis in the hip joint Management of end stage disease is successful with cemented and cementless total hip arthroplasty Bleeding is the most common intra- and post-operative complication of surgery
Gabel et al retrospectively reviewed thirteen patients who had had sixteen total knee arthroplasties for Pagetic gonarthrosis Unlike total hip arthroplasty surgery Paget disease did not increase the amount of blood lost during the operation or in the postoperative period The most common complication associated with total knee arthroplasty was malalignment
Hansen et al reviewed the incidence of osteosarcomas complicating Pagets Disease Of the typical sites that are usually involved in Pagets disease (eg spine pelvis femur tibia and humerus) secondary osteosarcoma tends to spare the spine
Shaylor et al reported the mortality rates in 26 patient with osteosarcoma secondary to Paget s disease There was a 47 mortality at 1 year and 75 at 2 years from diagnosis In their series no patient survived for 5 years All patients died of metastatic disease
Langston et al conducted a randomized trial that compared the results of symptomatic treatment versus intensive bisphosphonate therapy in patients with Pagets disease Clinical fractures occurred in 46 of 661 patients (70) in the treatment group compared with 49 of 663 patients (74) in the symptomatic treatment group They concluded that bisphosphonates did not show a significant beneficial impact on pain quality of life or fracture incidence
Hadjipavlou et al reviewed Pagets disease of the bone and its management Farmers have been shown to have an increased incidence of Pagets disease Average age at presentation is in the 5th and 6th decade Symptomatic individuals are recommended to be treated initially with medical management They suggest that bisphosphonates are more effective than calcitonin at suppressing the histological and biochemical activity in Pagetrsquos disease
Summary Epid Very common in elderly Path Abnormal osteoclastshellipuarrbone
turnoverhellipdeposition of abnormal bone SampS Pain deformity fracture arthropathy Labs uarrAlkPhos X-ray Characteristic coarse thickened
trabeculae Bone scan Very hot Rx Bisphosphonates Surgery for arthropathy fracture painful
deformity
A 65-year-old male presents with increasing shoulder pain over the past 9 months He is otherwise healthy and has no other complaints Radiograph of his shoulder is shown in Figure A Whole body bone scan and biopsy photograph are shown in Figures B and C What is the most appropriate treatment for this patient
1 Referral to endocrinology 2 Radiation therapy and chemotherapy 3 Wide resection and reconstruction 4 Radiation therapy wide resection and reconstruction 5 Chemotherapy wide resection and reconstruction
Histiocytosis X or Langerhans cell histiocytosis is a spectrum of diseases of the reticuloendothelial system with one of three general presentations Eosinophilic granuloma (EG)
usually a single self-limited lesion found in younger patients
Hand-Schuller-Christian disease (HSC) chronic disseminated form with bone and visceral lesions also known as Langerhans cell histiocytosis with visceral
involvement Letterer-Siwe disease (LSD)
fatal form that occurs in young children
Eosinophilic granuloma
Epidemiology demographics
most commonly occurs in children (80 of afflicted lt 20 years of age)
HSC disease presents in children gt 3 years of age LSD occurs in children lt 3 years of age Male to female ratio of 21
location eosinophilic granuloma
commonly presents in the skull ribs clavicle scapula mandible
isolated lesions of the spine (thoracic most common) can also occur in diaphyseal regions of long bones and the
pelvis HSC
multiple bony sites multiple lytic skull lesions visceral involvement of the lungs spleen liver skin lymph
nodes
Genetics no clear genetic pattern of inheritance or locus has
been determined Prognosis
EG isolated involvement generally treatable with local
management spine lesions can spontaneously resolve
HSC prognosis depends on response to chemotherapy worsening prognosis with increasing extraskeletal
involvement LSD
generally fatal in children lt 3 years of age
Symptoms skeletal involvement
pain and swelling at the region of involvement limping can be seen with pelvic or lower extremity
involvement vertebral involvement
localized or diffuse back pain increasingly kyphotic posture radiculopathy can occur with more aggressive lesions
HSC classic triad of
multiple lytic skull lesions diabetes insipidus
increased thirst and water intake exopthalmos
visceral involvement diffuse or nonspecific abdominal or chest pain
Radiographs general
known as the great mimicker as it appears similar to many lesions radiographic differential includes osteomyelitis leukemia lymphoma
fibrous dysplasia or Ewings sarcoma diaphyseal lesions
well defined intramedullary lytic or punched-out lesion cortex may be thinned expanded or destroyed may have periosteal reaction
metaphyseal lesions extend up to but not through the physis less central location than diaphyseal lesions
spinal lesions vertebra plana (flattened vertebrae) in spine increased kyphosis
cranial involvement multiple punched-out lytic lesions
MRI may show a soft tissue mass adjacent to boney lesions
Bone scan generally shows increased uptake in the region of boney lesion
Histology Langerhans cells
mononuclear histiocyte-like cells with oval nuclei with well-defined round or oval cytoplasm
a prominent nuclear groove (coffee bean nuclei) can be seen in most of the nuclei
eosinophilic cytoplasm (pink generally) stain with CD1A electronmicroscopy
birbeck granules seen inside Langerhans cells mixture of inflammatory cells also present giant cells are present lack of nuclear atypia and atypical mitoses
differentiates this condition from malignant conditions such as Ewings sarcoma lymphoma of bone and metastatic neuroblastoma which may look similar based on the round cells alone
eosinophilic cytoplasm (pink generally)
Treatment
bullNonoperative bull observation alone
bull indications bull a self-limited process and it is reasonable to treat with observation alone
bull bracing bull indications
bull to prevent progressive kyphosis of the spinebull outcomes
bull will correct deformity in 90 of patientsbull vertebral lesions generally regain 50 of their height
bull low dose irradiation (600-800 cGy) bull indications
bull indicated for lesions in the spine that compromise stability neurologic statusbull lesions not amenable to injection or open treatment
bull outcomes bull effective for most lesions
bull chemotherapy bull indications
bull diffuse HSCbull outcomes
bull prognosis is improved with less severe extraskeletal involvementbull corticosteroid injection
bull indications bull isolated lesions bull can be performed after curettage as well
Operative curettage and bone grafting
indications for lesions that endanger the articular surface or are a risk for
impending fractures spinal deformity correction
indications progressive spine deformity refractory to bracing
approximately 10 of patients with spine lesion will need operative intervention for deformity correction
Destructive multiple lesion in young patientsAre eosinophilic granuloma lymphoma and leukemiaLymphoma is unlikely to present with exopthalmos diabetes insipidus or vertebra plana Lymphoma bone lesions are lytic and appear moth eatenpermeative on radiographs
Figure A shows a skin lesion typical of eosinophillic granuloma Figure B shows a lytic lesions without significant surrounding sclerosis as is characteristic of eosinophilic granuloma Figure C shows the characteristic histology of multiple eosinophils with their characteristic oval coffee bean nuclei and staining pattern of purpleredpink cytoplasm (depending on the stain) Importantly the histology slide lacks a malignant appearance (no cellular atypia or mytotic complexes and low nuclearcytoplasmic ratio)
Formation of bone in atypical extraskeletal tissues usually occurs
spontaneously or following trauma within 2 months of neurologic injury (brain or spinal cord)
most common location is between muscle and joint capsule Epidemiology
incidence (see table below)
demographics malefemale = 21 especially men with hypertrophic osteoarthritis and women gt65y
location traumatic brain injury or stroke
hip gt elbow gt shoulder gt knee elbow HO more common following brain trauma
occurs on affected (spastic) side rarely in the knee (TBI)
spinal cord injury hip gt knee gt elbow gt shoulder hip flexors and abductors gt extensors or adductors medial aspect of the knee
Heterotopic Ossification
Risk factors
Pathophysiology exact cause of HO is not known but there appears to be a
genetic pre disposition experimental HO associated with
tissue expression of BMP IT IS SAID TO BE CAUSED BY activation and proliferation of
mesenchymal stem cells Associated conditions
orthopaedic manifestations pathologic fractures
from decreased joint ROM and osteoporotic bone nerve impingement soft tissue contractures contributing to the formation of
decubitus ulcers joint ankylosis HO after THA adversely affects outcome of THA
nonorthopaedic conditions skin maceration and hygiene problems
Pathophysiology Early in the formation of HO oedema with exudative
infiltrate is present followed by fibroblastic proliferation and immature connective tissue formation Posteriorly osteoid formation is seen with the subsequent deposition of bone matrix Primitive osteoid is deposited as small masses in the periphery early (within the first two weeks) and osteoblasts are noted located irregularly Osteoblasts produce tropocollagen which polymerizes to form collagen and secrete alkaline phosphatase which allows calcium to precipitate and the mineralization of bone matrix As mineralization progresses amorphous calcium phosphate is progressively replaced by hydroxyapatite crystals During the following weeks the lesion matures with a centripetal pattern and after 6-12 months an appearance of true bone is noted The new bone is always extra-articular and can be contiguous with the skeleton but generally does not involve the periosteum
IN SUMMARY It has been postulated that three conditions
must be met to achieve heterotopic bone formation ---a stimulating event oestrogenic precursor cells and a proper environment LIKE hypercalcaemia tissue hypoxia pH changes (alkalosis) or prolonged immobilization
ClassificationbullSubtypes
bull neurogenic HO bull Four clinical stages of HO in people with spinal cord injury were
described by Nicholas in 1973
bull traumatic myositis ossificans bull fibrodysplasia ossificans progressiva (Munchmeyers Disease)
Neurogenic HO Symptoms
painless loss of ROM interferes with ADL CRPS symptoms fever
Physical exam inspection
warm painful swollen joint may have effusion skin problems
decubitus ulcers from contractures around skin muscles ligaments
skin maceration and hygiene problems motion
decreased joint ROM joint ankylosis with HO after TKA might develop quad muscle snapping or patella
instability neurovascular
peripheral neuropathy HO often impinges on adjacent NV structures
Imaging
bullRadiographs bull findings
bull ossification usually easy to visualize bull maturity of HO
bull the appearance of a bony cortex suggests mature HObull sharp demarcation from surrounding tissue bull trabecular pattern
bull sensitivity and specificity bull not useful for early diagnosisbull only useful at 1 week after onset of symptoms
bull calcium is deposited 7-10 days later than symptom onsetbullUltrasound
bull indications bull for early diagnosis of hip HO
bull findings bull echogenic surfaces with posterior acoustic shadowing
bullCT bull indications
bull useful for preoperative planning bullTriphasic bone scan
bull indications bull best for early diagnosis bull most commonly used diagnostic study
Radiographs are extremely useful in the staging of heterotopic ossification and will show the development of sharp cortical margins once the lesion has reached maturity
Heterotopic bone is a condition in which lamellar bone forms in non-ossified soft tissues In the early stages studies such as MRI and bone scan are more sensitive for diagnosis as radiographs may appear normal for the first three weeks After the appropriate diagnosis is made sequential radiographs are useful for monitoring the progression of the ossification Once it has reached the mature stage sharp cortical margins will appear and surgical resection may be considered
lab
Labs elevated serum alkaline phosphatase (gt250IUL)
ALP removes inhibitors of mineralization nonspecific may be elevated with skeletal trauma cannot determine maturity of HO elevated 12wks after surgery is predictor
elevated CRP correlates with inflammatory activity of HO better than ESR normalization of CRP may correlate with maturity of HO
elevated ESR (gt35mmh) 12wks after THA is predictor
elevated CK correlates with involvement of muscle extent of muscle
involvement Histology
mature fatty bone marrow mature trabecular bone
Heterotopic ossification (HO) most commonly occurs at the amputation site if the amputation was performed thru the zone of injury especially if the injury was a blast mechanism
Symptomatic heterotopic ossification of the quadriceps may occur following placement of a large-diameter Steinmann pin for the purpose of temporary skeletal traction
TreatmentThe prevention of heterotopic ossification is focused on three basic principles disrupting the inductive signalling pathways altering the osteoprogenitor cells or modifying the environment
bullphysiotherapy should involve an assisted range of movement exercises with gentle stretch and terminal resistance trainingbullProphylaxis
bull bisphosphonates amp NSAIDS bull indications
bull although no literature supports are commonly usedbull technique
bull indomethacin is most commonly used bull dose is 75mgday for 10days to 6 weeks
bull perioperative radiation bull indications
bull although no literature supports commonly usedbull is thought to be effective by blocking osteoblast differentiation
bull technique bull a single perioperative dose of 700cGy can be given either 4
hours preop or within 72 hours postoperatively bull lt550cGy not effective
Nonsteroidal anti-inflammatory drugs (NSAIDs) These drugs have demonstrated good results in
preventing heterotopic ossification after total hip arthroplasty
A direct effect of NSAIDs on the formation of heterotopic ossification has been described due to the inhibition of the differentiation of mesenchymal cells into oestrogenic cells There is also an indirect effect which refers to the inhibition of bone remodelling by suppression of the prostagland unmediated inflammatory response (specifically PGE-2)
Indomethacin has been considered a useful medication for heterotopic ossification prophylaxis following total hip replacement
prescribed for three to six weeks in a dose of 75mgday within two months of the injury may reduce the incidence of heterotopic ossification by two to three times
Biphosphonates inhibits precipitation of calcium phosphate and blocks the aggregation and mineralisation of hydroxyapatite crystals In primary prevention Banovac et al [56] have suggested that the treatment should begin as soon as elevated alkaline phosphatase is diagnosed or positive findings in ultrasonography or bone scans are shown In addition disphosphonates could have long-term effects on prevention when the treatment is finished
Posttraumatic wide exposure and surgical resection
indications severe loss of motion and decreased function
technique wide exposure required to identify all neurovascular
structures that may be involved timing of resection (controversial)
marked decrease in bone scan activity AND normalization of ALP
6 months following general trauma 1 year following SCI 15 years following TBI
some data suggests equivalent results when comparing early versus late resection
postop follow with 5 day course of indomethacin early gentle joint mobilization
The surgery is necessary in patients with symptomatic HO and unsuccessful medical treatment such as
Loss of range of motion and ankylosis with associated functional disability such as sitting difficulties
Complications of immobility such as pressure ulcers
Facilitate rehabilitation and recovery of muscular atrophy secondary to prolonged immobilisation
Difficulties of appropriate hygiene because access to the perineum or bladder care is needed
Severe pain refractory to analgesia Vascular andor nerve compression
Advantages to early excision of heterotopic ossification (vs waiting for maturation) include decreased soft tissue contracture better definition between heterotopic and native bone and decreased waiting time for the patient When the soft tissue envelope is benign one may proceed with operative release While waiting for normalization of alkaline phosphatase levels inactivity on bone scan or radiographic maturity may decrease risk of recurrent heterotopic ossification delaying operative release for these reasons has not been shown to improve results of final elbow range of motion after contracture release
Gartland recommended surgery after six months following traumatic heterotopic ossification one year following spinal cord injury and 18 months after head injury
In the past waiting until maturity in order to minimize the rate of recurrence after the surgical treatment was recommended Nevertheless recent studies do not confirm a higher rate of recurrence when the HO is excised in an earlier phase In addition a long delay before surgery leads to ankylosis a high degree of osteoporosis and more extensive intra-articular injuries These findings are associated with bad functional results and potential complications
Should you wait till lesion maturation
Prevention byHandle tissue carefully Avoid excess bleeding Achieve good hemostasis Beware of lesions that span internervous tissue planes
but if it happens resection of a large enough amount of bone to allow improvement of the range of motion and trying to preserve the joint
Our aim must be
A reactive process that is characterized by a well-circumscribed proliferation of fibroblasts cartilage and bone within muscle
A form of heterotopic ossification that is the result direct trauma intramuscular hematoma
most common location is the diaphysis of long bones Must differentiate from tumors Fibrodysplasia ossificans progressiva (FOP) is a rare subtype of heterotopic ossification
involves mutation of the ACVR1 gene (activin A type I receptor gene a BMP type-1 receptor)
Epidemiology demographics
most common in young active males (15 to 35 years old) body locations
quadriceps brachialis and gluteal muscles Genetics
almost always a posttraumatic condition Prognosis
usually self limiting mass usually begins to decrease in size after 1 yea
Myositis ossificans
PresentationbullSymptoms
bull pain tenderness swelling and decreased range of motion that usually presents within days of the injury
bull pain and size of the mass decrease with timebull mass increases in size over several months(usually 3 to 6 cm)
bull after the mass stops growing it becomes firmbullPhysical exam
bull palpable soft tissue massbull restricted range of motion
ImagingbullRadiographs
bull peripheral bone formation with central lucent areabull may appear as dotted veil pattern
bullMRI with gadolinium bull rim enhancement is seen within the first 3 weeks
bullCT scan bull lesion has an eggshell appearance
bullCharacteristic histology shows zonal pattern bull periphery of lesion
bull mature trabeculae of lamellar and woven bonebull calcification seen on xray
bull center of the lesion bull irregular mass of immature fibroblastsbull cartilage component may be presentbull (no calcification seen on xray) bull no cellular atypia seen
Treatment
bullNonoperative bull rest range of motion exercises and activity modification
bull passive stretching is contraindicated (makes it worse)bull physical therapy
bull utilized to maintain range of motionbull radiographic monitoring
bull obtained to confirm maturation of the lesionbullOperative
bull surgical excision bull indicated only if it remains a problem after it maturesbull do not operate in acute phase wait at least six months
bull excision of the lesion within 6 to 12 months predisposes to local recurrence
A 26-year-old man presents with generalized back and joint stiffness and difficulty opening his mouth His elder sister has similar complaints Since childhood he has had 3 surgeries for excision of recurrent bony prominences around his knees He walks with a stooped over posture seen in Figure A Radiographs of his feet knee hip and spine are seen in Figures B-E respectively
fibrodysplasia ossificans progressiva
Stone Man Disease) which involves a mutation of the ACVR1
There are 2 hallmark characteristics progressive heterotopic ossification (muscles fascia tendons ligaments and joint capsules) and congenital malformation of the great toe (hallux valgus malformed first metatarsal and monophalangism) BMP4 which contributes to the formation of the skeleton in the normal embryo is implicated in this disease
Complications
bullHematoma and intraoperative bleedingbullInfection
bull higher rate of infection following joint arthroplasty if HO is present
bullFractures of osteoporotic bone bull osteopenic from disusebull during surgery or physiotherapy
bullRecurrence bull recurrence rate correlates with neurological injury
bull greater recurrence if severe neurological compromisebullAVN
bull if extensive dissection or stripping is required
HTO AND ISS
When ISS is below 25 the mortality risk is minimal and above 25 it is an almost linear increase
When ISS is 50 the mortality is 50 When above 70 it is close to 100 If an injury is assigned an AIS of 6 (unsurvivable injury) the ISS score is
automatically assigned to 75 Highest ISS score obtainable is 75 For trauma patients of vehicular accidents the scoring system is important
for assessing the effectiveness of medical care in reducing morbidity and mortality
Advantages virtually the only anatomical scoring system in use correlates linearly with
mortality morbidity hospital stay other measures of severity
Weaknesses Any error in AIS scoring increases the ISS error Many different injury patterns can yield the same ISS score Injuries to different body regions are not weighted Not a useful triage tool as a full description of patient injuries is not known
prior to full investigation amp operation
risk factors periosteal stripping off anterior femur male gender obesity post traumatic deformity Anterior and anterolateral approach Cementless
Neurogenic HO around the hip due to SCI occurs more often in the medial region than in the lateral region with ossified tissues extending from the pubic symphysis to the anteromedial femoral shaft posterior to the femoral neurovascular structures Ossification is also seen anteriorly involving the iliopsoas and femoral neurovascular structures laterally within gluteus minimus and posteriorly extending from the ilium to the posterior femur encasing the sciatic nerve
HTO AROUND hip and knee
The Brooker Classification of Heterotopic Ossification around the hip joint Class I has islands of bone within the soft tissues Class II has bone spurs from the pelvis or proximal end of the femur leaving at least 1 cm between opposing surfaces Class III has bone spurs from the pelvis andor proximal end of the femur reducing the space between opposing bone surfaces to less than 1 cm Class IV shows apparent bone ankylosis of the hip
Region I - Heterotopic ossifications are strictly below the tip of the greater trochanter
Region II - Heterotopic ossifications are below and above the tip of the greater trochanter
Region III - Heterotopic ossifications are strictly above the tip of the greater trochanter
Grade A - Single or multiple heterotopic ossifications are less than 10 mm in maximal extent without contact with the pelvis or the femur
Grade B - Heterotopic ossifications are greater than 10 mm without contact with the pelvis but with possible contact with the femur there is no bridging from the femur to the proximal part of the greater trochanter and no evidence of ankylosis
Grade C - Ankylosis by means of firm bridging from the femur to the pelvis is present
Shmidt classification
excision may be performed The results of this procedure are varied Patients may find that their range of movement improves but pain relief is likely to be limited
A patient with heterotopic ossification following total hip arthroplasty is thought to have a 90-100 chance of developing it on the contralateral hip if this hip also undergoes total arthroplasty
it would be prudent to minimize the risk of heterotopic ossification developing after arthroplasty by performing surgery whereby the following are ensured
Exposure is meticulous Retraction is performed carefully and soft tissue
is handled carefully Irrigation is adequate Devitalized tissue is excised Hemostasis is adequate Postoperative drains (when used) are not
retained for longer than necessary Perioperative antibiotic prophylaxis is used Postoperative anticoagulation (when used for
deep vein thrombosis prophylaxis) is carefully controlled
sources of knee stiffness 1-extrinsic severe osteoarthritis of the ipsilateral hip neurologic injury leading to muscle rigidity tight quadriceps or hamstring muscles secondary to muscle injury heterotopic ossification or long-standing juvenile inflammatory conditions limiting knee
range of motion prior to the completion of skeletal growth When extrinsic sources are identified revision total knee arthroplasty is unlikely to be associated with a favorable outcome without correction of the extrinsic problem
2-intrinsic (1) overstuffing of the patellofemoral articulation (2) an
excessively tight flexion andor extension gap (3) a tight posterior cruciate ligament (4) femoral andor tibial malrotation (5) arthrofibrosis and (6) limited bearing excursion in association with a highly conforming mobile-bearing prosthetic design
HTO after TKA
Heterotopic Ossification (HO) following primary Total Knee Replacement (TKR)
Occurs in 3-90 of TKRs 3-grade classification system No correlation between HO and component
alignment or component position
Clinical findings similar to early infection Continuing low-grade fever Warm swollen and erythematous knee Normal blood tests Possibly an association with HLA-A2 and B18 HO patients have worse KSS and function
scores
Patients at HIGH risk for developing HO after TKR (Knee Arthroplasty) (5)
Those with limited postoperative knee flexion
Increased lumbar bone mineral density (BMD) on multivariate analysis (3)
Hypertrophic arthrosis Excessive periosteal trauma Notching of the anterior femur Those who require forced manipulation
after TKA 47 in revision TKR surgery (6) Higher rates in revision TKR cases with
infection (up to 76
DaughertyBell classification of HO of the knee 0 No evidence of HO 1 Bone islands in periarticular soft tissue (no
involvement of femur patella or tibia) or HO within quadriceps expansion measuring lt1 cm
2 Spur formation measuring lt5 cm that involves the femur patella or tibia if more than one bone demonstrates HO separation of HO spurs
measure gt1 cm or HO within quadriceps expansion measuring ge1 cm but lt3 cm
3 Spur formation gt5 cm involving femur patella or tibia if more than one bone demonstrates HO separation of HO spurs measure lt1 cm or HO
within quadriceps expansion measuring ge3 cm 4 Extensive HO of the knee causing ankylosis
class 2 HO begins to involve the major bones of the knee joint with spur formation limited to a size of 5 cm
HO class 2 may be observed in select patients with complete ROM and no reported pain Patients with class 3 HO would likely always benefit from surgical excision
followed by RT prophylaxis Certainly patients in either cohort with a subclass ldquoBrdquo assignment (symptomatic) would
benefit from treatment All patients with class 4 HO require
treatment to alleviate ankylosis
treatment
References Whyte ldquoPagetrsquos Disease of Bonerdquo NEMJ vol 355
2006 Klein and Parvizi ldquoSurgical Manifestations of Pagetrsquos
Diseaserdquo JAAOS vol 14 2006 Orthobullets Campbell Apley Emedicinecom
-Chapter 15 Heterotopic Ossification after Traumatic Brain InjuryBy Jesuacutes Moreta and Joseacute Luis Martiacutenez-de los Mozos DOI 10577257343
Questions
Thank You
Radiographs coarsened trabeculae which give the bone a blastic
appearance both increased and decreased osteodensity may exist
depending on phase of disease lytic phase
lucent areas with expansion and thinned intact cortices blade of grass or flame-shaped lucent advancing edge
mixed phase combination of lysis and sclerosis with coarsened trabeculae
sclerotic phase bone enlargement with cortical thickening sclerotic and lucent
area
remodeled cortices loss of distinction between cortices and medullary cavity
long bone bowing bowing of femur or tibia
fractures hip and knee osteoarthritis osteitis circumscripta
(cotton wool exudates) in skull Pagets secondary sarcoma
shows cortical bone destruction soft tissue mass
MRI may show lumbar spinal stenosis
Bone scan accurately marks site of disease intensely hot in lytic and mixed phase less hot in sclerotic phase
CT scan cortical thickening and coarsened trabeculae
CTMRI Incidental finding Evaluation of atypical presentations
neurological involvement and possible malignant transformation
CT trabecularcortical thinning thickening irregularity
MRI non-specific marrow changes
BiochemistrySerum AlkPhosEnzyme found in osteoblastic membrane Indicator of osteoblastic activity uarrin Pagetrsquos but can be normal Levels correlate with disease extent and activity elevated urinary hydroxyproline (collagen breakdown marker) increased urinary N-telopeptide alpha-C-telopeptide
and deoxypyridinoline normal calcium levels
Other recommended tests ESR -elevation may indicate malignant transformation
CRP Ca -hypercalcemiamay occur in Pagetrsquos PO4 25-hydroxyvitamin D -rule out osteomalacia LFTs-rule out liver disease
Diagnostic Biopsy Diagnosis is usually achieved clinically and by
plain radiographic appearance Biopsy rarely required
Characteristic HistopathologyDisorganized immature trabeculararchitecture with irregular cement lines (ldquomosaicrdquopattern)
Rimming osteoblasts andor multinucleated osteoclasts
Management Options (May require no treatment if asymptomatic)
Supportive Care Pharmacologic Surgical (OrthopedicNeurosurgical
Supportive Care Occupational therapy Physical aides Counseling for fall+fracture prevention
Physical therapy Analgesics Weight control
Pharmacologic ManagementGoals Relieve symptoms and Prevent potential
complications Normalization of serum AlkPhos associated
with better long-term outcomes and disease control
Indications to treat Pain Deformity Neurologic symptoms Asymptomatic but high-risk for complications
(prophylactic) Management of hypercalcemia(rare) Pre-op reduce blood flow and potential
operative blood loss
Calcitonin is the most widely used It reduces bone resorption by decreasing both the activity and the number
of osteoclasts serum alkaline phosphatase and urinaryhydroxyproline levels are lowered Salmon calcitonin is more effective than the porcine variety subcutaneous injections of 50ndash100 MRC units are given daily until pain is relieved and the alkaline phosphatase levels are reduced and stabilized Maintenance injections once or twice weekly may have to be continued indefinitely but some authorities advocate stopping the drug and resuming treatment if symptoms recur Calcitonin can also be administered in a nasal spray Bisphosphonates bind to hydroxyapatite crystals
inhibiting their rate of growth and dissolution It is claimed that the reduction in bone turnover following their use is associated with the formation of lamellar rather than woven bone and that even after treatment is stopped there may be prolonged remission of disease (Bickerstaff et al 1990) Etidronate can be given orally (always on an empty stomach) but dosage should be kept low (eg 5 mgkg per day for up to 6 months) and vitamin D and calcium should also be given lest impaired bone mineralization results inosteomalacia The newer bisphosphonates (eg alendronate or pamidronate) do not have this disadvantage so they should be used as the treatment of choice they produce remissions even with shortcourses of 1 or 2 weeks
BisphosphonatesSynthetic analogues of inorganic phosphate adhere to mineralized surfaces
Ingested selectively by osteoclasts Disrupts enzyme pathways and reduces osteoclastic bone resorption
calcitonin causes osteoclasts to shrink in size and decreases their bone resorptive activity within minutes administered subcutaneously or intramuscularly
teriparatide is contraindicated in Pagets disease due to risk of secondary osteosarcoma
Surgical Management Few require surgery
Common Procedures Corrective osteotomy of long bone deformity indications
fractures through pathologic bowing of long bones impending pathologic fracture of long bone with bowing deformity
Arthroplasty (hip knee) the most common complications include
malalignment with knee arthroplasty bleeding with hip arthroplasty
Combination arthroplasty with osteotomy Fracture fixation
Preoperative Considerations Medical assessment for extraskeletalmanifestations eg high-
output heart failure
Medical treatment of active disease Preoperative autologousblood donation
Thorough planningeg good quality x-rays for templatingand device selection
Intraoperative Considerations Blood salvage system Expansileapproach + soft tissue release Sharp reamersburrsdrills for IM access Extramedullaryguidenavigation systems Concomitant osteotomy
PostoperativeConsiderations Monitoring for cardiac complications Continued medical tx of active disease
uarrHeterotopic ossification Prophylaxis against HO
Possible future excision of HO for painROM
1-Tieg provides a review of Pagets disease of bone and treatment indications In his review he discusses that most patients with Pagets disease are asymptomatic but in those that do present pain is the most common presenting symptom He recommends medical and surgical treatment of asymptomatic patients who have active disease at sites where complications are likely to develop
Altman did a review of 290 patients with Pagets disease of bone His findings showed 83 had one or more rheumatic syndromes He found the rate of osteoarthritis related to Pagets disease was elevated in the hip and knee Rheumatoid arthritis hyperuricemia and gout did not appear increased in this group
Mangham et al looked the rate of secondary sarcomas as a result of Pagets disease of bone They found the rate to be around 03 with male predominance They also found that widespread skeletal involvement by Pagets disease was not a significant risk factor for malignant transformation
Interesting views about pagets
Smith et al reviewed the pathologic complications of Pagets bone disease Pagets bone disease commonly causes osseous weakening (deformity and fracture) and arthritis in the hip joint Management of end stage disease is successful with cemented and cementless total hip arthroplasty Bleeding is the most common intra- and post-operative complication of surgery
Gabel et al retrospectively reviewed thirteen patients who had had sixteen total knee arthroplasties for Pagetic gonarthrosis Unlike total hip arthroplasty surgery Paget disease did not increase the amount of blood lost during the operation or in the postoperative period The most common complication associated with total knee arthroplasty was malalignment
Hansen et al reviewed the incidence of osteosarcomas complicating Pagets Disease Of the typical sites that are usually involved in Pagets disease (eg spine pelvis femur tibia and humerus) secondary osteosarcoma tends to spare the spine
Shaylor et al reported the mortality rates in 26 patient with osteosarcoma secondary to Paget s disease There was a 47 mortality at 1 year and 75 at 2 years from diagnosis In their series no patient survived for 5 years All patients died of metastatic disease
Langston et al conducted a randomized trial that compared the results of symptomatic treatment versus intensive bisphosphonate therapy in patients with Pagets disease Clinical fractures occurred in 46 of 661 patients (70) in the treatment group compared with 49 of 663 patients (74) in the symptomatic treatment group They concluded that bisphosphonates did not show a significant beneficial impact on pain quality of life or fracture incidence
Hadjipavlou et al reviewed Pagets disease of the bone and its management Farmers have been shown to have an increased incidence of Pagets disease Average age at presentation is in the 5th and 6th decade Symptomatic individuals are recommended to be treated initially with medical management They suggest that bisphosphonates are more effective than calcitonin at suppressing the histological and biochemical activity in Pagetrsquos disease
Summary Epid Very common in elderly Path Abnormal osteoclastshellipuarrbone
turnoverhellipdeposition of abnormal bone SampS Pain deformity fracture arthropathy Labs uarrAlkPhos X-ray Characteristic coarse thickened
trabeculae Bone scan Very hot Rx Bisphosphonates Surgery for arthropathy fracture painful
deformity
A 65-year-old male presents with increasing shoulder pain over the past 9 months He is otherwise healthy and has no other complaints Radiograph of his shoulder is shown in Figure A Whole body bone scan and biopsy photograph are shown in Figures B and C What is the most appropriate treatment for this patient
1 Referral to endocrinology 2 Radiation therapy and chemotherapy 3 Wide resection and reconstruction 4 Radiation therapy wide resection and reconstruction 5 Chemotherapy wide resection and reconstruction
Histiocytosis X or Langerhans cell histiocytosis is a spectrum of diseases of the reticuloendothelial system with one of three general presentations Eosinophilic granuloma (EG)
usually a single self-limited lesion found in younger patients
Hand-Schuller-Christian disease (HSC) chronic disseminated form with bone and visceral lesions also known as Langerhans cell histiocytosis with visceral
involvement Letterer-Siwe disease (LSD)
fatal form that occurs in young children
Eosinophilic granuloma
Epidemiology demographics
most commonly occurs in children (80 of afflicted lt 20 years of age)
HSC disease presents in children gt 3 years of age LSD occurs in children lt 3 years of age Male to female ratio of 21
location eosinophilic granuloma
commonly presents in the skull ribs clavicle scapula mandible
isolated lesions of the spine (thoracic most common) can also occur in diaphyseal regions of long bones and the
pelvis HSC
multiple bony sites multiple lytic skull lesions visceral involvement of the lungs spleen liver skin lymph
nodes
Genetics no clear genetic pattern of inheritance or locus has
been determined Prognosis
EG isolated involvement generally treatable with local
management spine lesions can spontaneously resolve
HSC prognosis depends on response to chemotherapy worsening prognosis with increasing extraskeletal
involvement LSD
generally fatal in children lt 3 years of age
Symptoms skeletal involvement
pain and swelling at the region of involvement limping can be seen with pelvic or lower extremity
involvement vertebral involvement
localized or diffuse back pain increasingly kyphotic posture radiculopathy can occur with more aggressive lesions
HSC classic triad of
multiple lytic skull lesions diabetes insipidus
increased thirst and water intake exopthalmos
visceral involvement diffuse or nonspecific abdominal or chest pain
Radiographs general
known as the great mimicker as it appears similar to many lesions radiographic differential includes osteomyelitis leukemia lymphoma
fibrous dysplasia or Ewings sarcoma diaphyseal lesions
well defined intramedullary lytic or punched-out lesion cortex may be thinned expanded or destroyed may have periosteal reaction
metaphyseal lesions extend up to but not through the physis less central location than diaphyseal lesions
spinal lesions vertebra plana (flattened vertebrae) in spine increased kyphosis
cranial involvement multiple punched-out lytic lesions
MRI may show a soft tissue mass adjacent to boney lesions
Bone scan generally shows increased uptake in the region of boney lesion
Histology Langerhans cells
mononuclear histiocyte-like cells with oval nuclei with well-defined round or oval cytoplasm
a prominent nuclear groove (coffee bean nuclei) can be seen in most of the nuclei
eosinophilic cytoplasm (pink generally) stain with CD1A electronmicroscopy
birbeck granules seen inside Langerhans cells mixture of inflammatory cells also present giant cells are present lack of nuclear atypia and atypical mitoses
differentiates this condition from malignant conditions such as Ewings sarcoma lymphoma of bone and metastatic neuroblastoma which may look similar based on the round cells alone
eosinophilic cytoplasm (pink generally)
Treatment
bullNonoperative bull observation alone
bull indications bull a self-limited process and it is reasonable to treat with observation alone
bull bracing bull indications
bull to prevent progressive kyphosis of the spinebull outcomes
bull will correct deformity in 90 of patientsbull vertebral lesions generally regain 50 of their height
bull low dose irradiation (600-800 cGy) bull indications
bull indicated for lesions in the spine that compromise stability neurologic statusbull lesions not amenable to injection or open treatment
bull outcomes bull effective for most lesions
bull chemotherapy bull indications
bull diffuse HSCbull outcomes
bull prognosis is improved with less severe extraskeletal involvementbull corticosteroid injection
bull indications bull isolated lesions bull can be performed after curettage as well
Operative curettage and bone grafting
indications for lesions that endanger the articular surface or are a risk for
impending fractures spinal deformity correction
indications progressive spine deformity refractory to bracing
approximately 10 of patients with spine lesion will need operative intervention for deformity correction
Destructive multiple lesion in young patientsAre eosinophilic granuloma lymphoma and leukemiaLymphoma is unlikely to present with exopthalmos diabetes insipidus or vertebra plana Lymphoma bone lesions are lytic and appear moth eatenpermeative on radiographs
Figure A shows a skin lesion typical of eosinophillic granuloma Figure B shows a lytic lesions without significant surrounding sclerosis as is characteristic of eosinophilic granuloma Figure C shows the characteristic histology of multiple eosinophils with their characteristic oval coffee bean nuclei and staining pattern of purpleredpink cytoplasm (depending on the stain) Importantly the histology slide lacks a malignant appearance (no cellular atypia or mytotic complexes and low nuclearcytoplasmic ratio)
Formation of bone in atypical extraskeletal tissues usually occurs
spontaneously or following trauma within 2 months of neurologic injury (brain or spinal cord)
most common location is between muscle and joint capsule Epidemiology
incidence (see table below)
demographics malefemale = 21 especially men with hypertrophic osteoarthritis and women gt65y
location traumatic brain injury or stroke
hip gt elbow gt shoulder gt knee elbow HO more common following brain trauma
occurs on affected (spastic) side rarely in the knee (TBI)
spinal cord injury hip gt knee gt elbow gt shoulder hip flexors and abductors gt extensors or adductors medial aspect of the knee
Heterotopic Ossification
Risk factors
Pathophysiology exact cause of HO is not known but there appears to be a
genetic pre disposition experimental HO associated with
tissue expression of BMP IT IS SAID TO BE CAUSED BY activation and proliferation of
mesenchymal stem cells Associated conditions
orthopaedic manifestations pathologic fractures
from decreased joint ROM and osteoporotic bone nerve impingement soft tissue contractures contributing to the formation of
decubitus ulcers joint ankylosis HO after THA adversely affects outcome of THA
nonorthopaedic conditions skin maceration and hygiene problems
Pathophysiology Early in the formation of HO oedema with exudative
infiltrate is present followed by fibroblastic proliferation and immature connective tissue formation Posteriorly osteoid formation is seen with the subsequent deposition of bone matrix Primitive osteoid is deposited as small masses in the periphery early (within the first two weeks) and osteoblasts are noted located irregularly Osteoblasts produce tropocollagen which polymerizes to form collagen and secrete alkaline phosphatase which allows calcium to precipitate and the mineralization of bone matrix As mineralization progresses amorphous calcium phosphate is progressively replaced by hydroxyapatite crystals During the following weeks the lesion matures with a centripetal pattern and after 6-12 months an appearance of true bone is noted The new bone is always extra-articular and can be contiguous with the skeleton but generally does not involve the periosteum
IN SUMMARY It has been postulated that three conditions
must be met to achieve heterotopic bone formation ---a stimulating event oestrogenic precursor cells and a proper environment LIKE hypercalcaemia tissue hypoxia pH changes (alkalosis) or prolonged immobilization
ClassificationbullSubtypes
bull neurogenic HO bull Four clinical stages of HO in people with spinal cord injury were
described by Nicholas in 1973
bull traumatic myositis ossificans bull fibrodysplasia ossificans progressiva (Munchmeyers Disease)
Neurogenic HO Symptoms
painless loss of ROM interferes with ADL CRPS symptoms fever
Physical exam inspection
warm painful swollen joint may have effusion skin problems
decubitus ulcers from contractures around skin muscles ligaments
skin maceration and hygiene problems motion
decreased joint ROM joint ankylosis with HO after TKA might develop quad muscle snapping or patella
instability neurovascular
peripheral neuropathy HO often impinges on adjacent NV structures
Imaging
bullRadiographs bull findings
bull ossification usually easy to visualize bull maturity of HO
bull the appearance of a bony cortex suggests mature HObull sharp demarcation from surrounding tissue bull trabecular pattern
bull sensitivity and specificity bull not useful for early diagnosisbull only useful at 1 week after onset of symptoms
bull calcium is deposited 7-10 days later than symptom onsetbullUltrasound
bull indications bull for early diagnosis of hip HO
bull findings bull echogenic surfaces with posterior acoustic shadowing
bullCT bull indications
bull useful for preoperative planning bullTriphasic bone scan
bull indications bull best for early diagnosis bull most commonly used diagnostic study
Radiographs are extremely useful in the staging of heterotopic ossification and will show the development of sharp cortical margins once the lesion has reached maturity
Heterotopic bone is a condition in which lamellar bone forms in non-ossified soft tissues In the early stages studies such as MRI and bone scan are more sensitive for diagnosis as radiographs may appear normal for the first three weeks After the appropriate diagnosis is made sequential radiographs are useful for monitoring the progression of the ossification Once it has reached the mature stage sharp cortical margins will appear and surgical resection may be considered
lab
Labs elevated serum alkaline phosphatase (gt250IUL)
ALP removes inhibitors of mineralization nonspecific may be elevated with skeletal trauma cannot determine maturity of HO elevated 12wks after surgery is predictor
elevated CRP correlates with inflammatory activity of HO better than ESR normalization of CRP may correlate with maturity of HO
elevated ESR (gt35mmh) 12wks after THA is predictor
elevated CK correlates with involvement of muscle extent of muscle
involvement Histology
mature fatty bone marrow mature trabecular bone
Heterotopic ossification (HO) most commonly occurs at the amputation site if the amputation was performed thru the zone of injury especially if the injury was a blast mechanism
Symptomatic heterotopic ossification of the quadriceps may occur following placement of a large-diameter Steinmann pin for the purpose of temporary skeletal traction
TreatmentThe prevention of heterotopic ossification is focused on three basic principles disrupting the inductive signalling pathways altering the osteoprogenitor cells or modifying the environment
bullphysiotherapy should involve an assisted range of movement exercises with gentle stretch and terminal resistance trainingbullProphylaxis
bull bisphosphonates amp NSAIDS bull indications
bull although no literature supports are commonly usedbull technique
bull indomethacin is most commonly used bull dose is 75mgday for 10days to 6 weeks
bull perioperative radiation bull indications
bull although no literature supports commonly usedbull is thought to be effective by blocking osteoblast differentiation
bull technique bull a single perioperative dose of 700cGy can be given either 4
hours preop or within 72 hours postoperatively bull lt550cGy not effective
Nonsteroidal anti-inflammatory drugs (NSAIDs) These drugs have demonstrated good results in
preventing heterotopic ossification after total hip arthroplasty
A direct effect of NSAIDs on the formation of heterotopic ossification has been described due to the inhibition of the differentiation of mesenchymal cells into oestrogenic cells There is also an indirect effect which refers to the inhibition of bone remodelling by suppression of the prostagland unmediated inflammatory response (specifically PGE-2)
Indomethacin has been considered a useful medication for heterotopic ossification prophylaxis following total hip replacement
prescribed for three to six weeks in a dose of 75mgday within two months of the injury may reduce the incidence of heterotopic ossification by two to three times
Biphosphonates inhibits precipitation of calcium phosphate and blocks the aggregation and mineralisation of hydroxyapatite crystals In primary prevention Banovac et al [56] have suggested that the treatment should begin as soon as elevated alkaline phosphatase is diagnosed or positive findings in ultrasonography or bone scans are shown In addition disphosphonates could have long-term effects on prevention when the treatment is finished
Posttraumatic wide exposure and surgical resection
indications severe loss of motion and decreased function
technique wide exposure required to identify all neurovascular
structures that may be involved timing of resection (controversial)
marked decrease in bone scan activity AND normalization of ALP
6 months following general trauma 1 year following SCI 15 years following TBI
some data suggests equivalent results when comparing early versus late resection
postop follow with 5 day course of indomethacin early gentle joint mobilization
The surgery is necessary in patients with symptomatic HO and unsuccessful medical treatment such as
Loss of range of motion and ankylosis with associated functional disability such as sitting difficulties
Complications of immobility such as pressure ulcers
Facilitate rehabilitation and recovery of muscular atrophy secondary to prolonged immobilisation
Difficulties of appropriate hygiene because access to the perineum or bladder care is needed
Severe pain refractory to analgesia Vascular andor nerve compression
Advantages to early excision of heterotopic ossification (vs waiting for maturation) include decreased soft tissue contracture better definition between heterotopic and native bone and decreased waiting time for the patient When the soft tissue envelope is benign one may proceed with operative release While waiting for normalization of alkaline phosphatase levels inactivity on bone scan or radiographic maturity may decrease risk of recurrent heterotopic ossification delaying operative release for these reasons has not been shown to improve results of final elbow range of motion after contracture release
Gartland recommended surgery after six months following traumatic heterotopic ossification one year following spinal cord injury and 18 months after head injury
In the past waiting until maturity in order to minimize the rate of recurrence after the surgical treatment was recommended Nevertheless recent studies do not confirm a higher rate of recurrence when the HO is excised in an earlier phase In addition a long delay before surgery leads to ankylosis a high degree of osteoporosis and more extensive intra-articular injuries These findings are associated with bad functional results and potential complications
Should you wait till lesion maturation
Prevention byHandle tissue carefully Avoid excess bleeding Achieve good hemostasis Beware of lesions that span internervous tissue planes
but if it happens resection of a large enough amount of bone to allow improvement of the range of motion and trying to preserve the joint
Our aim must be
A reactive process that is characterized by a well-circumscribed proliferation of fibroblasts cartilage and bone within muscle
A form of heterotopic ossification that is the result direct trauma intramuscular hematoma
most common location is the diaphysis of long bones Must differentiate from tumors Fibrodysplasia ossificans progressiva (FOP) is a rare subtype of heterotopic ossification
involves mutation of the ACVR1 gene (activin A type I receptor gene a BMP type-1 receptor)
Epidemiology demographics
most common in young active males (15 to 35 years old) body locations
quadriceps brachialis and gluteal muscles Genetics
almost always a posttraumatic condition Prognosis
usually self limiting mass usually begins to decrease in size after 1 yea
Myositis ossificans
PresentationbullSymptoms
bull pain tenderness swelling and decreased range of motion that usually presents within days of the injury
bull pain and size of the mass decrease with timebull mass increases in size over several months(usually 3 to 6 cm)
bull after the mass stops growing it becomes firmbullPhysical exam
bull palpable soft tissue massbull restricted range of motion
ImagingbullRadiographs
bull peripheral bone formation with central lucent areabull may appear as dotted veil pattern
bullMRI with gadolinium bull rim enhancement is seen within the first 3 weeks
bullCT scan bull lesion has an eggshell appearance
bullCharacteristic histology shows zonal pattern bull periphery of lesion
bull mature trabeculae of lamellar and woven bonebull calcification seen on xray
bull center of the lesion bull irregular mass of immature fibroblastsbull cartilage component may be presentbull (no calcification seen on xray) bull no cellular atypia seen
Treatment
bullNonoperative bull rest range of motion exercises and activity modification
bull passive stretching is contraindicated (makes it worse)bull physical therapy
bull utilized to maintain range of motionbull radiographic monitoring
bull obtained to confirm maturation of the lesionbullOperative
bull surgical excision bull indicated only if it remains a problem after it maturesbull do not operate in acute phase wait at least six months
bull excision of the lesion within 6 to 12 months predisposes to local recurrence
A 26-year-old man presents with generalized back and joint stiffness and difficulty opening his mouth His elder sister has similar complaints Since childhood he has had 3 surgeries for excision of recurrent bony prominences around his knees He walks with a stooped over posture seen in Figure A Radiographs of his feet knee hip and spine are seen in Figures B-E respectively
fibrodysplasia ossificans progressiva
Stone Man Disease) which involves a mutation of the ACVR1
There are 2 hallmark characteristics progressive heterotopic ossification (muscles fascia tendons ligaments and joint capsules) and congenital malformation of the great toe (hallux valgus malformed first metatarsal and monophalangism) BMP4 which contributes to the formation of the skeleton in the normal embryo is implicated in this disease
Complications
bullHematoma and intraoperative bleedingbullInfection
bull higher rate of infection following joint arthroplasty if HO is present
bullFractures of osteoporotic bone bull osteopenic from disusebull during surgery or physiotherapy
bullRecurrence bull recurrence rate correlates with neurological injury
bull greater recurrence if severe neurological compromisebullAVN
bull if extensive dissection or stripping is required
HTO AND ISS
When ISS is below 25 the mortality risk is minimal and above 25 it is an almost linear increase
When ISS is 50 the mortality is 50 When above 70 it is close to 100 If an injury is assigned an AIS of 6 (unsurvivable injury) the ISS score is
automatically assigned to 75 Highest ISS score obtainable is 75 For trauma patients of vehicular accidents the scoring system is important
for assessing the effectiveness of medical care in reducing morbidity and mortality
Advantages virtually the only anatomical scoring system in use correlates linearly with
mortality morbidity hospital stay other measures of severity
Weaknesses Any error in AIS scoring increases the ISS error Many different injury patterns can yield the same ISS score Injuries to different body regions are not weighted Not a useful triage tool as a full description of patient injuries is not known
prior to full investigation amp operation
risk factors periosteal stripping off anterior femur male gender obesity post traumatic deformity Anterior and anterolateral approach Cementless
Neurogenic HO around the hip due to SCI occurs more often in the medial region than in the lateral region with ossified tissues extending from the pubic symphysis to the anteromedial femoral shaft posterior to the femoral neurovascular structures Ossification is also seen anteriorly involving the iliopsoas and femoral neurovascular structures laterally within gluteus minimus and posteriorly extending from the ilium to the posterior femur encasing the sciatic nerve
HTO AROUND hip and knee
The Brooker Classification of Heterotopic Ossification around the hip joint Class I has islands of bone within the soft tissues Class II has bone spurs from the pelvis or proximal end of the femur leaving at least 1 cm between opposing surfaces Class III has bone spurs from the pelvis andor proximal end of the femur reducing the space between opposing bone surfaces to less than 1 cm Class IV shows apparent bone ankylosis of the hip
Region I - Heterotopic ossifications are strictly below the tip of the greater trochanter
Region II - Heterotopic ossifications are below and above the tip of the greater trochanter
Region III - Heterotopic ossifications are strictly above the tip of the greater trochanter
Grade A - Single or multiple heterotopic ossifications are less than 10 mm in maximal extent without contact with the pelvis or the femur
Grade B - Heterotopic ossifications are greater than 10 mm without contact with the pelvis but with possible contact with the femur there is no bridging from the femur to the proximal part of the greater trochanter and no evidence of ankylosis
Grade C - Ankylosis by means of firm bridging from the femur to the pelvis is present
Shmidt classification
excision may be performed The results of this procedure are varied Patients may find that their range of movement improves but pain relief is likely to be limited
A patient with heterotopic ossification following total hip arthroplasty is thought to have a 90-100 chance of developing it on the contralateral hip if this hip also undergoes total arthroplasty
it would be prudent to minimize the risk of heterotopic ossification developing after arthroplasty by performing surgery whereby the following are ensured
Exposure is meticulous Retraction is performed carefully and soft tissue
is handled carefully Irrigation is adequate Devitalized tissue is excised Hemostasis is adequate Postoperative drains (when used) are not
retained for longer than necessary Perioperative antibiotic prophylaxis is used Postoperative anticoagulation (when used for
deep vein thrombosis prophylaxis) is carefully controlled
sources of knee stiffness 1-extrinsic severe osteoarthritis of the ipsilateral hip neurologic injury leading to muscle rigidity tight quadriceps or hamstring muscles secondary to muscle injury heterotopic ossification or long-standing juvenile inflammatory conditions limiting knee
range of motion prior to the completion of skeletal growth When extrinsic sources are identified revision total knee arthroplasty is unlikely to be associated with a favorable outcome without correction of the extrinsic problem
2-intrinsic (1) overstuffing of the patellofemoral articulation (2) an
excessively tight flexion andor extension gap (3) a tight posterior cruciate ligament (4) femoral andor tibial malrotation (5) arthrofibrosis and (6) limited bearing excursion in association with a highly conforming mobile-bearing prosthetic design
HTO after TKA
Heterotopic Ossification (HO) following primary Total Knee Replacement (TKR)
Occurs in 3-90 of TKRs 3-grade classification system No correlation between HO and component
alignment or component position
Clinical findings similar to early infection Continuing low-grade fever Warm swollen and erythematous knee Normal blood tests Possibly an association with HLA-A2 and B18 HO patients have worse KSS and function
scores
Patients at HIGH risk for developing HO after TKR (Knee Arthroplasty) (5)
Those with limited postoperative knee flexion
Increased lumbar bone mineral density (BMD) on multivariate analysis (3)
Hypertrophic arthrosis Excessive periosteal trauma Notching of the anterior femur Those who require forced manipulation
after TKA 47 in revision TKR surgery (6) Higher rates in revision TKR cases with
infection (up to 76
DaughertyBell classification of HO of the knee 0 No evidence of HO 1 Bone islands in periarticular soft tissue (no
involvement of femur patella or tibia) or HO within quadriceps expansion measuring lt1 cm
2 Spur formation measuring lt5 cm that involves the femur patella or tibia if more than one bone demonstrates HO separation of HO spurs
measure gt1 cm or HO within quadriceps expansion measuring ge1 cm but lt3 cm
3 Spur formation gt5 cm involving femur patella or tibia if more than one bone demonstrates HO separation of HO spurs measure lt1 cm or HO
within quadriceps expansion measuring ge3 cm 4 Extensive HO of the knee causing ankylosis
class 2 HO begins to involve the major bones of the knee joint with spur formation limited to a size of 5 cm
HO class 2 may be observed in select patients with complete ROM and no reported pain Patients with class 3 HO would likely always benefit from surgical excision
followed by RT prophylaxis Certainly patients in either cohort with a subclass ldquoBrdquo assignment (symptomatic) would
benefit from treatment All patients with class 4 HO require
treatment to alleviate ankylosis
treatment
References Whyte ldquoPagetrsquos Disease of Bonerdquo NEMJ vol 355
2006 Klein and Parvizi ldquoSurgical Manifestations of Pagetrsquos
Diseaserdquo JAAOS vol 14 2006 Orthobullets Campbell Apley Emedicinecom
-Chapter 15 Heterotopic Ossification after Traumatic Brain InjuryBy Jesuacutes Moreta and Joseacute Luis Martiacutenez-de los Mozos DOI 10577257343
Questions
Thank You
remodeled cortices loss of distinction between cortices and medullary cavity
long bone bowing bowing of femur or tibia
fractures hip and knee osteoarthritis osteitis circumscripta
(cotton wool exudates) in skull Pagets secondary sarcoma
shows cortical bone destruction soft tissue mass
MRI may show lumbar spinal stenosis
Bone scan accurately marks site of disease intensely hot in lytic and mixed phase less hot in sclerotic phase
CT scan cortical thickening and coarsened trabeculae
CTMRI Incidental finding Evaluation of atypical presentations
neurological involvement and possible malignant transformation
CT trabecularcortical thinning thickening irregularity
MRI non-specific marrow changes
BiochemistrySerum AlkPhosEnzyme found in osteoblastic membrane Indicator of osteoblastic activity uarrin Pagetrsquos but can be normal Levels correlate with disease extent and activity elevated urinary hydroxyproline (collagen breakdown marker) increased urinary N-telopeptide alpha-C-telopeptide
and deoxypyridinoline normal calcium levels
Other recommended tests ESR -elevation may indicate malignant transformation
CRP Ca -hypercalcemiamay occur in Pagetrsquos PO4 25-hydroxyvitamin D -rule out osteomalacia LFTs-rule out liver disease
Diagnostic Biopsy Diagnosis is usually achieved clinically and by
plain radiographic appearance Biopsy rarely required
Characteristic HistopathologyDisorganized immature trabeculararchitecture with irregular cement lines (ldquomosaicrdquopattern)
Rimming osteoblasts andor multinucleated osteoclasts
Management Options (May require no treatment if asymptomatic)
Supportive Care Pharmacologic Surgical (OrthopedicNeurosurgical
Supportive Care Occupational therapy Physical aides Counseling for fall+fracture prevention
Physical therapy Analgesics Weight control
Pharmacologic ManagementGoals Relieve symptoms and Prevent potential
complications Normalization of serum AlkPhos associated
with better long-term outcomes and disease control
Indications to treat Pain Deformity Neurologic symptoms Asymptomatic but high-risk for complications
(prophylactic) Management of hypercalcemia(rare) Pre-op reduce blood flow and potential
operative blood loss
Calcitonin is the most widely used It reduces bone resorption by decreasing both the activity and the number
of osteoclasts serum alkaline phosphatase and urinaryhydroxyproline levels are lowered Salmon calcitonin is more effective than the porcine variety subcutaneous injections of 50ndash100 MRC units are given daily until pain is relieved and the alkaline phosphatase levels are reduced and stabilized Maintenance injections once or twice weekly may have to be continued indefinitely but some authorities advocate stopping the drug and resuming treatment if symptoms recur Calcitonin can also be administered in a nasal spray Bisphosphonates bind to hydroxyapatite crystals
inhibiting their rate of growth and dissolution It is claimed that the reduction in bone turnover following their use is associated with the formation of lamellar rather than woven bone and that even after treatment is stopped there may be prolonged remission of disease (Bickerstaff et al 1990) Etidronate can be given orally (always on an empty stomach) but dosage should be kept low (eg 5 mgkg per day for up to 6 months) and vitamin D and calcium should also be given lest impaired bone mineralization results inosteomalacia The newer bisphosphonates (eg alendronate or pamidronate) do not have this disadvantage so they should be used as the treatment of choice they produce remissions even with shortcourses of 1 or 2 weeks
BisphosphonatesSynthetic analogues of inorganic phosphate adhere to mineralized surfaces
Ingested selectively by osteoclasts Disrupts enzyme pathways and reduces osteoclastic bone resorption
calcitonin causes osteoclasts to shrink in size and decreases their bone resorptive activity within minutes administered subcutaneously or intramuscularly
teriparatide is contraindicated in Pagets disease due to risk of secondary osteosarcoma
Surgical Management Few require surgery
Common Procedures Corrective osteotomy of long bone deformity indications
fractures through pathologic bowing of long bones impending pathologic fracture of long bone with bowing deformity
Arthroplasty (hip knee) the most common complications include
malalignment with knee arthroplasty bleeding with hip arthroplasty
Combination arthroplasty with osteotomy Fracture fixation
Preoperative Considerations Medical assessment for extraskeletalmanifestations eg high-
output heart failure
Medical treatment of active disease Preoperative autologousblood donation
Thorough planningeg good quality x-rays for templatingand device selection
Intraoperative Considerations Blood salvage system Expansileapproach + soft tissue release Sharp reamersburrsdrills for IM access Extramedullaryguidenavigation systems Concomitant osteotomy
PostoperativeConsiderations Monitoring for cardiac complications Continued medical tx of active disease
uarrHeterotopic ossification Prophylaxis against HO
Possible future excision of HO for painROM
1-Tieg provides a review of Pagets disease of bone and treatment indications In his review he discusses that most patients with Pagets disease are asymptomatic but in those that do present pain is the most common presenting symptom He recommends medical and surgical treatment of asymptomatic patients who have active disease at sites where complications are likely to develop
Altman did a review of 290 patients with Pagets disease of bone His findings showed 83 had one or more rheumatic syndromes He found the rate of osteoarthritis related to Pagets disease was elevated in the hip and knee Rheumatoid arthritis hyperuricemia and gout did not appear increased in this group
Mangham et al looked the rate of secondary sarcomas as a result of Pagets disease of bone They found the rate to be around 03 with male predominance They also found that widespread skeletal involvement by Pagets disease was not a significant risk factor for malignant transformation
Interesting views about pagets
Smith et al reviewed the pathologic complications of Pagets bone disease Pagets bone disease commonly causes osseous weakening (deformity and fracture) and arthritis in the hip joint Management of end stage disease is successful with cemented and cementless total hip arthroplasty Bleeding is the most common intra- and post-operative complication of surgery
Gabel et al retrospectively reviewed thirteen patients who had had sixteen total knee arthroplasties for Pagetic gonarthrosis Unlike total hip arthroplasty surgery Paget disease did not increase the amount of blood lost during the operation or in the postoperative period The most common complication associated with total knee arthroplasty was malalignment
Hansen et al reviewed the incidence of osteosarcomas complicating Pagets Disease Of the typical sites that are usually involved in Pagets disease (eg spine pelvis femur tibia and humerus) secondary osteosarcoma tends to spare the spine
Shaylor et al reported the mortality rates in 26 patient with osteosarcoma secondary to Paget s disease There was a 47 mortality at 1 year and 75 at 2 years from diagnosis In their series no patient survived for 5 years All patients died of metastatic disease
Langston et al conducted a randomized trial that compared the results of symptomatic treatment versus intensive bisphosphonate therapy in patients with Pagets disease Clinical fractures occurred in 46 of 661 patients (70) in the treatment group compared with 49 of 663 patients (74) in the symptomatic treatment group They concluded that bisphosphonates did not show a significant beneficial impact on pain quality of life or fracture incidence
Hadjipavlou et al reviewed Pagets disease of the bone and its management Farmers have been shown to have an increased incidence of Pagets disease Average age at presentation is in the 5th and 6th decade Symptomatic individuals are recommended to be treated initially with medical management They suggest that bisphosphonates are more effective than calcitonin at suppressing the histological and biochemical activity in Pagetrsquos disease
Summary Epid Very common in elderly Path Abnormal osteoclastshellipuarrbone
turnoverhellipdeposition of abnormal bone SampS Pain deformity fracture arthropathy Labs uarrAlkPhos X-ray Characteristic coarse thickened
trabeculae Bone scan Very hot Rx Bisphosphonates Surgery for arthropathy fracture painful
deformity
A 65-year-old male presents with increasing shoulder pain over the past 9 months He is otherwise healthy and has no other complaints Radiograph of his shoulder is shown in Figure A Whole body bone scan and biopsy photograph are shown in Figures B and C What is the most appropriate treatment for this patient
1 Referral to endocrinology 2 Radiation therapy and chemotherapy 3 Wide resection and reconstruction 4 Radiation therapy wide resection and reconstruction 5 Chemotherapy wide resection and reconstruction
Histiocytosis X or Langerhans cell histiocytosis is a spectrum of diseases of the reticuloendothelial system with one of three general presentations Eosinophilic granuloma (EG)
usually a single self-limited lesion found in younger patients
Hand-Schuller-Christian disease (HSC) chronic disseminated form with bone and visceral lesions also known as Langerhans cell histiocytosis with visceral
involvement Letterer-Siwe disease (LSD)
fatal form that occurs in young children
Eosinophilic granuloma
Epidemiology demographics
most commonly occurs in children (80 of afflicted lt 20 years of age)
HSC disease presents in children gt 3 years of age LSD occurs in children lt 3 years of age Male to female ratio of 21
location eosinophilic granuloma
commonly presents in the skull ribs clavicle scapula mandible
isolated lesions of the spine (thoracic most common) can also occur in diaphyseal regions of long bones and the
pelvis HSC
multiple bony sites multiple lytic skull lesions visceral involvement of the lungs spleen liver skin lymph
nodes
Genetics no clear genetic pattern of inheritance or locus has
been determined Prognosis
EG isolated involvement generally treatable with local
management spine lesions can spontaneously resolve
HSC prognosis depends on response to chemotherapy worsening prognosis with increasing extraskeletal
involvement LSD
generally fatal in children lt 3 years of age
Symptoms skeletal involvement
pain and swelling at the region of involvement limping can be seen with pelvic or lower extremity
involvement vertebral involvement
localized or diffuse back pain increasingly kyphotic posture radiculopathy can occur with more aggressive lesions
HSC classic triad of
multiple lytic skull lesions diabetes insipidus
increased thirst and water intake exopthalmos
visceral involvement diffuse or nonspecific abdominal or chest pain
Radiographs general
known as the great mimicker as it appears similar to many lesions radiographic differential includes osteomyelitis leukemia lymphoma
fibrous dysplasia or Ewings sarcoma diaphyseal lesions
well defined intramedullary lytic or punched-out lesion cortex may be thinned expanded or destroyed may have periosteal reaction
metaphyseal lesions extend up to but not through the physis less central location than diaphyseal lesions
spinal lesions vertebra plana (flattened vertebrae) in spine increased kyphosis
cranial involvement multiple punched-out lytic lesions
MRI may show a soft tissue mass adjacent to boney lesions
Bone scan generally shows increased uptake in the region of boney lesion
Histology Langerhans cells
mononuclear histiocyte-like cells with oval nuclei with well-defined round or oval cytoplasm
a prominent nuclear groove (coffee bean nuclei) can be seen in most of the nuclei
eosinophilic cytoplasm (pink generally) stain with CD1A electronmicroscopy
birbeck granules seen inside Langerhans cells mixture of inflammatory cells also present giant cells are present lack of nuclear atypia and atypical mitoses
differentiates this condition from malignant conditions such as Ewings sarcoma lymphoma of bone and metastatic neuroblastoma which may look similar based on the round cells alone
eosinophilic cytoplasm (pink generally)
Treatment
bullNonoperative bull observation alone
bull indications bull a self-limited process and it is reasonable to treat with observation alone
bull bracing bull indications
bull to prevent progressive kyphosis of the spinebull outcomes
bull will correct deformity in 90 of patientsbull vertebral lesions generally regain 50 of their height
bull low dose irradiation (600-800 cGy) bull indications
bull indicated for lesions in the spine that compromise stability neurologic statusbull lesions not amenable to injection or open treatment
bull outcomes bull effective for most lesions
bull chemotherapy bull indications
bull diffuse HSCbull outcomes
bull prognosis is improved with less severe extraskeletal involvementbull corticosteroid injection
bull indications bull isolated lesions bull can be performed after curettage as well
Operative curettage and bone grafting
indications for lesions that endanger the articular surface or are a risk for
impending fractures spinal deformity correction
indications progressive spine deformity refractory to bracing
approximately 10 of patients with spine lesion will need operative intervention for deformity correction
Destructive multiple lesion in young patientsAre eosinophilic granuloma lymphoma and leukemiaLymphoma is unlikely to present with exopthalmos diabetes insipidus or vertebra plana Lymphoma bone lesions are lytic and appear moth eatenpermeative on radiographs
Figure A shows a skin lesion typical of eosinophillic granuloma Figure B shows a lytic lesions without significant surrounding sclerosis as is characteristic of eosinophilic granuloma Figure C shows the characteristic histology of multiple eosinophils with their characteristic oval coffee bean nuclei and staining pattern of purpleredpink cytoplasm (depending on the stain) Importantly the histology slide lacks a malignant appearance (no cellular atypia or mytotic complexes and low nuclearcytoplasmic ratio)
Formation of bone in atypical extraskeletal tissues usually occurs
spontaneously or following trauma within 2 months of neurologic injury (brain or spinal cord)
most common location is between muscle and joint capsule Epidemiology
incidence (see table below)
demographics malefemale = 21 especially men with hypertrophic osteoarthritis and women gt65y
location traumatic brain injury or stroke
hip gt elbow gt shoulder gt knee elbow HO more common following brain trauma
occurs on affected (spastic) side rarely in the knee (TBI)
spinal cord injury hip gt knee gt elbow gt shoulder hip flexors and abductors gt extensors or adductors medial aspect of the knee
Heterotopic Ossification
Risk factors
Pathophysiology exact cause of HO is not known but there appears to be a
genetic pre disposition experimental HO associated with
tissue expression of BMP IT IS SAID TO BE CAUSED BY activation and proliferation of
mesenchymal stem cells Associated conditions
orthopaedic manifestations pathologic fractures
from decreased joint ROM and osteoporotic bone nerve impingement soft tissue contractures contributing to the formation of
decubitus ulcers joint ankylosis HO after THA adversely affects outcome of THA
nonorthopaedic conditions skin maceration and hygiene problems
Pathophysiology Early in the formation of HO oedema with exudative
infiltrate is present followed by fibroblastic proliferation and immature connective tissue formation Posteriorly osteoid formation is seen with the subsequent deposition of bone matrix Primitive osteoid is deposited as small masses in the periphery early (within the first two weeks) and osteoblasts are noted located irregularly Osteoblasts produce tropocollagen which polymerizes to form collagen and secrete alkaline phosphatase which allows calcium to precipitate and the mineralization of bone matrix As mineralization progresses amorphous calcium phosphate is progressively replaced by hydroxyapatite crystals During the following weeks the lesion matures with a centripetal pattern and after 6-12 months an appearance of true bone is noted The new bone is always extra-articular and can be contiguous with the skeleton but generally does not involve the periosteum
IN SUMMARY It has been postulated that three conditions
must be met to achieve heterotopic bone formation ---a stimulating event oestrogenic precursor cells and a proper environment LIKE hypercalcaemia tissue hypoxia pH changes (alkalosis) or prolonged immobilization
ClassificationbullSubtypes
bull neurogenic HO bull Four clinical stages of HO in people with spinal cord injury were
described by Nicholas in 1973
bull traumatic myositis ossificans bull fibrodysplasia ossificans progressiva (Munchmeyers Disease)
Neurogenic HO Symptoms
painless loss of ROM interferes with ADL CRPS symptoms fever
Physical exam inspection
warm painful swollen joint may have effusion skin problems
decubitus ulcers from contractures around skin muscles ligaments
skin maceration and hygiene problems motion
decreased joint ROM joint ankylosis with HO after TKA might develop quad muscle snapping or patella
instability neurovascular
peripheral neuropathy HO often impinges on adjacent NV structures
Imaging
bullRadiographs bull findings
bull ossification usually easy to visualize bull maturity of HO
bull the appearance of a bony cortex suggests mature HObull sharp demarcation from surrounding tissue bull trabecular pattern
bull sensitivity and specificity bull not useful for early diagnosisbull only useful at 1 week after onset of symptoms
bull calcium is deposited 7-10 days later than symptom onsetbullUltrasound
bull indications bull for early diagnosis of hip HO
bull findings bull echogenic surfaces with posterior acoustic shadowing
bullCT bull indications
bull useful for preoperative planning bullTriphasic bone scan
bull indications bull best for early diagnosis bull most commonly used diagnostic study
Radiographs are extremely useful in the staging of heterotopic ossification and will show the development of sharp cortical margins once the lesion has reached maturity
Heterotopic bone is a condition in which lamellar bone forms in non-ossified soft tissues In the early stages studies such as MRI and bone scan are more sensitive for diagnosis as radiographs may appear normal for the first three weeks After the appropriate diagnosis is made sequential radiographs are useful for monitoring the progression of the ossification Once it has reached the mature stage sharp cortical margins will appear and surgical resection may be considered
lab
Labs elevated serum alkaline phosphatase (gt250IUL)
ALP removes inhibitors of mineralization nonspecific may be elevated with skeletal trauma cannot determine maturity of HO elevated 12wks after surgery is predictor
elevated CRP correlates with inflammatory activity of HO better than ESR normalization of CRP may correlate with maturity of HO
elevated ESR (gt35mmh) 12wks after THA is predictor
elevated CK correlates with involvement of muscle extent of muscle
involvement Histology
mature fatty bone marrow mature trabecular bone
Heterotopic ossification (HO) most commonly occurs at the amputation site if the amputation was performed thru the zone of injury especially if the injury was a blast mechanism
Symptomatic heterotopic ossification of the quadriceps may occur following placement of a large-diameter Steinmann pin for the purpose of temporary skeletal traction
TreatmentThe prevention of heterotopic ossification is focused on three basic principles disrupting the inductive signalling pathways altering the osteoprogenitor cells or modifying the environment
bullphysiotherapy should involve an assisted range of movement exercises with gentle stretch and terminal resistance trainingbullProphylaxis
bull bisphosphonates amp NSAIDS bull indications
bull although no literature supports are commonly usedbull technique
bull indomethacin is most commonly used bull dose is 75mgday for 10days to 6 weeks
bull perioperative radiation bull indications
bull although no literature supports commonly usedbull is thought to be effective by blocking osteoblast differentiation
bull technique bull a single perioperative dose of 700cGy can be given either 4
hours preop or within 72 hours postoperatively bull lt550cGy not effective
Nonsteroidal anti-inflammatory drugs (NSAIDs) These drugs have demonstrated good results in
preventing heterotopic ossification after total hip arthroplasty
A direct effect of NSAIDs on the formation of heterotopic ossification has been described due to the inhibition of the differentiation of mesenchymal cells into oestrogenic cells There is also an indirect effect which refers to the inhibition of bone remodelling by suppression of the prostagland unmediated inflammatory response (specifically PGE-2)
Indomethacin has been considered a useful medication for heterotopic ossification prophylaxis following total hip replacement
prescribed for three to six weeks in a dose of 75mgday within two months of the injury may reduce the incidence of heterotopic ossification by two to three times
Biphosphonates inhibits precipitation of calcium phosphate and blocks the aggregation and mineralisation of hydroxyapatite crystals In primary prevention Banovac et al [56] have suggested that the treatment should begin as soon as elevated alkaline phosphatase is diagnosed or positive findings in ultrasonography or bone scans are shown In addition disphosphonates could have long-term effects on prevention when the treatment is finished
Posttraumatic wide exposure and surgical resection
indications severe loss of motion and decreased function
technique wide exposure required to identify all neurovascular
structures that may be involved timing of resection (controversial)
marked decrease in bone scan activity AND normalization of ALP
6 months following general trauma 1 year following SCI 15 years following TBI
some data suggests equivalent results when comparing early versus late resection
postop follow with 5 day course of indomethacin early gentle joint mobilization
The surgery is necessary in patients with symptomatic HO and unsuccessful medical treatment such as
Loss of range of motion and ankylosis with associated functional disability such as sitting difficulties
Complications of immobility such as pressure ulcers
Facilitate rehabilitation and recovery of muscular atrophy secondary to prolonged immobilisation
Difficulties of appropriate hygiene because access to the perineum or bladder care is needed
Severe pain refractory to analgesia Vascular andor nerve compression
Advantages to early excision of heterotopic ossification (vs waiting for maturation) include decreased soft tissue contracture better definition between heterotopic and native bone and decreased waiting time for the patient When the soft tissue envelope is benign one may proceed with operative release While waiting for normalization of alkaline phosphatase levels inactivity on bone scan or radiographic maturity may decrease risk of recurrent heterotopic ossification delaying operative release for these reasons has not been shown to improve results of final elbow range of motion after contracture release
Gartland recommended surgery after six months following traumatic heterotopic ossification one year following spinal cord injury and 18 months after head injury
In the past waiting until maturity in order to minimize the rate of recurrence after the surgical treatment was recommended Nevertheless recent studies do not confirm a higher rate of recurrence when the HO is excised in an earlier phase In addition a long delay before surgery leads to ankylosis a high degree of osteoporosis and more extensive intra-articular injuries These findings are associated with bad functional results and potential complications
Should you wait till lesion maturation
Prevention byHandle tissue carefully Avoid excess bleeding Achieve good hemostasis Beware of lesions that span internervous tissue planes
but if it happens resection of a large enough amount of bone to allow improvement of the range of motion and trying to preserve the joint
Our aim must be
A reactive process that is characterized by a well-circumscribed proliferation of fibroblasts cartilage and bone within muscle
A form of heterotopic ossification that is the result direct trauma intramuscular hematoma
most common location is the diaphysis of long bones Must differentiate from tumors Fibrodysplasia ossificans progressiva (FOP) is a rare subtype of heterotopic ossification
involves mutation of the ACVR1 gene (activin A type I receptor gene a BMP type-1 receptor)
Epidemiology demographics
most common in young active males (15 to 35 years old) body locations
quadriceps brachialis and gluteal muscles Genetics
almost always a posttraumatic condition Prognosis
usually self limiting mass usually begins to decrease in size after 1 yea
Myositis ossificans
PresentationbullSymptoms
bull pain tenderness swelling and decreased range of motion that usually presents within days of the injury
bull pain and size of the mass decrease with timebull mass increases in size over several months(usually 3 to 6 cm)
bull after the mass stops growing it becomes firmbullPhysical exam
bull palpable soft tissue massbull restricted range of motion
ImagingbullRadiographs
bull peripheral bone formation with central lucent areabull may appear as dotted veil pattern
bullMRI with gadolinium bull rim enhancement is seen within the first 3 weeks
bullCT scan bull lesion has an eggshell appearance
bullCharacteristic histology shows zonal pattern bull periphery of lesion
bull mature trabeculae of lamellar and woven bonebull calcification seen on xray
bull center of the lesion bull irregular mass of immature fibroblastsbull cartilage component may be presentbull (no calcification seen on xray) bull no cellular atypia seen
Treatment
bullNonoperative bull rest range of motion exercises and activity modification
bull passive stretching is contraindicated (makes it worse)bull physical therapy
bull utilized to maintain range of motionbull radiographic monitoring
bull obtained to confirm maturation of the lesionbullOperative
bull surgical excision bull indicated only if it remains a problem after it maturesbull do not operate in acute phase wait at least six months
bull excision of the lesion within 6 to 12 months predisposes to local recurrence
A 26-year-old man presents with generalized back and joint stiffness and difficulty opening his mouth His elder sister has similar complaints Since childhood he has had 3 surgeries for excision of recurrent bony prominences around his knees He walks with a stooped over posture seen in Figure A Radiographs of his feet knee hip and spine are seen in Figures B-E respectively
fibrodysplasia ossificans progressiva
Stone Man Disease) which involves a mutation of the ACVR1
There are 2 hallmark characteristics progressive heterotopic ossification (muscles fascia tendons ligaments and joint capsules) and congenital malformation of the great toe (hallux valgus malformed first metatarsal and monophalangism) BMP4 which contributes to the formation of the skeleton in the normal embryo is implicated in this disease
Complications
bullHematoma and intraoperative bleedingbullInfection
bull higher rate of infection following joint arthroplasty if HO is present
bullFractures of osteoporotic bone bull osteopenic from disusebull during surgery or physiotherapy
bullRecurrence bull recurrence rate correlates with neurological injury
bull greater recurrence if severe neurological compromisebullAVN
bull if extensive dissection or stripping is required
HTO AND ISS
When ISS is below 25 the mortality risk is minimal and above 25 it is an almost linear increase
When ISS is 50 the mortality is 50 When above 70 it is close to 100 If an injury is assigned an AIS of 6 (unsurvivable injury) the ISS score is
automatically assigned to 75 Highest ISS score obtainable is 75 For trauma patients of vehicular accidents the scoring system is important
for assessing the effectiveness of medical care in reducing morbidity and mortality
Advantages virtually the only anatomical scoring system in use correlates linearly with
mortality morbidity hospital stay other measures of severity
Weaknesses Any error in AIS scoring increases the ISS error Many different injury patterns can yield the same ISS score Injuries to different body regions are not weighted Not a useful triage tool as a full description of patient injuries is not known
prior to full investigation amp operation
risk factors periosteal stripping off anterior femur male gender obesity post traumatic deformity Anterior and anterolateral approach Cementless
Neurogenic HO around the hip due to SCI occurs more often in the medial region than in the lateral region with ossified tissues extending from the pubic symphysis to the anteromedial femoral shaft posterior to the femoral neurovascular structures Ossification is also seen anteriorly involving the iliopsoas and femoral neurovascular structures laterally within gluteus minimus and posteriorly extending from the ilium to the posterior femur encasing the sciatic nerve
HTO AROUND hip and knee
The Brooker Classification of Heterotopic Ossification around the hip joint Class I has islands of bone within the soft tissues Class II has bone spurs from the pelvis or proximal end of the femur leaving at least 1 cm between opposing surfaces Class III has bone spurs from the pelvis andor proximal end of the femur reducing the space between opposing bone surfaces to less than 1 cm Class IV shows apparent bone ankylosis of the hip
Region I - Heterotopic ossifications are strictly below the tip of the greater trochanter
Region II - Heterotopic ossifications are below and above the tip of the greater trochanter
Region III - Heterotopic ossifications are strictly above the tip of the greater trochanter
Grade A - Single or multiple heterotopic ossifications are less than 10 mm in maximal extent without contact with the pelvis or the femur
Grade B - Heterotopic ossifications are greater than 10 mm without contact with the pelvis but with possible contact with the femur there is no bridging from the femur to the proximal part of the greater trochanter and no evidence of ankylosis
Grade C - Ankylosis by means of firm bridging from the femur to the pelvis is present
Shmidt classification
excision may be performed The results of this procedure are varied Patients may find that their range of movement improves but pain relief is likely to be limited
A patient with heterotopic ossification following total hip arthroplasty is thought to have a 90-100 chance of developing it on the contralateral hip if this hip also undergoes total arthroplasty
it would be prudent to minimize the risk of heterotopic ossification developing after arthroplasty by performing surgery whereby the following are ensured
Exposure is meticulous Retraction is performed carefully and soft tissue
is handled carefully Irrigation is adequate Devitalized tissue is excised Hemostasis is adequate Postoperative drains (when used) are not
retained for longer than necessary Perioperative antibiotic prophylaxis is used Postoperative anticoagulation (when used for
deep vein thrombosis prophylaxis) is carefully controlled
sources of knee stiffness 1-extrinsic severe osteoarthritis of the ipsilateral hip neurologic injury leading to muscle rigidity tight quadriceps or hamstring muscles secondary to muscle injury heterotopic ossification or long-standing juvenile inflammatory conditions limiting knee
range of motion prior to the completion of skeletal growth When extrinsic sources are identified revision total knee arthroplasty is unlikely to be associated with a favorable outcome without correction of the extrinsic problem
2-intrinsic (1) overstuffing of the patellofemoral articulation (2) an
excessively tight flexion andor extension gap (3) a tight posterior cruciate ligament (4) femoral andor tibial malrotation (5) arthrofibrosis and (6) limited bearing excursion in association with a highly conforming mobile-bearing prosthetic design
HTO after TKA
Heterotopic Ossification (HO) following primary Total Knee Replacement (TKR)
Occurs in 3-90 of TKRs 3-grade classification system No correlation between HO and component
alignment or component position
Clinical findings similar to early infection Continuing low-grade fever Warm swollen and erythematous knee Normal blood tests Possibly an association with HLA-A2 and B18 HO patients have worse KSS and function
scores
Patients at HIGH risk for developing HO after TKR (Knee Arthroplasty) (5)
Those with limited postoperative knee flexion
Increased lumbar bone mineral density (BMD) on multivariate analysis (3)
Hypertrophic arthrosis Excessive periosteal trauma Notching of the anterior femur Those who require forced manipulation
after TKA 47 in revision TKR surgery (6) Higher rates in revision TKR cases with
infection (up to 76
DaughertyBell classification of HO of the knee 0 No evidence of HO 1 Bone islands in periarticular soft tissue (no
involvement of femur patella or tibia) or HO within quadriceps expansion measuring lt1 cm
2 Spur formation measuring lt5 cm that involves the femur patella or tibia if more than one bone demonstrates HO separation of HO spurs
measure gt1 cm or HO within quadriceps expansion measuring ge1 cm but lt3 cm
3 Spur formation gt5 cm involving femur patella or tibia if more than one bone demonstrates HO separation of HO spurs measure lt1 cm or HO
within quadriceps expansion measuring ge3 cm 4 Extensive HO of the knee causing ankylosis
class 2 HO begins to involve the major bones of the knee joint with spur formation limited to a size of 5 cm
HO class 2 may be observed in select patients with complete ROM and no reported pain Patients with class 3 HO would likely always benefit from surgical excision
followed by RT prophylaxis Certainly patients in either cohort with a subclass ldquoBrdquo assignment (symptomatic) would
benefit from treatment All patients with class 4 HO require
treatment to alleviate ankylosis
treatment
References Whyte ldquoPagetrsquos Disease of Bonerdquo NEMJ vol 355
2006 Klein and Parvizi ldquoSurgical Manifestations of Pagetrsquos
Diseaserdquo JAAOS vol 14 2006 Orthobullets Campbell Apley Emedicinecom
-Chapter 15 Heterotopic Ossification after Traumatic Brain InjuryBy Jesuacutes Moreta and Joseacute Luis Martiacutenez-de los Mozos DOI 10577257343
Questions
Thank You
CTMRI Incidental finding Evaluation of atypical presentations
neurological involvement and possible malignant transformation
CT trabecularcortical thinning thickening irregularity
MRI non-specific marrow changes
BiochemistrySerum AlkPhosEnzyme found in osteoblastic membrane Indicator of osteoblastic activity uarrin Pagetrsquos but can be normal Levels correlate with disease extent and activity elevated urinary hydroxyproline (collagen breakdown marker) increased urinary N-telopeptide alpha-C-telopeptide
and deoxypyridinoline normal calcium levels
Other recommended tests ESR -elevation may indicate malignant transformation
CRP Ca -hypercalcemiamay occur in Pagetrsquos PO4 25-hydroxyvitamin D -rule out osteomalacia LFTs-rule out liver disease
Diagnostic Biopsy Diagnosis is usually achieved clinically and by
plain radiographic appearance Biopsy rarely required
Characteristic HistopathologyDisorganized immature trabeculararchitecture with irregular cement lines (ldquomosaicrdquopattern)
Rimming osteoblasts andor multinucleated osteoclasts
Management Options (May require no treatment if asymptomatic)
Supportive Care Pharmacologic Surgical (OrthopedicNeurosurgical
Supportive Care Occupational therapy Physical aides Counseling for fall+fracture prevention
Physical therapy Analgesics Weight control
Pharmacologic ManagementGoals Relieve symptoms and Prevent potential
complications Normalization of serum AlkPhos associated
with better long-term outcomes and disease control
Indications to treat Pain Deformity Neurologic symptoms Asymptomatic but high-risk for complications
(prophylactic) Management of hypercalcemia(rare) Pre-op reduce blood flow and potential
operative blood loss
Calcitonin is the most widely used It reduces bone resorption by decreasing both the activity and the number
of osteoclasts serum alkaline phosphatase and urinaryhydroxyproline levels are lowered Salmon calcitonin is more effective than the porcine variety subcutaneous injections of 50ndash100 MRC units are given daily until pain is relieved and the alkaline phosphatase levels are reduced and stabilized Maintenance injections once or twice weekly may have to be continued indefinitely but some authorities advocate stopping the drug and resuming treatment if symptoms recur Calcitonin can also be administered in a nasal spray Bisphosphonates bind to hydroxyapatite crystals
inhibiting their rate of growth and dissolution It is claimed that the reduction in bone turnover following their use is associated with the formation of lamellar rather than woven bone and that even after treatment is stopped there may be prolonged remission of disease (Bickerstaff et al 1990) Etidronate can be given orally (always on an empty stomach) but dosage should be kept low (eg 5 mgkg per day for up to 6 months) and vitamin D and calcium should also be given lest impaired bone mineralization results inosteomalacia The newer bisphosphonates (eg alendronate or pamidronate) do not have this disadvantage so they should be used as the treatment of choice they produce remissions even with shortcourses of 1 or 2 weeks
BisphosphonatesSynthetic analogues of inorganic phosphate adhere to mineralized surfaces
Ingested selectively by osteoclasts Disrupts enzyme pathways and reduces osteoclastic bone resorption
calcitonin causes osteoclasts to shrink in size and decreases their bone resorptive activity within minutes administered subcutaneously or intramuscularly
teriparatide is contraindicated in Pagets disease due to risk of secondary osteosarcoma
Surgical Management Few require surgery
Common Procedures Corrective osteotomy of long bone deformity indications
fractures through pathologic bowing of long bones impending pathologic fracture of long bone with bowing deformity
Arthroplasty (hip knee) the most common complications include
malalignment with knee arthroplasty bleeding with hip arthroplasty
Combination arthroplasty with osteotomy Fracture fixation
Preoperative Considerations Medical assessment for extraskeletalmanifestations eg high-
output heart failure
Medical treatment of active disease Preoperative autologousblood donation
Thorough planningeg good quality x-rays for templatingand device selection
Intraoperative Considerations Blood salvage system Expansileapproach + soft tissue release Sharp reamersburrsdrills for IM access Extramedullaryguidenavigation systems Concomitant osteotomy
PostoperativeConsiderations Monitoring for cardiac complications Continued medical tx of active disease
uarrHeterotopic ossification Prophylaxis against HO
Possible future excision of HO for painROM
1-Tieg provides a review of Pagets disease of bone and treatment indications In his review he discusses that most patients with Pagets disease are asymptomatic but in those that do present pain is the most common presenting symptom He recommends medical and surgical treatment of asymptomatic patients who have active disease at sites where complications are likely to develop
Altman did a review of 290 patients with Pagets disease of bone His findings showed 83 had one or more rheumatic syndromes He found the rate of osteoarthritis related to Pagets disease was elevated in the hip and knee Rheumatoid arthritis hyperuricemia and gout did not appear increased in this group
Mangham et al looked the rate of secondary sarcomas as a result of Pagets disease of bone They found the rate to be around 03 with male predominance They also found that widespread skeletal involvement by Pagets disease was not a significant risk factor for malignant transformation
Interesting views about pagets
Smith et al reviewed the pathologic complications of Pagets bone disease Pagets bone disease commonly causes osseous weakening (deformity and fracture) and arthritis in the hip joint Management of end stage disease is successful with cemented and cementless total hip arthroplasty Bleeding is the most common intra- and post-operative complication of surgery
Gabel et al retrospectively reviewed thirteen patients who had had sixteen total knee arthroplasties for Pagetic gonarthrosis Unlike total hip arthroplasty surgery Paget disease did not increase the amount of blood lost during the operation or in the postoperative period The most common complication associated with total knee arthroplasty was malalignment
Hansen et al reviewed the incidence of osteosarcomas complicating Pagets Disease Of the typical sites that are usually involved in Pagets disease (eg spine pelvis femur tibia and humerus) secondary osteosarcoma tends to spare the spine
Shaylor et al reported the mortality rates in 26 patient with osteosarcoma secondary to Paget s disease There was a 47 mortality at 1 year and 75 at 2 years from diagnosis In their series no patient survived for 5 years All patients died of metastatic disease
Langston et al conducted a randomized trial that compared the results of symptomatic treatment versus intensive bisphosphonate therapy in patients with Pagets disease Clinical fractures occurred in 46 of 661 patients (70) in the treatment group compared with 49 of 663 patients (74) in the symptomatic treatment group They concluded that bisphosphonates did not show a significant beneficial impact on pain quality of life or fracture incidence
Hadjipavlou et al reviewed Pagets disease of the bone and its management Farmers have been shown to have an increased incidence of Pagets disease Average age at presentation is in the 5th and 6th decade Symptomatic individuals are recommended to be treated initially with medical management They suggest that bisphosphonates are more effective than calcitonin at suppressing the histological and biochemical activity in Pagetrsquos disease
Summary Epid Very common in elderly Path Abnormal osteoclastshellipuarrbone
turnoverhellipdeposition of abnormal bone SampS Pain deformity fracture arthropathy Labs uarrAlkPhos X-ray Characteristic coarse thickened
trabeculae Bone scan Very hot Rx Bisphosphonates Surgery for arthropathy fracture painful
deformity
A 65-year-old male presents with increasing shoulder pain over the past 9 months He is otherwise healthy and has no other complaints Radiograph of his shoulder is shown in Figure A Whole body bone scan and biopsy photograph are shown in Figures B and C What is the most appropriate treatment for this patient
1 Referral to endocrinology 2 Radiation therapy and chemotherapy 3 Wide resection and reconstruction 4 Radiation therapy wide resection and reconstruction 5 Chemotherapy wide resection and reconstruction
Histiocytosis X or Langerhans cell histiocytosis is a spectrum of diseases of the reticuloendothelial system with one of three general presentations Eosinophilic granuloma (EG)
usually a single self-limited lesion found in younger patients
Hand-Schuller-Christian disease (HSC) chronic disseminated form with bone and visceral lesions also known as Langerhans cell histiocytosis with visceral
involvement Letterer-Siwe disease (LSD)
fatal form that occurs in young children
Eosinophilic granuloma
Epidemiology demographics
most commonly occurs in children (80 of afflicted lt 20 years of age)
HSC disease presents in children gt 3 years of age LSD occurs in children lt 3 years of age Male to female ratio of 21
location eosinophilic granuloma
commonly presents in the skull ribs clavicle scapula mandible
isolated lesions of the spine (thoracic most common) can also occur in diaphyseal regions of long bones and the
pelvis HSC
multiple bony sites multiple lytic skull lesions visceral involvement of the lungs spleen liver skin lymph
nodes
Genetics no clear genetic pattern of inheritance or locus has
been determined Prognosis
EG isolated involvement generally treatable with local
management spine lesions can spontaneously resolve
HSC prognosis depends on response to chemotherapy worsening prognosis with increasing extraskeletal
involvement LSD
generally fatal in children lt 3 years of age
Symptoms skeletal involvement
pain and swelling at the region of involvement limping can be seen with pelvic or lower extremity
involvement vertebral involvement
localized or diffuse back pain increasingly kyphotic posture radiculopathy can occur with more aggressive lesions
HSC classic triad of
multiple lytic skull lesions diabetes insipidus
increased thirst and water intake exopthalmos
visceral involvement diffuse or nonspecific abdominal or chest pain
Radiographs general
known as the great mimicker as it appears similar to many lesions radiographic differential includes osteomyelitis leukemia lymphoma
fibrous dysplasia or Ewings sarcoma diaphyseal lesions
well defined intramedullary lytic or punched-out lesion cortex may be thinned expanded or destroyed may have periosteal reaction
metaphyseal lesions extend up to but not through the physis less central location than diaphyseal lesions
spinal lesions vertebra plana (flattened vertebrae) in spine increased kyphosis
cranial involvement multiple punched-out lytic lesions
MRI may show a soft tissue mass adjacent to boney lesions
Bone scan generally shows increased uptake in the region of boney lesion
Histology Langerhans cells
mononuclear histiocyte-like cells with oval nuclei with well-defined round or oval cytoplasm
a prominent nuclear groove (coffee bean nuclei) can be seen in most of the nuclei
eosinophilic cytoplasm (pink generally) stain with CD1A electronmicroscopy
birbeck granules seen inside Langerhans cells mixture of inflammatory cells also present giant cells are present lack of nuclear atypia and atypical mitoses
differentiates this condition from malignant conditions such as Ewings sarcoma lymphoma of bone and metastatic neuroblastoma which may look similar based on the round cells alone
eosinophilic cytoplasm (pink generally)
Treatment
bullNonoperative bull observation alone
bull indications bull a self-limited process and it is reasonable to treat with observation alone
bull bracing bull indications
bull to prevent progressive kyphosis of the spinebull outcomes
bull will correct deformity in 90 of patientsbull vertebral lesions generally regain 50 of their height
bull low dose irradiation (600-800 cGy) bull indications
bull indicated for lesions in the spine that compromise stability neurologic statusbull lesions not amenable to injection or open treatment
bull outcomes bull effective for most lesions
bull chemotherapy bull indications
bull diffuse HSCbull outcomes
bull prognosis is improved with less severe extraskeletal involvementbull corticosteroid injection
bull indications bull isolated lesions bull can be performed after curettage as well
Operative curettage and bone grafting
indications for lesions that endanger the articular surface or are a risk for
impending fractures spinal deformity correction
indications progressive spine deformity refractory to bracing
approximately 10 of patients with spine lesion will need operative intervention for deformity correction
Destructive multiple lesion in young patientsAre eosinophilic granuloma lymphoma and leukemiaLymphoma is unlikely to present with exopthalmos diabetes insipidus or vertebra plana Lymphoma bone lesions are lytic and appear moth eatenpermeative on radiographs
Figure A shows a skin lesion typical of eosinophillic granuloma Figure B shows a lytic lesions without significant surrounding sclerosis as is characteristic of eosinophilic granuloma Figure C shows the characteristic histology of multiple eosinophils with their characteristic oval coffee bean nuclei and staining pattern of purpleredpink cytoplasm (depending on the stain) Importantly the histology slide lacks a malignant appearance (no cellular atypia or mytotic complexes and low nuclearcytoplasmic ratio)
Formation of bone in atypical extraskeletal tissues usually occurs
spontaneously or following trauma within 2 months of neurologic injury (brain or spinal cord)
most common location is between muscle and joint capsule Epidemiology
incidence (see table below)
demographics malefemale = 21 especially men with hypertrophic osteoarthritis and women gt65y
location traumatic brain injury or stroke
hip gt elbow gt shoulder gt knee elbow HO more common following brain trauma
occurs on affected (spastic) side rarely in the knee (TBI)
spinal cord injury hip gt knee gt elbow gt shoulder hip flexors and abductors gt extensors or adductors medial aspect of the knee
Heterotopic Ossification
Risk factors
Pathophysiology exact cause of HO is not known but there appears to be a
genetic pre disposition experimental HO associated with
tissue expression of BMP IT IS SAID TO BE CAUSED BY activation and proliferation of
mesenchymal stem cells Associated conditions
orthopaedic manifestations pathologic fractures
from decreased joint ROM and osteoporotic bone nerve impingement soft tissue contractures contributing to the formation of
decubitus ulcers joint ankylosis HO after THA adversely affects outcome of THA
nonorthopaedic conditions skin maceration and hygiene problems
Pathophysiology Early in the formation of HO oedema with exudative
infiltrate is present followed by fibroblastic proliferation and immature connective tissue formation Posteriorly osteoid formation is seen with the subsequent deposition of bone matrix Primitive osteoid is deposited as small masses in the periphery early (within the first two weeks) and osteoblasts are noted located irregularly Osteoblasts produce tropocollagen which polymerizes to form collagen and secrete alkaline phosphatase which allows calcium to precipitate and the mineralization of bone matrix As mineralization progresses amorphous calcium phosphate is progressively replaced by hydroxyapatite crystals During the following weeks the lesion matures with a centripetal pattern and after 6-12 months an appearance of true bone is noted The new bone is always extra-articular and can be contiguous with the skeleton but generally does not involve the periosteum
IN SUMMARY It has been postulated that three conditions
must be met to achieve heterotopic bone formation ---a stimulating event oestrogenic precursor cells and a proper environment LIKE hypercalcaemia tissue hypoxia pH changes (alkalosis) or prolonged immobilization
ClassificationbullSubtypes
bull neurogenic HO bull Four clinical stages of HO in people with spinal cord injury were
described by Nicholas in 1973
bull traumatic myositis ossificans bull fibrodysplasia ossificans progressiva (Munchmeyers Disease)
Neurogenic HO Symptoms
painless loss of ROM interferes with ADL CRPS symptoms fever
Physical exam inspection
warm painful swollen joint may have effusion skin problems
decubitus ulcers from contractures around skin muscles ligaments
skin maceration and hygiene problems motion
decreased joint ROM joint ankylosis with HO after TKA might develop quad muscle snapping or patella
instability neurovascular
peripheral neuropathy HO often impinges on adjacent NV structures
Imaging
bullRadiographs bull findings
bull ossification usually easy to visualize bull maturity of HO
bull the appearance of a bony cortex suggests mature HObull sharp demarcation from surrounding tissue bull trabecular pattern
bull sensitivity and specificity bull not useful for early diagnosisbull only useful at 1 week after onset of symptoms
bull calcium is deposited 7-10 days later than symptom onsetbullUltrasound
bull indications bull for early diagnosis of hip HO
bull findings bull echogenic surfaces with posterior acoustic shadowing
bullCT bull indications
bull useful for preoperative planning bullTriphasic bone scan
bull indications bull best for early diagnosis bull most commonly used diagnostic study
Radiographs are extremely useful in the staging of heterotopic ossification and will show the development of sharp cortical margins once the lesion has reached maturity
Heterotopic bone is a condition in which lamellar bone forms in non-ossified soft tissues In the early stages studies such as MRI and bone scan are more sensitive for diagnosis as radiographs may appear normal for the first three weeks After the appropriate diagnosis is made sequential radiographs are useful for monitoring the progression of the ossification Once it has reached the mature stage sharp cortical margins will appear and surgical resection may be considered
lab
Labs elevated serum alkaline phosphatase (gt250IUL)
ALP removes inhibitors of mineralization nonspecific may be elevated with skeletal trauma cannot determine maturity of HO elevated 12wks after surgery is predictor
elevated CRP correlates with inflammatory activity of HO better than ESR normalization of CRP may correlate with maturity of HO
elevated ESR (gt35mmh) 12wks after THA is predictor
elevated CK correlates with involvement of muscle extent of muscle
involvement Histology
mature fatty bone marrow mature trabecular bone
Heterotopic ossification (HO) most commonly occurs at the amputation site if the amputation was performed thru the zone of injury especially if the injury was a blast mechanism
Symptomatic heterotopic ossification of the quadriceps may occur following placement of a large-diameter Steinmann pin for the purpose of temporary skeletal traction
TreatmentThe prevention of heterotopic ossification is focused on three basic principles disrupting the inductive signalling pathways altering the osteoprogenitor cells or modifying the environment
bullphysiotherapy should involve an assisted range of movement exercises with gentle stretch and terminal resistance trainingbullProphylaxis
bull bisphosphonates amp NSAIDS bull indications
bull although no literature supports are commonly usedbull technique
bull indomethacin is most commonly used bull dose is 75mgday for 10days to 6 weeks
bull perioperative radiation bull indications
bull although no literature supports commonly usedbull is thought to be effective by blocking osteoblast differentiation
bull technique bull a single perioperative dose of 700cGy can be given either 4
hours preop or within 72 hours postoperatively bull lt550cGy not effective
Nonsteroidal anti-inflammatory drugs (NSAIDs) These drugs have demonstrated good results in
preventing heterotopic ossification after total hip arthroplasty
A direct effect of NSAIDs on the formation of heterotopic ossification has been described due to the inhibition of the differentiation of mesenchymal cells into oestrogenic cells There is also an indirect effect which refers to the inhibition of bone remodelling by suppression of the prostagland unmediated inflammatory response (specifically PGE-2)
Indomethacin has been considered a useful medication for heterotopic ossification prophylaxis following total hip replacement
prescribed for three to six weeks in a dose of 75mgday within two months of the injury may reduce the incidence of heterotopic ossification by two to three times
Biphosphonates inhibits precipitation of calcium phosphate and blocks the aggregation and mineralisation of hydroxyapatite crystals In primary prevention Banovac et al [56] have suggested that the treatment should begin as soon as elevated alkaline phosphatase is diagnosed or positive findings in ultrasonography or bone scans are shown In addition disphosphonates could have long-term effects on prevention when the treatment is finished
Posttraumatic wide exposure and surgical resection
indications severe loss of motion and decreased function
technique wide exposure required to identify all neurovascular
structures that may be involved timing of resection (controversial)
marked decrease in bone scan activity AND normalization of ALP
6 months following general trauma 1 year following SCI 15 years following TBI
some data suggests equivalent results when comparing early versus late resection
postop follow with 5 day course of indomethacin early gentle joint mobilization
The surgery is necessary in patients with symptomatic HO and unsuccessful medical treatment such as
Loss of range of motion and ankylosis with associated functional disability such as sitting difficulties
Complications of immobility such as pressure ulcers
Facilitate rehabilitation and recovery of muscular atrophy secondary to prolonged immobilisation
Difficulties of appropriate hygiene because access to the perineum or bladder care is needed
Severe pain refractory to analgesia Vascular andor nerve compression
Advantages to early excision of heterotopic ossification (vs waiting for maturation) include decreased soft tissue contracture better definition between heterotopic and native bone and decreased waiting time for the patient When the soft tissue envelope is benign one may proceed with operative release While waiting for normalization of alkaline phosphatase levels inactivity on bone scan or radiographic maturity may decrease risk of recurrent heterotopic ossification delaying operative release for these reasons has not been shown to improve results of final elbow range of motion after contracture release
Gartland recommended surgery after six months following traumatic heterotopic ossification one year following spinal cord injury and 18 months after head injury
In the past waiting until maturity in order to minimize the rate of recurrence after the surgical treatment was recommended Nevertheless recent studies do not confirm a higher rate of recurrence when the HO is excised in an earlier phase In addition a long delay before surgery leads to ankylosis a high degree of osteoporosis and more extensive intra-articular injuries These findings are associated with bad functional results and potential complications
Should you wait till lesion maturation
Prevention byHandle tissue carefully Avoid excess bleeding Achieve good hemostasis Beware of lesions that span internervous tissue planes
but if it happens resection of a large enough amount of bone to allow improvement of the range of motion and trying to preserve the joint
Our aim must be
A reactive process that is characterized by a well-circumscribed proliferation of fibroblasts cartilage and bone within muscle
A form of heterotopic ossification that is the result direct trauma intramuscular hematoma
most common location is the diaphysis of long bones Must differentiate from tumors Fibrodysplasia ossificans progressiva (FOP) is a rare subtype of heterotopic ossification
involves mutation of the ACVR1 gene (activin A type I receptor gene a BMP type-1 receptor)
Epidemiology demographics
most common in young active males (15 to 35 years old) body locations
quadriceps brachialis and gluteal muscles Genetics
almost always a posttraumatic condition Prognosis
usually self limiting mass usually begins to decrease in size after 1 yea
Myositis ossificans
PresentationbullSymptoms
bull pain tenderness swelling and decreased range of motion that usually presents within days of the injury
bull pain and size of the mass decrease with timebull mass increases in size over several months(usually 3 to 6 cm)
bull after the mass stops growing it becomes firmbullPhysical exam
bull palpable soft tissue massbull restricted range of motion
ImagingbullRadiographs
bull peripheral bone formation with central lucent areabull may appear as dotted veil pattern
bullMRI with gadolinium bull rim enhancement is seen within the first 3 weeks
bullCT scan bull lesion has an eggshell appearance
bullCharacteristic histology shows zonal pattern bull periphery of lesion
bull mature trabeculae of lamellar and woven bonebull calcification seen on xray
bull center of the lesion bull irregular mass of immature fibroblastsbull cartilage component may be presentbull (no calcification seen on xray) bull no cellular atypia seen
Treatment
bullNonoperative bull rest range of motion exercises and activity modification
bull passive stretching is contraindicated (makes it worse)bull physical therapy
bull utilized to maintain range of motionbull radiographic monitoring
bull obtained to confirm maturation of the lesionbullOperative
bull surgical excision bull indicated only if it remains a problem after it maturesbull do not operate in acute phase wait at least six months
bull excision of the lesion within 6 to 12 months predisposes to local recurrence
A 26-year-old man presents with generalized back and joint stiffness and difficulty opening his mouth His elder sister has similar complaints Since childhood he has had 3 surgeries for excision of recurrent bony prominences around his knees He walks with a stooped over posture seen in Figure A Radiographs of his feet knee hip and spine are seen in Figures B-E respectively
fibrodysplasia ossificans progressiva
Stone Man Disease) which involves a mutation of the ACVR1
There are 2 hallmark characteristics progressive heterotopic ossification (muscles fascia tendons ligaments and joint capsules) and congenital malformation of the great toe (hallux valgus malformed first metatarsal and monophalangism) BMP4 which contributes to the formation of the skeleton in the normal embryo is implicated in this disease
Complications
bullHematoma and intraoperative bleedingbullInfection
bull higher rate of infection following joint arthroplasty if HO is present
bullFractures of osteoporotic bone bull osteopenic from disusebull during surgery or physiotherapy
bullRecurrence bull recurrence rate correlates with neurological injury
bull greater recurrence if severe neurological compromisebullAVN
bull if extensive dissection or stripping is required
HTO AND ISS
When ISS is below 25 the mortality risk is minimal and above 25 it is an almost linear increase
When ISS is 50 the mortality is 50 When above 70 it is close to 100 If an injury is assigned an AIS of 6 (unsurvivable injury) the ISS score is
automatically assigned to 75 Highest ISS score obtainable is 75 For trauma patients of vehicular accidents the scoring system is important
for assessing the effectiveness of medical care in reducing morbidity and mortality
Advantages virtually the only anatomical scoring system in use correlates linearly with
mortality morbidity hospital stay other measures of severity
Weaknesses Any error in AIS scoring increases the ISS error Many different injury patterns can yield the same ISS score Injuries to different body regions are not weighted Not a useful triage tool as a full description of patient injuries is not known
prior to full investigation amp operation
risk factors periosteal stripping off anterior femur male gender obesity post traumatic deformity Anterior and anterolateral approach Cementless
Neurogenic HO around the hip due to SCI occurs more often in the medial region than in the lateral region with ossified tissues extending from the pubic symphysis to the anteromedial femoral shaft posterior to the femoral neurovascular structures Ossification is also seen anteriorly involving the iliopsoas and femoral neurovascular structures laterally within gluteus minimus and posteriorly extending from the ilium to the posterior femur encasing the sciatic nerve
HTO AROUND hip and knee
The Brooker Classification of Heterotopic Ossification around the hip joint Class I has islands of bone within the soft tissues Class II has bone spurs from the pelvis or proximal end of the femur leaving at least 1 cm between opposing surfaces Class III has bone spurs from the pelvis andor proximal end of the femur reducing the space between opposing bone surfaces to less than 1 cm Class IV shows apparent bone ankylosis of the hip
Region I - Heterotopic ossifications are strictly below the tip of the greater trochanter
Region II - Heterotopic ossifications are below and above the tip of the greater trochanter
Region III - Heterotopic ossifications are strictly above the tip of the greater trochanter
Grade A - Single or multiple heterotopic ossifications are less than 10 mm in maximal extent without contact with the pelvis or the femur
Grade B - Heterotopic ossifications are greater than 10 mm without contact with the pelvis but with possible contact with the femur there is no bridging from the femur to the proximal part of the greater trochanter and no evidence of ankylosis
Grade C - Ankylosis by means of firm bridging from the femur to the pelvis is present
Shmidt classification
excision may be performed The results of this procedure are varied Patients may find that their range of movement improves but pain relief is likely to be limited
A patient with heterotopic ossification following total hip arthroplasty is thought to have a 90-100 chance of developing it on the contralateral hip if this hip also undergoes total arthroplasty
it would be prudent to minimize the risk of heterotopic ossification developing after arthroplasty by performing surgery whereby the following are ensured
Exposure is meticulous Retraction is performed carefully and soft tissue
is handled carefully Irrigation is adequate Devitalized tissue is excised Hemostasis is adequate Postoperative drains (when used) are not
retained for longer than necessary Perioperative antibiotic prophylaxis is used Postoperative anticoagulation (when used for
deep vein thrombosis prophylaxis) is carefully controlled
sources of knee stiffness 1-extrinsic severe osteoarthritis of the ipsilateral hip neurologic injury leading to muscle rigidity tight quadriceps or hamstring muscles secondary to muscle injury heterotopic ossification or long-standing juvenile inflammatory conditions limiting knee
range of motion prior to the completion of skeletal growth When extrinsic sources are identified revision total knee arthroplasty is unlikely to be associated with a favorable outcome without correction of the extrinsic problem
2-intrinsic (1) overstuffing of the patellofemoral articulation (2) an
excessively tight flexion andor extension gap (3) a tight posterior cruciate ligament (4) femoral andor tibial malrotation (5) arthrofibrosis and (6) limited bearing excursion in association with a highly conforming mobile-bearing prosthetic design
HTO after TKA
Heterotopic Ossification (HO) following primary Total Knee Replacement (TKR)
Occurs in 3-90 of TKRs 3-grade classification system No correlation between HO and component
alignment or component position
Clinical findings similar to early infection Continuing low-grade fever Warm swollen and erythematous knee Normal blood tests Possibly an association with HLA-A2 and B18 HO patients have worse KSS and function
scores
Patients at HIGH risk for developing HO after TKR (Knee Arthroplasty) (5)
Those with limited postoperative knee flexion
Increased lumbar bone mineral density (BMD) on multivariate analysis (3)
Hypertrophic arthrosis Excessive periosteal trauma Notching of the anterior femur Those who require forced manipulation
after TKA 47 in revision TKR surgery (6) Higher rates in revision TKR cases with
infection (up to 76
DaughertyBell classification of HO of the knee 0 No evidence of HO 1 Bone islands in periarticular soft tissue (no
involvement of femur patella or tibia) or HO within quadriceps expansion measuring lt1 cm
2 Spur formation measuring lt5 cm that involves the femur patella or tibia if more than one bone demonstrates HO separation of HO spurs
measure gt1 cm or HO within quadriceps expansion measuring ge1 cm but lt3 cm
3 Spur formation gt5 cm involving femur patella or tibia if more than one bone demonstrates HO separation of HO spurs measure lt1 cm or HO
within quadriceps expansion measuring ge3 cm 4 Extensive HO of the knee causing ankylosis
class 2 HO begins to involve the major bones of the knee joint with spur formation limited to a size of 5 cm
HO class 2 may be observed in select patients with complete ROM and no reported pain Patients with class 3 HO would likely always benefit from surgical excision
followed by RT prophylaxis Certainly patients in either cohort with a subclass ldquoBrdquo assignment (symptomatic) would
benefit from treatment All patients with class 4 HO require
treatment to alleviate ankylosis
treatment
References Whyte ldquoPagetrsquos Disease of Bonerdquo NEMJ vol 355
2006 Klein and Parvizi ldquoSurgical Manifestations of Pagetrsquos
Diseaserdquo JAAOS vol 14 2006 Orthobullets Campbell Apley Emedicinecom
-Chapter 15 Heterotopic Ossification after Traumatic Brain InjuryBy Jesuacutes Moreta and Joseacute Luis Martiacutenez-de los Mozos DOI 10577257343
Questions
Thank You
BiochemistrySerum AlkPhosEnzyme found in osteoblastic membrane Indicator of osteoblastic activity uarrin Pagetrsquos but can be normal Levels correlate with disease extent and activity elevated urinary hydroxyproline (collagen breakdown marker) increased urinary N-telopeptide alpha-C-telopeptide
and deoxypyridinoline normal calcium levels
Other recommended tests ESR -elevation may indicate malignant transformation
CRP Ca -hypercalcemiamay occur in Pagetrsquos PO4 25-hydroxyvitamin D -rule out osteomalacia LFTs-rule out liver disease
Diagnostic Biopsy Diagnosis is usually achieved clinically and by
plain radiographic appearance Biopsy rarely required
Characteristic HistopathologyDisorganized immature trabeculararchitecture with irregular cement lines (ldquomosaicrdquopattern)
Rimming osteoblasts andor multinucleated osteoclasts
Management Options (May require no treatment if asymptomatic)
Supportive Care Pharmacologic Surgical (OrthopedicNeurosurgical
Supportive Care Occupational therapy Physical aides Counseling for fall+fracture prevention
Physical therapy Analgesics Weight control
Pharmacologic ManagementGoals Relieve symptoms and Prevent potential
complications Normalization of serum AlkPhos associated
with better long-term outcomes and disease control
Indications to treat Pain Deformity Neurologic symptoms Asymptomatic but high-risk for complications
(prophylactic) Management of hypercalcemia(rare) Pre-op reduce blood flow and potential
operative blood loss
Calcitonin is the most widely used It reduces bone resorption by decreasing both the activity and the number
of osteoclasts serum alkaline phosphatase and urinaryhydroxyproline levels are lowered Salmon calcitonin is more effective than the porcine variety subcutaneous injections of 50ndash100 MRC units are given daily until pain is relieved and the alkaline phosphatase levels are reduced and stabilized Maintenance injections once or twice weekly may have to be continued indefinitely but some authorities advocate stopping the drug and resuming treatment if symptoms recur Calcitonin can also be administered in a nasal spray Bisphosphonates bind to hydroxyapatite crystals
inhibiting their rate of growth and dissolution It is claimed that the reduction in bone turnover following their use is associated with the formation of lamellar rather than woven bone and that even after treatment is stopped there may be prolonged remission of disease (Bickerstaff et al 1990) Etidronate can be given orally (always on an empty stomach) but dosage should be kept low (eg 5 mgkg per day for up to 6 months) and vitamin D and calcium should also be given lest impaired bone mineralization results inosteomalacia The newer bisphosphonates (eg alendronate or pamidronate) do not have this disadvantage so they should be used as the treatment of choice they produce remissions even with shortcourses of 1 or 2 weeks
BisphosphonatesSynthetic analogues of inorganic phosphate adhere to mineralized surfaces
Ingested selectively by osteoclasts Disrupts enzyme pathways and reduces osteoclastic bone resorption
calcitonin causes osteoclasts to shrink in size and decreases their bone resorptive activity within minutes administered subcutaneously or intramuscularly
teriparatide is contraindicated in Pagets disease due to risk of secondary osteosarcoma
Surgical Management Few require surgery
Common Procedures Corrective osteotomy of long bone deformity indications
fractures through pathologic bowing of long bones impending pathologic fracture of long bone with bowing deformity
Arthroplasty (hip knee) the most common complications include
malalignment with knee arthroplasty bleeding with hip arthroplasty
Combination arthroplasty with osteotomy Fracture fixation
Preoperative Considerations Medical assessment for extraskeletalmanifestations eg high-
output heart failure
Medical treatment of active disease Preoperative autologousblood donation
Thorough planningeg good quality x-rays for templatingand device selection
Intraoperative Considerations Blood salvage system Expansileapproach + soft tissue release Sharp reamersburrsdrills for IM access Extramedullaryguidenavigation systems Concomitant osteotomy
PostoperativeConsiderations Monitoring for cardiac complications Continued medical tx of active disease
uarrHeterotopic ossification Prophylaxis against HO
Possible future excision of HO for painROM
1-Tieg provides a review of Pagets disease of bone and treatment indications In his review he discusses that most patients with Pagets disease are asymptomatic but in those that do present pain is the most common presenting symptom He recommends medical and surgical treatment of asymptomatic patients who have active disease at sites where complications are likely to develop
Altman did a review of 290 patients with Pagets disease of bone His findings showed 83 had one or more rheumatic syndromes He found the rate of osteoarthritis related to Pagets disease was elevated in the hip and knee Rheumatoid arthritis hyperuricemia and gout did not appear increased in this group
Mangham et al looked the rate of secondary sarcomas as a result of Pagets disease of bone They found the rate to be around 03 with male predominance They also found that widespread skeletal involvement by Pagets disease was not a significant risk factor for malignant transformation
Interesting views about pagets
Smith et al reviewed the pathologic complications of Pagets bone disease Pagets bone disease commonly causes osseous weakening (deformity and fracture) and arthritis in the hip joint Management of end stage disease is successful with cemented and cementless total hip arthroplasty Bleeding is the most common intra- and post-operative complication of surgery
Gabel et al retrospectively reviewed thirteen patients who had had sixteen total knee arthroplasties for Pagetic gonarthrosis Unlike total hip arthroplasty surgery Paget disease did not increase the amount of blood lost during the operation or in the postoperative period The most common complication associated with total knee arthroplasty was malalignment
Hansen et al reviewed the incidence of osteosarcomas complicating Pagets Disease Of the typical sites that are usually involved in Pagets disease (eg spine pelvis femur tibia and humerus) secondary osteosarcoma tends to spare the spine
Shaylor et al reported the mortality rates in 26 patient with osteosarcoma secondary to Paget s disease There was a 47 mortality at 1 year and 75 at 2 years from diagnosis In their series no patient survived for 5 years All patients died of metastatic disease
Langston et al conducted a randomized trial that compared the results of symptomatic treatment versus intensive bisphosphonate therapy in patients with Pagets disease Clinical fractures occurred in 46 of 661 patients (70) in the treatment group compared with 49 of 663 patients (74) in the symptomatic treatment group They concluded that bisphosphonates did not show a significant beneficial impact on pain quality of life or fracture incidence
Hadjipavlou et al reviewed Pagets disease of the bone and its management Farmers have been shown to have an increased incidence of Pagets disease Average age at presentation is in the 5th and 6th decade Symptomatic individuals are recommended to be treated initially with medical management They suggest that bisphosphonates are more effective than calcitonin at suppressing the histological and biochemical activity in Pagetrsquos disease
Summary Epid Very common in elderly Path Abnormal osteoclastshellipuarrbone
turnoverhellipdeposition of abnormal bone SampS Pain deformity fracture arthropathy Labs uarrAlkPhos X-ray Characteristic coarse thickened
trabeculae Bone scan Very hot Rx Bisphosphonates Surgery for arthropathy fracture painful
deformity
A 65-year-old male presents with increasing shoulder pain over the past 9 months He is otherwise healthy and has no other complaints Radiograph of his shoulder is shown in Figure A Whole body bone scan and biopsy photograph are shown in Figures B and C What is the most appropriate treatment for this patient
1 Referral to endocrinology 2 Radiation therapy and chemotherapy 3 Wide resection and reconstruction 4 Radiation therapy wide resection and reconstruction 5 Chemotherapy wide resection and reconstruction
Histiocytosis X or Langerhans cell histiocytosis is a spectrum of diseases of the reticuloendothelial system with one of three general presentations Eosinophilic granuloma (EG)
usually a single self-limited lesion found in younger patients
Hand-Schuller-Christian disease (HSC) chronic disseminated form with bone and visceral lesions also known as Langerhans cell histiocytosis with visceral
involvement Letterer-Siwe disease (LSD)
fatal form that occurs in young children
Eosinophilic granuloma
Epidemiology demographics
most commonly occurs in children (80 of afflicted lt 20 years of age)
HSC disease presents in children gt 3 years of age LSD occurs in children lt 3 years of age Male to female ratio of 21
location eosinophilic granuloma
commonly presents in the skull ribs clavicle scapula mandible
isolated lesions of the spine (thoracic most common) can also occur in diaphyseal regions of long bones and the
pelvis HSC
multiple bony sites multiple lytic skull lesions visceral involvement of the lungs spleen liver skin lymph
nodes
Genetics no clear genetic pattern of inheritance or locus has
been determined Prognosis
EG isolated involvement generally treatable with local
management spine lesions can spontaneously resolve
HSC prognosis depends on response to chemotherapy worsening prognosis with increasing extraskeletal
involvement LSD
generally fatal in children lt 3 years of age
Symptoms skeletal involvement
pain and swelling at the region of involvement limping can be seen with pelvic or lower extremity
involvement vertebral involvement
localized or diffuse back pain increasingly kyphotic posture radiculopathy can occur with more aggressive lesions
HSC classic triad of
multiple lytic skull lesions diabetes insipidus
increased thirst and water intake exopthalmos
visceral involvement diffuse or nonspecific abdominal or chest pain
Radiographs general
known as the great mimicker as it appears similar to many lesions radiographic differential includes osteomyelitis leukemia lymphoma
fibrous dysplasia or Ewings sarcoma diaphyseal lesions
well defined intramedullary lytic or punched-out lesion cortex may be thinned expanded or destroyed may have periosteal reaction
metaphyseal lesions extend up to but not through the physis less central location than diaphyseal lesions
spinal lesions vertebra plana (flattened vertebrae) in spine increased kyphosis
cranial involvement multiple punched-out lytic lesions
MRI may show a soft tissue mass adjacent to boney lesions
Bone scan generally shows increased uptake in the region of boney lesion
Histology Langerhans cells
mononuclear histiocyte-like cells with oval nuclei with well-defined round or oval cytoplasm
a prominent nuclear groove (coffee bean nuclei) can be seen in most of the nuclei
eosinophilic cytoplasm (pink generally) stain with CD1A electronmicroscopy
birbeck granules seen inside Langerhans cells mixture of inflammatory cells also present giant cells are present lack of nuclear atypia and atypical mitoses
differentiates this condition from malignant conditions such as Ewings sarcoma lymphoma of bone and metastatic neuroblastoma which may look similar based on the round cells alone
eosinophilic cytoplasm (pink generally)
Treatment
bullNonoperative bull observation alone
bull indications bull a self-limited process and it is reasonable to treat with observation alone
bull bracing bull indications
bull to prevent progressive kyphosis of the spinebull outcomes
bull will correct deformity in 90 of patientsbull vertebral lesions generally regain 50 of their height
bull low dose irradiation (600-800 cGy) bull indications
bull indicated for lesions in the spine that compromise stability neurologic statusbull lesions not amenable to injection or open treatment
bull outcomes bull effective for most lesions
bull chemotherapy bull indications
bull diffuse HSCbull outcomes
bull prognosis is improved with less severe extraskeletal involvementbull corticosteroid injection
bull indications bull isolated lesions bull can be performed after curettage as well
Operative curettage and bone grafting
indications for lesions that endanger the articular surface or are a risk for
impending fractures spinal deformity correction
indications progressive spine deformity refractory to bracing
approximately 10 of patients with spine lesion will need operative intervention for deformity correction
Destructive multiple lesion in young patientsAre eosinophilic granuloma lymphoma and leukemiaLymphoma is unlikely to present with exopthalmos diabetes insipidus or vertebra plana Lymphoma bone lesions are lytic and appear moth eatenpermeative on radiographs
Figure A shows a skin lesion typical of eosinophillic granuloma Figure B shows a lytic lesions without significant surrounding sclerosis as is characteristic of eosinophilic granuloma Figure C shows the characteristic histology of multiple eosinophils with their characteristic oval coffee bean nuclei and staining pattern of purpleredpink cytoplasm (depending on the stain) Importantly the histology slide lacks a malignant appearance (no cellular atypia or mytotic complexes and low nuclearcytoplasmic ratio)
Formation of bone in atypical extraskeletal tissues usually occurs
spontaneously or following trauma within 2 months of neurologic injury (brain or spinal cord)
most common location is between muscle and joint capsule Epidemiology
incidence (see table below)
demographics malefemale = 21 especially men with hypertrophic osteoarthritis and women gt65y
location traumatic brain injury or stroke
hip gt elbow gt shoulder gt knee elbow HO more common following brain trauma
occurs on affected (spastic) side rarely in the knee (TBI)
spinal cord injury hip gt knee gt elbow gt shoulder hip flexors and abductors gt extensors or adductors medial aspect of the knee
Heterotopic Ossification
Risk factors
Pathophysiology exact cause of HO is not known but there appears to be a
genetic pre disposition experimental HO associated with
tissue expression of BMP IT IS SAID TO BE CAUSED BY activation and proliferation of
mesenchymal stem cells Associated conditions
orthopaedic manifestations pathologic fractures
from decreased joint ROM and osteoporotic bone nerve impingement soft tissue contractures contributing to the formation of
decubitus ulcers joint ankylosis HO after THA adversely affects outcome of THA
nonorthopaedic conditions skin maceration and hygiene problems
Pathophysiology Early in the formation of HO oedema with exudative
infiltrate is present followed by fibroblastic proliferation and immature connective tissue formation Posteriorly osteoid formation is seen with the subsequent deposition of bone matrix Primitive osteoid is deposited as small masses in the periphery early (within the first two weeks) and osteoblasts are noted located irregularly Osteoblasts produce tropocollagen which polymerizes to form collagen and secrete alkaline phosphatase which allows calcium to precipitate and the mineralization of bone matrix As mineralization progresses amorphous calcium phosphate is progressively replaced by hydroxyapatite crystals During the following weeks the lesion matures with a centripetal pattern and after 6-12 months an appearance of true bone is noted The new bone is always extra-articular and can be contiguous with the skeleton but generally does not involve the periosteum
IN SUMMARY It has been postulated that three conditions
must be met to achieve heterotopic bone formation ---a stimulating event oestrogenic precursor cells and a proper environment LIKE hypercalcaemia tissue hypoxia pH changes (alkalosis) or prolonged immobilization
ClassificationbullSubtypes
bull neurogenic HO bull Four clinical stages of HO in people with spinal cord injury were
described by Nicholas in 1973
bull traumatic myositis ossificans bull fibrodysplasia ossificans progressiva (Munchmeyers Disease)
Neurogenic HO Symptoms
painless loss of ROM interferes with ADL CRPS symptoms fever
Physical exam inspection
warm painful swollen joint may have effusion skin problems
decubitus ulcers from contractures around skin muscles ligaments
skin maceration and hygiene problems motion
decreased joint ROM joint ankylosis with HO after TKA might develop quad muscle snapping or patella
instability neurovascular
peripheral neuropathy HO often impinges on adjacent NV structures
Imaging
bullRadiographs bull findings
bull ossification usually easy to visualize bull maturity of HO
bull the appearance of a bony cortex suggests mature HObull sharp demarcation from surrounding tissue bull trabecular pattern
bull sensitivity and specificity bull not useful for early diagnosisbull only useful at 1 week after onset of symptoms
bull calcium is deposited 7-10 days later than symptom onsetbullUltrasound
bull indications bull for early diagnosis of hip HO
bull findings bull echogenic surfaces with posterior acoustic shadowing
bullCT bull indications
bull useful for preoperative planning bullTriphasic bone scan
bull indications bull best for early diagnosis bull most commonly used diagnostic study
Radiographs are extremely useful in the staging of heterotopic ossification and will show the development of sharp cortical margins once the lesion has reached maturity
Heterotopic bone is a condition in which lamellar bone forms in non-ossified soft tissues In the early stages studies such as MRI and bone scan are more sensitive for diagnosis as radiographs may appear normal for the first three weeks After the appropriate diagnosis is made sequential radiographs are useful for monitoring the progression of the ossification Once it has reached the mature stage sharp cortical margins will appear and surgical resection may be considered
lab
Labs elevated serum alkaline phosphatase (gt250IUL)
ALP removes inhibitors of mineralization nonspecific may be elevated with skeletal trauma cannot determine maturity of HO elevated 12wks after surgery is predictor
elevated CRP correlates with inflammatory activity of HO better than ESR normalization of CRP may correlate with maturity of HO
elevated ESR (gt35mmh) 12wks after THA is predictor
elevated CK correlates with involvement of muscle extent of muscle
involvement Histology
mature fatty bone marrow mature trabecular bone
Heterotopic ossification (HO) most commonly occurs at the amputation site if the amputation was performed thru the zone of injury especially if the injury was a blast mechanism
Symptomatic heterotopic ossification of the quadriceps may occur following placement of a large-diameter Steinmann pin for the purpose of temporary skeletal traction
TreatmentThe prevention of heterotopic ossification is focused on three basic principles disrupting the inductive signalling pathways altering the osteoprogenitor cells or modifying the environment
bullphysiotherapy should involve an assisted range of movement exercises with gentle stretch and terminal resistance trainingbullProphylaxis
bull bisphosphonates amp NSAIDS bull indications
bull although no literature supports are commonly usedbull technique
bull indomethacin is most commonly used bull dose is 75mgday for 10days to 6 weeks
bull perioperative radiation bull indications
bull although no literature supports commonly usedbull is thought to be effective by blocking osteoblast differentiation
bull technique bull a single perioperative dose of 700cGy can be given either 4
hours preop or within 72 hours postoperatively bull lt550cGy not effective
Nonsteroidal anti-inflammatory drugs (NSAIDs) These drugs have demonstrated good results in
preventing heterotopic ossification after total hip arthroplasty
A direct effect of NSAIDs on the formation of heterotopic ossification has been described due to the inhibition of the differentiation of mesenchymal cells into oestrogenic cells There is also an indirect effect which refers to the inhibition of bone remodelling by suppression of the prostagland unmediated inflammatory response (specifically PGE-2)
Indomethacin has been considered a useful medication for heterotopic ossification prophylaxis following total hip replacement
prescribed for three to six weeks in a dose of 75mgday within two months of the injury may reduce the incidence of heterotopic ossification by two to three times
Biphosphonates inhibits precipitation of calcium phosphate and blocks the aggregation and mineralisation of hydroxyapatite crystals In primary prevention Banovac et al [56] have suggested that the treatment should begin as soon as elevated alkaline phosphatase is diagnosed or positive findings in ultrasonography or bone scans are shown In addition disphosphonates could have long-term effects on prevention when the treatment is finished
Posttraumatic wide exposure and surgical resection
indications severe loss of motion and decreased function
technique wide exposure required to identify all neurovascular
structures that may be involved timing of resection (controversial)
marked decrease in bone scan activity AND normalization of ALP
6 months following general trauma 1 year following SCI 15 years following TBI
some data suggests equivalent results when comparing early versus late resection
postop follow with 5 day course of indomethacin early gentle joint mobilization
The surgery is necessary in patients with symptomatic HO and unsuccessful medical treatment such as
Loss of range of motion and ankylosis with associated functional disability such as sitting difficulties
Complications of immobility such as pressure ulcers
Facilitate rehabilitation and recovery of muscular atrophy secondary to prolonged immobilisation
Difficulties of appropriate hygiene because access to the perineum or bladder care is needed
Severe pain refractory to analgesia Vascular andor nerve compression
Advantages to early excision of heterotopic ossification (vs waiting for maturation) include decreased soft tissue contracture better definition between heterotopic and native bone and decreased waiting time for the patient When the soft tissue envelope is benign one may proceed with operative release While waiting for normalization of alkaline phosphatase levels inactivity on bone scan or radiographic maturity may decrease risk of recurrent heterotopic ossification delaying operative release for these reasons has not been shown to improve results of final elbow range of motion after contracture release
Gartland recommended surgery after six months following traumatic heterotopic ossification one year following spinal cord injury and 18 months after head injury
In the past waiting until maturity in order to minimize the rate of recurrence after the surgical treatment was recommended Nevertheless recent studies do not confirm a higher rate of recurrence when the HO is excised in an earlier phase In addition a long delay before surgery leads to ankylosis a high degree of osteoporosis and more extensive intra-articular injuries These findings are associated with bad functional results and potential complications
Should you wait till lesion maturation
Prevention byHandle tissue carefully Avoid excess bleeding Achieve good hemostasis Beware of lesions that span internervous tissue planes
but if it happens resection of a large enough amount of bone to allow improvement of the range of motion and trying to preserve the joint
Our aim must be
A reactive process that is characterized by a well-circumscribed proliferation of fibroblasts cartilage and bone within muscle
A form of heterotopic ossification that is the result direct trauma intramuscular hematoma
most common location is the diaphysis of long bones Must differentiate from tumors Fibrodysplasia ossificans progressiva (FOP) is a rare subtype of heterotopic ossification
involves mutation of the ACVR1 gene (activin A type I receptor gene a BMP type-1 receptor)
Epidemiology demographics
most common in young active males (15 to 35 years old) body locations
quadriceps brachialis and gluteal muscles Genetics
almost always a posttraumatic condition Prognosis
usually self limiting mass usually begins to decrease in size after 1 yea
Myositis ossificans
PresentationbullSymptoms
bull pain tenderness swelling and decreased range of motion that usually presents within days of the injury
bull pain and size of the mass decrease with timebull mass increases in size over several months(usually 3 to 6 cm)
bull after the mass stops growing it becomes firmbullPhysical exam
bull palpable soft tissue massbull restricted range of motion
ImagingbullRadiographs
bull peripheral bone formation with central lucent areabull may appear as dotted veil pattern
bullMRI with gadolinium bull rim enhancement is seen within the first 3 weeks
bullCT scan bull lesion has an eggshell appearance
bullCharacteristic histology shows zonal pattern bull periphery of lesion
bull mature trabeculae of lamellar and woven bonebull calcification seen on xray
bull center of the lesion bull irregular mass of immature fibroblastsbull cartilage component may be presentbull (no calcification seen on xray) bull no cellular atypia seen
Treatment
bullNonoperative bull rest range of motion exercises and activity modification
bull passive stretching is contraindicated (makes it worse)bull physical therapy
bull utilized to maintain range of motionbull radiographic monitoring
bull obtained to confirm maturation of the lesionbullOperative
bull surgical excision bull indicated only if it remains a problem after it maturesbull do not operate in acute phase wait at least six months
bull excision of the lesion within 6 to 12 months predisposes to local recurrence
A 26-year-old man presents with generalized back and joint stiffness and difficulty opening his mouth His elder sister has similar complaints Since childhood he has had 3 surgeries for excision of recurrent bony prominences around his knees He walks with a stooped over posture seen in Figure A Radiographs of his feet knee hip and spine are seen in Figures B-E respectively
fibrodysplasia ossificans progressiva
Stone Man Disease) which involves a mutation of the ACVR1
There are 2 hallmark characteristics progressive heterotopic ossification (muscles fascia tendons ligaments and joint capsules) and congenital malformation of the great toe (hallux valgus malformed first metatarsal and monophalangism) BMP4 which contributes to the formation of the skeleton in the normal embryo is implicated in this disease
Complications
bullHematoma and intraoperative bleedingbullInfection
bull higher rate of infection following joint arthroplasty if HO is present
bullFractures of osteoporotic bone bull osteopenic from disusebull during surgery or physiotherapy
bullRecurrence bull recurrence rate correlates with neurological injury
bull greater recurrence if severe neurological compromisebullAVN
bull if extensive dissection or stripping is required
HTO AND ISS
When ISS is below 25 the mortality risk is minimal and above 25 it is an almost linear increase
When ISS is 50 the mortality is 50 When above 70 it is close to 100 If an injury is assigned an AIS of 6 (unsurvivable injury) the ISS score is
automatically assigned to 75 Highest ISS score obtainable is 75 For trauma patients of vehicular accidents the scoring system is important
for assessing the effectiveness of medical care in reducing morbidity and mortality
Advantages virtually the only anatomical scoring system in use correlates linearly with
mortality morbidity hospital stay other measures of severity
Weaknesses Any error in AIS scoring increases the ISS error Many different injury patterns can yield the same ISS score Injuries to different body regions are not weighted Not a useful triage tool as a full description of patient injuries is not known
prior to full investigation amp operation
risk factors periosteal stripping off anterior femur male gender obesity post traumatic deformity Anterior and anterolateral approach Cementless
Neurogenic HO around the hip due to SCI occurs more often in the medial region than in the lateral region with ossified tissues extending from the pubic symphysis to the anteromedial femoral shaft posterior to the femoral neurovascular structures Ossification is also seen anteriorly involving the iliopsoas and femoral neurovascular structures laterally within gluteus minimus and posteriorly extending from the ilium to the posterior femur encasing the sciatic nerve
HTO AROUND hip and knee
The Brooker Classification of Heterotopic Ossification around the hip joint Class I has islands of bone within the soft tissues Class II has bone spurs from the pelvis or proximal end of the femur leaving at least 1 cm between opposing surfaces Class III has bone spurs from the pelvis andor proximal end of the femur reducing the space between opposing bone surfaces to less than 1 cm Class IV shows apparent bone ankylosis of the hip
Region I - Heterotopic ossifications are strictly below the tip of the greater trochanter
Region II - Heterotopic ossifications are below and above the tip of the greater trochanter
Region III - Heterotopic ossifications are strictly above the tip of the greater trochanter
Grade A - Single or multiple heterotopic ossifications are less than 10 mm in maximal extent without contact with the pelvis or the femur
Grade B - Heterotopic ossifications are greater than 10 mm without contact with the pelvis but with possible contact with the femur there is no bridging from the femur to the proximal part of the greater trochanter and no evidence of ankylosis
Grade C - Ankylosis by means of firm bridging from the femur to the pelvis is present
Shmidt classification
excision may be performed The results of this procedure are varied Patients may find that their range of movement improves but pain relief is likely to be limited
A patient with heterotopic ossification following total hip arthroplasty is thought to have a 90-100 chance of developing it on the contralateral hip if this hip also undergoes total arthroplasty
it would be prudent to minimize the risk of heterotopic ossification developing after arthroplasty by performing surgery whereby the following are ensured
Exposure is meticulous Retraction is performed carefully and soft tissue
is handled carefully Irrigation is adequate Devitalized tissue is excised Hemostasis is adequate Postoperative drains (when used) are not
retained for longer than necessary Perioperative antibiotic prophylaxis is used Postoperative anticoagulation (when used for
deep vein thrombosis prophylaxis) is carefully controlled
sources of knee stiffness 1-extrinsic severe osteoarthritis of the ipsilateral hip neurologic injury leading to muscle rigidity tight quadriceps or hamstring muscles secondary to muscle injury heterotopic ossification or long-standing juvenile inflammatory conditions limiting knee
range of motion prior to the completion of skeletal growth When extrinsic sources are identified revision total knee arthroplasty is unlikely to be associated with a favorable outcome without correction of the extrinsic problem
2-intrinsic (1) overstuffing of the patellofemoral articulation (2) an
excessively tight flexion andor extension gap (3) a tight posterior cruciate ligament (4) femoral andor tibial malrotation (5) arthrofibrosis and (6) limited bearing excursion in association with a highly conforming mobile-bearing prosthetic design
HTO after TKA
Heterotopic Ossification (HO) following primary Total Knee Replacement (TKR)
Occurs in 3-90 of TKRs 3-grade classification system No correlation between HO and component
alignment or component position
Clinical findings similar to early infection Continuing low-grade fever Warm swollen and erythematous knee Normal blood tests Possibly an association with HLA-A2 and B18 HO patients have worse KSS and function
scores
Patients at HIGH risk for developing HO after TKR (Knee Arthroplasty) (5)
Those with limited postoperative knee flexion
Increased lumbar bone mineral density (BMD) on multivariate analysis (3)
Hypertrophic arthrosis Excessive periosteal trauma Notching of the anterior femur Those who require forced manipulation
after TKA 47 in revision TKR surgery (6) Higher rates in revision TKR cases with
infection (up to 76
DaughertyBell classification of HO of the knee 0 No evidence of HO 1 Bone islands in periarticular soft tissue (no
involvement of femur patella or tibia) or HO within quadriceps expansion measuring lt1 cm
2 Spur formation measuring lt5 cm that involves the femur patella or tibia if more than one bone demonstrates HO separation of HO spurs
measure gt1 cm or HO within quadriceps expansion measuring ge1 cm but lt3 cm
3 Spur formation gt5 cm involving femur patella or tibia if more than one bone demonstrates HO separation of HO spurs measure lt1 cm or HO
within quadriceps expansion measuring ge3 cm 4 Extensive HO of the knee causing ankylosis
class 2 HO begins to involve the major bones of the knee joint with spur formation limited to a size of 5 cm
HO class 2 may be observed in select patients with complete ROM and no reported pain Patients with class 3 HO would likely always benefit from surgical excision
followed by RT prophylaxis Certainly patients in either cohort with a subclass ldquoBrdquo assignment (symptomatic) would
benefit from treatment All patients with class 4 HO require
treatment to alleviate ankylosis
treatment
References Whyte ldquoPagetrsquos Disease of Bonerdquo NEMJ vol 355
2006 Klein and Parvizi ldquoSurgical Manifestations of Pagetrsquos
Diseaserdquo JAAOS vol 14 2006 Orthobullets Campbell Apley Emedicinecom
-Chapter 15 Heterotopic Ossification after Traumatic Brain InjuryBy Jesuacutes Moreta and Joseacute Luis Martiacutenez-de los Mozos DOI 10577257343
Questions
Thank You
Diagnostic Biopsy Diagnosis is usually achieved clinically and by
plain radiographic appearance Biopsy rarely required
Characteristic HistopathologyDisorganized immature trabeculararchitecture with irregular cement lines (ldquomosaicrdquopattern)
Rimming osteoblasts andor multinucleated osteoclasts
Management Options (May require no treatment if asymptomatic)
Supportive Care Pharmacologic Surgical (OrthopedicNeurosurgical
Supportive Care Occupational therapy Physical aides Counseling for fall+fracture prevention
Physical therapy Analgesics Weight control
Pharmacologic ManagementGoals Relieve symptoms and Prevent potential
complications Normalization of serum AlkPhos associated
with better long-term outcomes and disease control
Indications to treat Pain Deformity Neurologic symptoms Asymptomatic but high-risk for complications
(prophylactic) Management of hypercalcemia(rare) Pre-op reduce blood flow and potential
operative blood loss
Calcitonin is the most widely used It reduces bone resorption by decreasing both the activity and the number
of osteoclasts serum alkaline phosphatase and urinaryhydroxyproline levels are lowered Salmon calcitonin is more effective than the porcine variety subcutaneous injections of 50ndash100 MRC units are given daily until pain is relieved and the alkaline phosphatase levels are reduced and stabilized Maintenance injections once or twice weekly may have to be continued indefinitely but some authorities advocate stopping the drug and resuming treatment if symptoms recur Calcitonin can also be administered in a nasal spray Bisphosphonates bind to hydroxyapatite crystals
inhibiting their rate of growth and dissolution It is claimed that the reduction in bone turnover following their use is associated with the formation of lamellar rather than woven bone and that even after treatment is stopped there may be prolonged remission of disease (Bickerstaff et al 1990) Etidronate can be given orally (always on an empty stomach) but dosage should be kept low (eg 5 mgkg per day for up to 6 months) and vitamin D and calcium should also be given lest impaired bone mineralization results inosteomalacia The newer bisphosphonates (eg alendronate or pamidronate) do not have this disadvantage so they should be used as the treatment of choice they produce remissions even with shortcourses of 1 or 2 weeks
BisphosphonatesSynthetic analogues of inorganic phosphate adhere to mineralized surfaces
Ingested selectively by osteoclasts Disrupts enzyme pathways and reduces osteoclastic bone resorption
calcitonin causes osteoclasts to shrink in size and decreases their bone resorptive activity within minutes administered subcutaneously or intramuscularly
teriparatide is contraindicated in Pagets disease due to risk of secondary osteosarcoma
Surgical Management Few require surgery
Common Procedures Corrective osteotomy of long bone deformity indications
fractures through pathologic bowing of long bones impending pathologic fracture of long bone with bowing deformity
Arthroplasty (hip knee) the most common complications include
malalignment with knee arthroplasty bleeding with hip arthroplasty
Combination arthroplasty with osteotomy Fracture fixation
Preoperative Considerations Medical assessment for extraskeletalmanifestations eg high-
output heart failure
Medical treatment of active disease Preoperative autologousblood donation
Thorough planningeg good quality x-rays for templatingand device selection
Intraoperative Considerations Blood salvage system Expansileapproach + soft tissue release Sharp reamersburrsdrills for IM access Extramedullaryguidenavigation systems Concomitant osteotomy
PostoperativeConsiderations Monitoring for cardiac complications Continued medical tx of active disease
uarrHeterotopic ossification Prophylaxis against HO
Possible future excision of HO for painROM
1-Tieg provides a review of Pagets disease of bone and treatment indications In his review he discusses that most patients with Pagets disease are asymptomatic but in those that do present pain is the most common presenting symptom He recommends medical and surgical treatment of asymptomatic patients who have active disease at sites where complications are likely to develop
Altman did a review of 290 patients with Pagets disease of bone His findings showed 83 had one or more rheumatic syndromes He found the rate of osteoarthritis related to Pagets disease was elevated in the hip and knee Rheumatoid arthritis hyperuricemia and gout did not appear increased in this group
Mangham et al looked the rate of secondary sarcomas as a result of Pagets disease of bone They found the rate to be around 03 with male predominance They also found that widespread skeletal involvement by Pagets disease was not a significant risk factor for malignant transformation
Interesting views about pagets
Smith et al reviewed the pathologic complications of Pagets bone disease Pagets bone disease commonly causes osseous weakening (deformity and fracture) and arthritis in the hip joint Management of end stage disease is successful with cemented and cementless total hip arthroplasty Bleeding is the most common intra- and post-operative complication of surgery
Gabel et al retrospectively reviewed thirteen patients who had had sixteen total knee arthroplasties for Pagetic gonarthrosis Unlike total hip arthroplasty surgery Paget disease did not increase the amount of blood lost during the operation or in the postoperative period The most common complication associated with total knee arthroplasty was malalignment
Hansen et al reviewed the incidence of osteosarcomas complicating Pagets Disease Of the typical sites that are usually involved in Pagets disease (eg spine pelvis femur tibia and humerus) secondary osteosarcoma tends to spare the spine
Shaylor et al reported the mortality rates in 26 patient with osteosarcoma secondary to Paget s disease There was a 47 mortality at 1 year and 75 at 2 years from diagnosis In their series no patient survived for 5 years All patients died of metastatic disease
Langston et al conducted a randomized trial that compared the results of symptomatic treatment versus intensive bisphosphonate therapy in patients with Pagets disease Clinical fractures occurred in 46 of 661 patients (70) in the treatment group compared with 49 of 663 patients (74) in the symptomatic treatment group They concluded that bisphosphonates did not show a significant beneficial impact on pain quality of life or fracture incidence
Hadjipavlou et al reviewed Pagets disease of the bone and its management Farmers have been shown to have an increased incidence of Pagets disease Average age at presentation is in the 5th and 6th decade Symptomatic individuals are recommended to be treated initially with medical management They suggest that bisphosphonates are more effective than calcitonin at suppressing the histological and biochemical activity in Pagetrsquos disease
Summary Epid Very common in elderly Path Abnormal osteoclastshellipuarrbone
turnoverhellipdeposition of abnormal bone SampS Pain deformity fracture arthropathy Labs uarrAlkPhos X-ray Characteristic coarse thickened
trabeculae Bone scan Very hot Rx Bisphosphonates Surgery for arthropathy fracture painful
deformity
A 65-year-old male presents with increasing shoulder pain over the past 9 months He is otherwise healthy and has no other complaints Radiograph of his shoulder is shown in Figure A Whole body bone scan and biopsy photograph are shown in Figures B and C What is the most appropriate treatment for this patient
1 Referral to endocrinology 2 Radiation therapy and chemotherapy 3 Wide resection and reconstruction 4 Radiation therapy wide resection and reconstruction 5 Chemotherapy wide resection and reconstruction
Histiocytosis X or Langerhans cell histiocytosis is a spectrum of diseases of the reticuloendothelial system with one of three general presentations Eosinophilic granuloma (EG)
usually a single self-limited lesion found in younger patients
Hand-Schuller-Christian disease (HSC) chronic disseminated form with bone and visceral lesions also known as Langerhans cell histiocytosis with visceral
involvement Letterer-Siwe disease (LSD)
fatal form that occurs in young children
Eosinophilic granuloma
Epidemiology demographics
most commonly occurs in children (80 of afflicted lt 20 years of age)
HSC disease presents in children gt 3 years of age LSD occurs in children lt 3 years of age Male to female ratio of 21
location eosinophilic granuloma
commonly presents in the skull ribs clavicle scapula mandible
isolated lesions of the spine (thoracic most common) can also occur in diaphyseal regions of long bones and the
pelvis HSC
multiple bony sites multiple lytic skull lesions visceral involvement of the lungs spleen liver skin lymph
nodes
Genetics no clear genetic pattern of inheritance or locus has
been determined Prognosis
EG isolated involvement generally treatable with local
management spine lesions can spontaneously resolve
HSC prognosis depends on response to chemotherapy worsening prognosis with increasing extraskeletal
involvement LSD
generally fatal in children lt 3 years of age
Symptoms skeletal involvement
pain and swelling at the region of involvement limping can be seen with pelvic or lower extremity
involvement vertebral involvement
localized or diffuse back pain increasingly kyphotic posture radiculopathy can occur with more aggressive lesions
HSC classic triad of
multiple lytic skull lesions diabetes insipidus
increased thirst and water intake exopthalmos
visceral involvement diffuse or nonspecific abdominal or chest pain
Radiographs general
known as the great mimicker as it appears similar to many lesions radiographic differential includes osteomyelitis leukemia lymphoma
fibrous dysplasia or Ewings sarcoma diaphyseal lesions
well defined intramedullary lytic or punched-out lesion cortex may be thinned expanded or destroyed may have periosteal reaction
metaphyseal lesions extend up to but not through the physis less central location than diaphyseal lesions
spinal lesions vertebra plana (flattened vertebrae) in spine increased kyphosis
cranial involvement multiple punched-out lytic lesions
MRI may show a soft tissue mass adjacent to boney lesions
Bone scan generally shows increased uptake in the region of boney lesion
Histology Langerhans cells
mononuclear histiocyte-like cells with oval nuclei with well-defined round or oval cytoplasm
a prominent nuclear groove (coffee bean nuclei) can be seen in most of the nuclei
eosinophilic cytoplasm (pink generally) stain with CD1A electronmicroscopy
birbeck granules seen inside Langerhans cells mixture of inflammatory cells also present giant cells are present lack of nuclear atypia and atypical mitoses
differentiates this condition from malignant conditions such as Ewings sarcoma lymphoma of bone and metastatic neuroblastoma which may look similar based on the round cells alone
eosinophilic cytoplasm (pink generally)
Treatment
bullNonoperative bull observation alone
bull indications bull a self-limited process and it is reasonable to treat with observation alone
bull bracing bull indications
bull to prevent progressive kyphosis of the spinebull outcomes
bull will correct deformity in 90 of patientsbull vertebral lesions generally regain 50 of their height
bull low dose irradiation (600-800 cGy) bull indications
bull indicated for lesions in the spine that compromise stability neurologic statusbull lesions not amenable to injection or open treatment
bull outcomes bull effective for most lesions
bull chemotherapy bull indications
bull diffuse HSCbull outcomes
bull prognosis is improved with less severe extraskeletal involvementbull corticosteroid injection
bull indications bull isolated lesions bull can be performed after curettage as well
Operative curettage and bone grafting
indications for lesions that endanger the articular surface or are a risk for
impending fractures spinal deformity correction
indications progressive spine deformity refractory to bracing
approximately 10 of patients with spine lesion will need operative intervention for deformity correction
Destructive multiple lesion in young patientsAre eosinophilic granuloma lymphoma and leukemiaLymphoma is unlikely to present with exopthalmos diabetes insipidus or vertebra plana Lymphoma bone lesions are lytic and appear moth eatenpermeative on radiographs
Figure A shows a skin lesion typical of eosinophillic granuloma Figure B shows a lytic lesions without significant surrounding sclerosis as is characteristic of eosinophilic granuloma Figure C shows the characteristic histology of multiple eosinophils with their characteristic oval coffee bean nuclei and staining pattern of purpleredpink cytoplasm (depending on the stain) Importantly the histology slide lacks a malignant appearance (no cellular atypia or mytotic complexes and low nuclearcytoplasmic ratio)
Formation of bone in atypical extraskeletal tissues usually occurs
spontaneously or following trauma within 2 months of neurologic injury (brain or spinal cord)
most common location is between muscle and joint capsule Epidemiology
incidence (see table below)
demographics malefemale = 21 especially men with hypertrophic osteoarthritis and women gt65y
location traumatic brain injury or stroke
hip gt elbow gt shoulder gt knee elbow HO more common following brain trauma
occurs on affected (spastic) side rarely in the knee (TBI)
spinal cord injury hip gt knee gt elbow gt shoulder hip flexors and abductors gt extensors or adductors medial aspect of the knee
Heterotopic Ossification
Risk factors
Pathophysiology exact cause of HO is not known but there appears to be a
genetic pre disposition experimental HO associated with
tissue expression of BMP IT IS SAID TO BE CAUSED BY activation and proliferation of
mesenchymal stem cells Associated conditions
orthopaedic manifestations pathologic fractures
from decreased joint ROM and osteoporotic bone nerve impingement soft tissue contractures contributing to the formation of
decubitus ulcers joint ankylosis HO after THA adversely affects outcome of THA
nonorthopaedic conditions skin maceration and hygiene problems
Pathophysiology Early in the formation of HO oedema with exudative
infiltrate is present followed by fibroblastic proliferation and immature connective tissue formation Posteriorly osteoid formation is seen with the subsequent deposition of bone matrix Primitive osteoid is deposited as small masses in the periphery early (within the first two weeks) and osteoblasts are noted located irregularly Osteoblasts produce tropocollagen which polymerizes to form collagen and secrete alkaline phosphatase which allows calcium to precipitate and the mineralization of bone matrix As mineralization progresses amorphous calcium phosphate is progressively replaced by hydroxyapatite crystals During the following weeks the lesion matures with a centripetal pattern and after 6-12 months an appearance of true bone is noted The new bone is always extra-articular and can be contiguous with the skeleton but generally does not involve the periosteum
IN SUMMARY It has been postulated that three conditions
must be met to achieve heterotopic bone formation ---a stimulating event oestrogenic precursor cells and a proper environment LIKE hypercalcaemia tissue hypoxia pH changes (alkalosis) or prolonged immobilization
ClassificationbullSubtypes
bull neurogenic HO bull Four clinical stages of HO in people with spinal cord injury were
described by Nicholas in 1973
bull traumatic myositis ossificans bull fibrodysplasia ossificans progressiva (Munchmeyers Disease)
Neurogenic HO Symptoms
painless loss of ROM interferes with ADL CRPS symptoms fever
Physical exam inspection
warm painful swollen joint may have effusion skin problems
decubitus ulcers from contractures around skin muscles ligaments
skin maceration and hygiene problems motion
decreased joint ROM joint ankylosis with HO after TKA might develop quad muscle snapping or patella
instability neurovascular
peripheral neuropathy HO often impinges on adjacent NV structures
Imaging
bullRadiographs bull findings
bull ossification usually easy to visualize bull maturity of HO
bull the appearance of a bony cortex suggests mature HObull sharp demarcation from surrounding tissue bull trabecular pattern
bull sensitivity and specificity bull not useful for early diagnosisbull only useful at 1 week after onset of symptoms
bull calcium is deposited 7-10 days later than symptom onsetbullUltrasound
bull indications bull for early diagnosis of hip HO
bull findings bull echogenic surfaces with posterior acoustic shadowing
bullCT bull indications
bull useful for preoperative planning bullTriphasic bone scan
bull indications bull best for early diagnosis bull most commonly used diagnostic study
Radiographs are extremely useful in the staging of heterotopic ossification and will show the development of sharp cortical margins once the lesion has reached maturity
Heterotopic bone is a condition in which lamellar bone forms in non-ossified soft tissues In the early stages studies such as MRI and bone scan are more sensitive for diagnosis as radiographs may appear normal for the first three weeks After the appropriate diagnosis is made sequential radiographs are useful for monitoring the progression of the ossification Once it has reached the mature stage sharp cortical margins will appear and surgical resection may be considered
lab
Labs elevated serum alkaline phosphatase (gt250IUL)
ALP removes inhibitors of mineralization nonspecific may be elevated with skeletal trauma cannot determine maturity of HO elevated 12wks after surgery is predictor
elevated CRP correlates with inflammatory activity of HO better than ESR normalization of CRP may correlate with maturity of HO
elevated ESR (gt35mmh) 12wks after THA is predictor
elevated CK correlates with involvement of muscle extent of muscle
involvement Histology
mature fatty bone marrow mature trabecular bone
Heterotopic ossification (HO) most commonly occurs at the amputation site if the amputation was performed thru the zone of injury especially if the injury was a blast mechanism
Symptomatic heterotopic ossification of the quadriceps may occur following placement of a large-diameter Steinmann pin for the purpose of temporary skeletal traction
TreatmentThe prevention of heterotopic ossification is focused on three basic principles disrupting the inductive signalling pathways altering the osteoprogenitor cells or modifying the environment
bullphysiotherapy should involve an assisted range of movement exercises with gentle stretch and terminal resistance trainingbullProphylaxis
bull bisphosphonates amp NSAIDS bull indications
bull although no literature supports are commonly usedbull technique
bull indomethacin is most commonly used bull dose is 75mgday for 10days to 6 weeks
bull perioperative radiation bull indications
bull although no literature supports commonly usedbull is thought to be effective by blocking osteoblast differentiation
bull technique bull a single perioperative dose of 700cGy can be given either 4
hours preop or within 72 hours postoperatively bull lt550cGy not effective
Nonsteroidal anti-inflammatory drugs (NSAIDs) These drugs have demonstrated good results in
preventing heterotopic ossification after total hip arthroplasty
A direct effect of NSAIDs on the formation of heterotopic ossification has been described due to the inhibition of the differentiation of mesenchymal cells into oestrogenic cells There is also an indirect effect which refers to the inhibition of bone remodelling by suppression of the prostagland unmediated inflammatory response (specifically PGE-2)
Indomethacin has been considered a useful medication for heterotopic ossification prophylaxis following total hip replacement
prescribed for three to six weeks in a dose of 75mgday within two months of the injury may reduce the incidence of heterotopic ossification by two to three times
Biphosphonates inhibits precipitation of calcium phosphate and blocks the aggregation and mineralisation of hydroxyapatite crystals In primary prevention Banovac et al [56] have suggested that the treatment should begin as soon as elevated alkaline phosphatase is diagnosed or positive findings in ultrasonography or bone scans are shown In addition disphosphonates could have long-term effects on prevention when the treatment is finished
Posttraumatic wide exposure and surgical resection
indications severe loss of motion and decreased function
technique wide exposure required to identify all neurovascular
structures that may be involved timing of resection (controversial)
marked decrease in bone scan activity AND normalization of ALP
6 months following general trauma 1 year following SCI 15 years following TBI
some data suggests equivalent results when comparing early versus late resection
postop follow with 5 day course of indomethacin early gentle joint mobilization
The surgery is necessary in patients with symptomatic HO and unsuccessful medical treatment such as
Loss of range of motion and ankylosis with associated functional disability such as sitting difficulties
Complications of immobility such as pressure ulcers
Facilitate rehabilitation and recovery of muscular atrophy secondary to prolonged immobilisation
Difficulties of appropriate hygiene because access to the perineum or bladder care is needed
Severe pain refractory to analgesia Vascular andor nerve compression
Advantages to early excision of heterotopic ossification (vs waiting for maturation) include decreased soft tissue contracture better definition between heterotopic and native bone and decreased waiting time for the patient When the soft tissue envelope is benign one may proceed with operative release While waiting for normalization of alkaline phosphatase levels inactivity on bone scan or radiographic maturity may decrease risk of recurrent heterotopic ossification delaying operative release for these reasons has not been shown to improve results of final elbow range of motion after contracture release
Gartland recommended surgery after six months following traumatic heterotopic ossification one year following spinal cord injury and 18 months after head injury
In the past waiting until maturity in order to minimize the rate of recurrence after the surgical treatment was recommended Nevertheless recent studies do not confirm a higher rate of recurrence when the HO is excised in an earlier phase In addition a long delay before surgery leads to ankylosis a high degree of osteoporosis and more extensive intra-articular injuries These findings are associated with bad functional results and potential complications
Should you wait till lesion maturation
Prevention byHandle tissue carefully Avoid excess bleeding Achieve good hemostasis Beware of lesions that span internervous tissue planes
but if it happens resection of a large enough amount of bone to allow improvement of the range of motion and trying to preserve the joint
Our aim must be
A reactive process that is characterized by a well-circumscribed proliferation of fibroblasts cartilage and bone within muscle
A form of heterotopic ossification that is the result direct trauma intramuscular hematoma
most common location is the diaphysis of long bones Must differentiate from tumors Fibrodysplasia ossificans progressiva (FOP) is a rare subtype of heterotopic ossification
involves mutation of the ACVR1 gene (activin A type I receptor gene a BMP type-1 receptor)
Epidemiology demographics
most common in young active males (15 to 35 years old) body locations
quadriceps brachialis and gluteal muscles Genetics
almost always a posttraumatic condition Prognosis
usually self limiting mass usually begins to decrease in size after 1 yea
Myositis ossificans
PresentationbullSymptoms
bull pain tenderness swelling and decreased range of motion that usually presents within days of the injury
bull pain and size of the mass decrease with timebull mass increases in size over several months(usually 3 to 6 cm)
bull after the mass stops growing it becomes firmbullPhysical exam
bull palpable soft tissue massbull restricted range of motion
ImagingbullRadiographs
bull peripheral bone formation with central lucent areabull may appear as dotted veil pattern
bullMRI with gadolinium bull rim enhancement is seen within the first 3 weeks
bullCT scan bull lesion has an eggshell appearance
bullCharacteristic histology shows zonal pattern bull periphery of lesion
bull mature trabeculae of lamellar and woven bonebull calcification seen on xray
bull center of the lesion bull irregular mass of immature fibroblastsbull cartilage component may be presentbull (no calcification seen on xray) bull no cellular atypia seen
Treatment
bullNonoperative bull rest range of motion exercises and activity modification
bull passive stretching is contraindicated (makes it worse)bull physical therapy
bull utilized to maintain range of motionbull radiographic monitoring
bull obtained to confirm maturation of the lesionbullOperative
bull surgical excision bull indicated only if it remains a problem after it maturesbull do not operate in acute phase wait at least six months
bull excision of the lesion within 6 to 12 months predisposes to local recurrence
A 26-year-old man presents with generalized back and joint stiffness and difficulty opening his mouth His elder sister has similar complaints Since childhood he has had 3 surgeries for excision of recurrent bony prominences around his knees He walks with a stooped over posture seen in Figure A Radiographs of his feet knee hip and spine are seen in Figures B-E respectively
fibrodysplasia ossificans progressiva
Stone Man Disease) which involves a mutation of the ACVR1
There are 2 hallmark characteristics progressive heterotopic ossification (muscles fascia tendons ligaments and joint capsules) and congenital malformation of the great toe (hallux valgus malformed first metatarsal and monophalangism) BMP4 which contributes to the formation of the skeleton in the normal embryo is implicated in this disease
Complications
bullHematoma and intraoperative bleedingbullInfection
bull higher rate of infection following joint arthroplasty if HO is present
bullFractures of osteoporotic bone bull osteopenic from disusebull during surgery or physiotherapy
bullRecurrence bull recurrence rate correlates with neurological injury
bull greater recurrence if severe neurological compromisebullAVN
bull if extensive dissection or stripping is required
HTO AND ISS
When ISS is below 25 the mortality risk is minimal and above 25 it is an almost linear increase
When ISS is 50 the mortality is 50 When above 70 it is close to 100 If an injury is assigned an AIS of 6 (unsurvivable injury) the ISS score is
automatically assigned to 75 Highest ISS score obtainable is 75 For trauma patients of vehicular accidents the scoring system is important
for assessing the effectiveness of medical care in reducing morbidity and mortality
Advantages virtually the only anatomical scoring system in use correlates linearly with
mortality morbidity hospital stay other measures of severity
Weaknesses Any error in AIS scoring increases the ISS error Many different injury patterns can yield the same ISS score Injuries to different body regions are not weighted Not a useful triage tool as a full description of patient injuries is not known
prior to full investigation amp operation
risk factors periosteal stripping off anterior femur male gender obesity post traumatic deformity Anterior and anterolateral approach Cementless
Neurogenic HO around the hip due to SCI occurs more often in the medial region than in the lateral region with ossified tissues extending from the pubic symphysis to the anteromedial femoral shaft posterior to the femoral neurovascular structures Ossification is also seen anteriorly involving the iliopsoas and femoral neurovascular structures laterally within gluteus minimus and posteriorly extending from the ilium to the posterior femur encasing the sciatic nerve
HTO AROUND hip and knee
The Brooker Classification of Heterotopic Ossification around the hip joint Class I has islands of bone within the soft tissues Class II has bone spurs from the pelvis or proximal end of the femur leaving at least 1 cm between opposing surfaces Class III has bone spurs from the pelvis andor proximal end of the femur reducing the space between opposing bone surfaces to less than 1 cm Class IV shows apparent bone ankylosis of the hip
Region I - Heterotopic ossifications are strictly below the tip of the greater trochanter
Region II - Heterotopic ossifications are below and above the tip of the greater trochanter
Region III - Heterotopic ossifications are strictly above the tip of the greater trochanter
Grade A - Single or multiple heterotopic ossifications are less than 10 mm in maximal extent without contact with the pelvis or the femur
Grade B - Heterotopic ossifications are greater than 10 mm without contact with the pelvis but with possible contact with the femur there is no bridging from the femur to the proximal part of the greater trochanter and no evidence of ankylosis
Grade C - Ankylosis by means of firm bridging from the femur to the pelvis is present
Shmidt classification
excision may be performed The results of this procedure are varied Patients may find that their range of movement improves but pain relief is likely to be limited
A patient with heterotopic ossification following total hip arthroplasty is thought to have a 90-100 chance of developing it on the contralateral hip if this hip also undergoes total arthroplasty
it would be prudent to minimize the risk of heterotopic ossification developing after arthroplasty by performing surgery whereby the following are ensured
Exposure is meticulous Retraction is performed carefully and soft tissue
is handled carefully Irrigation is adequate Devitalized tissue is excised Hemostasis is adequate Postoperative drains (when used) are not
retained for longer than necessary Perioperative antibiotic prophylaxis is used Postoperative anticoagulation (when used for
deep vein thrombosis prophylaxis) is carefully controlled
sources of knee stiffness 1-extrinsic severe osteoarthritis of the ipsilateral hip neurologic injury leading to muscle rigidity tight quadriceps or hamstring muscles secondary to muscle injury heterotopic ossification or long-standing juvenile inflammatory conditions limiting knee
range of motion prior to the completion of skeletal growth When extrinsic sources are identified revision total knee arthroplasty is unlikely to be associated with a favorable outcome without correction of the extrinsic problem
2-intrinsic (1) overstuffing of the patellofemoral articulation (2) an
excessively tight flexion andor extension gap (3) a tight posterior cruciate ligament (4) femoral andor tibial malrotation (5) arthrofibrosis and (6) limited bearing excursion in association with a highly conforming mobile-bearing prosthetic design
HTO after TKA
Heterotopic Ossification (HO) following primary Total Knee Replacement (TKR)
Occurs in 3-90 of TKRs 3-grade classification system No correlation between HO and component
alignment or component position
Clinical findings similar to early infection Continuing low-grade fever Warm swollen and erythematous knee Normal blood tests Possibly an association with HLA-A2 and B18 HO patients have worse KSS and function
scores
Patients at HIGH risk for developing HO after TKR (Knee Arthroplasty) (5)
Those with limited postoperative knee flexion
Increased lumbar bone mineral density (BMD) on multivariate analysis (3)
Hypertrophic arthrosis Excessive periosteal trauma Notching of the anterior femur Those who require forced manipulation
after TKA 47 in revision TKR surgery (6) Higher rates in revision TKR cases with
infection (up to 76
DaughertyBell classification of HO of the knee 0 No evidence of HO 1 Bone islands in periarticular soft tissue (no
involvement of femur patella or tibia) or HO within quadriceps expansion measuring lt1 cm
2 Spur formation measuring lt5 cm that involves the femur patella or tibia if more than one bone demonstrates HO separation of HO spurs
measure gt1 cm or HO within quadriceps expansion measuring ge1 cm but lt3 cm
3 Spur formation gt5 cm involving femur patella or tibia if more than one bone demonstrates HO separation of HO spurs measure lt1 cm or HO
within quadriceps expansion measuring ge3 cm 4 Extensive HO of the knee causing ankylosis
class 2 HO begins to involve the major bones of the knee joint with spur formation limited to a size of 5 cm
HO class 2 may be observed in select patients with complete ROM and no reported pain Patients with class 3 HO would likely always benefit from surgical excision
followed by RT prophylaxis Certainly patients in either cohort with a subclass ldquoBrdquo assignment (symptomatic) would
benefit from treatment All patients with class 4 HO require
treatment to alleviate ankylosis
treatment
References Whyte ldquoPagetrsquos Disease of Bonerdquo NEMJ vol 355
2006 Klein and Parvizi ldquoSurgical Manifestations of Pagetrsquos
Diseaserdquo JAAOS vol 14 2006 Orthobullets Campbell Apley Emedicinecom
-Chapter 15 Heterotopic Ossification after Traumatic Brain InjuryBy Jesuacutes Moreta and Joseacute Luis Martiacutenez-de los Mozos DOI 10577257343
Questions
Thank You
Management Options (May require no treatment if asymptomatic)
Supportive Care Pharmacologic Surgical (OrthopedicNeurosurgical
Supportive Care Occupational therapy Physical aides Counseling for fall+fracture prevention
Physical therapy Analgesics Weight control
Pharmacologic ManagementGoals Relieve symptoms and Prevent potential
complications Normalization of serum AlkPhos associated
with better long-term outcomes and disease control
Indications to treat Pain Deformity Neurologic symptoms Asymptomatic but high-risk for complications
(prophylactic) Management of hypercalcemia(rare) Pre-op reduce blood flow and potential
operative blood loss
Calcitonin is the most widely used It reduces bone resorption by decreasing both the activity and the number
of osteoclasts serum alkaline phosphatase and urinaryhydroxyproline levels are lowered Salmon calcitonin is more effective than the porcine variety subcutaneous injections of 50ndash100 MRC units are given daily until pain is relieved and the alkaline phosphatase levels are reduced and stabilized Maintenance injections once or twice weekly may have to be continued indefinitely but some authorities advocate stopping the drug and resuming treatment if symptoms recur Calcitonin can also be administered in a nasal spray Bisphosphonates bind to hydroxyapatite crystals
inhibiting their rate of growth and dissolution It is claimed that the reduction in bone turnover following their use is associated with the formation of lamellar rather than woven bone and that even after treatment is stopped there may be prolonged remission of disease (Bickerstaff et al 1990) Etidronate can be given orally (always on an empty stomach) but dosage should be kept low (eg 5 mgkg per day for up to 6 months) and vitamin D and calcium should also be given lest impaired bone mineralization results inosteomalacia The newer bisphosphonates (eg alendronate or pamidronate) do not have this disadvantage so they should be used as the treatment of choice they produce remissions even with shortcourses of 1 or 2 weeks
BisphosphonatesSynthetic analogues of inorganic phosphate adhere to mineralized surfaces
Ingested selectively by osteoclasts Disrupts enzyme pathways and reduces osteoclastic bone resorption
calcitonin causes osteoclasts to shrink in size and decreases their bone resorptive activity within minutes administered subcutaneously or intramuscularly
teriparatide is contraindicated in Pagets disease due to risk of secondary osteosarcoma
Surgical Management Few require surgery
Common Procedures Corrective osteotomy of long bone deformity indications
fractures through pathologic bowing of long bones impending pathologic fracture of long bone with bowing deformity
Arthroplasty (hip knee) the most common complications include
malalignment with knee arthroplasty bleeding with hip arthroplasty
Combination arthroplasty with osteotomy Fracture fixation
Preoperative Considerations Medical assessment for extraskeletalmanifestations eg high-
output heart failure
Medical treatment of active disease Preoperative autologousblood donation
Thorough planningeg good quality x-rays for templatingand device selection
Intraoperative Considerations Blood salvage system Expansileapproach + soft tissue release Sharp reamersburrsdrills for IM access Extramedullaryguidenavigation systems Concomitant osteotomy
PostoperativeConsiderations Monitoring for cardiac complications Continued medical tx of active disease
uarrHeterotopic ossification Prophylaxis against HO
Possible future excision of HO for painROM
1-Tieg provides a review of Pagets disease of bone and treatment indications In his review he discusses that most patients with Pagets disease are asymptomatic but in those that do present pain is the most common presenting symptom He recommends medical and surgical treatment of asymptomatic patients who have active disease at sites where complications are likely to develop
Altman did a review of 290 patients with Pagets disease of bone His findings showed 83 had one or more rheumatic syndromes He found the rate of osteoarthritis related to Pagets disease was elevated in the hip and knee Rheumatoid arthritis hyperuricemia and gout did not appear increased in this group
Mangham et al looked the rate of secondary sarcomas as a result of Pagets disease of bone They found the rate to be around 03 with male predominance They also found that widespread skeletal involvement by Pagets disease was not a significant risk factor for malignant transformation
Interesting views about pagets
Smith et al reviewed the pathologic complications of Pagets bone disease Pagets bone disease commonly causes osseous weakening (deformity and fracture) and arthritis in the hip joint Management of end stage disease is successful with cemented and cementless total hip arthroplasty Bleeding is the most common intra- and post-operative complication of surgery
Gabel et al retrospectively reviewed thirteen patients who had had sixteen total knee arthroplasties for Pagetic gonarthrosis Unlike total hip arthroplasty surgery Paget disease did not increase the amount of blood lost during the operation or in the postoperative period The most common complication associated with total knee arthroplasty was malalignment
Hansen et al reviewed the incidence of osteosarcomas complicating Pagets Disease Of the typical sites that are usually involved in Pagets disease (eg spine pelvis femur tibia and humerus) secondary osteosarcoma tends to spare the spine
Shaylor et al reported the mortality rates in 26 patient with osteosarcoma secondary to Paget s disease There was a 47 mortality at 1 year and 75 at 2 years from diagnosis In their series no patient survived for 5 years All patients died of metastatic disease
Langston et al conducted a randomized trial that compared the results of symptomatic treatment versus intensive bisphosphonate therapy in patients with Pagets disease Clinical fractures occurred in 46 of 661 patients (70) in the treatment group compared with 49 of 663 patients (74) in the symptomatic treatment group They concluded that bisphosphonates did not show a significant beneficial impact on pain quality of life or fracture incidence
Hadjipavlou et al reviewed Pagets disease of the bone and its management Farmers have been shown to have an increased incidence of Pagets disease Average age at presentation is in the 5th and 6th decade Symptomatic individuals are recommended to be treated initially with medical management They suggest that bisphosphonates are more effective than calcitonin at suppressing the histological and biochemical activity in Pagetrsquos disease
Summary Epid Very common in elderly Path Abnormal osteoclastshellipuarrbone
turnoverhellipdeposition of abnormal bone SampS Pain deformity fracture arthropathy Labs uarrAlkPhos X-ray Characteristic coarse thickened
trabeculae Bone scan Very hot Rx Bisphosphonates Surgery for arthropathy fracture painful
deformity
A 65-year-old male presents with increasing shoulder pain over the past 9 months He is otherwise healthy and has no other complaints Radiograph of his shoulder is shown in Figure A Whole body bone scan and biopsy photograph are shown in Figures B and C What is the most appropriate treatment for this patient
1 Referral to endocrinology 2 Radiation therapy and chemotherapy 3 Wide resection and reconstruction 4 Radiation therapy wide resection and reconstruction 5 Chemotherapy wide resection and reconstruction
Histiocytosis X or Langerhans cell histiocytosis is a spectrum of diseases of the reticuloendothelial system with one of three general presentations Eosinophilic granuloma (EG)
usually a single self-limited lesion found in younger patients
Hand-Schuller-Christian disease (HSC) chronic disseminated form with bone and visceral lesions also known as Langerhans cell histiocytosis with visceral
involvement Letterer-Siwe disease (LSD)
fatal form that occurs in young children
Eosinophilic granuloma
Epidemiology demographics
most commonly occurs in children (80 of afflicted lt 20 years of age)
HSC disease presents in children gt 3 years of age LSD occurs in children lt 3 years of age Male to female ratio of 21
location eosinophilic granuloma
commonly presents in the skull ribs clavicle scapula mandible
isolated lesions of the spine (thoracic most common) can also occur in diaphyseal regions of long bones and the
pelvis HSC
multiple bony sites multiple lytic skull lesions visceral involvement of the lungs spleen liver skin lymph
nodes
Genetics no clear genetic pattern of inheritance or locus has
been determined Prognosis
EG isolated involvement generally treatable with local
management spine lesions can spontaneously resolve
HSC prognosis depends on response to chemotherapy worsening prognosis with increasing extraskeletal
involvement LSD
generally fatal in children lt 3 years of age
Symptoms skeletal involvement
pain and swelling at the region of involvement limping can be seen with pelvic or lower extremity
involvement vertebral involvement
localized or diffuse back pain increasingly kyphotic posture radiculopathy can occur with more aggressive lesions
HSC classic triad of
multiple lytic skull lesions diabetes insipidus
increased thirst and water intake exopthalmos
visceral involvement diffuse or nonspecific abdominal or chest pain
Radiographs general
known as the great mimicker as it appears similar to many lesions radiographic differential includes osteomyelitis leukemia lymphoma
fibrous dysplasia or Ewings sarcoma diaphyseal lesions
well defined intramedullary lytic or punched-out lesion cortex may be thinned expanded or destroyed may have periosteal reaction
metaphyseal lesions extend up to but not through the physis less central location than diaphyseal lesions
spinal lesions vertebra plana (flattened vertebrae) in spine increased kyphosis
cranial involvement multiple punched-out lytic lesions
MRI may show a soft tissue mass adjacent to boney lesions
Bone scan generally shows increased uptake in the region of boney lesion
Histology Langerhans cells
mononuclear histiocyte-like cells with oval nuclei with well-defined round or oval cytoplasm
a prominent nuclear groove (coffee bean nuclei) can be seen in most of the nuclei
eosinophilic cytoplasm (pink generally) stain with CD1A electronmicroscopy
birbeck granules seen inside Langerhans cells mixture of inflammatory cells also present giant cells are present lack of nuclear atypia and atypical mitoses
differentiates this condition from malignant conditions such as Ewings sarcoma lymphoma of bone and metastatic neuroblastoma which may look similar based on the round cells alone
eosinophilic cytoplasm (pink generally)
Treatment
bullNonoperative bull observation alone
bull indications bull a self-limited process and it is reasonable to treat with observation alone
bull bracing bull indications
bull to prevent progressive kyphosis of the spinebull outcomes
bull will correct deformity in 90 of patientsbull vertebral lesions generally regain 50 of their height
bull low dose irradiation (600-800 cGy) bull indications
bull indicated for lesions in the spine that compromise stability neurologic statusbull lesions not amenable to injection or open treatment
bull outcomes bull effective for most lesions
bull chemotherapy bull indications
bull diffuse HSCbull outcomes
bull prognosis is improved with less severe extraskeletal involvementbull corticosteroid injection
bull indications bull isolated lesions bull can be performed after curettage as well
Operative curettage and bone grafting
indications for lesions that endanger the articular surface or are a risk for
impending fractures spinal deformity correction
indications progressive spine deformity refractory to bracing
approximately 10 of patients with spine lesion will need operative intervention for deformity correction
Destructive multiple lesion in young patientsAre eosinophilic granuloma lymphoma and leukemiaLymphoma is unlikely to present with exopthalmos diabetes insipidus or vertebra plana Lymphoma bone lesions are lytic and appear moth eatenpermeative on radiographs
Figure A shows a skin lesion typical of eosinophillic granuloma Figure B shows a lytic lesions without significant surrounding sclerosis as is characteristic of eosinophilic granuloma Figure C shows the characteristic histology of multiple eosinophils with their characteristic oval coffee bean nuclei and staining pattern of purpleredpink cytoplasm (depending on the stain) Importantly the histology slide lacks a malignant appearance (no cellular atypia or mytotic complexes and low nuclearcytoplasmic ratio)
Formation of bone in atypical extraskeletal tissues usually occurs
spontaneously or following trauma within 2 months of neurologic injury (brain or spinal cord)
most common location is between muscle and joint capsule Epidemiology
incidence (see table below)
demographics malefemale = 21 especially men with hypertrophic osteoarthritis and women gt65y
location traumatic brain injury or stroke
hip gt elbow gt shoulder gt knee elbow HO more common following brain trauma
occurs on affected (spastic) side rarely in the knee (TBI)
spinal cord injury hip gt knee gt elbow gt shoulder hip flexors and abductors gt extensors or adductors medial aspect of the knee
Heterotopic Ossification
Risk factors
Pathophysiology exact cause of HO is not known but there appears to be a
genetic pre disposition experimental HO associated with
tissue expression of BMP IT IS SAID TO BE CAUSED BY activation and proliferation of
mesenchymal stem cells Associated conditions
orthopaedic manifestations pathologic fractures
from decreased joint ROM and osteoporotic bone nerve impingement soft tissue contractures contributing to the formation of
decubitus ulcers joint ankylosis HO after THA adversely affects outcome of THA
nonorthopaedic conditions skin maceration and hygiene problems
Pathophysiology Early in the formation of HO oedema with exudative
infiltrate is present followed by fibroblastic proliferation and immature connective tissue formation Posteriorly osteoid formation is seen with the subsequent deposition of bone matrix Primitive osteoid is deposited as small masses in the periphery early (within the first two weeks) and osteoblasts are noted located irregularly Osteoblasts produce tropocollagen which polymerizes to form collagen and secrete alkaline phosphatase which allows calcium to precipitate and the mineralization of bone matrix As mineralization progresses amorphous calcium phosphate is progressively replaced by hydroxyapatite crystals During the following weeks the lesion matures with a centripetal pattern and after 6-12 months an appearance of true bone is noted The new bone is always extra-articular and can be contiguous with the skeleton but generally does not involve the periosteum
IN SUMMARY It has been postulated that three conditions
must be met to achieve heterotopic bone formation ---a stimulating event oestrogenic precursor cells and a proper environment LIKE hypercalcaemia tissue hypoxia pH changes (alkalosis) or prolonged immobilization
ClassificationbullSubtypes
bull neurogenic HO bull Four clinical stages of HO in people with spinal cord injury were
described by Nicholas in 1973
bull traumatic myositis ossificans bull fibrodysplasia ossificans progressiva (Munchmeyers Disease)
Neurogenic HO Symptoms
painless loss of ROM interferes with ADL CRPS symptoms fever
Physical exam inspection
warm painful swollen joint may have effusion skin problems
decubitus ulcers from contractures around skin muscles ligaments
skin maceration and hygiene problems motion
decreased joint ROM joint ankylosis with HO after TKA might develop quad muscle snapping or patella
instability neurovascular
peripheral neuropathy HO often impinges on adjacent NV structures
Imaging
bullRadiographs bull findings
bull ossification usually easy to visualize bull maturity of HO
bull the appearance of a bony cortex suggests mature HObull sharp demarcation from surrounding tissue bull trabecular pattern
bull sensitivity and specificity bull not useful for early diagnosisbull only useful at 1 week after onset of symptoms
bull calcium is deposited 7-10 days later than symptom onsetbullUltrasound
bull indications bull for early diagnosis of hip HO
bull findings bull echogenic surfaces with posterior acoustic shadowing
bullCT bull indications
bull useful for preoperative planning bullTriphasic bone scan
bull indications bull best for early diagnosis bull most commonly used diagnostic study
Radiographs are extremely useful in the staging of heterotopic ossification and will show the development of sharp cortical margins once the lesion has reached maturity
Heterotopic bone is a condition in which lamellar bone forms in non-ossified soft tissues In the early stages studies such as MRI and bone scan are more sensitive for diagnosis as radiographs may appear normal for the first three weeks After the appropriate diagnosis is made sequential radiographs are useful for monitoring the progression of the ossification Once it has reached the mature stage sharp cortical margins will appear and surgical resection may be considered
lab
Labs elevated serum alkaline phosphatase (gt250IUL)
ALP removes inhibitors of mineralization nonspecific may be elevated with skeletal trauma cannot determine maturity of HO elevated 12wks after surgery is predictor
elevated CRP correlates with inflammatory activity of HO better than ESR normalization of CRP may correlate with maturity of HO
elevated ESR (gt35mmh) 12wks after THA is predictor
elevated CK correlates with involvement of muscle extent of muscle
involvement Histology
mature fatty bone marrow mature trabecular bone
Heterotopic ossification (HO) most commonly occurs at the amputation site if the amputation was performed thru the zone of injury especially if the injury was a blast mechanism
Symptomatic heterotopic ossification of the quadriceps may occur following placement of a large-diameter Steinmann pin for the purpose of temporary skeletal traction
TreatmentThe prevention of heterotopic ossification is focused on three basic principles disrupting the inductive signalling pathways altering the osteoprogenitor cells or modifying the environment
bullphysiotherapy should involve an assisted range of movement exercises with gentle stretch and terminal resistance trainingbullProphylaxis
bull bisphosphonates amp NSAIDS bull indications
bull although no literature supports are commonly usedbull technique
bull indomethacin is most commonly used bull dose is 75mgday for 10days to 6 weeks
bull perioperative radiation bull indications
bull although no literature supports commonly usedbull is thought to be effective by blocking osteoblast differentiation
bull technique bull a single perioperative dose of 700cGy can be given either 4
hours preop or within 72 hours postoperatively bull lt550cGy not effective
Nonsteroidal anti-inflammatory drugs (NSAIDs) These drugs have demonstrated good results in
preventing heterotopic ossification after total hip arthroplasty
A direct effect of NSAIDs on the formation of heterotopic ossification has been described due to the inhibition of the differentiation of mesenchymal cells into oestrogenic cells There is also an indirect effect which refers to the inhibition of bone remodelling by suppression of the prostagland unmediated inflammatory response (specifically PGE-2)
Indomethacin has been considered a useful medication for heterotopic ossification prophylaxis following total hip replacement
prescribed for three to six weeks in a dose of 75mgday within two months of the injury may reduce the incidence of heterotopic ossification by two to three times
Biphosphonates inhibits precipitation of calcium phosphate and blocks the aggregation and mineralisation of hydroxyapatite crystals In primary prevention Banovac et al [56] have suggested that the treatment should begin as soon as elevated alkaline phosphatase is diagnosed or positive findings in ultrasonography or bone scans are shown In addition disphosphonates could have long-term effects on prevention when the treatment is finished
Posttraumatic wide exposure and surgical resection
indications severe loss of motion and decreased function
technique wide exposure required to identify all neurovascular
structures that may be involved timing of resection (controversial)
marked decrease in bone scan activity AND normalization of ALP
6 months following general trauma 1 year following SCI 15 years following TBI
some data suggests equivalent results when comparing early versus late resection
postop follow with 5 day course of indomethacin early gentle joint mobilization
The surgery is necessary in patients with symptomatic HO and unsuccessful medical treatment such as
Loss of range of motion and ankylosis with associated functional disability such as sitting difficulties
Complications of immobility such as pressure ulcers
Facilitate rehabilitation and recovery of muscular atrophy secondary to prolonged immobilisation
Difficulties of appropriate hygiene because access to the perineum or bladder care is needed
Severe pain refractory to analgesia Vascular andor nerve compression
Advantages to early excision of heterotopic ossification (vs waiting for maturation) include decreased soft tissue contracture better definition between heterotopic and native bone and decreased waiting time for the patient When the soft tissue envelope is benign one may proceed with operative release While waiting for normalization of alkaline phosphatase levels inactivity on bone scan or radiographic maturity may decrease risk of recurrent heterotopic ossification delaying operative release for these reasons has not been shown to improve results of final elbow range of motion after contracture release
Gartland recommended surgery after six months following traumatic heterotopic ossification one year following spinal cord injury and 18 months after head injury
In the past waiting until maturity in order to minimize the rate of recurrence after the surgical treatment was recommended Nevertheless recent studies do not confirm a higher rate of recurrence when the HO is excised in an earlier phase In addition a long delay before surgery leads to ankylosis a high degree of osteoporosis and more extensive intra-articular injuries These findings are associated with bad functional results and potential complications
Should you wait till lesion maturation
Prevention byHandle tissue carefully Avoid excess bleeding Achieve good hemostasis Beware of lesions that span internervous tissue planes
but if it happens resection of a large enough amount of bone to allow improvement of the range of motion and trying to preserve the joint
Our aim must be
A reactive process that is characterized by a well-circumscribed proliferation of fibroblasts cartilage and bone within muscle
A form of heterotopic ossification that is the result direct trauma intramuscular hematoma
most common location is the diaphysis of long bones Must differentiate from tumors Fibrodysplasia ossificans progressiva (FOP) is a rare subtype of heterotopic ossification
involves mutation of the ACVR1 gene (activin A type I receptor gene a BMP type-1 receptor)
Epidemiology demographics
most common in young active males (15 to 35 years old) body locations
quadriceps brachialis and gluteal muscles Genetics
almost always a posttraumatic condition Prognosis
usually self limiting mass usually begins to decrease in size after 1 yea
Myositis ossificans
PresentationbullSymptoms
bull pain tenderness swelling and decreased range of motion that usually presents within days of the injury
bull pain and size of the mass decrease with timebull mass increases in size over several months(usually 3 to 6 cm)
bull after the mass stops growing it becomes firmbullPhysical exam
bull palpable soft tissue massbull restricted range of motion
ImagingbullRadiographs
bull peripheral bone formation with central lucent areabull may appear as dotted veil pattern
bullMRI with gadolinium bull rim enhancement is seen within the first 3 weeks
bullCT scan bull lesion has an eggshell appearance
bullCharacteristic histology shows zonal pattern bull periphery of lesion
bull mature trabeculae of lamellar and woven bonebull calcification seen on xray
bull center of the lesion bull irregular mass of immature fibroblastsbull cartilage component may be presentbull (no calcification seen on xray) bull no cellular atypia seen
Treatment
bullNonoperative bull rest range of motion exercises and activity modification
bull passive stretching is contraindicated (makes it worse)bull physical therapy
bull utilized to maintain range of motionbull radiographic monitoring
bull obtained to confirm maturation of the lesionbullOperative
bull surgical excision bull indicated only if it remains a problem after it maturesbull do not operate in acute phase wait at least six months
bull excision of the lesion within 6 to 12 months predisposes to local recurrence
A 26-year-old man presents with generalized back and joint stiffness and difficulty opening his mouth His elder sister has similar complaints Since childhood he has had 3 surgeries for excision of recurrent bony prominences around his knees He walks with a stooped over posture seen in Figure A Radiographs of his feet knee hip and spine are seen in Figures B-E respectively
fibrodysplasia ossificans progressiva
Stone Man Disease) which involves a mutation of the ACVR1
There are 2 hallmark characteristics progressive heterotopic ossification (muscles fascia tendons ligaments and joint capsules) and congenital malformation of the great toe (hallux valgus malformed first metatarsal and monophalangism) BMP4 which contributes to the formation of the skeleton in the normal embryo is implicated in this disease
Complications
bullHematoma and intraoperative bleedingbullInfection
bull higher rate of infection following joint arthroplasty if HO is present
bullFractures of osteoporotic bone bull osteopenic from disusebull during surgery or physiotherapy
bullRecurrence bull recurrence rate correlates with neurological injury
bull greater recurrence if severe neurological compromisebullAVN
bull if extensive dissection or stripping is required
HTO AND ISS
When ISS is below 25 the mortality risk is minimal and above 25 it is an almost linear increase
When ISS is 50 the mortality is 50 When above 70 it is close to 100 If an injury is assigned an AIS of 6 (unsurvivable injury) the ISS score is
automatically assigned to 75 Highest ISS score obtainable is 75 For trauma patients of vehicular accidents the scoring system is important
for assessing the effectiveness of medical care in reducing morbidity and mortality
Advantages virtually the only anatomical scoring system in use correlates linearly with
mortality morbidity hospital stay other measures of severity
Weaknesses Any error in AIS scoring increases the ISS error Many different injury patterns can yield the same ISS score Injuries to different body regions are not weighted Not a useful triage tool as a full description of patient injuries is not known
prior to full investigation amp operation
risk factors periosteal stripping off anterior femur male gender obesity post traumatic deformity Anterior and anterolateral approach Cementless
Neurogenic HO around the hip due to SCI occurs more often in the medial region than in the lateral region with ossified tissues extending from the pubic symphysis to the anteromedial femoral shaft posterior to the femoral neurovascular structures Ossification is also seen anteriorly involving the iliopsoas and femoral neurovascular structures laterally within gluteus minimus and posteriorly extending from the ilium to the posterior femur encasing the sciatic nerve
HTO AROUND hip and knee
The Brooker Classification of Heterotopic Ossification around the hip joint Class I has islands of bone within the soft tissues Class II has bone spurs from the pelvis or proximal end of the femur leaving at least 1 cm between opposing surfaces Class III has bone spurs from the pelvis andor proximal end of the femur reducing the space between opposing bone surfaces to less than 1 cm Class IV shows apparent bone ankylosis of the hip
Region I - Heterotopic ossifications are strictly below the tip of the greater trochanter
Region II - Heterotopic ossifications are below and above the tip of the greater trochanter
Region III - Heterotopic ossifications are strictly above the tip of the greater trochanter
Grade A - Single or multiple heterotopic ossifications are less than 10 mm in maximal extent without contact with the pelvis or the femur
Grade B - Heterotopic ossifications are greater than 10 mm without contact with the pelvis but with possible contact with the femur there is no bridging from the femur to the proximal part of the greater trochanter and no evidence of ankylosis
Grade C - Ankylosis by means of firm bridging from the femur to the pelvis is present
Shmidt classification
excision may be performed The results of this procedure are varied Patients may find that their range of movement improves but pain relief is likely to be limited
A patient with heterotopic ossification following total hip arthroplasty is thought to have a 90-100 chance of developing it on the contralateral hip if this hip also undergoes total arthroplasty
it would be prudent to minimize the risk of heterotopic ossification developing after arthroplasty by performing surgery whereby the following are ensured
Exposure is meticulous Retraction is performed carefully and soft tissue
is handled carefully Irrigation is adequate Devitalized tissue is excised Hemostasis is adequate Postoperative drains (when used) are not
retained for longer than necessary Perioperative antibiotic prophylaxis is used Postoperative anticoagulation (when used for
deep vein thrombosis prophylaxis) is carefully controlled
sources of knee stiffness 1-extrinsic severe osteoarthritis of the ipsilateral hip neurologic injury leading to muscle rigidity tight quadriceps or hamstring muscles secondary to muscle injury heterotopic ossification or long-standing juvenile inflammatory conditions limiting knee
range of motion prior to the completion of skeletal growth When extrinsic sources are identified revision total knee arthroplasty is unlikely to be associated with a favorable outcome without correction of the extrinsic problem
2-intrinsic (1) overstuffing of the patellofemoral articulation (2) an
excessively tight flexion andor extension gap (3) a tight posterior cruciate ligament (4) femoral andor tibial malrotation (5) arthrofibrosis and (6) limited bearing excursion in association with a highly conforming mobile-bearing prosthetic design
HTO after TKA
Heterotopic Ossification (HO) following primary Total Knee Replacement (TKR)
Occurs in 3-90 of TKRs 3-grade classification system No correlation between HO and component
alignment or component position
Clinical findings similar to early infection Continuing low-grade fever Warm swollen and erythematous knee Normal blood tests Possibly an association with HLA-A2 and B18 HO patients have worse KSS and function
scores
Patients at HIGH risk for developing HO after TKR (Knee Arthroplasty) (5)
Those with limited postoperative knee flexion
Increased lumbar bone mineral density (BMD) on multivariate analysis (3)
Hypertrophic arthrosis Excessive periosteal trauma Notching of the anterior femur Those who require forced manipulation
after TKA 47 in revision TKR surgery (6) Higher rates in revision TKR cases with
infection (up to 76
DaughertyBell classification of HO of the knee 0 No evidence of HO 1 Bone islands in periarticular soft tissue (no
involvement of femur patella or tibia) or HO within quadriceps expansion measuring lt1 cm
2 Spur formation measuring lt5 cm that involves the femur patella or tibia if more than one bone demonstrates HO separation of HO spurs
measure gt1 cm or HO within quadriceps expansion measuring ge1 cm but lt3 cm
3 Spur formation gt5 cm involving femur patella or tibia if more than one bone demonstrates HO separation of HO spurs measure lt1 cm or HO
within quadriceps expansion measuring ge3 cm 4 Extensive HO of the knee causing ankylosis
class 2 HO begins to involve the major bones of the knee joint with spur formation limited to a size of 5 cm
HO class 2 may be observed in select patients with complete ROM and no reported pain Patients with class 3 HO would likely always benefit from surgical excision
followed by RT prophylaxis Certainly patients in either cohort with a subclass ldquoBrdquo assignment (symptomatic) would
benefit from treatment All patients with class 4 HO require
treatment to alleviate ankylosis
treatment
References Whyte ldquoPagetrsquos Disease of Bonerdquo NEMJ vol 355
2006 Klein and Parvizi ldquoSurgical Manifestations of Pagetrsquos
Diseaserdquo JAAOS vol 14 2006 Orthobullets Campbell Apley Emedicinecom
-Chapter 15 Heterotopic Ossification after Traumatic Brain InjuryBy Jesuacutes Moreta and Joseacute Luis Martiacutenez-de los Mozos DOI 10577257343
Questions
Thank You
Pharmacologic ManagementGoals Relieve symptoms and Prevent potential
complications Normalization of serum AlkPhos associated
with better long-term outcomes and disease control
Indications to treat Pain Deformity Neurologic symptoms Asymptomatic but high-risk for complications
(prophylactic) Management of hypercalcemia(rare) Pre-op reduce blood flow and potential
operative blood loss
Calcitonin is the most widely used It reduces bone resorption by decreasing both the activity and the number
of osteoclasts serum alkaline phosphatase and urinaryhydroxyproline levels are lowered Salmon calcitonin is more effective than the porcine variety subcutaneous injections of 50ndash100 MRC units are given daily until pain is relieved and the alkaline phosphatase levels are reduced and stabilized Maintenance injections once or twice weekly may have to be continued indefinitely but some authorities advocate stopping the drug and resuming treatment if symptoms recur Calcitonin can also be administered in a nasal spray Bisphosphonates bind to hydroxyapatite crystals
inhibiting their rate of growth and dissolution It is claimed that the reduction in bone turnover following their use is associated with the formation of lamellar rather than woven bone and that even after treatment is stopped there may be prolonged remission of disease (Bickerstaff et al 1990) Etidronate can be given orally (always on an empty stomach) but dosage should be kept low (eg 5 mgkg per day for up to 6 months) and vitamin D and calcium should also be given lest impaired bone mineralization results inosteomalacia The newer bisphosphonates (eg alendronate or pamidronate) do not have this disadvantage so they should be used as the treatment of choice they produce remissions even with shortcourses of 1 or 2 weeks
BisphosphonatesSynthetic analogues of inorganic phosphate adhere to mineralized surfaces
Ingested selectively by osteoclasts Disrupts enzyme pathways and reduces osteoclastic bone resorption
calcitonin causes osteoclasts to shrink in size and decreases their bone resorptive activity within minutes administered subcutaneously or intramuscularly
teriparatide is contraindicated in Pagets disease due to risk of secondary osteosarcoma
Surgical Management Few require surgery
Common Procedures Corrective osteotomy of long bone deformity indications
fractures through pathologic bowing of long bones impending pathologic fracture of long bone with bowing deformity
Arthroplasty (hip knee) the most common complications include
malalignment with knee arthroplasty bleeding with hip arthroplasty
Combination arthroplasty with osteotomy Fracture fixation
Preoperative Considerations Medical assessment for extraskeletalmanifestations eg high-
output heart failure
Medical treatment of active disease Preoperative autologousblood donation
Thorough planningeg good quality x-rays for templatingand device selection
Intraoperative Considerations Blood salvage system Expansileapproach + soft tissue release Sharp reamersburrsdrills for IM access Extramedullaryguidenavigation systems Concomitant osteotomy
PostoperativeConsiderations Monitoring for cardiac complications Continued medical tx of active disease
uarrHeterotopic ossification Prophylaxis against HO
Possible future excision of HO for painROM
1-Tieg provides a review of Pagets disease of bone and treatment indications In his review he discusses that most patients with Pagets disease are asymptomatic but in those that do present pain is the most common presenting symptom He recommends medical and surgical treatment of asymptomatic patients who have active disease at sites where complications are likely to develop
Altman did a review of 290 patients with Pagets disease of bone His findings showed 83 had one or more rheumatic syndromes He found the rate of osteoarthritis related to Pagets disease was elevated in the hip and knee Rheumatoid arthritis hyperuricemia and gout did not appear increased in this group
Mangham et al looked the rate of secondary sarcomas as a result of Pagets disease of bone They found the rate to be around 03 with male predominance They also found that widespread skeletal involvement by Pagets disease was not a significant risk factor for malignant transformation
Interesting views about pagets
Smith et al reviewed the pathologic complications of Pagets bone disease Pagets bone disease commonly causes osseous weakening (deformity and fracture) and arthritis in the hip joint Management of end stage disease is successful with cemented and cementless total hip arthroplasty Bleeding is the most common intra- and post-operative complication of surgery
Gabel et al retrospectively reviewed thirteen patients who had had sixteen total knee arthroplasties for Pagetic gonarthrosis Unlike total hip arthroplasty surgery Paget disease did not increase the amount of blood lost during the operation or in the postoperative period The most common complication associated with total knee arthroplasty was malalignment
Hansen et al reviewed the incidence of osteosarcomas complicating Pagets Disease Of the typical sites that are usually involved in Pagets disease (eg spine pelvis femur tibia and humerus) secondary osteosarcoma tends to spare the spine
Shaylor et al reported the mortality rates in 26 patient with osteosarcoma secondary to Paget s disease There was a 47 mortality at 1 year and 75 at 2 years from diagnosis In their series no patient survived for 5 years All patients died of metastatic disease
Langston et al conducted a randomized trial that compared the results of symptomatic treatment versus intensive bisphosphonate therapy in patients with Pagets disease Clinical fractures occurred in 46 of 661 patients (70) in the treatment group compared with 49 of 663 patients (74) in the symptomatic treatment group They concluded that bisphosphonates did not show a significant beneficial impact on pain quality of life or fracture incidence
Hadjipavlou et al reviewed Pagets disease of the bone and its management Farmers have been shown to have an increased incidence of Pagets disease Average age at presentation is in the 5th and 6th decade Symptomatic individuals are recommended to be treated initially with medical management They suggest that bisphosphonates are more effective than calcitonin at suppressing the histological and biochemical activity in Pagetrsquos disease
Summary Epid Very common in elderly Path Abnormal osteoclastshellipuarrbone
turnoverhellipdeposition of abnormal bone SampS Pain deformity fracture arthropathy Labs uarrAlkPhos X-ray Characteristic coarse thickened
trabeculae Bone scan Very hot Rx Bisphosphonates Surgery for arthropathy fracture painful
deformity
A 65-year-old male presents with increasing shoulder pain over the past 9 months He is otherwise healthy and has no other complaints Radiograph of his shoulder is shown in Figure A Whole body bone scan and biopsy photograph are shown in Figures B and C What is the most appropriate treatment for this patient
1 Referral to endocrinology 2 Radiation therapy and chemotherapy 3 Wide resection and reconstruction 4 Radiation therapy wide resection and reconstruction 5 Chemotherapy wide resection and reconstruction
Histiocytosis X or Langerhans cell histiocytosis is a spectrum of diseases of the reticuloendothelial system with one of three general presentations Eosinophilic granuloma (EG)
usually a single self-limited lesion found in younger patients
Hand-Schuller-Christian disease (HSC) chronic disseminated form with bone and visceral lesions also known as Langerhans cell histiocytosis with visceral
involvement Letterer-Siwe disease (LSD)
fatal form that occurs in young children
Eosinophilic granuloma
Epidemiology demographics
most commonly occurs in children (80 of afflicted lt 20 years of age)
HSC disease presents in children gt 3 years of age LSD occurs in children lt 3 years of age Male to female ratio of 21
location eosinophilic granuloma
commonly presents in the skull ribs clavicle scapula mandible
isolated lesions of the spine (thoracic most common) can also occur in diaphyseal regions of long bones and the
pelvis HSC
multiple bony sites multiple lytic skull lesions visceral involvement of the lungs spleen liver skin lymph
nodes
Genetics no clear genetic pattern of inheritance or locus has
been determined Prognosis
EG isolated involvement generally treatable with local
management spine lesions can spontaneously resolve
HSC prognosis depends on response to chemotherapy worsening prognosis with increasing extraskeletal
involvement LSD
generally fatal in children lt 3 years of age
Symptoms skeletal involvement
pain and swelling at the region of involvement limping can be seen with pelvic or lower extremity
involvement vertebral involvement
localized or diffuse back pain increasingly kyphotic posture radiculopathy can occur with more aggressive lesions
HSC classic triad of
multiple lytic skull lesions diabetes insipidus
increased thirst and water intake exopthalmos
visceral involvement diffuse or nonspecific abdominal or chest pain
Radiographs general
known as the great mimicker as it appears similar to many lesions radiographic differential includes osteomyelitis leukemia lymphoma
fibrous dysplasia or Ewings sarcoma diaphyseal lesions
well defined intramedullary lytic or punched-out lesion cortex may be thinned expanded or destroyed may have periosteal reaction
metaphyseal lesions extend up to but not through the physis less central location than diaphyseal lesions
spinal lesions vertebra plana (flattened vertebrae) in spine increased kyphosis
cranial involvement multiple punched-out lytic lesions
MRI may show a soft tissue mass adjacent to boney lesions
Bone scan generally shows increased uptake in the region of boney lesion
Histology Langerhans cells
mononuclear histiocyte-like cells with oval nuclei with well-defined round or oval cytoplasm
a prominent nuclear groove (coffee bean nuclei) can be seen in most of the nuclei
eosinophilic cytoplasm (pink generally) stain with CD1A electronmicroscopy
birbeck granules seen inside Langerhans cells mixture of inflammatory cells also present giant cells are present lack of nuclear atypia and atypical mitoses
differentiates this condition from malignant conditions such as Ewings sarcoma lymphoma of bone and metastatic neuroblastoma which may look similar based on the round cells alone
eosinophilic cytoplasm (pink generally)
Treatment
bullNonoperative bull observation alone
bull indications bull a self-limited process and it is reasonable to treat with observation alone
bull bracing bull indications
bull to prevent progressive kyphosis of the spinebull outcomes
bull will correct deformity in 90 of patientsbull vertebral lesions generally regain 50 of their height
bull low dose irradiation (600-800 cGy) bull indications
bull indicated for lesions in the spine that compromise stability neurologic statusbull lesions not amenable to injection or open treatment
bull outcomes bull effective for most lesions
bull chemotherapy bull indications
bull diffuse HSCbull outcomes
bull prognosis is improved with less severe extraskeletal involvementbull corticosteroid injection
bull indications bull isolated lesions bull can be performed after curettage as well
Operative curettage and bone grafting
indications for lesions that endanger the articular surface or are a risk for
impending fractures spinal deformity correction
indications progressive spine deformity refractory to bracing
approximately 10 of patients with spine lesion will need operative intervention for deformity correction
Destructive multiple lesion in young patientsAre eosinophilic granuloma lymphoma and leukemiaLymphoma is unlikely to present with exopthalmos diabetes insipidus or vertebra plana Lymphoma bone lesions are lytic and appear moth eatenpermeative on radiographs
Figure A shows a skin lesion typical of eosinophillic granuloma Figure B shows a lytic lesions without significant surrounding sclerosis as is characteristic of eosinophilic granuloma Figure C shows the characteristic histology of multiple eosinophils with their characteristic oval coffee bean nuclei and staining pattern of purpleredpink cytoplasm (depending on the stain) Importantly the histology slide lacks a malignant appearance (no cellular atypia or mytotic complexes and low nuclearcytoplasmic ratio)
Formation of bone in atypical extraskeletal tissues usually occurs
spontaneously or following trauma within 2 months of neurologic injury (brain or spinal cord)
most common location is between muscle and joint capsule Epidemiology
incidence (see table below)
demographics malefemale = 21 especially men with hypertrophic osteoarthritis and women gt65y
location traumatic brain injury or stroke
hip gt elbow gt shoulder gt knee elbow HO more common following brain trauma
occurs on affected (spastic) side rarely in the knee (TBI)
spinal cord injury hip gt knee gt elbow gt shoulder hip flexors and abductors gt extensors or adductors medial aspect of the knee
Heterotopic Ossification
Risk factors
Pathophysiology exact cause of HO is not known but there appears to be a
genetic pre disposition experimental HO associated with
tissue expression of BMP IT IS SAID TO BE CAUSED BY activation and proliferation of
mesenchymal stem cells Associated conditions
orthopaedic manifestations pathologic fractures
from decreased joint ROM and osteoporotic bone nerve impingement soft tissue contractures contributing to the formation of
decubitus ulcers joint ankylosis HO after THA adversely affects outcome of THA
nonorthopaedic conditions skin maceration and hygiene problems
Pathophysiology Early in the formation of HO oedema with exudative
infiltrate is present followed by fibroblastic proliferation and immature connective tissue formation Posteriorly osteoid formation is seen with the subsequent deposition of bone matrix Primitive osteoid is deposited as small masses in the periphery early (within the first two weeks) and osteoblasts are noted located irregularly Osteoblasts produce tropocollagen which polymerizes to form collagen and secrete alkaline phosphatase which allows calcium to precipitate and the mineralization of bone matrix As mineralization progresses amorphous calcium phosphate is progressively replaced by hydroxyapatite crystals During the following weeks the lesion matures with a centripetal pattern and after 6-12 months an appearance of true bone is noted The new bone is always extra-articular and can be contiguous with the skeleton but generally does not involve the periosteum
IN SUMMARY It has been postulated that three conditions
must be met to achieve heterotopic bone formation ---a stimulating event oestrogenic precursor cells and a proper environment LIKE hypercalcaemia tissue hypoxia pH changes (alkalosis) or prolonged immobilization
ClassificationbullSubtypes
bull neurogenic HO bull Four clinical stages of HO in people with spinal cord injury were
described by Nicholas in 1973
bull traumatic myositis ossificans bull fibrodysplasia ossificans progressiva (Munchmeyers Disease)
Neurogenic HO Symptoms
painless loss of ROM interferes with ADL CRPS symptoms fever
Physical exam inspection
warm painful swollen joint may have effusion skin problems
decubitus ulcers from contractures around skin muscles ligaments
skin maceration and hygiene problems motion
decreased joint ROM joint ankylosis with HO after TKA might develop quad muscle snapping or patella
instability neurovascular
peripheral neuropathy HO often impinges on adjacent NV structures
Imaging
bullRadiographs bull findings
bull ossification usually easy to visualize bull maturity of HO
bull the appearance of a bony cortex suggests mature HObull sharp demarcation from surrounding tissue bull trabecular pattern
bull sensitivity and specificity bull not useful for early diagnosisbull only useful at 1 week after onset of symptoms
bull calcium is deposited 7-10 days later than symptom onsetbullUltrasound
bull indications bull for early diagnosis of hip HO
bull findings bull echogenic surfaces with posterior acoustic shadowing
bullCT bull indications
bull useful for preoperative planning bullTriphasic bone scan
bull indications bull best for early diagnosis bull most commonly used diagnostic study
Radiographs are extremely useful in the staging of heterotopic ossification and will show the development of sharp cortical margins once the lesion has reached maturity
Heterotopic bone is a condition in which lamellar bone forms in non-ossified soft tissues In the early stages studies such as MRI and bone scan are more sensitive for diagnosis as radiographs may appear normal for the first three weeks After the appropriate diagnosis is made sequential radiographs are useful for monitoring the progression of the ossification Once it has reached the mature stage sharp cortical margins will appear and surgical resection may be considered
lab
Labs elevated serum alkaline phosphatase (gt250IUL)
ALP removes inhibitors of mineralization nonspecific may be elevated with skeletal trauma cannot determine maturity of HO elevated 12wks after surgery is predictor
elevated CRP correlates with inflammatory activity of HO better than ESR normalization of CRP may correlate with maturity of HO
elevated ESR (gt35mmh) 12wks after THA is predictor
elevated CK correlates with involvement of muscle extent of muscle
involvement Histology
mature fatty bone marrow mature trabecular bone
Heterotopic ossification (HO) most commonly occurs at the amputation site if the amputation was performed thru the zone of injury especially if the injury was a blast mechanism
Symptomatic heterotopic ossification of the quadriceps may occur following placement of a large-diameter Steinmann pin for the purpose of temporary skeletal traction
TreatmentThe prevention of heterotopic ossification is focused on three basic principles disrupting the inductive signalling pathways altering the osteoprogenitor cells or modifying the environment
bullphysiotherapy should involve an assisted range of movement exercises with gentle stretch and terminal resistance trainingbullProphylaxis
bull bisphosphonates amp NSAIDS bull indications
bull although no literature supports are commonly usedbull technique
bull indomethacin is most commonly used bull dose is 75mgday for 10days to 6 weeks
bull perioperative radiation bull indications
bull although no literature supports commonly usedbull is thought to be effective by blocking osteoblast differentiation
bull technique bull a single perioperative dose of 700cGy can be given either 4
hours preop or within 72 hours postoperatively bull lt550cGy not effective
Nonsteroidal anti-inflammatory drugs (NSAIDs) These drugs have demonstrated good results in
preventing heterotopic ossification after total hip arthroplasty
A direct effect of NSAIDs on the formation of heterotopic ossification has been described due to the inhibition of the differentiation of mesenchymal cells into oestrogenic cells There is also an indirect effect which refers to the inhibition of bone remodelling by suppression of the prostagland unmediated inflammatory response (specifically PGE-2)
Indomethacin has been considered a useful medication for heterotopic ossification prophylaxis following total hip replacement
prescribed for three to six weeks in a dose of 75mgday within two months of the injury may reduce the incidence of heterotopic ossification by two to three times
Biphosphonates inhibits precipitation of calcium phosphate and blocks the aggregation and mineralisation of hydroxyapatite crystals In primary prevention Banovac et al [56] have suggested that the treatment should begin as soon as elevated alkaline phosphatase is diagnosed or positive findings in ultrasonography or bone scans are shown In addition disphosphonates could have long-term effects on prevention when the treatment is finished
Posttraumatic wide exposure and surgical resection
indications severe loss of motion and decreased function
technique wide exposure required to identify all neurovascular
structures that may be involved timing of resection (controversial)
marked decrease in bone scan activity AND normalization of ALP
6 months following general trauma 1 year following SCI 15 years following TBI
some data suggests equivalent results when comparing early versus late resection
postop follow with 5 day course of indomethacin early gentle joint mobilization
The surgery is necessary in patients with symptomatic HO and unsuccessful medical treatment such as
Loss of range of motion and ankylosis with associated functional disability such as sitting difficulties
Complications of immobility such as pressure ulcers
Facilitate rehabilitation and recovery of muscular atrophy secondary to prolonged immobilisation
Difficulties of appropriate hygiene because access to the perineum or bladder care is needed
Severe pain refractory to analgesia Vascular andor nerve compression
Advantages to early excision of heterotopic ossification (vs waiting for maturation) include decreased soft tissue contracture better definition between heterotopic and native bone and decreased waiting time for the patient When the soft tissue envelope is benign one may proceed with operative release While waiting for normalization of alkaline phosphatase levels inactivity on bone scan or radiographic maturity may decrease risk of recurrent heterotopic ossification delaying operative release for these reasons has not been shown to improve results of final elbow range of motion after contracture release
Gartland recommended surgery after six months following traumatic heterotopic ossification one year following spinal cord injury and 18 months after head injury
In the past waiting until maturity in order to minimize the rate of recurrence after the surgical treatment was recommended Nevertheless recent studies do not confirm a higher rate of recurrence when the HO is excised in an earlier phase In addition a long delay before surgery leads to ankylosis a high degree of osteoporosis and more extensive intra-articular injuries These findings are associated with bad functional results and potential complications
Should you wait till lesion maturation
Prevention byHandle tissue carefully Avoid excess bleeding Achieve good hemostasis Beware of lesions that span internervous tissue planes
but if it happens resection of a large enough amount of bone to allow improvement of the range of motion and trying to preserve the joint
Our aim must be
A reactive process that is characterized by a well-circumscribed proliferation of fibroblasts cartilage and bone within muscle
A form of heterotopic ossification that is the result direct trauma intramuscular hematoma
most common location is the diaphysis of long bones Must differentiate from tumors Fibrodysplasia ossificans progressiva (FOP) is a rare subtype of heterotopic ossification
involves mutation of the ACVR1 gene (activin A type I receptor gene a BMP type-1 receptor)
Epidemiology demographics
most common in young active males (15 to 35 years old) body locations
quadriceps brachialis and gluteal muscles Genetics
almost always a posttraumatic condition Prognosis
usually self limiting mass usually begins to decrease in size after 1 yea
Myositis ossificans
PresentationbullSymptoms
bull pain tenderness swelling and decreased range of motion that usually presents within days of the injury
bull pain and size of the mass decrease with timebull mass increases in size over several months(usually 3 to 6 cm)
bull after the mass stops growing it becomes firmbullPhysical exam
bull palpable soft tissue massbull restricted range of motion
ImagingbullRadiographs
bull peripheral bone formation with central lucent areabull may appear as dotted veil pattern
bullMRI with gadolinium bull rim enhancement is seen within the first 3 weeks
bullCT scan bull lesion has an eggshell appearance
bullCharacteristic histology shows zonal pattern bull periphery of lesion
bull mature trabeculae of lamellar and woven bonebull calcification seen on xray
bull center of the lesion bull irregular mass of immature fibroblastsbull cartilage component may be presentbull (no calcification seen on xray) bull no cellular atypia seen
Treatment
bullNonoperative bull rest range of motion exercises and activity modification
bull passive stretching is contraindicated (makes it worse)bull physical therapy
bull utilized to maintain range of motionbull radiographic monitoring
bull obtained to confirm maturation of the lesionbullOperative
bull surgical excision bull indicated only if it remains a problem after it maturesbull do not operate in acute phase wait at least six months
bull excision of the lesion within 6 to 12 months predisposes to local recurrence
A 26-year-old man presents with generalized back and joint stiffness and difficulty opening his mouth His elder sister has similar complaints Since childhood he has had 3 surgeries for excision of recurrent bony prominences around his knees He walks with a stooped over posture seen in Figure A Radiographs of his feet knee hip and spine are seen in Figures B-E respectively
fibrodysplasia ossificans progressiva
Stone Man Disease) which involves a mutation of the ACVR1
There are 2 hallmark characteristics progressive heterotopic ossification (muscles fascia tendons ligaments and joint capsules) and congenital malformation of the great toe (hallux valgus malformed first metatarsal and monophalangism) BMP4 which contributes to the formation of the skeleton in the normal embryo is implicated in this disease
Complications
bullHematoma and intraoperative bleedingbullInfection
bull higher rate of infection following joint arthroplasty if HO is present
bullFractures of osteoporotic bone bull osteopenic from disusebull during surgery or physiotherapy
bullRecurrence bull recurrence rate correlates with neurological injury
bull greater recurrence if severe neurological compromisebullAVN
bull if extensive dissection or stripping is required
HTO AND ISS
When ISS is below 25 the mortality risk is minimal and above 25 it is an almost linear increase
When ISS is 50 the mortality is 50 When above 70 it is close to 100 If an injury is assigned an AIS of 6 (unsurvivable injury) the ISS score is
automatically assigned to 75 Highest ISS score obtainable is 75 For trauma patients of vehicular accidents the scoring system is important
for assessing the effectiveness of medical care in reducing morbidity and mortality
Advantages virtually the only anatomical scoring system in use correlates linearly with
mortality morbidity hospital stay other measures of severity
Weaknesses Any error in AIS scoring increases the ISS error Many different injury patterns can yield the same ISS score Injuries to different body regions are not weighted Not a useful triage tool as a full description of patient injuries is not known
prior to full investigation amp operation
risk factors periosteal stripping off anterior femur male gender obesity post traumatic deformity Anterior and anterolateral approach Cementless
Neurogenic HO around the hip due to SCI occurs more often in the medial region than in the lateral region with ossified tissues extending from the pubic symphysis to the anteromedial femoral shaft posterior to the femoral neurovascular structures Ossification is also seen anteriorly involving the iliopsoas and femoral neurovascular structures laterally within gluteus minimus and posteriorly extending from the ilium to the posterior femur encasing the sciatic nerve
HTO AROUND hip and knee
The Brooker Classification of Heterotopic Ossification around the hip joint Class I has islands of bone within the soft tissues Class II has bone spurs from the pelvis or proximal end of the femur leaving at least 1 cm between opposing surfaces Class III has bone spurs from the pelvis andor proximal end of the femur reducing the space between opposing bone surfaces to less than 1 cm Class IV shows apparent bone ankylosis of the hip
Region I - Heterotopic ossifications are strictly below the tip of the greater trochanter
Region II - Heterotopic ossifications are below and above the tip of the greater trochanter
Region III - Heterotopic ossifications are strictly above the tip of the greater trochanter
Grade A - Single or multiple heterotopic ossifications are less than 10 mm in maximal extent without contact with the pelvis or the femur
Grade B - Heterotopic ossifications are greater than 10 mm without contact with the pelvis but with possible contact with the femur there is no bridging from the femur to the proximal part of the greater trochanter and no evidence of ankylosis
Grade C - Ankylosis by means of firm bridging from the femur to the pelvis is present
Shmidt classification
excision may be performed The results of this procedure are varied Patients may find that their range of movement improves but pain relief is likely to be limited
A patient with heterotopic ossification following total hip arthroplasty is thought to have a 90-100 chance of developing it on the contralateral hip if this hip also undergoes total arthroplasty
it would be prudent to minimize the risk of heterotopic ossification developing after arthroplasty by performing surgery whereby the following are ensured
Exposure is meticulous Retraction is performed carefully and soft tissue
is handled carefully Irrigation is adequate Devitalized tissue is excised Hemostasis is adequate Postoperative drains (when used) are not
retained for longer than necessary Perioperative antibiotic prophylaxis is used Postoperative anticoagulation (when used for
deep vein thrombosis prophylaxis) is carefully controlled
sources of knee stiffness 1-extrinsic severe osteoarthritis of the ipsilateral hip neurologic injury leading to muscle rigidity tight quadriceps or hamstring muscles secondary to muscle injury heterotopic ossification or long-standing juvenile inflammatory conditions limiting knee
range of motion prior to the completion of skeletal growth When extrinsic sources are identified revision total knee arthroplasty is unlikely to be associated with a favorable outcome without correction of the extrinsic problem
2-intrinsic (1) overstuffing of the patellofemoral articulation (2) an
excessively tight flexion andor extension gap (3) a tight posterior cruciate ligament (4) femoral andor tibial malrotation (5) arthrofibrosis and (6) limited bearing excursion in association with a highly conforming mobile-bearing prosthetic design
HTO after TKA
Heterotopic Ossification (HO) following primary Total Knee Replacement (TKR)
Occurs in 3-90 of TKRs 3-grade classification system No correlation between HO and component
alignment or component position
Clinical findings similar to early infection Continuing low-grade fever Warm swollen and erythematous knee Normal blood tests Possibly an association with HLA-A2 and B18 HO patients have worse KSS and function
scores
Patients at HIGH risk for developing HO after TKR (Knee Arthroplasty) (5)
Those with limited postoperative knee flexion
Increased lumbar bone mineral density (BMD) on multivariate analysis (3)
Hypertrophic arthrosis Excessive periosteal trauma Notching of the anterior femur Those who require forced manipulation
after TKA 47 in revision TKR surgery (6) Higher rates in revision TKR cases with
infection (up to 76
DaughertyBell classification of HO of the knee 0 No evidence of HO 1 Bone islands in periarticular soft tissue (no
involvement of femur patella or tibia) or HO within quadriceps expansion measuring lt1 cm
2 Spur formation measuring lt5 cm that involves the femur patella or tibia if more than one bone demonstrates HO separation of HO spurs
measure gt1 cm or HO within quadriceps expansion measuring ge1 cm but lt3 cm
3 Spur formation gt5 cm involving femur patella or tibia if more than one bone demonstrates HO separation of HO spurs measure lt1 cm or HO
within quadriceps expansion measuring ge3 cm 4 Extensive HO of the knee causing ankylosis
class 2 HO begins to involve the major bones of the knee joint with spur formation limited to a size of 5 cm
HO class 2 may be observed in select patients with complete ROM and no reported pain Patients with class 3 HO would likely always benefit from surgical excision
followed by RT prophylaxis Certainly patients in either cohort with a subclass ldquoBrdquo assignment (symptomatic) would
benefit from treatment All patients with class 4 HO require
treatment to alleviate ankylosis
treatment
References Whyte ldquoPagetrsquos Disease of Bonerdquo NEMJ vol 355
2006 Klein and Parvizi ldquoSurgical Manifestations of Pagetrsquos
Diseaserdquo JAAOS vol 14 2006 Orthobullets Campbell Apley Emedicinecom
-Chapter 15 Heterotopic Ossification after Traumatic Brain InjuryBy Jesuacutes Moreta and Joseacute Luis Martiacutenez-de los Mozos DOI 10577257343
Questions
Thank You
Calcitonin is the most widely used It reduces bone resorption by decreasing both the activity and the number
of osteoclasts serum alkaline phosphatase and urinaryhydroxyproline levels are lowered Salmon calcitonin is more effective than the porcine variety subcutaneous injections of 50ndash100 MRC units are given daily until pain is relieved and the alkaline phosphatase levels are reduced and stabilized Maintenance injections once or twice weekly may have to be continued indefinitely but some authorities advocate stopping the drug and resuming treatment if symptoms recur Calcitonin can also be administered in a nasal spray Bisphosphonates bind to hydroxyapatite crystals
inhibiting their rate of growth and dissolution It is claimed that the reduction in bone turnover following their use is associated with the formation of lamellar rather than woven bone and that even after treatment is stopped there may be prolonged remission of disease (Bickerstaff et al 1990) Etidronate can be given orally (always on an empty stomach) but dosage should be kept low (eg 5 mgkg per day for up to 6 months) and vitamin D and calcium should also be given lest impaired bone mineralization results inosteomalacia The newer bisphosphonates (eg alendronate or pamidronate) do not have this disadvantage so they should be used as the treatment of choice they produce remissions even with shortcourses of 1 or 2 weeks
BisphosphonatesSynthetic analogues of inorganic phosphate adhere to mineralized surfaces
Ingested selectively by osteoclasts Disrupts enzyme pathways and reduces osteoclastic bone resorption
calcitonin causes osteoclasts to shrink in size and decreases their bone resorptive activity within minutes administered subcutaneously or intramuscularly
teriparatide is contraindicated in Pagets disease due to risk of secondary osteosarcoma
Surgical Management Few require surgery
Common Procedures Corrective osteotomy of long bone deformity indications
fractures through pathologic bowing of long bones impending pathologic fracture of long bone with bowing deformity
Arthroplasty (hip knee) the most common complications include
malalignment with knee arthroplasty bleeding with hip arthroplasty
Combination arthroplasty with osteotomy Fracture fixation
Preoperative Considerations Medical assessment for extraskeletalmanifestations eg high-
output heart failure
Medical treatment of active disease Preoperative autologousblood donation
Thorough planningeg good quality x-rays for templatingand device selection
Intraoperative Considerations Blood salvage system Expansileapproach + soft tissue release Sharp reamersburrsdrills for IM access Extramedullaryguidenavigation systems Concomitant osteotomy
PostoperativeConsiderations Monitoring for cardiac complications Continued medical tx of active disease
uarrHeterotopic ossification Prophylaxis against HO
Possible future excision of HO for painROM
1-Tieg provides a review of Pagets disease of bone and treatment indications In his review he discusses that most patients with Pagets disease are asymptomatic but in those that do present pain is the most common presenting symptom He recommends medical and surgical treatment of asymptomatic patients who have active disease at sites where complications are likely to develop
Altman did a review of 290 patients with Pagets disease of bone His findings showed 83 had one or more rheumatic syndromes He found the rate of osteoarthritis related to Pagets disease was elevated in the hip and knee Rheumatoid arthritis hyperuricemia and gout did not appear increased in this group
Mangham et al looked the rate of secondary sarcomas as a result of Pagets disease of bone They found the rate to be around 03 with male predominance They also found that widespread skeletal involvement by Pagets disease was not a significant risk factor for malignant transformation
Interesting views about pagets
Smith et al reviewed the pathologic complications of Pagets bone disease Pagets bone disease commonly causes osseous weakening (deformity and fracture) and arthritis in the hip joint Management of end stage disease is successful with cemented and cementless total hip arthroplasty Bleeding is the most common intra- and post-operative complication of surgery
Gabel et al retrospectively reviewed thirteen patients who had had sixteen total knee arthroplasties for Pagetic gonarthrosis Unlike total hip arthroplasty surgery Paget disease did not increase the amount of blood lost during the operation or in the postoperative period The most common complication associated with total knee arthroplasty was malalignment
Hansen et al reviewed the incidence of osteosarcomas complicating Pagets Disease Of the typical sites that are usually involved in Pagets disease (eg spine pelvis femur tibia and humerus) secondary osteosarcoma tends to spare the spine
Shaylor et al reported the mortality rates in 26 patient with osteosarcoma secondary to Paget s disease There was a 47 mortality at 1 year and 75 at 2 years from diagnosis In their series no patient survived for 5 years All patients died of metastatic disease
Langston et al conducted a randomized trial that compared the results of symptomatic treatment versus intensive bisphosphonate therapy in patients with Pagets disease Clinical fractures occurred in 46 of 661 patients (70) in the treatment group compared with 49 of 663 patients (74) in the symptomatic treatment group They concluded that bisphosphonates did not show a significant beneficial impact on pain quality of life or fracture incidence
Hadjipavlou et al reviewed Pagets disease of the bone and its management Farmers have been shown to have an increased incidence of Pagets disease Average age at presentation is in the 5th and 6th decade Symptomatic individuals are recommended to be treated initially with medical management They suggest that bisphosphonates are more effective than calcitonin at suppressing the histological and biochemical activity in Pagetrsquos disease
Summary Epid Very common in elderly Path Abnormal osteoclastshellipuarrbone
turnoverhellipdeposition of abnormal bone SampS Pain deformity fracture arthropathy Labs uarrAlkPhos X-ray Characteristic coarse thickened
trabeculae Bone scan Very hot Rx Bisphosphonates Surgery for arthropathy fracture painful
deformity
A 65-year-old male presents with increasing shoulder pain over the past 9 months He is otherwise healthy and has no other complaints Radiograph of his shoulder is shown in Figure A Whole body bone scan and biopsy photograph are shown in Figures B and C What is the most appropriate treatment for this patient
1 Referral to endocrinology 2 Radiation therapy and chemotherapy 3 Wide resection and reconstruction 4 Radiation therapy wide resection and reconstruction 5 Chemotherapy wide resection and reconstruction
Histiocytosis X or Langerhans cell histiocytosis is a spectrum of diseases of the reticuloendothelial system with one of three general presentations Eosinophilic granuloma (EG)
usually a single self-limited lesion found in younger patients
Hand-Schuller-Christian disease (HSC) chronic disseminated form with bone and visceral lesions also known as Langerhans cell histiocytosis with visceral
involvement Letterer-Siwe disease (LSD)
fatal form that occurs in young children
Eosinophilic granuloma
Epidemiology demographics
most commonly occurs in children (80 of afflicted lt 20 years of age)
HSC disease presents in children gt 3 years of age LSD occurs in children lt 3 years of age Male to female ratio of 21
location eosinophilic granuloma
commonly presents in the skull ribs clavicle scapula mandible
isolated lesions of the spine (thoracic most common) can also occur in diaphyseal regions of long bones and the
pelvis HSC
multiple bony sites multiple lytic skull lesions visceral involvement of the lungs spleen liver skin lymph
nodes
Genetics no clear genetic pattern of inheritance or locus has
been determined Prognosis
EG isolated involvement generally treatable with local
management spine lesions can spontaneously resolve
HSC prognosis depends on response to chemotherapy worsening prognosis with increasing extraskeletal
involvement LSD
generally fatal in children lt 3 years of age
Symptoms skeletal involvement
pain and swelling at the region of involvement limping can be seen with pelvic or lower extremity
involvement vertebral involvement
localized or diffuse back pain increasingly kyphotic posture radiculopathy can occur with more aggressive lesions
HSC classic triad of
multiple lytic skull lesions diabetes insipidus
increased thirst and water intake exopthalmos
visceral involvement diffuse or nonspecific abdominal or chest pain
Radiographs general
known as the great mimicker as it appears similar to many lesions radiographic differential includes osteomyelitis leukemia lymphoma
fibrous dysplasia or Ewings sarcoma diaphyseal lesions
well defined intramedullary lytic or punched-out lesion cortex may be thinned expanded or destroyed may have periosteal reaction
metaphyseal lesions extend up to but not through the physis less central location than diaphyseal lesions
spinal lesions vertebra plana (flattened vertebrae) in spine increased kyphosis
cranial involvement multiple punched-out lytic lesions
MRI may show a soft tissue mass adjacent to boney lesions
Bone scan generally shows increased uptake in the region of boney lesion
Histology Langerhans cells
mononuclear histiocyte-like cells with oval nuclei with well-defined round or oval cytoplasm
a prominent nuclear groove (coffee bean nuclei) can be seen in most of the nuclei
eosinophilic cytoplasm (pink generally) stain with CD1A electronmicroscopy
birbeck granules seen inside Langerhans cells mixture of inflammatory cells also present giant cells are present lack of nuclear atypia and atypical mitoses
differentiates this condition from malignant conditions such as Ewings sarcoma lymphoma of bone and metastatic neuroblastoma which may look similar based on the round cells alone
eosinophilic cytoplasm (pink generally)
Treatment
bullNonoperative bull observation alone
bull indications bull a self-limited process and it is reasonable to treat with observation alone
bull bracing bull indications
bull to prevent progressive kyphosis of the spinebull outcomes
bull will correct deformity in 90 of patientsbull vertebral lesions generally regain 50 of their height
bull low dose irradiation (600-800 cGy) bull indications
bull indicated for lesions in the spine that compromise stability neurologic statusbull lesions not amenable to injection or open treatment
bull outcomes bull effective for most lesions
bull chemotherapy bull indications
bull diffuse HSCbull outcomes
bull prognosis is improved with less severe extraskeletal involvementbull corticosteroid injection
bull indications bull isolated lesions bull can be performed after curettage as well
Operative curettage and bone grafting
indications for lesions that endanger the articular surface or are a risk for
impending fractures spinal deformity correction
indications progressive spine deformity refractory to bracing
approximately 10 of patients with spine lesion will need operative intervention for deformity correction
Destructive multiple lesion in young patientsAre eosinophilic granuloma lymphoma and leukemiaLymphoma is unlikely to present with exopthalmos diabetes insipidus or vertebra plana Lymphoma bone lesions are lytic and appear moth eatenpermeative on radiographs
Figure A shows a skin lesion typical of eosinophillic granuloma Figure B shows a lytic lesions without significant surrounding sclerosis as is characteristic of eosinophilic granuloma Figure C shows the characteristic histology of multiple eosinophils with their characteristic oval coffee bean nuclei and staining pattern of purpleredpink cytoplasm (depending on the stain) Importantly the histology slide lacks a malignant appearance (no cellular atypia or mytotic complexes and low nuclearcytoplasmic ratio)
Formation of bone in atypical extraskeletal tissues usually occurs
spontaneously or following trauma within 2 months of neurologic injury (brain or spinal cord)
most common location is between muscle and joint capsule Epidemiology
incidence (see table below)
demographics malefemale = 21 especially men with hypertrophic osteoarthritis and women gt65y
location traumatic brain injury or stroke
hip gt elbow gt shoulder gt knee elbow HO more common following brain trauma
occurs on affected (spastic) side rarely in the knee (TBI)
spinal cord injury hip gt knee gt elbow gt shoulder hip flexors and abductors gt extensors or adductors medial aspect of the knee
Heterotopic Ossification
Risk factors
Pathophysiology exact cause of HO is not known but there appears to be a
genetic pre disposition experimental HO associated with
tissue expression of BMP IT IS SAID TO BE CAUSED BY activation and proliferation of
mesenchymal stem cells Associated conditions
orthopaedic manifestations pathologic fractures
from decreased joint ROM and osteoporotic bone nerve impingement soft tissue contractures contributing to the formation of
decubitus ulcers joint ankylosis HO after THA adversely affects outcome of THA
nonorthopaedic conditions skin maceration and hygiene problems
Pathophysiology Early in the formation of HO oedema with exudative
infiltrate is present followed by fibroblastic proliferation and immature connective tissue formation Posteriorly osteoid formation is seen with the subsequent deposition of bone matrix Primitive osteoid is deposited as small masses in the periphery early (within the first two weeks) and osteoblasts are noted located irregularly Osteoblasts produce tropocollagen which polymerizes to form collagen and secrete alkaline phosphatase which allows calcium to precipitate and the mineralization of bone matrix As mineralization progresses amorphous calcium phosphate is progressively replaced by hydroxyapatite crystals During the following weeks the lesion matures with a centripetal pattern and after 6-12 months an appearance of true bone is noted The new bone is always extra-articular and can be contiguous with the skeleton but generally does not involve the periosteum
IN SUMMARY It has been postulated that three conditions
must be met to achieve heterotopic bone formation ---a stimulating event oestrogenic precursor cells and a proper environment LIKE hypercalcaemia tissue hypoxia pH changes (alkalosis) or prolonged immobilization
ClassificationbullSubtypes
bull neurogenic HO bull Four clinical stages of HO in people with spinal cord injury were
described by Nicholas in 1973
bull traumatic myositis ossificans bull fibrodysplasia ossificans progressiva (Munchmeyers Disease)
Neurogenic HO Symptoms
painless loss of ROM interferes with ADL CRPS symptoms fever
Physical exam inspection
warm painful swollen joint may have effusion skin problems
decubitus ulcers from contractures around skin muscles ligaments
skin maceration and hygiene problems motion
decreased joint ROM joint ankylosis with HO after TKA might develop quad muscle snapping or patella
instability neurovascular
peripheral neuropathy HO often impinges on adjacent NV structures
Imaging
bullRadiographs bull findings
bull ossification usually easy to visualize bull maturity of HO
bull the appearance of a bony cortex suggests mature HObull sharp demarcation from surrounding tissue bull trabecular pattern
bull sensitivity and specificity bull not useful for early diagnosisbull only useful at 1 week after onset of symptoms
bull calcium is deposited 7-10 days later than symptom onsetbullUltrasound
bull indications bull for early diagnosis of hip HO
bull findings bull echogenic surfaces with posterior acoustic shadowing
bullCT bull indications
bull useful for preoperative planning bullTriphasic bone scan
bull indications bull best for early diagnosis bull most commonly used diagnostic study
Radiographs are extremely useful in the staging of heterotopic ossification and will show the development of sharp cortical margins once the lesion has reached maturity
Heterotopic bone is a condition in which lamellar bone forms in non-ossified soft tissues In the early stages studies such as MRI and bone scan are more sensitive for diagnosis as radiographs may appear normal for the first three weeks After the appropriate diagnosis is made sequential radiographs are useful for monitoring the progression of the ossification Once it has reached the mature stage sharp cortical margins will appear and surgical resection may be considered
lab
Labs elevated serum alkaline phosphatase (gt250IUL)
ALP removes inhibitors of mineralization nonspecific may be elevated with skeletal trauma cannot determine maturity of HO elevated 12wks after surgery is predictor
elevated CRP correlates with inflammatory activity of HO better than ESR normalization of CRP may correlate with maturity of HO
elevated ESR (gt35mmh) 12wks after THA is predictor
elevated CK correlates with involvement of muscle extent of muscle
involvement Histology
mature fatty bone marrow mature trabecular bone
Heterotopic ossification (HO) most commonly occurs at the amputation site if the amputation was performed thru the zone of injury especially if the injury was a blast mechanism
Symptomatic heterotopic ossification of the quadriceps may occur following placement of a large-diameter Steinmann pin for the purpose of temporary skeletal traction
TreatmentThe prevention of heterotopic ossification is focused on three basic principles disrupting the inductive signalling pathways altering the osteoprogenitor cells or modifying the environment
bullphysiotherapy should involve an assisted range of movement exercises with gentle stretch and terminal resistance trainingbullProphylaxis
bull bisphosphonates amp NSAIDS bull indications
bull although no literature supports are commonly usedbull technique
bull indomethacin is most commonly used bull dose is 75mgday for 10days to 6 weeks
bull perioperative radiation bull indications
bull although no literature supports commonly usedbull is thought to be effective by blocking osteoblast differentiation
bull technique bull a single perioperative dose of 700cGy can be given either 4
hours preop or within 72 hours postoperatively bull lt550cGy not effective
Nonsteroidal anti-inflammatory drugs (NSAIDs) These drugs have demonstrated good results in
preventing heterotopic ossification after total hip arthroplasty
A direct effect of NSAIDs on the formation of heterotopic ossification has been described due to the inhibition of the differentiation of mesenchymal cells into oestrogenic cells There is also an indirect effect which refers to the inhibition of bone remodelling by suppression of the prostagland unmediated inflammatory response (specifically PGE-2)
Indomethacin has been considered a useful medication for heterotopic ossification prophylaxis following total hip replacement
prescribed for three to six weeks in a dose of 75mgday within two months of the injury may reduce the incidence of heterotopic ossification by two to three times
Biphosphonates inhibits precipitation of calcium phosphate and blocks the aggregation and mineralisation of hydroxyapatite crystals In primary prevention Banovac et al [56] have suggested that the treatment should begin as soon as elevated alkaline phosphatase is diagnosed or positive findings in ultrasonography or bone scans are shown In addition disphosphonates could have long-term effects on prevention when the treatment is finished
Posttraumatic wide exposure and surgical resection
indications severe loss of motion and decreased function
technique wide exposure required to identify all neurovascular
structures that may be involved timing of resection (controversial)
marked decrease in bone scan activity AND normalization of ALP
6 months following general trauma 1 year following SCI 15 years following TBI
some data suggests equivalent results when comparing early versus late resection
postop follow with 5 day course of indomethacin early gentle joint mobilization
The surgery is necessary in patients with symptomatic HO and unsuccessful medical treatment such as
Loss of range of motion and ankylosis with associated functional disability such as sitting difficulties
Complications of immobility such as pressure ulcers
Facilitate rehabilitation and recovery of muscular atrophy secondary to prolonged immobilisation
Difficulties of appropriate hygiene because access to the perineum or bladder care is needed
Severe pain refractory to analgesia Vascular andor nerve compression
Advantages to early excision of heterotopic ossification (vs waiting for maturation) include decreased soft tissue contracture better definition between heterotopic and native bone and decreased waiting time for the patient When the soft tissue envelope is benign one may proceed with operative release While waiting for normalization of alkaline phosphatase levels inactivity on bone scan or radiographic maturity may decrease risk of recurrent heterotopic ossification delaying operative release for these reasons has not been shown to improve results of final elbow range of motion after contracture release
Gartland recommended surgery after six months following traumatic heterotopic ossification one year following spinal cord injury and 18 months after head injury
In the past waiting until maturity in order to minimize the rate of recurrence after the surgical treatment was recommended Nevertheless recent studies do not confirm a higher rate of recurrence when the HO is excised in an earlier phase In addition a long delay before surgery leads to ankylosis a high degree of osteoporosis and more extensive intra-articular injuries These findings are associated with bad functional results and potential complications
Should you wait till lesion maturation
Prevention byHandle tissue carefully Avoid excess bleeding Achieve good hemostasis Beware of lesions that span internervous tissue planes
but if it happens resection of a large enough amount of bone to allow improvement of the range of motion and trying to preserve the joint
Our aim must be
A reactive process that is characterized by a well-circumscribed proliferation of fibroblasts cartilage and bone within muscle
A form of heterotopic ossification that is the result direct trauma intramuscular hematoma
most common location is the diaphysis of long bones Must differentiate from tumors Fibrodysplasia ossificans progressiva (FOP) is a rare subtype of heterotopic ossification
involves mutation of the ACVR1 gene (activin A type I receptor gene a BMP type-1 receptor)
Epidemiology demographics
most common in young active males (15 to 35 years old) body locations
quadriceps brachialis and gluteal muscles Genetics
almost always a posttraumatic condition Prognosis
usually self limiting mass usually begins to decrease in size after 1 yea
Myositis ossificans
PresentationbullSymptoms
bull pain tenderness swelling and decreased range of motion that usually presents within days of the injury
bull pain and size of the mass decrease with timebull mass increases in size over several months(usually 3 to 6 cm)
bull after the mass stops growing it becomes firmbullPhysical exam
bull palpable soft tissue massbull restricted range of motion
ImagingbullRadiographs
bull peripheral bone formation with central lucent areabull may appear as dotted veil pattern
bullMRI with gadolinium bull rim enhancement is seen within the first 3 weeks
bullCT scan bull lesion has an eggshell appearance
bullCharacteristic histology shows zonal pattern bull periphery of lesion
bull mature trabeculae of lamellar and woven bonebull calcification seen on xray
bull center of the lesion bull irregular mass of immature fibroblastsbull cartilage component may be presentbull (no calcification seen on xray) bull no cellular atypia seen
Treatment
bullNonoperative bull rest range of motion exercises and activity modification
bull passive stretching is contraindicated (makes it worse)bull physical therapy
bull utilized to maintain range of motionbull radiographic monitoring
bull obtained to confirm maturation of the lesionbullOperative
bull surgical excision bull indicated only if it remains a problem after it maturesbull do not operate in acute phase wait at least six months
bull excision of the lesion within 6 to 12 months predisposes to local recurrence
A 26-year-old man presents with generalized back and joint stiffness and difficulty opening his mouth His elder sister has similar complaints Since childhood he has had 3 surgeries for excision of recurrent bony prominences around his knees He walks with a stooped over posture seen in Figure A Radiographs of his feet knee hip and spine are seen in Figures B-E respectively
fibrodysplasia ossificans progressiva
Stone Man Disease) which involves a mutation of the ACVR1
There are 2 hallmark characteristics progressive heterotopic ossification (muscles fascia tendons ligaments and joint capsules) and congenital malformation of the great toe (hallux valgus malformed first metatarsal and monophalangism) BMP4 which contributes to the formation of the skeleton in the normal embryo is implicated in this disease
Complications
bullHematoma and intraoperative bleedingbullInfection
bull higher rate of infection following joint arthroplasty if HO is present
bullFractures of osteoporotic bone bull osteopenic from disusebull during surgery or physiotherapy
bullRecurrence bull recurrence rate correlates with neurological injury
bull greater recurrence if severe neurological compromisebullAVN
bull if extensive dissection or stripping is required
HTO AND ISS
When ISS is below 25 the mortality risk is minimal and above 25 it is an almost linear increase
When ISS is 50 the mortality is 50 When above 70 it is close to 100 If an injury is assigned an AIS of 6 (unsurvivable injury) the ISS score is
automatically assigned to 75 Highest ISS score obtainable is 75 For trauma patients of vehicular accidents the scoring system is important
for assessing the effectiveness of medical care in reducing morbidity and mortality
Advantages virtually the only anatomical scoring system in use correlates linearly with
mortality morbidity hospital stay other measures of severity
Weaknesses Any error in AIS scoring increases the ISS error Many different injury patterns can yield the same ISS score Injuries to different body regions are not weighted Not a useful triage tool as a full description of patient injuries is not known
prior to full investigation amp operation
risk factors periosteal stripping off anterior femur male gender obesity post traumatic deformity Anterior and anterolateral approach Cementless
Neurogenic HO around the hip due to SCI occurs more often in the medial region than in the lateral region with ossified tissues extending from the pubic symphysis to the anteromedial femoral shaft posterior to the femoral neurovascular structures Ossification is also seen anteriorly involving the iliopsoas and femoral neurovascular structures laterally within gluteus minimus and posteriorly extending from the ilium to the posterior femur encasing the sciatic nerve
HTO AROUND hip and knee
The Brooker Classification of Heterotopic Ossification around the hip joint Class I has islands of bone within the soft tissues Class II has bone spurs from the pelvis or proximal end of the femur leaving at least 1 cm between opposing surfaces Class III has bone spurs from the pelvis andor proximal end of the femur reducing the space between opposing bone surfaces to less than 1 cm Class IV shows apparent bone ankylosis of the hip
Region I - Heterotopic ossifications are strictly below the tip of the greater trochanter
Region II - Heterotopic ossifications are below and above the tip of the greater trochanter
Region III - Heterotopic ossifications are strictly above the tip of the greater trochanter
Grade A - Single or multiple heterotopic ossifications are less than 10 mm in maximal extent without contact with the pelvis or the femur
Grade B - Heterotopic ossifications are greater than 10 mm without contact with the pelvis but with possible contact with the femur there is no bridging from the femur to the proximal part of the greater trochanter and no evidence of ankylosis
Grade C - Ankylosis by means of firm bridging from the femur to the pelvis is present
Shmidt classification
excision may be performed The results of this procedure are varied Patients may find that their range of movement improves but pain relief is likely to be limited
A patient with heterotopic ossification following total hip arthroplasty is thought to have a 90-100 chance of developing it on the contralateral hip if this hip also undergoes total arthroplasty
it would be prudent to minimize the risk of heterotopic ossification developing after arthroplasty by performing surgery whereby the following are ensured
Exposure is meticulous Retraction is performed carefully and soft tissue
is handled carefully Irrigation is adequate Devitalized tissue is excised Hemostasis is adequate Postoperative drains (when used) are not
retained for longer than necessary Perioperative antibiotic prophylaxis is used Postoperative anticoagulation (when used for
deep vein thrombosis prophylaxis) is carefully controlled
sources of knee stiffness 1-extrinsic severe osteoarthritis of the ipsilateral hip neurologic injury leading to muscle rigidity tight quadriceps or hamstring muscles secondary to muscle injury heterotopic ossification or long-standing juvenile inflammatory conditions limiting knee
range of motion prior to the completion of skeletal growth When extrinsic sources are identified revision total knee arthroplasty is unlikely to be associated with a favorable outcome without correction of the extrinsic problem
2-intrinsic (1) overstuffing of the patellofemoral articulation (2) an
excessively tight flexion andor extension gap (3) a tight posterior cruciate ligament (4) femoral andor tibial malrotation (5) arthrofibrosis and (6) limited bearing excursion in association with a highly conforming mobile-bearing prosthetic design
HTO after TKA
Heterotopic Ossification (HO) following primary Total Knee Replacement (TKR)
Occurs in 3-90 of TKRs 3-grade classification system No correlation between HO and component
alignment or component position
Clinical findings similar to early infection Continuing low-grade fever Warm swollen and erythematous knee Normal blood tests Possibly an association with HLA-A2 and B18 HO patients have worse KSS and function
scores
Patients at HIGH risk for developing HO after TKR (Knee Arthroplasty) (5)
Those with limited postoperative knee flexion
Increased lumbar bone mineral density (BMD) on multivariate analysis (3)
Hypertrophic arthrosis Excessive periosteal trauma Notching of the anterior femur Those who require forced manipulation
after TKA 47 in revision TKR surgery (6) Higher rates in revision TKR cases with
infection (up to 76
DaughertyBell classification of HO of the knee 0 No evidence of HO 1 Bone islands in periarticular soft tissue (no
involvement of femur patella or tibia) or HO within quadriceps expansion measuring lt1 cm
2 Spur formation measuring lt5 cm that involves the femur patella or tibia if more than one bone demonstrates HO separation of HO spurs
measure gt1 cm or HO within quadriceps expansion measuring ge1 cm but lt3 cm
3 Spur formation gt5 cm involving femur patella or tibia if more than one bone demonstrates HO separation of HO spurs measure lt1 cm or HO
within quadriceps expansion measuring ge3 cm 4 Extensive HO of the knee causing ankylosis
class 2 HO begins to involve the major bones of the knee joint with spur formation limited to a size of 5 cm
HO class 2 may be observed in select patients with complete ROM and no reported pain Patients with class 3 HO would likely always benefit from surgical excision
followed by RT prophylaxis Certainly patients in either cohort with a subclass ldquoBrdquo assignment (symptomatic) would
benefit from treatment All patients with class 4 HO require
treatment to alleviate ankylosis
treatment
References Whyte ldquoPagetrsquos Disease of Bonerdquo NEMJ vol 355
2006 Klein and Parvizi ldquoSurgical Manifestations of Pagetrsquos
Diseaserdquo JAAOS vol 14 2006 Orthobullets Campbell Apley Emedicinecom
-Chapter 15 Heterotopic Ossification after Traumatic Brain InjuryBy Jesuacutes Moreta and Joseacute Luis Martiacutenez-de los Mozos DOI 10577257343
Questions
Thank You
inhibiting their rate of growth and dissolution It is claimed that the reduction in bone turnover following their use is associated with the formation of lamellar rather than woven bone and that even after treatment is stopped there may be prolonged remission of disease (Bickerstaff et al 1990) Etidronate can be given orally (always on an empty stomach) but dosage should be kept low (eg 5 mgkg per day for up to 6 months) and vitamin D and calcium should also be given lest impaired bone mineralization results inosteomalacia The newer bisphosphonates (eg alendronate or pamidronate) do not have this disadvantage so they should be used as the treatment of choice they produce remissions even with shortcourses of 1 or 2 weeks
BisphosphonatesSynthetic analogues of inorganic phosphate adhere to mineralized surfaces
Ingested selectively by osteoclasts Disrupts enzyme pathways and reduces osteoclastic bone resorption
calcitonin causes osteoclasts to shrink in size and decreases their bone resorptive activity within minutes administered subcutaneously or intramuscularly
teriparatide is contraindicated in Pagets disease due to risk of secondary osteosarcoma
Surgical Management Few require surgery
Common Procedures Corrective osteotomy of long bone deformity indications
fractures through pathologic bowing of long bones impending pathologic fracture of long bone with bowing deformity
Arthroplasty (hip knee) the most common complications include
malalignment with knee arthroplasty bleeding with hip arthroplasty
Combination arthroplasty with osteotomy Fracture fixation
Preoperative Considerations Medical assessment for extraskeletalmanifestations eg high-
output heart failure
Medical treatment of active disease Preoperative autologousblood donation
Thorough planningeg good quality x-rays for templatingand device selection
Intraoperative Considerations Blood salvage system Expansileapproach + soft tissue release Sharp reamersburrsdrills for IM access Extramedullaryguidenavigation systems Concomitant osteotomy
PostoperativeConsiderations Monitoring for cardiac complications Continued medical tx of active disease
uarrHeterotopic ossification Prophylaxis against HO
Possible future excision of HO for painROM
1-Tieg provides a review of Pagets disease of bone and treatment indications In his review he discusses that most patients with Pagets disease are asymptomatic but in those that do present pain is the most common presenting symptom He recommends medical and surgical treatment of asymptomatic patients who have active disease at sites where complications are likely to develop
Altman did a review of 290 patients with Pagets disease of bone His findings showed 83 had one or more rheumatic syndromes He found the rate of osteoarthritis related to Pagets disease was elevated in the hip and knee Rheumatoid arthritis hyperuricemia and gout did not appear increased in this group
Mangham et al looked the rate of secondary sarcomas as a result of Pagets disease of bone They found the rate to be around 03 with male predominance They also found that widespread skeletal involvement by Pagets disease was not a significant risk factor for malignant transformation
Interesting views about pagets
Smith et al reviewed the pathologic complications of Pagets bone disease Pagets bone disease commonly causes osseous weakening (deformity and fracture) and arthritis in the hip joint Management of end stage disease is successful with cemented and cementless total hip arthroplasty Bleeding is the most common intra- and post-operative complication of surgery
Gabel et al retrospectively reviewed thirteen patients who had had sixteen total knee arthroplasties for Pagetic gonarthrosis Unlike total hip arthroplasty surgery Paget disease did not increase the amount of blood lost during the operation or in the postoperative period The most common complication associated with total knee arthroplasty was malalignment
Hansen et al reviewed the incidence of osteosarcomas complicating Pagets Disease Of the typical sites that are usually involved in Pagets disease (eg spine pelvis femur tibia and humerus) secondary osteosarcoma tends to spare the spine
Shaylor et al reported the mortality rates in 26 patient with osteosarcoma secondary to Paget s disease There was a 47 mortality at 1 year and 75 at 2 years from diagnosis In their series no patient survived for 5 years All patients died of metastatic disease
Langston et al conducted a randomized trial that compared the results of symptomatic treatment versus intensive bisphosphonate therapy in patients with Pagets disease Clinical fractures occurred in 46 of 661 patients (70) in the treatment group compared with 49 of 663 patients (74) in the symptomatic treatment group They concluded that bisphosphonates did not show a significant beneficial impact on pain quality of life or fracture incidence
Hadjipavlou et al reviewed Pagets disease of the bone and its management Farmers have been shown to have an increased incidence of Pagets disease Average age at presentation is in the 5th and 6th decade Symptomatic individuals are recommended to be treated initially with medical management They suggest that bisphosphonates are more effective than calcitonin at suppressing the histological and biochemical activity in Pagetrsquos disease
Summary Epid Very common in elderly Path Abnormal osteoclastshellipuarrbone
turnoverhellipdeposition of abnormal bone SampS Pain deformity fracture arthropathy Labs uarrAlkPhos X-ray Characteristic coarse thickened
trabeculae Bone scan Very hot Rx Bisphosphonates Surgery for arthropathy fracture painful
deformity
A 65-year-old male presents with increasing shoulder pain over the past 9 months He is otherwise healthy and has no other complaints Radiograph of his shoulder is shown in Figure A Whole body bone scan and biopsy photograph are shown in Figures B and C What is the most appropriate treatment for this patient
1 Referral to endocrinology 2 Radiation therapy and chemotherapy 3 Wide resection and reconstruction 4 Radiation therapy wide resection and reconstruction 5 Chemotherapy wide resection and reconstruction
Histiocytosis X or Langerhans cell histiocytosis is a spectrum of diseases of the reticuloendothelial system with one of three general presentations Eosinophilic granuloma (EG)
usually a single self-limited lesion found in younger patients
Hand-Schuller-Christian disease (HSC) chronic disseminated form with bone and visceral lesions also known as Langerhans cell histiocytosis with visceral
involvement Letterer-Siwe disease (LSD)
fatal form that occurs in young children
Eosinophilic granuloma
Epidemiology demographics
most commonly occurs in children (80 of afflicted lt 20 years of age)
HSC disease presents in children gt 3 years of age LSD occurs in children lt 3 years of age Male to female ratio of 21
location eosinophilic granuloma
commonly presents in the skull ribs clavicle scapula mandible
isolated lesions of the spine (thoracic most common) can also occur in diaphyseal regions of long bones and the
pelvis HSC
multiple bony sites multiple lytic skull lesions visceral involvement of the lungs spleen liver skin lymph
nodes
Genetics no clear genetic pattern of inheritance or locus has
been determined Prognosis
EG isolated involvement generally treatable with local
management spine lesions can spontaneously resolve
HSC prognosis depends on response to chemotherapy worsening prognosis with increasing extraskeletal
involvement LSD
generally fatal in children lt 3 years of age
Symptoms skeletal involvement
pain and swelling at the region of involvement limping can be seen with pelvic or lower extremity
involvement vertebral involvement
localized or diffuse back pain increasingly kyphotic posture radiculopathy can occur with more aggressive lesions
HSC classic triad of
multiple lytic skull lesions diabetes insipidus
increased thirst and water intake exopthalmos
visceral involvement diffuse or nonspecific abdominal or chest pain
Radiographs general
known as the great mimicker as it appears similar to many lesions radiographic differential includes osteomyelitis leukemia lymphoma
fibrous dysplasia or Ewings sarcoma diaphyseal lesions
well defined intramedullary lytic or punched-out lesion cortex may be thinned expanded or destroyed may have periosteal reaction
metaphyseal lesions extend up to but not through the physis less central location than diaphyseal lesions
spinal lesions vertebra plana (flattened vertebrae) in spine increased kyphosis
cranial involvement multiple punched-out lytic lesions
MRI may show a soft tissue mass adjacent to boney lesions
Bone scan generally shows increased uptake in the region of boney lesion
Histology Langerhans cells
mononuclear histiocyte-like cells with oval nuclei with well-defined round or oval cytoplasm
a prominent nuclear groove (coffee bean nuclei) can be seen in most of the nuclei
eosinophilic cytoplasm (pink generally) stain with CD1A electronmicroscopy
birbeck granules seen inside Langerhans cells mixture of inflammatory cells also present giant cells are present lack of nuclear atypia and atypical mitoses
differentiates this condition from malignant conditions such as Ewings sarcoma lymphoma of bone and metastatic neuroblastoma which may look similar based on the round cells alone
eosinophilic cytoplasm (pink generally)
Treatment
bullNonoperative bull observation alone
bull indications bull a self-limited process and it is reasonable to treat with observation alone
bull bracing bull indications
bull to prevent progressive kyphosis of the spinebull outcomes
bull will correct deformity in 90 of patientsbull vertebral lesions generally regain 50 of their height
bull low dose irradiation (600-800 cGy) bull indications
bull indicated for lesions in the spine that compromise stability neurologic statusbull lesions not amenable to injection or open treatment
bull outcomes bull effective for most lesions
bull chemotherapy bull indications
bull diffuse HSCbull outcomes
bull prognosis is improved with less severe extraskeletal involvementbull corticosteroid injection
bull indications bull isolated lesions bull can be performed after curettage as well
Operative curettage and bone grafting
indications for lesions that endanger the articular surface or are a risk for
impending fractures spinal deformity correction
indications progressive spine deformity refractory to bracing
approximately 10 of patients with spine lesion will need operative intervention for deformity correction
Destructive multiple lesion in young patientsAre eosinophilic granuloma lymphoma and leukemiaLymphoma is unlikely to present with exopthalmos diabetes insipidus or vertebra plana Lymphoma bone lesions are lytic and appear moth eatenpermeative on radiographs
Figure A shows a skin lesion typical of eosinophillic granuloma Figure B shows a lytic lesions without significant surrounding sclerosis as is characteristic of eosinophilic granuloma Figure C shows the characteristic histology of multiple eosinophils with their characteristic oval coffee bean nuclei and staining pattern of purpleredpink cytoplasm (depending on the stain) Importantly the histology slide lacks a malignant appearance (no cellular atypia or mytotic complexes and low nuclearcytoplasmic ratio)
Formation of bone in atypical extraskeletal tissues usually occurs
spontaneously or following trauma within 2 months of neurologic injury (brain or spinal cord)
most common location is between muscle and joint capsule Epidemiology
incidence (see table below)
demographics malefemale = 21 especially men with hypertrophic osteoarthritis and women gt65y
location traumatic brain injury or stroke
hip gt elbow gt shoulder gt knee elbow HO more common following brain trauma
occurs on affected (spastic) side rarely in the knee (TBI)
spinal cord injury hip gt knee gt elbow gt shoulder hip flexors and abductors gt extensors or adductors medial aspect of the knee
Heterotopic Ossification
Risk factors
Pathophysiology exact cause of HO is not known but there appears to be a
genetic pre disposition experimental HO associated with
tissue expression of BMP IT IS SAID TO BE CAUSED BY activation and proliferation of
mesenchymal stem cells Associated conditions
orthopaedic manifestations pathologic fractures
from decreased joint ROM and osteoporotic bone nerve impingement soft tissue contractures contributing to the formation of
decubitus ulcers joint ankylosis HO after THA adversely affects outcome of THA
nonorthopaedic conditions skin maceration and hygiene problems
Pathophysiology Early in the formation of HO oedema with exudative
infiltrate is present followed by fibroblastic proliferation and immature connective tissue formation Posteriorly osteoid formation is seen with the subsequent deposition of bone matrix Primitive osteoid is deposited as small masses in the periphery early (within the first two weeks) and osteoblasts are noted located irregularly Osteoblasts produce tropocollagen which polymerizes to form collagen and secrete alkaline phosphatase which allows calcium to precipitate and the mineralization of bone matrix As mineralization progresses amorphous calcium phosphate is progressively replaced by hydroxyapatite crystals During the following weeks the lesion matures with a centripetal pattern and after 6-12 months an appearance of true bone is noted The new bone is always extra-articular and can be contiguous with the skeleton but generally does not involve the periosteum
IN SUMMARY It has been postulated that three conditions
must be met to achieve heterotopic bone formation ---a stimulating event oestrogenic precursor cells and a proper environment LIKE hypercalcaemia tissue hypoxia pH changes (alkalosis) or prolonged immobilization
ClassificationbullSubtypes
bull neurogenic HO bull Four clinical stages of HO in people with spinal cord injury were
described by Nicholas in 1973
bull traumatic myositis ossificans bull fibrodysplasia ossificans progressiva (Munchmeyers Disease)
Neurogenic HO Symptoms
painless loss of ROM interferes with ADL CRPS symptoms fever
Physical exam inspection
warm painful swollen joint may have effusion skin problems
decubitus ulcers from contractures around skin muscles ligaments
skin maceration and hygiene problems motion
decreased joint ROM joint ankylosis with HO after TKA might develop quad muscle snapping or patella
instability neurovascular
peripheral neuropathy HO often impinges on adjacent NV structures
Imaging
bullRadiographs bull findings
bull ossification usually easy to visualize bull maturity of HO
bull the appearance of a bony cortex suggests mature HObull sharp demarcation from surrounding tissue bull trabecular pattern
bull sensitivity and specificity bull not useful for early diagnosisbull only useful at 1 week after onset of symptoms
bull calcium is deposited 7-10 days later than symptom onsetbullUltrasound
bull indications bull for early diagnosis of hip HO
bull findings bull echogenic surfaces with posterior acoustic shadowing
bullCT bull indications
bull useful for preoperative planning bullTriphasic bone scan
bull indications bull best for early diagnosis bull most commonly used diagnostic study
Radiographs are extremely useful in the staging of heterotopic ossification and will show the development of sharp cortical margins once the lesion has reached maturity
Heterotopic bone is a condition in which lamellar bone forms in non-ossified soft tissues In the early stages studies such as MRI and bone scan are more sensitive for diagnosis as radiographs may appear normal for the first three weeks After the appropriate diagnosis is made sequential radiographs are useful for monitoring the progression of the ossification Once it has reached the mature stage sharp cortical margins will appear and surgical resection may be considered
lab
Labs elevated serum alkaline phosphatase (gt250IUL)
ALP removes inhibitors of mineralization nonspecific may be elevated with skeletal trauma cannot determine maturity of HO elevated 12wks after surgery is predictor
elevated CRP correlates with inflammatory activity of HO better than ESR normalization of CRP may correlate with maturity of HO
elevated ESR (gt35mmh) 12wks after THA is predictor
elevated CK correlates with involvement of muscle extent of muscle
involvement Histology
mature fatty bone marrow mature trabecular bone
Heterotopic ossification (HO) most commonly occurs at the amputation site if the amputation was performed thru the zone of injury especially if the injury was a blast mechanism
Symptomatic heterotopic ossification of the quadriceps may occur following placement of a large-diameter Steinmann pin for the purpose of temporary skeletal traction
TreatmentThe prevention of heterotopic ossification is focused on three basic principles disrupting the inductive signalling pathways altering the osteoprogenitor cells or modifying the environment
bullphysiotherapy should involve an assisted range of movement exercises with gentle stretch and terminal resistance trainingbullProphylaxis
bull bisphosphonates amp NSAIDS bull indications
bull although no literature supports are commonly usedbull technique
bull indomethacin is most commonly used bull dose is 75mgday for 10days to 6 weeks
bull perioperative radiation bull indications
bull although no literature supports commonly usedbull is thought to be effective by blocking osteoblast differentiation
bull technique bull a single perioperative dose of 700cGy can be given either 4
hours preop or within 72 hours postoperatively bull lt550cGy not effective
Nonsteroidal anti-inflammatory drugs (NSAIDs) These drugs have demonstrated good results in
preventing heterotopic ossification after total hip arthroplasty
A direct effect of NSAIDs on the formation of heterotopic ossification has been described due to the inhibition of the differentiation of mesenchymal cells into oestrogenic cells There is also an indirect effect which refers to the inhibition of bone remodelling by suppression of the prostagland unmediated inflammatory response (specifically PGE-2)
Indomethacin has been considered a useful medication for heterotopic ossification prophylaxis following total hip replacement
prescribed for three to six weeks in a dose of 75mgday within two months of the injury may reduce the incidence of heterotopic ossification by two to three times
Biphosphonates inhibits precipitation of calcium phosphate and blocks the aggregation and mineralisation of hydroxyapatite crystals In primary prevention Banovac et al [56] have suggested that the treatment should begin as soon as elevated alkaline phosphatase is diagnosed or positive findings in ultrasonography or bone scans are shown In addition disphosphonates could have long-term effects on prevention when the treatment is finished
Posttraumatic wide exposure and surgical resection
indications severe loss of motion and decreased function
technique wide exposure required to identify all neurovascular
structures that may be involved timing of resection (controversial)
marked decrease in bone scan activity AND normalization of ALP
6 months following general trauma 1 year following SCI 15 years following TBI
some data suggests equivalent results when comparing early versus late resection
postop follow with 5 day course of indomethacin early gentle joint mobilization
The surgery is necessary in patients with symptomatic HO and unsuccessful medical treatment such as
Loss of range of motion and ankylosis with associated functional disability such as sitting difficulties
Complications of immobility such as pressure ulcers
Facilitate rehabilitation and recovery of muscular atrophy secondary to prolonged immobilisation
Difficulties of appropriate hygiene because access to the perineum or bladder care is needed
Severe pain refractory to analgesia Vascular andor nerve compression
Advantages to early excision of heterotopic ossification (vs waiting for maturation) include decreased soft tissue contracture better definition between heterotopic and native bone and decreased waiting time for the patient When the soft tissue envelope is benign one may proceed with operative release While waiting for normalization of alkaline phosphatase levels inactivity on bone scan or radiographic maturity may decrease risk of recurrent heterotopic ossification delaying operative release for these reasons has not been shown to improve results of final elbow range of motion after contracture release
Gartland recommended surgery after six months following traumatic heterotopic ossification one year following spinal cord injury and 18 months after head injury
In the past waiting until maturity in order to minimize the rate of recurrence after the surgical treatment was recommended Nevertheless recent studies do not confirm a higher rate of recurrence when the HO is excised in an earlier phase In addition a long delay before surgery leads to ankylosis a high degree of osteoporosis and more extensive intra-articular injuries These findings are associated with bad functional results and potential complications
Should you wait till lesion maturation
Prevention byHandle tissue carefully Avoid excess bleeding Achieve good hemostasis Beware of lesions that span internervous tissue planes
but if it happens resection of a large enough amount of bone to allow improvement of the range of motion and trying to preserve the joint
Our aim must be
A reactive process that is characterized by a well-circumscribed proliferation of fibroblasts cartilage and bone within muscle
A form of heterotopic ossification that is the result direct trauma intramuscular hematoma
most common location is the diaphysis of long bones Must differentiate from tumors Fibrodysplasia ossificans progressiva (FOP) is a rare subtype of heterotopic ossification
involves mutation of the ACVR1 gene (activin A type I receptor gene a BMP type-1 receptor)
Epidemiology demographics
most common in young active males (15 to 35 years old) body locations
quadriceps brachialis and gluteal muscles Genetics
almost always a posttraumatic condition Prognosis
usually self limiting mass usually begins to decrease in size after 1 yea
Myositis ossificans
PresentationbullSymptoms
bull pain tenderness swelling and decreased range of motion that usually presents within days of the injury
bull pain and size of the mass decrease with timebull mass increases in size over several months(usually 3 to 6 cm)
bull after the mass stops growing it becomes firmbullPhysical exam
bull palpable soft tissue massbull restricted range of motion
ImagingbullRadiographs
bull peripheral bone formation with central lucent areabull may appear as dotted veil pattern
bullMRI with gadolinium bull rim enhancement is seen within the first 3 weeks
bullCT scan bull lesion has an eggshell appearance
bullCharacteristic histology shows zonal pattern bull periphery of lesion
bull mature trabeculae of lamellar and woven bonebull calcification seen on xray
bull center of the lesion bull irregular mass of immature fibroblastsbull cartilage component may be presentbull (no calcification seen on xray) bull no cellular atypia seen
Treatment
bullNonoperative bull rest range of motion exercises and activity modification
bull passive stretching is contraindicated (makes it worse)bull physical therapy
bull utilized to maintain range of motionbull radiographic monitoring
bull obtained to confirm maturation of the lesionbullOperative
bull surgical excision bull indicated only if it remains a problem after it maturesbull do not operate in acute phase wait at least six months
bull excision of the lesion within 6 to 12 months predisposes to local recurrence
A 26-year-old man presents with generalized back and joint stiffness and difficulty opening his mouth His elder sister has similar complaints Since childhood he has had 3 surgeries for excision of recurrent bony prominences around his knees He walks with a stooped over posture seen in Figure A Radiographs of his feet knee hip and spine are seen in Figures B-E respectively
fibrodysplasia ossificans progressiva
Stone Man Disease) which involves a mutation of the ACVR1
There are 2 hallmark characteristics progressive heterotopic ossification (muscles fascia tendons ligaments and joint capsules) and congenital malformation of the great toe (hallux valgus malformed first metatarsal and monophalangism) BMP4 which contributes to the formation of the skeleton in the normal embryo is implicated in this disease
Complications
bullHematoma and intraoperative bleedingbullInfection
bull higher rate of infection following joint arthroplasty if HO is present
bullFractures of osteoporotic bone bull osteopenic from disusebull during surgery or physiotherapy
bullRecurrence bull recurrence rate correlates with neurological injury
bull greater recurrence if severe neurological compromisebullAVN
bull if extensive dissection or stripping is required
HTO AND ISS
When ISS is below 25 the mortality risk is minimal and above 25 it is an almost linear increase
When ISS is 50 the mortality is 50 When above 70 it is close to 100 If an injury is assigned an AIS of 6 (unsurvivable injury) the ISS score is
automatically assigned to 75 Highest ISS score obtainable is 75 For trauma patients of vehicular accidents the scoring system is important
for assessing the effectiveness of medical care in reducing morbidity and mortality
Advantages virtually the only anatomical scoring system in use correlates linearly with
mortality morbidity hospital stay other measures of severity
Weaknesses Any error in AIS scoring increases the ISS error Many different injury patterns can yield the same ISS score Injuries to different body regions are not weighted Not a useful triage tool as a full description of patient injuries is not known
prior to full investigation amp operation
risk factors periosteal stripping off anterior femur male gender obesity post traumatic deformity Anterior and anterolateral approach Cementless
Neurogenic HO around the hip due to SCI occurs more often in the medial region than in the lateral region with ossified tissues extending from the pubic symphysis to the anteromedial femoral shaft posterior to the femoral neurovascular structures Ossification is also seen anteriorly involving the iliopsoas and femoral neurovascular structures laterally within gluteus minimus and posteriorly extending from the ilium to the posterior femur encasing the sciatic nerve
HTO AROUND hip and knee
The Brooker Classification of Heterotopic Ossification around the hip joint Class I has islands of bone within the soft tissues Class II has bone spurs from the pelvis or proximal end of the femur leaving at least 1 cm between opposing surfaces Class III has bone spurs from the pelvis andor proximal end of the femur reducing the space between opposing bone surfaces to less than 1 cm Class IV shows apparent bone ankylosis of the hip
Region I - Heterotopic ossifications are strictly below the tip of the greater trochanter
Region II - Heterotopic ossifications are below and above the tip of the greater trochanter
Region III - Heterotopic ossifications are strictly above the tip of the greater trochanter
Grade A - Single or multiple heterotopic ossifications are less than 10 mm in maximal extent without contact with the pelvis or the femur
Grade B - Heterotopic ossifications are greater than 10 mm without contact with the pelvis but with possible contact with the femur there is no bridging from the femur to the proximal part of the greater trochanter and no evidence of ankylosis
Grade C - Ankylosis by means of firm bridging from the femur to the pelvis is present
Shmidt classification
excision may be performed The results of this procedure are varied Patients may find that their range of movement improves but pain relief is likely to be limited
A patient with heterotopic ossification following total hip arthroplasty is thought to have a 90-100 chance of developing it on the contralateral hip if this hip also undergoes total arthroplasty
it would be prudent to minimize the risk of heterotopic ossification developing after arthroplasty by performing surgery whereby the following are ensured
Exposure is meticulous Retraction is performed carefully and soft tissue
is handled carefully Irrigation is adequate Devitalized tissue is excised Hemostasis is adequate Postoperative drains (when used) are not
retained for longer than necessary Perioperative antibiotic prophylaxis is used Postoperative anticoagulation (when used for
deep vein thrombosis prophylaxis) is carefully controlled
sources of knee stiffness 1-extrinsic severe osteoarthritis of the ipsilateral hip neurologic injury leading to muscle rigidity tight quadriceps or hamstring muscles secondary to muscle injury heterotopic ossification or long-standing juvenile inflammatory conditions limiting knee
range of motion prior to the completion of skeletal growth When extrinsic sources are identified revision total knee arthroplasty is unlikely to be associated with a favorable outcome without correction of the extrinsic problem
2-intrinsic (1) overstuffing of the patellofemoral articulation (2) an
excessively tight flexion andor extension gap (3) a tight posterior cruciate ligament (4) femoral andor tibial malrotation (5) arthrofibrosis and (6) limited bearing excursion in association with a highly conforming mobile-bearing prosthetic design
HTO after TKA
Heterotopic Ossification (HO) following primary Total Knee Replacement (TKR)
Occurs in 3-90 of TKRs 3-grade classification system No correlation between HO and component
alignment or component position
Clinical findings similar to early infection Continuing low-grade fever Warm swollen and erythematous knee Normal blood tests Possibly an association with HLA-A2 and B18 HO patients have worse KSS and function
scores
Patients at HIGH risk for developing HO after TKR (Knee Arthroplasty) (5)
Those with limited postoperative knee flexion
Increased lumbar bone mineral density (BMD) on multivariate analysis (3)
Hypertrophic arthrosis Excessive periosteal trauma Notching of the anterior femur Those who require forced manipulation
after TKA 47 in revision TKR surgery (6) Higher rates in revision TKR cases with
infection (up to 76
DaughertyBell classification of HO of the knee 0 No evidence of HO 1 Bone islands in periarticular soft tissue (no
involvement of femur patella or tibia) or HO within quadriceps expansion measuring lt1 cm
2 Spur formation measuring lt5 cm that involves the femur patella or tibia if more than one bone demonstrates HO separation of HO spurs
measure gt1 cm or HO within quadriceps expansion measuring ge1 cm but lt3 cm
3 Spur formation gt5 cm involving femur patella or tibia if more than one bone demonstrates HO separation of HO spurs measure lt1 cm or HO
within quadriceps expansion measuring ge3 cm 4 Extensive HO of the knee causing ankylosis
class 2 HO begins to involve the major bones of the knee joint with spur formation limited to a size of 5 cm
HO class 2 may be observed in select patients with complete ROM and no reported pain Patients with class 3 HO would likely always benefit from surgical excision
followed by RT prophylaxis Certainly patients in either cohort with a subclass ldquoBrdquo assignment (symptomatic) would
benefit from treatment All patients with class 4 HO require
treatment to alleviate ankylosis
treatment
References Whyte ldquoPagetrsquos Disease of Bonerdquo NEMJ vol 355
2006 Klein and Parvizi ldquoSurgical Manifestations of Pagetrsquos
Diseaserdquo JAAOS vol 14 2006 Orthobullets Campbell Apley Emedicinecom
-Chapter 15 Heterotopic Ossification after Traumatic Brain InjuryBy Jesuacutes Moreta and Joseacute Luis Martiacutenez-de los Mozos DOI 10577257343
Questions
Thank You
BisphosphonatesSynthetic analogues of inorganic phosphate adhere to mineralized surfaces
Ingested selectively by osteoclasts Disrupts enzyme pathways and reduces osteoclastic bone resorption
calcitonin causes osteoclasts to shrink in size and decreases their bone resorptive activity within minutes administered subcutaneously or intramuscularly
teriparatide is contraindicated in Pagets disease due to risk of secondary osteosarcoma
Surgical Management Few require surgery
Common Procedures Corrective osteotomy of long bone deformity indications
fractures through pathologic bowing of long bones impending pathologic fracture of long bone with bowing deformity
Arthroplasty (hip knee) the most common complications include
malalignment with knee arthroplasty bleeding with hip arthroplasty
Combination arthroplasty with osteotomy Fracture fixation
Preoperative Considerations Medical assessment for extraskeletalmanifestations eg high-
output heart failure
Medical treatment of active disease Preoperative autologousblood donation
Thorough planningeg good quality x-rays for templatingand device selection
Intraoperative Considerations Blood salvage system Expansileapproach + soft tissue release Sharp reamersburrsdrills for IM access Extramedullaryguidenavigation systems Concomitant osteotomy
PostoperativeConsiderations Monitoring for cardiac complications Continued medical tx of active disease
uarrHeterotopic ossification Prophylaxis against HO
Possible future excision of HO for painROM
1-Tieg provides a review of Pagets disease of bone and treatment indications In his review he discusses that most patients with Pagets disease are asymptomatic but in those that do present pain is the most common presenting symptom He recommends medical and surgical treatment of asymptomatic patients who have active disease at sites where complications are likely to develop
Altman did a review of 290 patients with Pagets disease of bone His findings showed 83 had one or more rheumatic syndromes He found the rate of osteoarthritis related to Pagets disease was elevated in the hip and knee Rheumatoid arthritis hyperuricemia and gout did not appear increased in this group
Mangham et al looked the rate of secondary sarcomas as a result of Pagets disease of bone They found the rate to be around 03 with male predominance They also found that widespread skeletal involvement by Pagets disease was not a significant risk factor for malignant transformation
Interesting views about pagets
Smith et al reviewed the pathologic complications of Pagets bone disease Pagets bone disease commonly causes osseous weakening (deformity and fracture) and arthritis in the hip joint Management of end stage disease is successful with cemented and cementless total hip arthroplasty Bleeding is the most common intra- and post-operative complication of surgery
Gabel et al retrospectively reviewed thirteen patients who had had sixteen total knee arthroplasties for Pagetic gonarthrosis Unlike total hip arthroplasty surgery Paget disease did not increase the amount of blood lost during the operation or in the postoperative period The most common complication associated with total knee arthroplasty was malalignment
Hansen et al reviewed the incidence of osteosarcomas complicating Pagets Disease Of the typical sites that are usually involved in Pagets disease (eg spine pelvis femur tibia and humerus) secondary osteosarcoma tends to spare the spine
Shaylor et al reported the mortality rates in 26 patient with osteosarcoma secondary to Paget s disease There was a 47 mortality at 1 year and 75 at 2 years from diagnosis In their series no patient survived for 5 years All patients died of metastatic disease
Langston et al conducted a randomized trial that compared the results of symptomatic treatment versus intensive bisphosphonate therapy in patients with Pagets disease Clinical fractures occurred in 46 of 661 patients (70) in the treatment group compared with 49 of 663 patients (74) in the symptomatic treatment group They concluded that bisphosphonates did not show a significant beneficial impact on pain quality of life or fracture incidence
Hadjipavlou et al reviewed Pagets disease of the bone and its management Farmers have been shown to have an increased incidence of Pagets disease Average age at presentation is in the 5th and 6th decade Symptomatic individuals are recommended to be treated initially with medical management They suggest that bisphosphonates are more effective than calcitonin at suppressing the histological and biochemical activity in Pagetrsquos disease
Summary Epid Very common in elderly Path Abnormal osteoclastshellipuarrbone
turnoverhellipdeposition of abnormal bone SampS Pain deformity fracture arthropathy Labs uarrAlkPhos X-ray Characteristic coarse thickened
trabeculae Bone scan Very hot Rx Bisphosphonates Surgery for arthropathy fracture painful
deformity
A 65-year-old male presents with increasing shoulder pain over the past 9 months He is otherwise healthy and has no other complaints Radiograph of his shoulder is shown in Figure A Whole body bone scan and biopsy photograph are shown in Figures B and C What is the most appropriate treatment for this patient
1 Referral to endocrinology 2 Radiation therapy and chemotherapy 3 Wide resection and reconstruction 4 Radiation therapy wide resection and reconstruction 5 Chemotherapy wide resection and reconstruction
Histiocytosis X or Langerhans cell histiocytosis is a spectrum of diseases of the reticuloendothelial system with one of three general presentations Eosinophilic granuloma (EG)
usually a single self-limited lesion found in younger patients
Hand-Schuller-Christian disease (HSC) chronic disseminated form with bone and visceral lesions also known as Langerhans cell histiocytosis with visceral
involvement Letterer-Siwe disease (LSD)
fatal form that occurs in young children
Eosinophilic granuloma
Epidemiology demographics
most commonly occurs in children (80 of afflicted lt 20 years of age)
HSC disease presents in children gt 3 years of age LSD occurs in children lt 3 years of age Male to female ratio of 21
location eosinophilic granuloma
commonly presents in the skull ribs clavicle scapula mandible
isolated lesions of the spine (thoracic most common) can also occur in diaphyseal regions of long bones and the
pelvis HSC
multiple bony sites multiple lytic skull lesions visceral involvement of the lungs spleen liver skin lymph
nodes
Genetics no clear genetic pattern of inheritance or locus has
been determined Prognosis
EG isolated involvement generally treatable with local
management spine lesions can spontaneously resolve
HSC prognosis depends on response to chemotherapy worsening prognosis with increasing extraskeletal
involvement LSD
generally fatal in children lt 3 years of age
Symptoms skeletal involvement
pain and swelling at the region of involvement limping can be seen with pelvic or lower extremity
involvement vertebral involvement
localized or diffuse back pain increasingly kyphotic posture radiculopathy can occur with more aggressive lesions
HSC classic triad of
multiple lytic skull lesions diabetes insipidus
increased thirst and water intake exopthalmos
visceral involvement diffuse or nonspecific abdominal or chest pain
Radiographs general
known as the great mimicker as it appears similar to many lesions radiographic differential includes osteomyelitis leukemia lymphoma
fibrous dysplasia or Ewings sarcoma diaphyseal lesions
well defined intramedullary lytic or punched-out lesion cortex may be thinned expanded or destroyed may have periosteal reaction
metaphyseal lesions extend up to but not through the physis less central location than diaphyseal lesions
spinal lesions vertebra plana (flattened vertebrae) in spine increased kyphosis
cranial involvement multiple punched-out lytic lesions
MRI may show a soft tissue mass adjacent to boney lesions
Bone scan generally shows increased uptake in the region of boney lesion
Histology Langerhans cells
mononuclear histiocyte-like cells with oval nuclei with well-defined round or oval cytoplasm
a prominent nuclear groove (coffee bean nuclei) can be seen in most of the nuclei
eosinophilic cytoplasm (pink generally) stain with CD1A electronmicroscopy
birbeck granules seen inside Langerhans cells mixture of inflammatory cells also present giant cells are present lack of nuclear atypia and atypical mitoses
differentiates this condition from malignant conditions such as Ewings sarcoma lymphoma of bone and metastatic neuroblastoma which may look similar based on the round cells alone
eosinophilic cytoplasm (pink generally)
Treatment
bullNonoperative bull observation alone
bull indications bull a self-limited process and it is reasonable to treat with observation alone
bull bracing bull indications
bull to prevent progressive kyphosis of the spinebull outcomes
bull will correct deformity in 90 of patientsbull vertebral lesions generally regain 50 of their height
bull low dose irradiation (600-800 cGy) bull indications
bull indicated for lesions in the spine that compromise stability neurologic statusbull lesions not amenable to injection or open treatment
bull outcomes bull effective for most lesions
bull chemotherapy bull indications
bull diffuse HSCbull outcomes
bull prognosis is improved with less severe extraskeletal involvementbull corticosteroid injection
bull indications bull isolated lesions bull can be performed after curettage as well
Operative curettage and bone grafting
indications for lesions that endanger the articular surface or are a risk for
impending fractures spinal deformity correction
indications progressive spine deformity refractory to bracing
approximately 10 of patients with spine lesion will need operative intervention for deformity correction
Destructive multiple lesion in young patientsAre eosinophilic granuloma lymphoma and leukemiaLymphoma is unlikely to present with exopthalmos diabetes insipidus or vertebra plana Lymphoma bone lesions are lytic and appear moth eatenpermeative on radiographs
Figure A shows a skin lesion typical of eosinophillic granuloma Figure B shows a lytic lesions without significant surrounding sclerosis as is characteristic of eosinophilic granuloma Figure C shows the characteristic histology of multiple eosinophils with their characteristic oval coffee bean nuclei and staining pattern of purpleredpink cytoplasm (depending on the stain) Importantly the histology slide lacks a malignant appearance (no cellular atypia or mytotic complexes and low nuclearcytoplasmic ratio)
Formation of bone in atypical extraskeletal tissues usually occurs
spontaneously or following trauma within 2 months of neurologic injury (brain or spinal cord)
most common location is between muscle and joint capsule Epidemiology
incidence (see table below)
demographics malefemale = 21 especially men with hypertrophic osteoarthritis and women gt65y
location traumatic brain injury or stroke
hip gt elbow gt shoulder gt knee elbow HO more common following brain trauma
occurs on affected (spastic) side rarely in the knee (TBI)
spinal cord injury hip gt knee gt elbow gt shoulder hip flexors and abductors gt extensors or adductors medial aspect of the knee
Heterotopic Ossification
Risk factors
Pathophysiology exact cause of HO is not known but there appears to be a
genetic pre disposition experimental HO associated with
tissue expression of BMP IT IS SAID TO BE CAUSED BY activation and proliferation of
mesenchymal stem cells Associated conditions
orthopaedic manifestations pathologic fractures
from decreased joint ROM and osteoporotic bone nerve impingement soft tissue contractures contributing to the formation of
decubitus ulcers joint ankylosis HO after THA adversely affects outcome of THA
nonorthopaedic conditions skin maceration and hygiene problems
Pathophysiology Early in the formation of HO oedema with exudative
infiltrate is present followed by fibroblastic proliferation and immature connective tissue formation Posteriorly osteoid formation is seen with the subsequent deposition of bone matrix Primitive osteoid is deposited as small masses in the periphery early (within the first two weeks) and osteoblasts are noted located irregularly Osteoblasts produce tropocollagen which polymerizes to form collagen and secrete alkaline phosphatase which allows calcium to precipitate and the mineralization of bone matrix As mineralization progresses amorphous calcium phosphate is progressively replaced by hydroxyapatite crystals During the following weeks the lesion matures with a centripetal pattern and after 6-12 months an appearance of true bone is noted The new bone is always extra-articular and can be contiguous with the skeleton but generally does not involve the periosteum
IN SUMMARY It has been postulated that three conditions
must be met to achieve heterotopic bone formation ---a stimulating event oestrogenic precursor cells and a proper environment LIKE hypercalcaemia tissue hypoxia pH changes (alkalosis) or prolonged immobilization
ClassificationbullSubtypes
bull neurogenic HO bull Four clinical stages of HO in people with spinal cord injury were
described by Nicholas in 1973
bull traumatic myositis ossificans bull fibrodysplasia ossificans progressiva (Munchmeyers Disease)
Neurogenic HO Symptoms
painless loss of ROM interferes with ADL CRPS symptoms fever
Physical exam inspection
warm painful swollen joint may have effusion skin problems
decubitus ulcers from contractures around skin muscles ligaments
skin maceration and hygiene problems motion
decreased joint ROM joint ankylosis with HO after TKA might develop quad muscle snapping or patella
instability neurovascular
peripheral neuropathy HO often impinges on adjacent NV structures
Imaging
bullRadiographs bull findings
bull ossification usually easy to visualize bull maturity of HO
bull the appearance of a bony cortex suggests mature HObull sharp demarcation from surrounding tissue bull trabecular pattern
bull sensitivity and specificity bull not useful for early diagnosisbull only useful at 1 week after onset of symptoms
bull calcium is deposited 7-10 days later than symptom onsetbullUltrasound
bull indications bull for early diagnosis of hip HO
bull findings bull echogenic surfaces with posterior acoustic shadowing
bullCT bull indications
bull useful for preoperative planning bullTriphasic bone scan
bull indications bull best for early diagnosis bull most commonly used diagnostic study
Radiographs are extremely useful in the staging of heterotopic ossification and will show the development of sharp cortical margins once the lesion has reached maturity
Heterotopic bone is a condition in which lamellar bone forms in non-ossified soft tissues In the early stages studies such as MRI and bone scan are more sensitive for diagnosis as radiographs may appear normal for the first three weeks After the appropriate diagnosis is made sequential radiographs are useful for monitoring the progression of the ossification Once it has reached the mature stage sharp cortical margins will appear and surgical resection may be considered
lab
Labs elevated serum alkaline phosphatase (gt250IUL)
ALP removes inhibitors of mineralization nonspecific may be elevated with skeletal trauma cannot determine maturity of HO elevated 12wks after surgery is predictor
elevated CRP correlates with inflammatory activity of HO better than ESR normalization of CRP may correlate with maturity of HO
elevated ESR (gt35mmh) 12wks after THA is predictor
elevated CK correlates with involvement of muscle extent of muscle
involvement Histology
mature fatty bone marrow mature trabecular bone
Heterotopic ossification (HO) most commonly occurs at the amputation site if the amputation was performed thru the zone of injury especially if the injury was a blast mechanism
Symptomatic heterotopic ossification of the quadriceps may occur following placement of a large-diameter Steinmann pin for the purpose of temporary skeletal traction
TreatmentThe prevention of heterotopic ossification is focused on three basic principles disrupting the inductive signalling pathways altering the osteoprogenitor cells or modifying the environment
bullphysiotherapy should involve an assisted range of movement exercises with gentle stretch and terminal resistance trainingbullProphylaxis
bull bisphosphonates amp NSAIDS bull indications
bull although no literature supports are commonly usedbull technique
bull indomethacin is most commonly used bull dose is 75mgday for 10days to 6 weeks
bull perioperative radiation bull indications
bull although no literature supports commonly usedbull is thought to be effective by blocking osteoblast differentiation
bull technique bull a single perioperative dose of 700cGy can be given either 4
hours preop or within 72 hours postoperatively bull lt550cGy not effective
Nonsteroidal anti-inflammatory drugs (NSAIDs) These drugs have demonstrated good results in
preventing heterotopic ossification after total hip arthroplasty
A direct effect of NSAIDs on the formation of heterotopic ossification has been described due to the inhibition of the differentiation of mesenchymal cells into oestrogenic cells There is also an indirect effect which refers to the inhibition of bone remodelling by suppression of the prostagland unmediated inflammatory response (specifically PGE-2)
Indomethacin has been considered a useful medication for heterotopic ossification prophylaxis following total hip replacement
prescribed for three to six weeks in a dose of 75mgday within two months of the injury may reduce the incidence of heterotopic ossification by two to three times
Biphosphonates inhibits precipitation of calcium phosphate and blocks the aggregation and mineralisation of hydroxyapatite crystals In primary prevention Banovac et al [56] have suggested that the treatment should begin as soon as elevated alkaline phosphatase is diagnosed or positive findings in ultrasonography or bone scans are shown In addition disphosphonates could have long-term effects on prevention when the treatment is finished
Posttraumatic wide exposure and surgical resection
indications severe loss of motion and decreased function
technique wide exposure required to identify all neurovascular
structures that may be involved timing of resection (controversial)
marked decrease in bone scan activity AND normalization of ALP
6 months following general trauma 1 year following SCI 15 years following TBI
some data suggests equivalent results when comparing early versus late resection
postop follow with 5 day course of indomethacin early gentle joint mobilization
The surgery is necessary in patients with symptomatic HO and unsuccessful medical treatment such as
Loss of range of motion and ankylosis with associated functional disability such as sitting difficulties
Complications of immobility such as pressure ulcers
Facilitate rehabilitation and recovery of muscular atrophy secondary to prolonged immobilisation
Difficulties of appropriate hygiene because access to the perineum or bladder care is needed
Severe pain refractory to analgesia Vascular andor nerve compression
Advantages to early excision of heterotopic ossification (vs waiting for maturation) include decreased soft tissue contracture better definition between heterotopic and native bone and decreased waiting time for the patient When the soft tissue envelope is benign one may proceed with operative release While waiting for normalization of alkaline phosphatase levels inactivity on bone scan or radiographic maturity may decrease risk of recurrent heterotopic ossification delaying operative release for these reasons has not been shown to improve results of final elbow range of motion after contracture release
Gartland recommended surgery after six months following traumatic heterotopic ossification one year following spinal cord injury and 18 months after head injury
In the past waiting until maturity in order to minimize the rate of recurrence after the surgical treatment was recommended Nevertheless recent studies do not confirm a higher rate of recurrence when the HO is excised in an earlier phase In addition a long delay before surgery leads to ankylosis a high degree of osteoporosis and more extensive intra-articular injuries These findings are associated with bad functional results and potential complications
Should you wait till lesion maturation
Prevention byHandle tissue carefully Avoid excess bleeding Achieve good hemostasis Beware of lesions that span internervous tissue planes
but if it happens resection of a large enough amount of bone to allow improvement of the range of motion and trying to preserve the joint
Our aim must be
A reactive process that is characterized by a well-circumscribed proliferation of fibroblasts cartilage and bone within muscle
A form of heterotopic ossification that is the result direct trauma intramuscular hematoma
most common location is the diaphysis of long bones Must differentiate from tumors Fibrodysplasia ossificans progressiva (FOP) is a rare subtype of heterotopic ossification
involves mutation of the ACVR1 gene (activin A type I receptor gene a BMP type-1 receptor)
Epidemiology demographics
most common in young active males (15 to 35 years old) body locations
quadriceps brachialis and gluteal muscles Genetics
almost always a posttraumatic condition Prognosis
usually self limiting mass usually begins to decrease in size after 1 yea
Myositis ossificans
PresentationbullSymptoms
bull pain tenderness swelling and decreased range of motion that usually presents within days of the injury
bull pain and size of the mass decrease with timebull mass increases in size over several months(usually 3 to 6 cm)
bull after the mass stops growing it becomes firmbullPhysical exam
bull palpable soft tissue massbull restricted range of motion
ImagingbullRadiographs
bull peripheral bone formation with central lucent areabull may appear as dotted veil pattern
bullMRI with gadolinium bull rim enhancement is seen within the first 3 weeks
bullCT scan bull lesion has an eggshell appearance
bullCharacteristic histology shows zonal pattern bull periphery of lesion
bull mature trabeculae of lamellar and woven bonebull calcification seen on xray
bull center of the lesion bull irregular mass of immature fibroblastsbull cartilage component may be presentbull (no calcification seen on xray) bull no cellular atypia seen
Treatment
bullNonoperative bull rest range of motion exercises and activity modification
bull passive stretching is contraindicated (makes it worse)bull physical therapy
bull utilized to maintain range of motionbull radiographic monitoring
bull obtained to confirm maturation of the lesionbullOperative
bull surgical excision bull indicated only if it remains a problem after it maturesbull do not operate in acute phase wait at least six months
bull excision of the lesion within 6 to 12 months predisposes to local recurrence
A 26-year-old man presents with generalized back and joint stiffness and difficulty opening his mouth His elder sister has similar complaints Since childhood he has had 3 surgeries for excision of recurrent bony prominences around his knees He walks with a stooped over posture seen in Figure A Radiographs of his feet knee hip and spine are seen in Figures B-E respectively
fibrodysplasia ossificans progressiva
Stone Man Disease) which involves a mutation of the ACVR1
There are 2 hallmark characteristics progressive heterotopic ossification (muscles fascia tendons ligaments and joint capsules) and congenital malformation of the great toe (hallux valgus malformed first metatarsal and monophalangism) BMP4 which contributes to the formation of the skeleton in the normal embryo is implicated in this disease
Complications
bullHematoma and intraoperative bleedingbullInfection
bull higher rate of infection following joint arthroplasty if HO is present
bullFractures of osteoporotic bone bull osteopenic from disusebull during surgery or physiotherapy
bullRecurrence bull recurrence rate correlates with neurological injury
bull greater recurrence if severe neurological compromisebullAVN
bull if extensive dissection or stripping is required
HTO AND ISS
When ISS is below 25 the mortality risk is minimal and above 25 it is an almost linear increase
When ISS is 50 the mortality is 50 When above 70 it is close to 100 If an injury is assigned an AIS of 6 (unsurvivable injury) the ISS score is
automatically assigned to 75 Highest ISS score obtainable is 75 For trauma patients of vehicular accidents the scoring system is important
for assessing the effectiveness of medical care in reducing morbidity and mortality
Advantages virtually the only anatomical scoring system in use correlates linearly with
mortality morbidity hospital stay other measures of severity
Weaknesses Any error in AIS scoring increases the ISS error Many different injury patterns can yield the same ISS score Injuries to different body regions are not weighted Not a useful triage tool as a full description of patient injuries is not known
prior to full investigation amp operation
risk factors periosteal stripping off anterior femur male gender obesity post traumatic deformity Anterior and anterolateral approach Cementless
Neurogenic HO around the hip due to SCI occurs more often in the medial region than in the lateral region with ossified tissues extending from the pubic symphysis to the anteromedial femoral shaft posterior to the femoral neurovascular structures Ossification is also seen anteriorly involving the iliopsoas and femoral neurovascular structures laterally within gluteus minimus and posteriorly extending from the ilium to the posterior femur encasing the sciatic nerve
HTO AROUND hip and knee
The Brooker Classification of Heterotopic Ossification around the hip joint Class I has islands of bone within the soft tissues Class II has bone spurs from the pelvis or proximal end of the femur leaving at least 1 cm between opposing surfaces Class III has bone spurs from the pelvis andor proximal end of the femur reducing the space between opposing bone surfaces to less than 1 cm Class IV shows apparent bone ankylosis of the hip
Region I - Heterotopic ossifications are strictly below the tip of the greater trochanter
Region II - Heterotopic ossifications are below and above the tip of the greater trochanter
Region III - Heterotopic ossifications are strictly above the tip of the greater trochanter
Grade A - Single or multiple heterotopic ossifications are less than 10 mm in maximal extent without contact with the pelvis or the femur
Grade B - Heterotopic ossifications are greater than 10 mm without contact with the pelvis but with possible contact with the femur there is no bridging from the femur to the proximal part of the greater trochanter and no evidence of ankylosis
Grade C - Ankylosis by means of firm bridging from the femur to the pelvis is present
Shmidt classification
excision may be performed The results of this procedure are varied Patients may find that their range of movement improves but pain relief is likely to be limited
A patient with heterotopic ossification following total hip arthroplasty is thought to have a 90-100 chance of developing it on the contralateral hip if this hip also undergoes total arthroplasty
it would be prudent to minimize the risk of heterotopic ossification developing after arthroplasty by performing surgery whereby the following are ensured
Exposure is meticulous Retraction is performed carefully and soft tissue
is handled carefully Irrigation is adequate Devitalized tissue is excised Hemostasis is adequate Postoperative drains (when used) are not
retained for longer than necessary Perioperative antibiotic prophylaxis is used Postoperative anticoagulation (when used for
deep vein thrombosis prophylaxis) is carefully controlled
sources of knee stiffness 1-extrinsic severe osteoarthritis of the ipsilateral hip neurologic injury leading to muscle rigidity tight quadriceps or hamstring muscles secondary to muscle injury heterotopic ossification or long-standing juvenile inflammatory conditions limiting knee
range of motion prior to the completion of skeletal growth When extrinsic sources are identified revision total knee arthroplasty is unlikely to be associated with a favorable outcome without correction of the extrinsic problem
2-intrinsic (1) overstuffing of the patellofemoral articulation (2) an
excessively tight flexion andor extension gap (3) a tight posterior cruciate ligament (4) femoral andor tibial malrotation (5) arthrofibrosis and (6) limited bearing excursion in association with a highly conforming mobile-bearing prosthetic design
HTO after TKA
Heterotopic Ossification (HO) following primary Total Knee Replacement (TKR)
Occurs in 3-90 of TKRs 3-grade classification system No correlation between HO and component
alignment or component position
Clinical findings similar to early infection Continuing low-grade fever Warm swollen and erythematous knee Normal blood tests Possibly an association with HLA-A2 and B18 HO patients have worse KSS and function
scores
Patients at HIGH risk for developing HO after TKR (Knee Arthroplasty) (5)
Those with limited postoperative knee flexion
Increased lumbar bone mineral density (BMD) on multivariate analysis (3)
Hypertrophic arthrosis Excessive periosteal trauma Notching of the anterior femur Those who require forced manipulation
after TKA 47 in revision TKR surgery (6) Higher rates in revision TKR cases with
infection (up to 76
DaughertyBell classification of HO of the knee 0 No evidence of HO 1 Bone islands in periarticular soft tissue (no
involvement of femur patella or tibia) or HO within quadriceps expansion measuring lt1 cm
2 Spur formation measuring lt5 cm that involves the femur patella or tibia if more than one bone demonstrates HO separation of HO spurs
measure gt1 cm or HO within quadriceps expansion measuring ge1 cm but lt3 cm
3 Spur formation gt5 cm involving femur patella or tibia if more than one bone demonstrates HO separation of HO spurs measure lt1 cm or HO
within quadriceps expansion measuring ge3 cm 4 Extensive HO of the knee causing ankylosis
class 2 HO begins to involve the major bones of the knee joint with spur formation limited to a size of 5 cm
HO class 2 may be observed in select patients with complete ROM and no reported pain Patients with class 3 HO would likely always benefit from surgical excision
followed by RT prophylaxis Certainly patients in either cohort with a subclass ldquoBrdquo assignment (symptomatic) would
benefit from treatment All patients with class 4 HO require
treatment to alleviate ankylosis
treatment
References Whyte ldquoPagetrsquos Disease of Bonerdquo NEMJ vol 355
2006 Klein and Parvizi ldquoSurgical Manifestations of Pagetrsquos
Diseaserdquo JAAOS vol 14 2006 Orthobullets Campbell Apley Emedicinecom
-Chapter 15 Heterotopic Ossification after Traumatic Brain InjuryBy Jesuacutes Moreta and Joseacute Luis Martiacutenez-de los Mozos DOI 10577257343
Questions
Thank You
Preoperative Considerations Medical assessment for extraskeletalmanifestations eg high-
output heart failure
Medical treatment of active disease Preoperative autologousblood donation
Thorough planningeg good quality x-rays for templatingand device selection
Intraoperative Considerations Blood salvage system Expansileapproach + soft tissue release Sharp reamersburrsdrills for IM access Extramedullaryguidenavigation systems Concomitant osteotomy
PostoperativeConsiderations Monitoring for cardiac complications Continued medical tx of active disease
uarrHeterotopic ossification Prophylaxis against HO
Possible future excision of HO for painROM
1-Tieg provides a review of Pagets disease of bone and treatment indications In his review he discusses that most patients with Pagets disease are asymptomatic but in those that do present pain is the most common presenting symptom He recommends medical and surgical treatment of asymptomatic patients who have active disease at sites where complications are likely to develop
Altman did a review of 290 patients with Pagets disease of bone His findings showed 83 had one or more rheumatic syndromes He found the rate of osteoarthritis related to Pagets disease was elevated in the hip and knee Rheumatoid arthritis hyperuricemia and gout did not appear increased in this group
Mangham et al looked the rate of secondary sarcomas as a result of Pagets disease of bone They found the rate to be around 03 with male predominance They also found that widespread skeletal involvement by Pagets disease was not a significant risk factor for malignant transformation
Interesting views about pagets
Smith et al reviewed the pathologic complications of Pagets bone disease Pagets bone disease commonly causes osseous weakening (deformity and fracture) and arthritis in the hip joint Management of end stage disease is successful with cemented and cementless total hip arthroplasty Bleeding is the most common intra- and post-operative complication of surgery
Gabel et al retrospectively reviewed thirteen patients who had had sixteen total knee arthroplasties for Pagetic gonarthrosis Unlike total hip arthroplasty surgery Paget disease did not increase the amount of blood lost during the operation or in the postoperative period The most common complication associated with total knee arthroplasty was malalignment
Hansen et al reviewed the incidence of osteosarcomas complicating Pagets Disease Of the typical sites that are usually involved in Pagets disease (eg spine pelvis femur tibia and humerus) secondary osteosarcoma tends to spare the spine
Shaylor et al reported the mortality rates in 26 patient with osteosarcoma secondary to Paget s disease There was a 47 mortality at 1 year and 75 at 2 years from diagnosis In their series no patient survived for 5 years All patients died of metastatic disease
Langston et al conducted a randomized trial that compared the results of symptomatic treatment versus intensive bisphosphonate therapy in patients with Pagets disease Clinical fractures occurred in 46 of 661 patients (70) in the treatment group compared with 49 of 663 patients (74) in the symptomatic treatment group They concluded that bisphosphonates did not show a significant beneficial impact on pain quality of life or fracture incidence
Hadjipavlou et al reviewed Pagets disease of the bone and its management Farmers have been shown to have an increased incidence of Pagets disease Average age at presentation is in the 5th and 6th decade Symptomatic individuals are recommended to be treated initially with medical management They suggest that bisphosphonates are more effective than calcitonin at suppressing the histological and biochemical activity in Pagetrsquos disease
Summary Epid Very common in elderly Path Abnormal osteoclastshellipuarrbone
turnoverhellipdeposition of abnormal bone SampS Pain deformity fracture arthropathy Labs uarrAlkPhos X-ray Characteristic coarse thickened
trabeculae Bone scan Very hot Rx Bisphosphonates Surgery for arthropathy fracture painful
deformity
A 65-year-old male presents with increasing shoulder pain over the past 9 months He is otherwise healthy and has no other complaints Radiograph of his shoulder is shown in Figure A Whole body bone scan and biopsy photograph are shown in Figures B and C What is the most appropriate treatment for this patient
1 Referral to endocrinology 2 Radiation therapy and chemotherapy 3 Wide resection and reconstruction 4 Radiation therapy wide resection and reconstruction 5 Chemotherapy wide resection and reconstruction
Histiocytosis X or Langerhans cell histiocytosis is a spectrum of diseases of the reticuloendothelial system with one of three general presentations Eosinophilic granuloma (EG)
usually a single self-limited lesion found in younger patients
Hand-Schuller-Christian disease (HSC) chronic disseminated form with bone and visceral lesions also known as Langerhans cell histiocytosis with visceral
involvement Letterer-Siwe disease (LSD)
fatal form that occurs in young children
Eosinophilic granuloma
Epidemiology demographics
most commonly occurs in children (80 of afflicted lt 20 years of age)
HSC disease presents in children gt 3 years of age LSD occurs in children lt 3 years of age Male to female ratio of 21
location eosinophilic granuloma
commonly presents in the skull ribs clavicle scapula mandible
isolated lesions of the spine (thoracic most common) can also occur in diaphyseal regions of long bones and the
pelvis HSC
multiple bony sites multiple lytic skull lesions visceral involvement of the lungs spleen liver skin lymph
nodes
Genetics no clear genetic pattern of inheritance or locus has
been determined Prognosis
EG isolated involvement generally treatable with local
management spine lesions can spontaneously resolve
HSC prognosis depends on response to chemotherapy worsening prognosis with increasing extraskeletal
involvement LSD
generally fatal in children lt 3 years of age
Symptoms skeletal involvement
pain and swelling at the region of involvement limping can be seen with pelvic or lower extremity
involvement vertebral involvement
localized or diffuse back pain increasingly kyphotic posture radiculopathy can occur with more aggressive lesions
HSC classic triad of
multiple lytic skull lesions diabetes insipidus
increased thirst and water intake exopthalmos
visceral involvement diffuse or nonspecific abdominal or chest pain
Radiographs general
known as the great mimicker as it appears similar to many lesions radiographic differential includes osteomyelitis leukemia lymphoma
fibrous dysplasia or Ewings sarcoma diaphyseal lesions
well defined intramedullary lytic or punched-out lesion cortex may be thinned expanded or destroyed may have periosteal reaction
metaphyseal lesions extend up to but not through the physis less central location than diaphyseal lesions
spinal lesions vertebra plana (flattened vertebrae) in spine increased kyphosis
cranial involvement multiple punched-out lytic lesions
MRI may show a soft tissue mass adjacent to boney lesions
Bone scan generally shows increased uptake in the region of boney lesion
Histology Langerhans cells
mononuclear histiocyte-like cells with oval nuclei with well-defined round or oval cytoplasm
a prominent nuclear groove (coffee bean nuclei) can be seen in most of the nuclei
eosinophilic cytoplasm (pink generally) stain with CD1A electronmicroscopy
birbeck granules seen inside Langerhans cells mixture of inflammatory cells also present giant cells are present lack of nuclear atypia and atypical mitoses
differentiates this condition from malignant conditions such as Ewings sarcoma lymphoma of bone and metastatic neuroblastoma which may look similar based on the round cells alone
eosinophilic cytoplasm (pink generally)
Treatment
bullNonoperative bull observation alone
bull indications bull a self-limited process and it is reasonable to treat with observation alone
bull bracing bull indications
bull to prevent progressive kyphosis of the spinebull outcomes
bull will correct deformity in 90 of patientsbull vertebral lesions generally regain 50 of their height
bull low dose irradiation (600-800 cGy) bull indications
bull indicated for lesions in the spine that compromise stability neurologic statusbull lesions not amenable to injection or open treatment
bull outcomes bull effective for most lesions
bull chemotherapy bull indications
bull diffuse HSCbull outcomes
bull prognosis is improved with less severe extraskeletal involvementbull corticosteroid injection
bull indications bull isolated lesions bull can be performed after curettage as well
Operative curettage and bone grafting
indications for lesions that endanger the articular surface or are a risk for
impending fractures spinal deformity correction
indications progressive spine deformity refractory to bracing
approximately 10 of patients with spine lesion will need operative intervention for deformity correction
Destructive multiple lesion in young patientsAre eosinophilic granuloma lymphoma and leukemiaLymphoma is unlikely to present with exopthalmos diabetes insipidus or vertebra plana Lymphoma bone lesions are lytic and appear moth eatenpermeative on radiographs
Figure A shows a skin lesion typical of eosinophillic granuloma Figure B shows a lytic lesions without significant surrounding sclerosis as is characteristic of eosinophilic granuloma Figure C shows the characteristic histology of multiple eosinophils with their characteristic oval coffee bean nuclei and staining pattern of purpleredpink cytoplasm (depending on the stain) Importantly the histology slide lacks a malignant appearance (no cellular atypia or mytotic complexes and low nuclearcytoplasmic ratio)
Formation of bone in atypical extraskeletal tissues usually occurs
spontaneously or following trauma within 2 months of neurologic injury (brain or spinal cord)
most common location is between muscle and joint capsule Epidemiology
incidence (see table below)
demographics malefemale = 21 especially men with hypertrophic osteoarthritis and women gt65y
location traumatic brain injury or stroke
hip gt elbow gt shoulder gt knee elbow HO more common following brain trauma
occurs on affected (spastic) side rarely in the knee (TBI)
spinal cord injury hip gt knee gt elbow gt shoulder hip flexors and abductors gt extensors or adductors medial aspect of the knee
Heterotopic Ossification
Risk factors
Pathophysiology exact cause of HO is not known but there appears to be a
genetic pre disposition experimental HO associated with
tissue expression of BMP IT IS SAID TO BE CAUSED BY activation and proliferation of
mesenchymal stem cells Associated conditions
orthopaedic manifestations pathologic fractures
from decreased joint ROM and osteoporotic bone nerve impingement soft tissue contractures contributing to the formation of
decubitus ulcers joint ankylosis HO after THA adversely affects outcome of THA
nonorthopaedic conditions skin maceration and hygiene problems
Pathophysiology Early in the formation of HO oedema with exudative
infiltrate is present followed by fibroblastic proliferation and immature connective tissue formation Posteriorly osteoid formation is seen with the subsequent deposition of bone matrix Primitive osteoid is deposited as small masses in the periphery early (within the first two weeks) and osteoblasts are noted located irregularly Osteoblasts produce tropocollagen which polymerizes to form collagen and secrete alkaline phosphatase which allows calcium to precipitate and the mineralization of bone matrix As mineralization progresses amorphous calcium phosphate is progressively replaced by hydroxyapatite crystals During the following weeks the lesion matures with a centripetal pattern and after 6-12 months an appearance of true bone is noted The new bone is always extra-articular and can be contiguous with the skeleton but generally does not involve the periosteum
IN SUMMARY It has been postulated that three conditions
must be met to achieve heterotopic bone formation ---a stimulating event oestrogenic precursor cells and a proper environment LIKE hypercalcaemia tissue hypoxia pH changes (alkalosis) or prolonged immobilization
ClassificationbullSubtypes
bull neurogenic HO bull Four clinical stages of HO in people with spinal cord injury were
described by Nicholas in 1973
bull traumatic myositis ossificans bull fibrodysplasia ossificans progressiva (Munchmeyers Disease)
Neurogenic HO Symptoms
painless loss of ROM interferes with ADL CRPS symptoms fever
Physical exam inspection
warm painful swollen joint may have effusion skin problems
decubitus ulcers from contractures around skin muscles ligaments
skin maceration and hygiene problems motion
decreased joint ROM joint ankylosis with HO after TKA might develop quad muscle snapping or patella
instability neurovascular
peripheral neuropathy HO often impinges on adjacent NV structures
Imaging
bullRadiographs bull findings
bull ossification usually easy to visualize bull maturity of HO
bull the appearance of a bony cortex suggests mature HObull sharp demarcation from surrounding tissue bull trabecular pattern
bull sensitivity and specificity bull not useful for early diagnosisbull only useful at 1 week after onset of symptoms
bull calcium is deposited 7-10 days later than symptom onsetbullUltrasound
bull indications bull for early diagnosis of hip HO
bull findings bull echogenic surfaces with posterior acoustic shadowing
bullCT bull indications
bull useful for preoperative planning bullTriphasic bone scan
bull indications bull best for early diagnosis bull most commonly used diagnostic study
Radiographs are extremely useful in the staging of heterotopic ossification and will show the development of sharp cortical margins once the lesion has reached maturity
Heterotopic bone is a condition in which lamellar bone forms in non-ossified soft tissues In the early stages studies such as MRI and bone scan are more sensitive for diagnosis as radiographs may appear normal for the first three weeks After the appropriate diagnosis is made sequential radiographs are useful for monitoring the progression of the ossification Once it has reached the mature stage sharp cortical margins will appear and surgical resection may be considered
lab
Labs elevated serum alkaline phosphatase (gt250IUL)
ALP removes inhibitors of mineralization nonspecific may be elevated with skeletal trauma cannot determine maturity of HO elevated 12wks after surgery is predictor
elevated CRP correlates with inflammatory activity of HO better than ESR normalization of CRP may correlate with maturity of HO
elevated ESR (gt35mmh) 12wks after THA is predictor
elevated CK correlates with involvement of muscle extent of muscle
involvement Histology
mature fatty bone marrow mature trabecular bone
Heterotopic ossification (HO) most commonly occurs at the amputation site if the amputation was performed thru the zone of injury especially if the injury was a blast mechanism
Symptomatic heterotopic ossification of the quadriceps may occur following placement of a large-diameter Steinmann pin for the purpose of temporary skeletal traction
TreatmentThe prevention of heterotopic ossification is focused on three basic principles disrupting the inductive signalling pathways altering the osteoprogenitor cells or modifying the environment
bullphysiotherapy should involve an assisted range of movement exercises with gentle stretch and terminal resistance trainingbullProphylaxis
bull bisphosphonates amp NSAIDS bull indications
bull although no literature supports are commonly usedbull technique
bull indomethacin is most commonly used bull dose is 75mgday for 10days to 6 weeks
bull perioperative radiation bull indications
bull although no literature supports commonly usedbull is thought to be effective by blocking osteoblast differentiation
bull technique bull a single perioperative dose of 700cGy can be given either 4
hours preop or within 72 hours postoperatively bull lt550cGy not effective
Nonsteroidal anti-inflammatory drugs (NSAIDs) These drugs have demonstrated good results in
preventing heterotopic ossification after total hip arthroplasty
A direct effect of NSAIDs on the formation of heterotopic ossification has been described due to the inhibition of the differentiation of mesenchymal cells into oestrogenic cells There is also an indirect effect which refers to the inhibition of bone remodelling by suppression of the prostagland unmediated inflammatory response (specifically PGE-2)
Indomethacin has been considered a useful medication for heterotopic ossification prophylaxis following total hip replacement
prescribed for three to six weeks in a dose of 75mgday within two months of the injury may reduce the incidence of heterotopic ossification by two to three times
Biphosphonates inhibits precipitation of calcium phosphate and blocks the aggregation and mineralisation of hydroxyapatite crystals In primary prevention Banovac et al [56] have suggested that the treatment should begin as soon as elevated alkaline phosphatase is diagnosed or positive findings in ultrasonography or bone scans are shown In addition disphosphonates could have long-term effects on prevention when the treatment is finished
Posttraumatic wide exposure and surgical resection
indications severe loss of motion and decreased function
technique wide exposure required to identify all neurovascular
structures that may be involved timing of resection (controversial)
marked decrease in bone scan activity AND normalization of ALP
6 months following general trauma 1 year following SCI 15 years following TBI
some data suggests equivalent results when comparing early versus late resection
postop follow with 5 day course of indomethacin early gentle joint mobilization
The surgery is necessary in patients with symptomatic HO and unsuccessful medical treatment such as
Loss of range of motion and ankylosis with associated functional disability such as sitting difficulties
Complications of immobility such as pressure ulcers
Facilitate rehabilitation and recovery of muscular atrophy secondary to prolonged immobilisation
Difficulties of appropriate hygiene because access to the perineum or bladder care is needed
Severe pain refractory to analgesia Vascular andor nerve compression
Advantages to early excision of heterotopic ossification (vs waiting for maturation) include decreased soft tissue contracture better definition between heterotopic and native bone and decreased waiting time for the patient When the soft tissue envelope is benign one may proceed with operative release While waiting for normalization of alkaline phosphatase levels inactivity on bone scan or radiographic maturity may decrease risk of recurrent heterotopic ossification delaying operative release for these reasons has not been shown to improve results of final elbow range of motion after contracture release
Gartland recommended surgery after six months following traumatic heterotopic ossification one year following spinal cord injury and 18 months after head injury
In the past waiting until maturity in order to minimize the rate of recurrence after the surgical treatment was recommended Nevertheless recent studies do not confirm a higher rate of recurrence when the HO is excised in an earlier phase In addition a long delay before surgery leads to ankylosis a high degree of osteoporosis and more extensive intra-articular injuries These findings are associated with bad functional results and potential complications
Should you wait till lesion maturation
Prevention byHandle tissue carefully Avoid excess bleeding Achieve good hemostasis Beware of lesions that span internervous tissue planes
but if it happens resection of a large enough amount of bone to allow improvement of the range of motion and trying to preserve the joint
Our aim must be
A reactive process that is characterized by a well-circumscribed proliferation of fibroblasts cartilage and bone within muscle
A form of heterotopic ossification that is the result direct trauma intramuscular hematoma
most common location is the diaphysis of long bones Must differentiate from tumors Fibrodysplasia ossificans progressiva (FOP) is a rare subtype of heterotopic ossification
involves mutation of the ACVR1 gene (activin A type I receptor gene a BMP type-1 receptor)
Epidemiology demographics
most common in young active males (15 to 35 years old) body locations
quadriceps brachialis and gluteal muscles Genetics
almost always a posttraumatic condition Prognosis
usually self limiting mass usually begins to decrease in size after 1 yea
Myositis ossificans
PresentationbullSymptoms
bull pain tenderness swelling and decreased range of motion that usually presents within days of the injury
bull pain and size of the mass decrease with timebull mass increases in size over several months(usually 3 to 6 cm)
bull after the mass stops growing it becomes firmbullPhysical exam
bull palpable soft tissue massbull restricted range of motion
ImagingbullRadiographs
bull peripheral bone formation with central lucent areabull may appear as dotted veil pattern
bullMRI with gadolinium bull rim enhancement is seen within the first 3 weeks
bullCT scan bull lesion has an eggshell appearance
bullCharacteristic histology shows zonal pattern bull periphery of lesion
bull mature trabeculae of lamellar and woven bonebull calcification seen on xray
bull center of the lesion bull irregular mass of immature fibroblastsbull cartilage component may be presentbull (no calcification seen on xray) bull no cellular atypia seen
Treatment
bullNonoperative bull rest range of motion exercises and activity modification
bull passive stretching is contraindicated (makes it worse)bull physical therapy
bull utilized to maintain range of motionbull radiographic monitoring
bull obtained to confirm maturation of the lesionbullOperative
bull surgical excision bull indicated only if it remains a problem after it maturesbull do not operate in acute phase wait at least six months
bull excision of the lesion within 6 to 12 months predisposes to local recurrence
A 26-year-old man presents with generalized back and joint stiffness and difficulty opening his mouth His elder sister has similar complaints Since childhood he has had 3 surgeries for excision of recurrent bony prominences around his knees He walks with a stooped over posture seen in Figure A Radiographs of his feet knee hip and spine are seen in Figures B-E respectively
fibrodysplasia ossificans progressiva
Stone Man Disease) which involves a mutation of the ACVR1
There are 2 hallmark characteristics progressive heterotopic ossification (muscles fascia tendons ligaments and joint capsules) and congenital malformation of the great toe (hallux valgus malformed first metatarsal and monophalangism) BMP4 which contributes to the formation of the skeleton in the normal embryo is implicated in this disease
Complications
bullHematoma and intraoperative bleedingbullInfection
bull higher rate of infection following joint arthroplasty if HO is present
bullFractures of osteoporotic bone bull osteopenic from disusebull during surgery or physiotherapy
bullRecurrence bull recurrence rate correlates with neurological injury
bull greater recurrence if severe neurological compromisebullAVN
bull if extensive dissection or stripping is required
HTO AND ISS
When ISS is below 25 the mortality risk is minimal and above 25 it is an almost linear increase
When ISS is 50 the mortality is 50 When above 70 it is close to 100 If an injury is assigned an AIS of 6 (unsurvivable injury) the ISS score is
automatically assigned to 75 Highest ISS score obtainable is 75 For trauma patients of vehicular accidents the scoring system is important
for assessing the effectiveness of medical care in reducing morbidity and mortality
Advantages virtually the only anatomical scoring system in use correlates linearly with
mortality morbidity hospital stay other measures of severity
Weaknesses Any error in AIS scoring increases the ISS error Many different injury patterns can yield the same ISS score Injuries to different body regions are not weighted Not a useful triage tool as a full description of patient injuries is not known
prior to full investigation amp operation
risk factors periosteal stripping off anterior femur male gender obesity post traumatic deformity Anterior and anterolateral approach Cementless
Neurogenic HO around the hip due to SCI occurs more often in the medial region than in the lateral region with ossified tissues extending from the pubic symphysis to the anteromedial femoral shaft posterior to the femoral neurovascular structures Ossification is also seen anteriorly involving the iliopsoas and femoral neurovascular structures laterally within gluteus minimus and posteriorly extending from the ilium to the posterior femur encasing the sciatic nerve
HTO AROUND hip and knee
The Brooker Classification of Heterotopic Ossification around the hip joint Class I has islands of bone within the soft tissues Class II has bone spurs from the pelvis or proximal end of the femur leaving at least 1 cm between opposing surfaces Class III has bone spurs from the pelvis andor proximal end of the femur reducing the space between opposing bone surfaces to less than 1 cm Class IV shows apparent bone ankylosis of the hip
Region I - Heterotopic ossifications are strictly below the tip of the greater trochanter
Region II - Heterotopic ossifications are below and above the tip of the greater trochanter
Region III - Heterotopic ossifications are strictly above the tip of the greater trochanter
Grade A - Single or multiple heterotopic ossifications are less than 10 mm in maximal extent without contact with the pelvis or the femur
Grade B - Heterotopic ossifications are greater than 10 mm without contact with the pelvis but with possible contact with the femur there is no bridging from the femur to the proximal part of the greater trochanter and no evidence of ankylosis
Grade C - Ankylosis by means of firm bridging from the femur to the pelvis is present
Shmidt classification
excision may be performed The results of this procedure are varied Patients may find that their range of movement improves but pain relief is likely to be limited
A patient with heterotopic ossification following total hip arthroplasty is thought to have a 90-100 chance of developing it on the contralateral hip if this hip also undergoes total arthroplasty
it would be prudent to minimize the risk of heterotopic ossification developing after arthroplasty by performing surgery whereby the following are ensured
Exposure is meticulous Retraction is performed carefully and soft tissue
is handled carefully Irrigation is adequate Devitalized tissue is excised Hemostasis is adequate Postoperative drains (when used) are not
retained for longer than necessary Perioperative antibiotic prophylaxis is used Postoperative anticoagulation (when used for
deep vein thrombosis prophylaxis) is carefully controlled
sources of knee stiffness 1-extrinsic severe osteoarthritis of the ipsilateral hip neurologic injury leading to muscle rigidity tight quadriceps or hamstring muscles secondary to muscle injury heterotopic ossification or long-standing juvenile inflammatory conditions limiting knee
range of motion prior to the completion of skeletal growth When extrinsic sources are identified revision total knee arthroplasty is unlikely to be associated with a favorable outcome without correction of the extrinsic problem
2-intrinsic (1) overstuffing of the patellofemoral articulation (2) an
excessively tight flexion andor extension gap (3) a tight posterior cruciate ligament (4) femoral andor tibial malrotation (5) arthrofibrosis and (6) limited bearing excursion in association with a highly conforming mobile-bearing prosthetic design
HTO after TKA
Heterotopic Ossification (HO) following primary Total Knee Replacement (TKR)
Occurs in 3-90 of TKRs 3-grade classification system No correlation between HO and component
alignment or component position
Clinical findings similar to early infection Continuing low-grade fever Warm swollen and erythematous knee Normal blood tests Possibly an association with HLA-A2 and B18 HO patients have worse KSS and function
scores
Patients at HIGH risk for developing HO after TKR (Knee Arthroplasty) (5)
Those with limited postoperative knee flexion
Increased lumbar bone mineral density (BMD) on multivariate analysis (3)
Hypertrophic arthrosis Excessive periosteal trauma Notching of the anterior femur Those who require forced manipulation
after TKA 47 in revision TKR surgery (6) Higher rates in revision TKR cases with
infection (up to 76
DaughertyBell classification of HO of the knee 0 No evidence of HO 1 Bone islands in periarticular soft tissue (no
involvement of femur patella or tibia) or HO within quadriceps expansion measuring lt1 cm
2 Spur formation measuring lt5 cm that involves the femur patella or tibia if more than one bone demonstrates HO separation of HO spurs
measure gt1 cm or HO within quadriceps expansion measuring ge1 cm but lt3 cm
3 Spur formation gt5 cm involving femur patella or tibia if more than one bone demonstrates HO separation of HO spurs measure lt1 cm or HO
within quadriceps expansion measuring ge3 cm 4 Extensive HO of the knee causing ankylosis
class 2 HO begins to involve the major bones of the knee joint with spur formation limited to a size of 5 cm
HO class 2 may be observed in select patients with complete ROM and no reported pain Patients with class 3 HO would likely always benefit from surgical excision
followed by RT prophylaxis Certainly patients in either cohort with a subclass ldquoBrdquo assignment (symptomatic) would
benefit from treatment All patients with class 4 HO require
treatment to alleviate ankylosis
treatment
References Whyte ldquoPagetrsquos Disease of Bonerdquo NEMJ vol 355
2006 Klein and Parvizi ldquoSurgical Manifestations of Pagetrsquos
Diseaserdquo JAAOS vol 14 2006 Orthobullets Campbell Apley Emedicinecom
-Chapter 15 Heterotopic Ossification after Traumatic Brain InjuryBy Jesuacutes Moreta and Joseacute Luis Martiacutenez-de los Mozos DOI 10577257343
Questions
Thank You
PostoperativeConsiderations Monitoring for cardiac complications Continued medical tx of active disease
uarrHeterotopic ossification Prophylaxis against HO
Possible future excision of HO for painROM
1-Tieg provides a review of Pagets disease of bone and treatment indications In his review he discusses that most patients with Pagets disease are asymptomatic but in those that do present pain is the most common presenting symptom He recommends medical and surgical treatment of asymptomatic patients who have active disease at sites where complications are likely to develop
Altman did a review of 290 patients with Pagets disease of bone His findings showed 83 had one or more rheumatic syndromes He found the rate of osteoarthritis related to Pagets disease was elevated in the hip and knee Rheumatoid arthritis hyperuricemia and gout did not appear increased in this group
Mangham et al looked the rate of secondary sarcomas as a result of Pagets disease of bone They found the rate to be around 03 with male predominance They also found that widespread skeletal involvement by Pagets disease was not a significant risk factor for malignant transformation
Interesting views about pagets
Smith et al reviewed the pathologic complications of Pagets bone disease Pagets bone disease commonly causes osseous weakening (deformity and fracture) and arthritis in the hip joint Management of end stage disease is successful with cemented and cementless total hip arthroplasty Bleeding is the most common intra- and post-operative complication of surgery
Gabel et al retrospectively reviewed thirteen patients who had had sixteen total knee arthroplasties for Pagetic gonarthrosis Unlike total hip arthroplasty surgery Paget disease did not increase the amount of blood lost during the operation or in the postoperative period The most common complication associated with total knee arthroplasty was malalignment
Hansen et al reviewed the incidence of osteosarcomas complicating Pagets Disease Of the typical sites that are usually involved in Pagets disease (eg spine pelvis femur tibia and humerus) secondary osteosarcoma tends to spare the spine
Shaylor et al reported the mortality rates in 26 patient with osteosarcoma secondary to Paget s disease There was a 47 mortality at 1 year and 75 at 2 years from diagnosis In their series no patient survived for 5 years All patients died of metastatic disease
Langston et al conducted a randomized trial that compared the results of symptomatic treatment versus intensive bisphosphonate therapy in patients with Pagets disease Clinical fractures occurred in 46 of 661 patients (70) in the treatment group compared with 49 of 663 patients (74) in the symptomatic treatment group They concluded that bisphosphonates did not show a significant beneficial impact on pain quality of life or fracture incidence
Hadjipavlou et al reviewed Pagets disease of the bone and its management Farmers have been shown to have an increased incidence of Pagets disease Average age at presentation is in the 5th and 6th decade Symptomatic individuals are recommended to be treated initially with medical management They suggest that bisphosphonates are more effective than calcitonin at suppressing the histological and biochemical activity in Pagetrsquos disease
Summary Epid Very common in elderly Path Abnormal osteoclastshellipuarrbone
turnoverhellipdeposition of abnormal bone SampS Pain deformity fracture arthropathy Labs uarrAlkPhos X-ray Characteristic coarse thickened
trabeculae Bone scan Very hot Rx Bisphosphonates Surgery for arthropathy fracture painful
deformity
A 65-year-old male presents with increasing shoulder pain over the past 9 months He is otherwise healthy and has no other complaints Radiograph of his shoulder is shown in Figure A Whole body bone scan and biopsy photograph are shown in Figures B and C What is the most appropriate treatment for this patient
1 Referral to endocrinology 2 Radiation therapy and chemotherapy 3 Wide resection and reconstruction 4 Radiation therapy wide resection and reconstruction 5 Chemotherapy wide resection and reconstruction
Histiocytosis X or Langerhans cell histiocytosis is a spectrum of diseases of the reticuloendothelial system with one of three general presentations Eosinophilic granuloma (EG)
usually a single self-limited lesion found in younger patients
Hand-Schuller-Christian disease (HSC) chronic disseminated form with bone and visceral lesions also known as Langerhans cell histiocytosis with visceral
involvement Letterer-Siwe disease (LSD)
fatal form that occurs in young children
Eosinophilic granuloma
Epidemiology demographics
most commonly occurs in children (80 of afflicted lt 20 years of age)
HSC disease presents in children gt 3 years of age LSD occurs in children lt 3 years of age Male to female ratio of 21
location eosinophilic granuloma
commonly presents in the skull ribs clavicle scapula mandible
isolated lesions of the spine (thoracic most common) can also occur in diaphyseal regions of long bones and the
pelvis HSC
multiple bony sites multiple lytic skull lesions visceral involvement of the lungs spleen liver skin lymph
nodes
Genetics no clear genetic pattern of inheritance or locus has
been determined Prognosis
EG isolated involvement generally treatable with local
management spine lesions can spontaneously resolve
HSC prognosis depends on response to chemotherapy worsening prognosis with increasing extraskeletal
involvement LSD
generally fatal in children lt 3 years of age
Symptoms skeletal involvement
pain and swelling at the region of involvement limping can be seen with pelvic or lower extremity
involvement vertebral involvement
localized or diffuse back pain increasingly kyphotic posture radiculopathy can occur with more aggressive lesions
HSC classic triad of
multiple lytic skull lesions diabetes insipidus
increased thirst and water intake exopthalmos
visceral involvement diffuse or nonspecific abdominal or chest pain
Radiographs general
known as the great mimicker as it appears similar to many lesions radiographic differential includes osteomyelitis leukemia lymphoma
fibrous dysplasia or Ewings sarcoma diaphyseal lesions
well defined intramedullary lytic or punched-out lesion cortex may be thinned expanded or destroyed may have periosteal reaction
metaphyseal lesions extend up to but not through the physis less central location than diaphyseal lesions
spinal lesions vertebra plana (flattened vertebrae) in spine increased kyphosis
cranial involvement multiple punched-out lytic lesions
MRI may show a soft tissue mass adjacent to boney lesions
Bone scan generally shows increased uptake in the region of boney lesion
Histology Langerhans cells
mononuclear histiocyte-like cells with oval nuclei with well-defined round or oval cytoplasm
a prominent nuclear groove (coffee bean nuclei) can be seen in most of the nuclei
eosinophilic cytoplasm (pink generally) stain with CD1A electronmicroscopy
birbeck granules seen inside Langerhans cells mixture of inflammatory cells also present giant cells are present lack of nuclear atypia and atypical mitoses
differentiates this condition from malignant conditions such as Ewings sarcoma lymphoma of bone and metastatic neuroblastoma which may look similar based on the round cells alone
eosinophilic cytoplasm (pink generally)
Treatment
bullNonoperative bull observation alone
bull indications bull a self-limited process and it is reasonable to treat with observation alone
bull bracing bull indications
bull to prevent progressive kyphosis of the spinebull outcomes
bull will correct deformity in 90 of patientsbull vertebral lesions generally regain 50 of their height
bull low dose irradiation (600-800 cGy) bull indications
bull indicated for lesions in the spine that compromise stability neurologic statusbull lesions not amenable to injection or open treatment
bull outcomes bull effective for most lesions
bull chemotherapy bull indications
bull diffuse HSCbull outcomes
bull prognosis is improved with less severe extraskeletal involvementbull corticosteroid injection
bull indications bull isolated lesions bull can be performed after curettage as well
Operative curettage and bone grafting
indications for lesions that endanger the articular surface or are a risk for
impending fractures spinal deformity correction
indications progressive spine deformity refractory to bracing
approximately 10 of patients with spine lesion will need operative intervention for deformity correction
Destructive multiple lesion in young patientsAre eosinophilic granuloma lymphoma and leukemiaLymphoma is unlikely to present with exopthalmos diabetes insipidus or vertebra plana Lymphoma bone lesions are lytic and appear moth eatenpermeative on radiographs
Figure A shows a skin lesion typical of eosinophillic granuloma Figure B shows a lytic lesions without significant surrounding sclerosis as is characteristic of eosinophilic granuloma Figure C shows the characteristic histology of multiple eosinophils with their characteristic oval coffee bean nuclei and staining pattern of purpleredpink cytoplasm (depending on the stain) Importantly the histology slide lacks a malignant appearance (no cellular atypia or mytotic complexes and low nuclearcytoplasmic ratio)
Formation of bone in atypical extraskeletal tissues usually occurs
spontaneously or following trauma within 2 months of neurologic injury (brain or spinal cord)
most common location is between muscle and joint capsule Epidemiology
incidence (see table below)
demographics malefemale = 21 especially men with hypertrophic osteoarthritis and women gt65y
location traumatic brain injury or stroke
hip gt elbow gt shoulder gt knee elbow HO more common following brain trauma
occurs on affected (spastic) side rarely in the knee (TBI)
spinal cord injury hip gt knee gt elbow gt shoulder hip flexors and abductors gt extensors or adductors medial aspect of the knee
Heterotopic Ossification
Risk factors
Pathophysiology exact cause of HO is not known but there appears to be a
genetic pre disposition experimental HO associated with
tissue expression of BMP IT IS SAID TO BE CAUSED BY activation and proliferation of
mesenchymal stem cells Associated conditions
orthopaedic manifestations pathologic fractures
from decreased joint ROM and osteoporotic bone nerve impingement soft tissue contractures contributing to the formation of
decubitus ulcers joint ankylosis HO after THA adversely affects outcome of THA
nonorthopaedic conditions skin maceration and hygiene problems
Pathophysiology Early in the formation of HO oedema with exudative
infiltrate is present followed by fibroblastic proliferation and immature connective tissue formation Posteriorly osteoid formation is seen with the subsequent deposition of bone matrix Primitive osteoid is deposited as small masses in the periphery early (within the first two weeks) and osteoblasts are noted located irregularly Osteoblasts produce tropocollagen which polymerizes to form collagen and secrete alkaline phosphatase which allows calcium to precipitate and the mineralization of bone matrix As mineralization progresses amorphous calcium phosphate is progressively replaced by hydroxyapatite crystals During the following weeks the lesion matures with a centripetal pattern and after 6-12 months an appearance of true bone is noted The new bone is always extra-articular and can be contiguous with the skeleton but generally does not involve the periosteum
IN SUMMARY It has been postulated that three conditions
must be met to achieve heterotopic bone formation ---a stimulating event oestrogenic precursor cells and a proper environment LIKE hypercalcaemia tissue hypoxia pH changes (alkalosis) or prolonged immobilization
ClassificationbullSubtypes
bull neurogenic HO bull Four clinical stages of HO in people with spinal cord injury were
described by Nicholas in 1973
bull traumatic myositis ossificans bull fibrodysplasia ossificans progressiva (Munchmeyers Disease)
Neurogenic HO Symptoms
painless loss of ROM interferes with ADL CRPS symptoms fever
Physical exam inspection
warm painful swollen joint may have effusion skin problems
decubitus ulcers from contractures around skin muscles ligaments
skin maceration and hygiene problems motion
decreased joint ROM joint ankylosis with HO after TKA might develop quad muscle snapping or patella
instability neurovascular
peripheral neuropathy HO often impinges on adjacent NV structures
Imaging
bullRadiographs bull findings
bull ossification usually easy to visualize bull maturity of HO
bull the appearance of a bony cortex suggests mature HObull sharp demarcation from surrounding tissue bull trabecular pattern
bull sensitivity and specificity bull not useful for early diagnosisbull only useful at 1 week after onset of symptoms
bull calcium is deposited 7-10 days later than symptom onsetbullUltrasound
bull indications bull for early diagnosis of hip HO
bull findings bull echogenic surfaces with posterior acoustic shadowing
bullCT bull indications
bull useful for preoperative planning bullTriphasic bone scan
bull indications bull best for early diagnosis bull most commonly used diagnostic study
Radiographs are extremely useful in the staging of heterotopic ossification and will show the development of sharp cortical margins once the lesion has reached maturity
Heterotopic bone is a condition in which lamellar bone forms in non-ossified soft tissues In the early stages studies such as MRI and bone scan are more sensitive for diagnosis as radiographs may appear normal for the first three weeks After the appropriate diagnosis is made sequential radiographs are useful for monitoring the progression of the ossification Once it has reached the mature stage sharp cortical margins will appear and surgical resection may be considered
lab
Labs elevated serum alkaline phosphatase (gt250IUL)
ALP removes inhibitors of mineralization nonspecific may be elevated with skeletal trauma cannot determine maturity of HO elevated 12wks after surgery is predictor
elevated CRP correlates with inflammatory activity of HO better than ESR normalization of CRP may correlate with maturity of HO
elevated ESR (gt35mmh) 12wks after THA is predictor
elevated CK correlates with involvement of muscle extent of muscle
involvement Histology
mature fatty bone marrow mature trabecular bone
Heterotopic ossification (HO) most commonly occurs at the amputation site if the amputation was performed thru the zone of injury especially if the injury was a blast mechanism
Symptomatic heterotopic ossification of the quadriceps may occur following placement of a large-diameter Steinmann pin for the purpose of temporary skeletal traction
TreatmentThe prevention of heterotopic ossification is focused on three basic principles disrupting the inductive signalling pathways altering the osteoprogenitor cells or modifying the environment
bullphysiotherapy should involve an assisted range of movement exercises with gentle stretch and terminal resistance trainingbullProphylaxis
bull bisphosphonates amp NSAIDS bull indications
bull although no literature supports are commonly usedbull technique
bull indomethacin is most commonly used bull dose is 75mgday for 10days to 6 weeks
bull perioperative radiation bull indications
bull although no literature supports commonly usedbull is thought to be effective by blocking osteoblast differentiation
bull technique bull a single perioperative dose of 700cGy can be given either 4
hours preop or within 72 hours postoperatively bull lt550cGy not effective
Nonsteroidal anti-inflammatory drugs (NSAIDs) These drugs have demonstrated good results in
preventing heterotopic ossification after total hip arthroplasty
A direct effect of NSAIDs on the formation of heterotopic ossification has been described due to the inhibition of the differentiation of mesenchymal cells into oestrogenic cells There is also an indirect effect which refers to the inhibition of bone remodelling by suppression of the prostagland unmediated inflammatory response (specifically PGE-2)
Indomethacin has been considered a useful medication for heterotopic ossification prophylaxis following total hip replacement
prescribed for three to six weeks in a dose of 75mgday within two months of the injury may reduce the incidence of heterotopic ossification by two to three times
Biphosphonates inhibits precipitation of calcium phosphate and blocks the aggregation and mineralisation of hydroxyapatite crystals In primary prevention Banovac et al [56] have suggested that the treatment should begin as soon as elevated alkaline phosphatase is diagnosed or positive findings in ultrasonography or bone scans are shown In addition disphosphonates could have long-term effects on prevention when the treatment is finished
Posttraumatic wide exposure and surgical resection
indications severe loss of motion and decreased function
technique wide exposure required to identify all neurovascular
structures that may be involved timing of resection (controversial)
marked decrease in bone scan activity AND normalization of ALP
6 months following general trauma 1 year following SCI 15 years following TBI
some data suggests equivalent results when comparing early versus late resection
postop follow with 5 day course of indomethacin early gentle joint mobilization
The surgery is necessary in patients with symptomatic HO and unsuccessful medical treatment such as
Loss of range of motion and ankylosis with associated functional disability such as sitting difficulties
Complications of immobility such as pressure ulcers
Facilitate rehabilitation and recovery of muscular atrophy secondary to prolonged immobilisation
Difficulties of appropriate hygiene because access to the perineum or bladder care is needed
Severe pain refractory to analgesia Vascular andor nerve compression
Advantages to early excision of heterotopic ossification (vs waiting for maturation) include decreased soft tissue contracture better definition between heterotopic and native bone and decreased waiting time for the patient When the soft tissue envelope is benign one may proceed with operative release While waiting for normalization of alkaline phosphatase levels inactivity on bone scan or radiographic maturity may decrease risk of recurrent heterotopic ossification delaying operative release for these reasons has not been shown to improve results of final elbow range of motion after contracture release
Gartland recommended surgery after six months following traumatic heterotopic ossification one year following spinal cord injury and 18 months after head injury
In the past waiting until maturity in order to minimize the rate of recurrence after the surgical treatment was recommended Nevertheless recent studies do not confirm a higher rate of recurrence when the HO is excised in an earlier phase In addition a long delay before surgery leads to ankylosis a high degree of osteoporosis and more extensive intra-articular injuries These findings are associated with bad functional results and potential complications
Should you wait till lesion maturation
Prevention byHandle tissue carefully Avoid excess bleeding Achieve good hemostasis Beware of lesions that span internervous tissue planes
but if it happens resection of a large enough amount of bone to allow improvement of the range of motion and trying to preserve the joint
Our aim must be
A reactive process that is characterized by a well-circumscribed proliferation of fibroblasts cartilage and bone within muscle
A form of heterotopic ossification that is the result direct trauma intramuscular hematoma
most common location is the diaphysis of long bones Must differentiate from tumors Fibrodysplasia ossificans progressiva (FOP) is a rare subtype of heterotopic ossification
involves mutation of the ACVR1 gene (activin A type I receptor gene a BMP type-1 receptor)
Epidemiology demographics
most common in young active males (15 to 35 years old) body locations
quadriceps brachialis and gluteal muscles Genetics
almost always a posttraumatic condition Prognosis
usually self limiting mass usually begins to decrease in size after 1 yea
Myositis ossificans
PresentationbullSymptoms
bull pain tenderness swelling and decreased range of motion that usually presents within days of the injury
bull pain and size of the mass decrease with timebull mass increases in size over several months(usually 3 to 6 cm)
bull after the mass stops growing it becomes firmbullPhysical exam
bull palpable soft tissue massbull restricted range of motion
ImagingbullRadiographs
bull peripheral bone formation with central lucent areabull may appear as dotted veil pattern
bullMRI with gadolinium bull rim enhancement is seen within the first 3 weeks
bullCT scan bull lesion has an eggshell appearance
bullCharacteristic histology shows zonal pattern bull periphery of lesion
bull mature trabeculae of lamellar and woven bonebull calcification seen on xray
bull center of the lesion bull irregular mass of immature fibroblastsbull cartilage component may be presentbull (no calcification seen on xray) bull no cellular atypia seen
Treatment
bullNonoperative bull rest range of motion exercises and activity modification
bull passive stretching is contraindicated (makes it worse)bull physical therapy
bull utilized to maintain range of motionbull radiographic monitoring
bull obtained to confirm maturation of the lesionbullOperative
bull surgical excision bull indicated only if it remains a problem after it maturesbull do not operate in acute phase wait at least six months
bull excision of the lesion within 6 to 12 months predisposes to local recurrence
A 26-year-old man presents with generalized back and joint stiffness and difficulty opening his mouth His elder sister has similar complaints Since childhood he has had 3 surgeries for excision of recurrent bony prominences around his knees He walks with a stooped over posture seen in Figure A Radiographs of his feet knee hip and spine are seen in Figures B-E respectively
fibrodysplasia ossificans progressiva
Stone Man Disease) which involves a mutation of the ACVR1
There are 2 hallmark characteristics progressive heterotopic ossification (muscles fascia tendons ligaments and joint capsules) and congenital malformation of the great toe (hallux valgus malformed first metatarsal and monophalangism) BMP4 which contributes to the formation of the skeleton in the normal embryo is implicated in this disease
Complications
bullHematoma and intraoperative bleedingbullInfection
bull higher rate of infection following joint arthroplasty if HO is present
bullFractures of osteoporotic bone bull osteopenic from disusebull during surgery or physiotherapy
bullRecurrence bull recurrence rate correlates with neurological injury
bull greater recurrence if severe neurological compromisebullAVN
bull if extensive dissection or stripping is required
HTO AND ISS
When ISS is below 25 the mortality risk is minimal and above 25 it is an almost linear increase
When ISS is 50 the mortality is 50 When above 70 it is close to 100 If an injury is assigned an AIS of 6 (unsurvivable injury) the ISS score is
automatically assigned to 75 Highest ISS score obtainable is 75 For trauma patients of vehicular accidents the scoring system is important
for assessing the effectiveness of medical care in reducing morbidity and mortality
Advantages virtually the only anatomical scoring system in use correlates linearly with
mortality morbidity hospital stay other measures of severity
Weaknesses Any error in AIS scoring increases the ISS error Many different injury patterns can yield the same ISS score Injuries to different body regions are not weighted Not a useful triage tool as a full description of patient injuries is not known
prior to full investigation amp operation
risk factors periosteal stripping off anterior femur male gender obesity post traumatic deformity Anterior and anterolateral approach Cementless
Neurogenic HO around the hip due to SCI occurs more often in the medial region than in the lateral region with ossified tissues extending from the pubic symphysis to the anteromedial femoral shaft posterior to the femoral neurovascular structures Ossification is also seen anteriorly involving the iliopsoas and femoral neurovascular structures laterally within gluteus minimus and posteriorly extending from the ilium to the posterior femur encasing the sciatic nerve
HTO AROUND hip and knee
The Brooker Classification of Heterotopic Ossification around the hip joint Class I has islands of bone within the soft tissues Class II has bone spurs from the pelvis or proximal end of the femur leaving at least 1 cm between opposing surfaces Class III has bone spurs from the pelvis andor proximal end of the femur reducing the space between opposing bone surfaces to less than 1 cm Class IV shows apparent bone ankylosis of the hip
Region I - Heterotopic ossifications are strictly below the tip of the greater trochanter
Region II - Heterotopic ossifications are below and above the tip of the greater trochanter
Region III - Heterotopic ossifications are strictly above the tip of the greater trochanter
Grade A - Single or multiple heterotopic ossifications are less than 10 mm in maximal extent without contact with the pelvis or the femur
Grade B - Heterotopic ossifications are greater than 10 mm without contact with the pelvis but with possible contact with the femur there is no bridging from the femur to the proximal part of the greater trochanter and no evidence of ankylosis
Grade C - Ankylosis by means of firm bridging from the femur to the pelvis is present
Shmidt classification
excision may be performed The results of this procedure are varied Patients may find that their range of movement improves but pain relief is likely to be limited
A patient with heterotopic ossification following total hip arthroplasty is thought to have a 90-100 chance of developing it on the contralateral hip if this hip also undergoes total arthroplasty
it would be prudent to minimize the risk of heterotopic ossification developing after arthroplasty by performing surgery whereby the following are ensured
Exposure is meticulous Retraction is performed carefully and soft tissue
is handled carefully Irrigation is adequate Devitalized tissue is excised Hemostasis is adequate Postoperative drains (when used) are not
retained for longer than necessary Perioperative antibiotic prophylaxis is used Postoperative anticoagulation (when used for
deep vein thrombosis prophylaxis) is carefully controlled
sources of knee stiffness 1-extrinsic severe osteoarthritis of the ipsilateral hip neurologic injury leading to muscle rigidity tight quadriceps or hamstring muscles secondary to muscle injury heterotopic ossification or long-standing juvenile inflammatory conditions limiting knee
range of motion prior to the completion of skeletal growth When extrinsic sources are identified revision total knee arthroplasty is unlikely to be associated with a favorable outcome without correction of the extrinsic problem
2-intrinsic (1) overstuffing of the patellofemoral articulation (2) an
excessively tight flexion andor extension gap (3) a tight posterior cruciate ligament (4) femoral andor tibial malrotation (5) arthrofibrosis and (6) limited bearing excursion in association with a highly conforming mobile-bearing prosthetic design
HTO after TKA
Heterotopic Ossification (HO) following primary Total Knee Replacement (TKR)
Occurs in 3-90 of TKRs 3-grade classification system No correlation between HO and component
alignment or component position
Clinical findings similar to early infection Continuing low-grade fever Warm swollen and erythematous knee Normal blood tests Possibly an association with HLA-A2 and B18 HO patients have worse KSS and function
scores
Patients at HIGH risk for developing HO after TKR (Knee Arthroplasty) (5)
Those with limited postoperative knee flexion
Increased lumbar bone mineral density (BMD) on multivariate analysis (3)
Hypertrophic arthrosis Excessive periosteal trauma Notching of the anterior femur Those who require forced manipulation
after TKA 47 in revision TKR surgery (6) Higher rates in revision TKR cases with
infection (up to 76
DaughertyBell classification of HO of the knee 0 No evidence of HO 1 Bone islands in periarticular soft tissue (no
involvement of femur patella or tibia) or HO within quadriceps expansion measuring lt1 cm
2 Spur formation measuring lt5 cm that involves the femur patella or tibia if more than one bone demonstrates HO separation of HO spurs
measure gt1 cm or HO within quadriceps expansion measuring ge1 cm but lt3 cm
3 Spur formation gt5 cm involving femur patella or tibia if more than one bone demonstrates HO separation of HO spurs measure lt1 cm or HO
within quadriceps expansion measuring ge3 cm 4 Extensive HO of the knee causing ankylosis
class 2 HO begins to involve the major bones of the knee joint with spur formation limited to a size of 5 cm
HO class 2 may be observed in select patients with complete ROM and no reported pain Patients with class 3 HO would likely always benefit from surgical excision
followed by RT prophylaxis Certainly patients in either cohort with a subclass ldquoBrdquo assignment (symptomatic) would
benefit from treatment All patients with class 4 HO require
treatment to alleviate ankylosis
treatment
References Whyte ldquoPagetrsquos Disease of Bonerdquo NEMJ vol 355
2006 Klein and Parvizi ldquoSurgical Manifestations of Pagetrsquos
Diseaserdquo JAAOS vol 14 2006 Orthobullets Campbell Apley Emedicinecom
-Chapter 15 Heterotopic Ossification after Traumatic Brain InjuryBy Jesuacutes Moreta and Joseacute Luis Martiacutenez-de los Mozos DOI 10577257343
Questions
Thank You
1-Tieg provides a review of Pagets disease of bone and treatment indications In his review he discusses that most patients with Pagets disease are asymptomatic but in those that do present pain is the most common presenting symptom He recommends medical and surgical treatment of asymptomatic patients who have active disease at sites where complications are likely to develop
Altman did a review of 290 patients with Pagets disease of bone His findings showed 83 had one or more rheumatic syndromes He found the rate of osteoarthritis related to Pagets disease was elevated in the hip and knee Rheumatoid arthritis hyperuricemia and gout did not appear increased in this group
Mangham et al looked the rate of secondary sarcomas as a result of Pagets disease of bone They found the rate to be around 03 with male predominance They also found that widespread skeletal involvement by Pagets disease was not a significant risk factor for malignant transformation
Interesting views about pagets
Smith et al reviewed the pathologic complications of Pagets bone disease Pagets bone disease commonly causes osseous weakening (deformity and fracture) and arthritis in the hip joint Management of end stage disease is successful with cemented and cementless total hip arthroplasty Bleeding is the most common intra- and post-operative complication of surgery
Gabel et al retrospectively reviewed thirteen patients who had had sixteen total knee arthroplasties for Pagetic gonarthrosis Unlike total hip arthroplasty surgery Paget disease did not increase the amount of blood lost during the operation or in the postoperative period The most common complication associated with total knee arthroplasty was malalignment
Hansen et al reviewed the incidence of osteosarcomas complicating Pagets Disease Of the typical sites that are usually involved in Pagets disease (eg spine pelvis femur tibia and humerus) secondary osteosarcoma tends to spare the spine
Shaylor et al reported the mortality rates in 26 patient with osteosarcoma secondary to Paget s disease There was a 47 mortality at 1 year and 75 at 2 years from diagnosis In their series no patient survived for 5 years All patients died of metastatic disease
Langston et al conducted a randomized trial that compared the results of symptomatic treatment versus intensive bisphosphonate therapy in patients with Pagets disease Clinical fractures occurred in 46 of 661 patients (70) in the treatment group compared with 49 of 663 patients (74) in the symptomatic treatment group They concluded that bisphosphonates did not show a significant beneficial impact on pain quality of life or fracture incidence
Hadjipavlou et al reviewed Pagets disease of the bone and its management Farmers have been shown to have an increased incidence of Pagets disease Average age at presentation is in the 5th and 6th decade Symptomatic individuals are recommended to be treated initially with medical management They suggest that bisphosphonates are more effective than calcitonin at suppressing the histological and biochemical activity in Pagetrsquos disease
Summary Epid Very common in elderly Path Abnormal osteoclastshellipuarrbone
turnoverhellipdeposition of abnormal bone SampS Pain deformity fracture arthropathy Labs uarrAlkPhos X-ray Characteristic coarse thickened
trabeculae Bone scan Very hot Rx Bisphosphonates Surgery for arthropathy fracture painful
deformity
A 65-year-old male presents with increasing shoulder pain over the past 9 months He is otherwise healthy and has no other complaints Radiograph of his shoulder is shown in Figure A Whole body bone scan and biopsy photograph are shown in Figures B and C What is the most appropriate treatment for this patient
1 Referral to endocrinology 2 Radiation therapy and chemotherapy 3 Wide resection and reconstruction 4 Radiation therapy wide resection and reconstruction 5 Chemotherapy wide resection and reconstruction
Histiocytosis X or Langerhans cell histiocytosis is a spectrum of diseases of the reticuloendothelial system with one of three general presentations Eosinophilic granuloma (EG)
usually a single self-limited lesion found in younger patients
Hand-Schuller-Christian disease (HSC) chronic disseminated form with bone and visceral lesions also known as Langerhans cell histiocytosis with visceral
involvement Letterer-Siwe disease (LSD)
fatal form that occurs in young children
Eosinophilic granuloma
Epidemiology demographics
most commonly occurs in children (80 of afflicted lt 20 years of age)
HSC disease presents in children gt 3 years of age LSD occurs in children lt 3 years of age Male to female ratio of 21
location eosinophilic granuloma
commonly presents in the skull ribs clavicle scapula mandible
isolated lesions of the spine (thoracic most common) can also occur in diaphyseal regions of long bones and the
pelvis HSC
multiple bony sites multiple lytic skull lesions visceral involvement of the lungs spleen liver skin lymph
nodes
Genetics no clear genetic pattern of inheritance or locus has
been determined Prognosis
EG isolated involvement generally treatable with local
management spine lesions can spontaneously resolve
HSC prognosis depends on response to chemotherapy worsening prognosis with increasing extraskeletal
involvement LSD
generally fatal in children lt 3 years of age
Symptoms skeletal involvement
pain and swelling at the region of involvement limping can be seen with pelvic or lower extremity
involvement vertebral involvement
localized or diffuse back pain increasingly kyphotic posture radiculopathy can occur with more aggressive lesions
HSC classic triad of
multiple lytic skull lesions diabetes insipidus
increased thirst and water intake exopthalmos
visceral involvement diffuse or nonspecific abdominal or chest pain
Radiographs general
known as the great mimicker as it appears similar to many lesions radiographic differential includes osteomyelitis leukemia lymphoma
fibrous dysplasia or Ewings sarcoma diaphyseal lesions
well defined intramedullary lytic or punched-out lesion cortex may be thinned expanded or destroyed may have periosteal reaction
metaphyseal lesions extend up to but not through the physis less central location than diaphyseal lesions
spinal lesions vertebra plana (flattened vertebrae) in spine increased kyphosis
cranial involvement multiple punched-out lytic lesions
MRI may show a soft tissue mass adjacent to boney lesions
Bone scan generally shows increased uptake in the region of boney lesion
Histology Langerhans cells
mononuclear histiocyte-like cells with oval nuclei with well-defined round or oval cytoplasm
a prominent nuclear groove (coffee bean nuclei) can be seen in most of the nuclei
eosinophilic cytoplasm (pink generally) stain with CD1A electronmicroscopy
birbeck granules seen inside Langerhans cells mixture of inflammatory cells also present giant cells are present lack of nuclear atypia and atypical mitoses
differentiates this condition from malignant conditions such as Ewings sarcoma lymphoma of bone and metastatic neuroblastoma which may look similar based on the round cells alone
eosinophilic cytoplasm (pink generally)
Treatment
bullNonoperative bull observation alone
bull indications bull a self-limited process and it is reasonable to treat with observation alone
bull bracing bull indications
bull to prevent progressive kyphosis of the spinebull outcomes
bull will correct deformity in 90 of patientsbull vertebral lesions generally regain 50 of their height
bull low dose irradiation (600-800 cGy) bull indications
bull indicated for lesions in the spine that compromise stability neurologic statusbull lesions not amenable to injection or open treatment
bull outcomes bull effective for most lesions
bull chemotherapy bull indications
bull diffuse HSCbull outcomes
bull prognosis is improved with less severe extraskeletal involvementbull corticosteroid injection
bull indications bull isolated lesions bull can be performed after curettage as well
Operative curettage and bone grafting
indications for lesions that endanger the articular surface or are a risk for
impending fractures spinal deformity correction
indications progressive spine deformity refractory to bracing
approximately 10 of patients with spine lesion will need operative intervention for deformity correction
Destructive multiple lesion in young patientsAre eosinophilic granuloma lymphoma and leukemiaLymphoma is unlikely to present with exopthalmos diabetes insipidus or vertebra plana Lymphoma bone lesions are lytic and appear moth eatenpermeative on radiographs
Figure A shows a skin lesion typical of eosinophillic granuloma Figure B shows a lytic lesions without significant surrounding sclerosis as is characteristic of eosinophilic granuloma Figure C shows the characteristic histology of multiple eosinophils with their characteristic oval coffee bean nuclei and staining pattern of purpleredpink cytoplasm (depending on the stain) Importantly the histology slide lacks a malignant appearance (no cellular atypia or mytotic complexes and low nuclearcytoplasmic ratio)
Formation of bone in atypical extraskeletal tissues usually occurs
spontaneously or following trauma within 2 months of neurologic injury (brain or spinal cord)
most common location is between muscle and joint capsule Epidemiology
incidence (see table below)
demographics malefemale = 21 especially men with hypertrophic osteoarthritis and women gt65y
location traumatic brain injury or stroke
hip gt elbow gt shoulder gt knee elbow HO more common following brain trauma
occurs on affected (spastic) side rarely in the knee (TBI)
spinal cord injury hip gt knee gt elbow gt shoulder hip flexors and abductors gt extensors or adductors medial aspect of the knee
Heterotopic Ossification
Risk factors
Pathophysiology exact cause of HO is not known but there appears to be a
genetic pre disposition experimental HO associated with
tissue expression of BMP IT IS SAID TO BE CAUSED BY activation and proliferation of
mesenchymal stem cells Associated conditions
orthopaedic manifestations pathologic fractures
from decreased joint ROM and osteoporotic bone nerve impingement soft tissue contractures contributing to the formation of
decubitus ulcers joint ankylosis HO after THA adversely affects outcome of THA
nonorthopaedic conditions skin maceration and hygiene problems
Pathophysiology Early in the formation of HO oedema with exudative
infiltrate is present followed by fibroblastic proliferation and immature connective tissue formation Posteriorly osteoid formation is seen with the subsequent deposition of bone matrix Primitive osteoid is deposited as small masses in the periphery early (within the first two weeks) and osteoblasts are noted located irregularly Osteoblasts produce tropocollagen which polymerizes to form collagen and secrete alkaline phosphatase which allows calcium to precipitate and the mineralization of bone matrix As mineralization progresses amorphous calcium phosphate is progressively replaced by hydroxyapatite crystals During the following weeks the lesion matures with a centripetal pattern and after 6-12 months an appearance of true bone is noted The new bone is always extra-articular and can be contiguous with the skeleton but generally does not involve the periosteum
IN SUMMARY It has been postulated that three conditions
must be met to achieve heterotopic bone formation ---a stimulating event oestrogenic precursor cells and a proper environment LIKE hypercalcaemia tissue hypoxia pH changes (alkalosis) or prolonged immobilization
ClassificationbullSubtypes
bull neurogenic HO bull Four clinical stages of HO in people with spinal cord injury were
described by Nicholas in 1973
bull traumatic myositis ossificans bull fibrodysplasia ossificans progressiva (Munchmeyers Disease)
Neurogenic HO Symptoms
painless loss of ROM interferes with ADL CRPS symptoms fever
Physical exam inspection
warm painful swollen joint may have effusion skin problems
decubitus ulcers from contractures around skin muscles ligaments
skin maceration and hygiene problems motion
decreased joint ROM joint ankylosis with HO after TKA might develop quad muscle snapping or patella
instability neurovascular
peripheral neuropathy HO often impinges on adjacent NV structures
Imaging
bullRadiographs bull findings
bull ossification usually easy to visualize bull maturity of HO
bull the appearance of a bony cortex suggests mature HObull sharp demarcation from surrounding tissue bull trabecular pattern
bull sensitivity and specificity bull not useful for early diagnosisbull only useful at 1 week after onset of symptoms
bull calcium is deposited 7-10 days later than symptom onsetbullUltrasound
bull indications bull for early diagnosis of hip HO
bull findings bull echogenic surfaces with posterior acoustic shadowing
bullCT bull indications
bull useful for preoperative planning bullTriphasic bone scan
bull indications bull best for early diagnosis bull most commonly used diagnostic study
Radiographs are extremely useful in the staging of heterotopic ossification and will show the development of sharp cortical margins once the lesion has reached maturity
Heterotopic bone is a condition in which lamellar bone forms in non-ossified soft tissues In the early stages studies such as MRI and bone scan are more sensitive for diagnosis as radiographs may appear normal for the first three weeks After the appropriate diagnosis is made sequential radiographs are useful for monitoring the progression of the ossification Once it has reached the mature stage sharp cortical margins will appear and surgical resection may be considered
lab
Labs elevated serum alkaline phosphatase (gt250IUL)
ALP removes inhibitors of mineralization nonspecific may be elevated with skeletal trauma cannot determine maturity of HO elevated 12wks after surgery is predictor
elevated CRP correlates with inflammatory activity of HO better than ESR normalization of CRP may correlate with maturity of HO
elevated ESR (gt35mmh) 12wks after THA is predictor
elevated CK correlates with involvement of muscle extent of muscle
involvement Histology
mature fatty bone marrow mature trabecular bone
Heterotopic ossification (HO) most commonly occurs at the amputation site if the amputation was performed thru the zone of injury especially if the injury was a blast mechanism
Symptomatic heterotopic ossification of the quadriceps may occur following placement of a large-diameter Steinmann pin for the purpose of temporary skeletal traction
TreatmentThe prevention of heterotopic ossification is focused on three basic principles disrupting the inductive signalling pathways altering the osteoprogenitor cells or modifying the environment
bullphysiotherapy should involve an assisted range of movement exercises with gentle stretch and terminal resistance trainingbullProphylaxis
bull bisphosphonates amp NSAIDS bull indications
bull although no literature supports are commonly usedbull technique
bull indomethacin is most commonly used bull dose is 75mgday for 10days to 6 weeks
bull perioperative radiation bull indications
bull although no literature supports commonly usedbull is thought to be effective by blocking osteoblast differentiation
bull technique bull a single perioperative dose of 700cGy can be given either 4
hours preop or within 72 hours postoperatively bull lt550cGy not effective
Nonsteroidal anti-inflammatory drugs (NSAIDs) These drugs have demonstrated good results in
preventing heterotopic ossification after total hip arthroplasty
A direct effect of NSAIDs on the formation of heterotopic ossification has been described due to the inhibition of the differentiation of mesenchymal cells into oestrogenic cells There is also an indirect effect which refers to the inhibition of bone remodelling by suppression of the prostagland unmediated inflammatory response (specifically PGE-2)
Indomethacin has been considered a useful medication for heterotopic ossification prophylaxis following total hip replacement
prescribed for three to six weeks in a dose of 75mgday within two months of the injury may reduce the incidence of heterotopic ossification by two to three times
Biphosphonates inhibits precipitation of calcium phosphate and blocks the aggregation and mineralisation of hydroxyapatite crystals In primary prevention Banovac et al [56] have suggested that the treatment should begin as soon as elevated alkaline phosphatase is diagnosed or positive findings in ultrasonography or bone scans are shown In addition disphosphonates could have long-term effects on prevention when the treatment is finished
Posttraumatic wide exposure and surgical resection
indications severe loss of motion and decreased function
technique wide exposure required to identify all neurovascular
structures that may be involved timing of resection (controversial)
marked decrease in bone scan activity AND normalization of ALP
6 months following general trauma 1 year following SCI 15 years following TBI
some data suggests equivalent results when comparing early versus late resection
postop follow with 5 day course of indomethacin early gentle joint mobilization
The surgery is necessary in patients with symptomatic HO and unsuccessful medical treatment such as
Loss of range of motion and ankylosis with associated functional disability such as sitting difficulties
Complications of immobility such as pressure ulcers
Facilitate rehabilitation and recovery of muscular atrophy secondary to prolonged immobilisation
Difficulties of appropriate hygiene because access to the perineum or bladder care is needed
Severe pain refractory to analgesia Vascular andor nerve compression
Advantages to early excision of heterotopic ossification (vs waiting for maturation) include decreased soft tissue contracture better definition between heterotopic and native bone and decreased waiting time for the patient When the soft tissue envelope is benign one may proceed with operative release While waiting for normalization of alkaline phosphatase levels inactivity on bone scan or radiographic maturity may decrease risk of recurrent heterotopic ossification delaying operative release for these reasons has not been shown to improve results of final elbow range of motion after contracture release
Gartland recommended surgery after six months following traumatic heterotopic ossification one year following spinal cord injury and 18 months after head injury
In the past waiting until maturity in order to minimize the rate of recurrence after the surgical treatment was recommended Nevertheless recent studies do not confirm a higher rate of recurrence when the HO is excised in an earlier phase In addition a long delay before surgery leads to ankylosis a high degree of osteoporosis and more extensive intra-articular injuries These findings are associated with bad functional results and potential complications
Should you wait till lesion maturation
Prevention byHandle tissue carefully Avoid excess bleeding Achieve good hemostasis Beware of lesions that span internervous tissue planes
but if it happens resection of a large enough amount of bone to allow improvement of the range of motion and trying to preserve the joint
Our aim must be
A reactive process that is characterized by a well-circumscribed proliferation of fibroblasts cartilage and bone within muscle
A form of heterotopic ossification that is the result direct trauma intramuscular hematoma
most common location is the diaphysis of long bones Must differentiate from tumors Fibrodysplasia ossificans progressiva (FOP) is a rare subtype of heterotopic ossification
involves mutation of the ACVR1 gene (activin A type I receptor gene a BMP type-1 receptor)
Epidemiology demographics
most common in young active males (15 to 35 years old) body locations
quadriceps brachialis and gluteal muscles Genetics
almost always a posttraumatic condition Prognosis
usually self limiting mass usually begins to decrease in size after 1 yea
Myositis ossificans
PresentationbullSymptoms
bull pain tenderness swelling and decreased range of motion that usually presents within days of the injury
bull pain and size of the mass decrease with timebull mass increases in size over several months(usually 3 to 6 cm)
bull after the mass stops growing it becomes firmbullPhysical exam
bull palpable soft tissue massbull restricted range of motion
ImagingbullRadiographs
bull peripheral bone formation with central lucent areabull may appear as dotted veil pattern
bullMRI with gadolinium bull rim enhancement is seen within the first 3 weeks
bullCT scan bull lesion has an eggshell appearance
bullCharacteristic histology shows zonal pattern bull periphery of lesion
bull mature trabeculae of lamellar and woven bonebull calcification seen on xray
bull center of the lesion bull irregular mass of immature fibroblastsbull cartilage component may be presentbull (no calcification seen on xray) bull no cellular atypia seen
Treatment
bullNonoperative bull rest range of motion exercises and activity modification
bull passive stretching is contraindicated (makes it worse)bull physical therapy
bull utilized to maintain range of motionbull radiographic monitoring
bull obtained to confirm maturation of the lesionbullOperative
bull surgical excision bull indicated only if it remains a problem after it maturesbull do not operate in acute phase wait at least six months
bull excision of the lesion within 6 to 12 months predisposes to local recurrence
A 26-year-old man presents with generalized back and joint stiffness and difficulty opening his mouth His elder sister has similar complaints Since childhood he has had 3 surgeries for excision of recurrent bony prominences around his knees He walks with a stooped over posture seen in Figure A Radiographs of his feet knee hip and spine are seen in Figures B-E respectively
fibrodysplasia ossificans progressiva
Stone Man Disease) which involves a mutation of the ACVR1
There are 2 hallmark characteristics progressive heterotopic ossification (muscles fascia tendons ligaments and joint capsules) and congenital malformation of the great toe (hallux valgus malformed first metatarsal and monophalangism) BMP4 which contributes to the formation of the skeleton in the normal embryo is implicated in this disease
Complications
bullHematoma and intraoperative bleedingbullInfection
bull higher rate of infection following joint arthroplasty if HO is present
bullFractures of osteoporotic bone bull osteopenic from disusebull during surgery or physiotherapy
bullRecurrence bull recurrence rate correlates with neurological injury
bull greater recurrence if severe neurological compromisebullAVN
bull if extensive dissection or stripping is required
HTO AND ISS
When ISS is below 25 the mortality risk is minimal and above 25 it is an almost linear increase
When ISS is 50 the mortality is 50 When above 70 it is close to 100 If an injury is assigned an AIS of 6 (unsurvivable injury) the ISS score is
automatically assigned to 75 Highest ISS score obtainable is 75 For trauma patients of vehicular accidents the scoring system is important
for assessing the effectiveness of medical care in reducing morbidity and mortality
Advantages virtually the only anatomical scoring system in use correlates linearly with
mortality morbidity hospital stay other measures of severity
Weaknesses Any error in AIS scoring increases the ISS error Many different injury patterns can yield the same ISS score Injuries to different body regions are not weighted Not a useful triage tool as a full description of patient injuries is not known
prior to full investigation amp operation
risk factors periosteal stripping off anterior femur male gender obesity post traumatic deformity Anterior and anterolateral approach Cementless
Neurogenic HO around the hip due to SCI occurs more often in the medial region than in the lateral region with ossified tissues extending from the pubic symphysis to the anteromedial femoral shaft posterior to the femoral neurovascular structures Ossification is also seen anteriorly involving the iliopsoas and femoral neurovascular structures laterally within gluteus minimus and posteriorly extending from the ilium to the posterior femur encasing the sciatic nerve
HTO AROUND hip and knee
The Brooker Classification of Heterotopic Ossification around the hip joint Class I has islands of bone within the soft tissues Class II has bone spurs from the pelvis or proximal end of the femur leaving at least 1 cm between opposing surfaces Class III has bone spurs from the pelvis andor proximal end of the femur reducing the space between opposing bone surfaces to less than 1 cm Class IV shows apparent bone ankylosis of the hip
Region I - Heterotopic ossifications are strictly below the tip of the greater trochanter
Region II - Heterotopic ossifications are below and above the tip of the greater trochanter
Region III - Heterotopic ossifications are strictly above the tip of the greater trochanter
Grade A - Single or multiple heterotopic ossifications are less than 10 mm in maximal extent without contact with the pelvis or the femur
Grade B - Heterotopic ossifications are greater than 10 mm without contact with the pelvis but with possible contact with the femur there is no bridging from the femur to the proximal part of the greater trochanter and no evidence of ankylosis
Grade C - Ankylosis by means of firm bridging from the femur to the pelvis is present
Shmidt classification
excision may be performed The results of this procedure are varied Patients may find that their range of movement improves but pain relief is likely to be limited
A patient with heterotopic ossification following total hip arthroplasty is thought to have a 90-100 chance of developing it on the contralateral hip if this hip also undergoes total arthroplasty
it would be prudent to minimize the risk of heterotopic ossification developing after arthroplasty by performing surgery whereby the following are ensured
Exposure is meticulous Retraction is performed carefully and soft tissue
is handled carefully Irrigation is adequate Devitalized tissue is excised Hemostasis is adequate Postoperative drains (when used) are not
retained for longer than necessary Perioperative antibiotic prophylaxis is used Postoperative anticoagulation (when used for
deep vein thrombosis prophylaxis) is carefully controlled
sources of knee stiffness 1-extrinsic severe osteoarthritis of the ipsilateral hip neurologic injury leading to muscle rigidity tight quadriceps or hamstring muscles secondary to muscle injury heterotopic ossification or long-standing juvenile inflammatory conditions limiting knee
range of motion prior to the completion of skeletal growth When extrinsic sources are identified revision total knee arthroplasty is unlikely to be associated with a favorable outcome without correction of the extrinsic problem
2-intrinsic (1) overstuffing of the patellofemoral articulation (2) an
excessively tight flexion andor extension gap (3) a tight posterior cruciate ligament (4) femoral andor tibial malrotation (5) arthrofibrosis and (6) limited bearing excursion in association with a highly conforming mobile-bearing prosthetic design
HTO after TKA
Heterotopic Ossification (HO) following primary Total Knee Replacement (TKR)
Occurs in 3-90 of TKRs 3-grade classification system No correlation between HO and component
alignment or component position
Clinical findings similar to early infection Continuing low-grade fever Warm swollen and erythematous knee Normal blood tests Possibly an association with HLA-A2 and B18 HO patients have worse KSS and function
scores
Patients at HIGH risk for developing HO after TKR (Knee Arthroplasty) (5)
Those with limited postoperative knee flexion
Increased lumbar bone mineral density (BMD) on multivariate analysis (3)
Hypertrophic arthrosis Excessive periosteal trauma Notching of the anterior femur Those who require forced manipulation
after TKA 47 in revision TKR surgery (6) Higher rates in revision TKR cases with
infection (up to 76
DaughertyBell classification of HO of the knee 0 No evidence of HO 1 Bone islands in periarticular soft tissue (no
involvement of femur patella or tibia) or HO within quadriceps expansion measuring lt1 cm
2 Spur formation measuring lt5 cm that involves the femur patella or tibia if more than one bone demonstrates HO separation of HO spurs
measure gt1 cm or HO within quadriceps expansion measuring ge1 cm but lt3 cm
3 Spur formation gt5 cm involving femur patella or tibia if more than one bone demonstrates HO separation of HO spurs measure lt1 cm or HO
within quadriceps expansion measuring ge3 cm 4 Extensive HO of the knee causing ankylosis
class 2 HO begins to involve the major bones of the knee joint with spur formation limited to a size of 5 cm
HO class 2 may be observed in select patients with complete ROM and no reported pain Patients with class 3 HO would likely always benefit from surgical excision
followed by RT prophylaxis Certainly patients in either cohort with a subclass ldquoBrdquo assignment (symptomatic) would
benefit from treatment All patients with class 4 HO require
treatment to alleviate ankylosis
treatment
References Whyte ldquoPagetrsquos Disease of Bonerdquo NEMJ vol 355
2006 Klein and Parvizi ldquoSurgical Manifestations of Pagetrsquos
Diseaserdquo JAAOS vol 14 2006 Orthobullets Campbell Apley Emedicinecom
-Chapter 15 Heterotopic Ossification after Traumatic Brain InjuryBy Jesuacutes Moreta and Joseacute Luis Martiacutenez-de los Mozos DOI 10577257343
Questions
Thank You
Smith et al reviewed the pathologic complications of Pagets bone disease Pagets bone disease commonly causes osseous weakening (deformity and fracture) and arthritis in the hip joint Management of end stage disease is successful with cemented and cementless total hip arthroplasty Bleeding is the most common intra- and post-operative complication of surgery
Gabel et al retrospectively reviewed thirteen patients who had had sixteen total knee arthroplasties for Pagetic gonarthrosis Unlike total hip arthroplasty surgery Paget disease did not increase the amount of blood lost during the operation or in the postoperative period The most common complication associated with total knee arthroplasty was malalignment
Hansen et al reviewed the incidence of osteosarcomas complicating Pagets Disease Of the typical sites that are usually involved in Pagets disease (eg spine pelvis femur tibia and humerus) secondary osteosarcoma tends to spare the spine
Shaylor et al reported the mortality rates in 26 patient with osteosarcoma secondary to Paget s disease There was a 47 mortality at 1 year and 75 at 2 years from diagnosis In their series no patient survived for 5 years All patients died of metastatic disease
Langston et al conducted a randomized trial that compared the results of symptomatic treatment versus intensive bisphosphonate therapy in patients with Pagets disease Clinical fractures occurred in 46 of 661 patients (70) in the treatment group compared with 49 of 663 patients (74) in the symptomatic treatment group They concluded that bisphosphonates did not show a significant beneficial impact on pain quality of life or fracture incidence
Hadjipavlou et al reviewed Pagets disease of the bone and its management Farmers have been shown to have an increased incidence of Pagets disease Average age at presentation is in the 5th and 6th decade Symptomatic individuals are recommended to be treated initially with medical management They suggest that bisphosphonates are more effective than calcitonin at suppressing the histological and biochemical activity in Pagetrsquos disease
Summary Epid Very common in elderly Path Abnormal osteoclastshellipuarrbone
turnoverhellipdeposition of abnormal bone SampS Pain deformity fracture arthropathy Labs uarrAlkPhos X-ray Characteristic coarse thickened
trabeculae Bone scan Very hot Rx Bisphosphonates Surgery for arthropathy fracture painful
deformity
A 65-year-old male presents with increasing shoulder pain over the past 9 months He is otherwise healthy and has no other complaints Radiograph of his shoulder is shown in Figure A Whole body bone scan and biopsy photograph are shown in Figures B and C What is the most appropriate treatment for this patient
1 Referral to endocrinology 2 Radiation therapy and chemotherapy 3 Wide resection and reconstruction 4 Radiation therapy wide resection and reconstruction 5 Chemotherapy wide resection and reconstruction
Histiocytosis X or Langerhans cell histiocytosis is a spectrum of diseases of the reticuloendothelial system with one of three general presentations Eosinophilic granuloma (EG)
usually a single self-limited lesion found in younger patients
Hand-Schuller-Christian disease (HSC) chronic disseminated form with bone and visceral lesions also known as Langerhans cell histiocytosis with visceral
involvement Letterer-Siwe disease (LSD)
fatal form that occurs in young children
Eosinophilic granuloma
Epidemiology demographics
most commonly occurs in children (80 of afflicted lt 20 years of age)
HSC disease presents in children gt 3 years of age LSD occurs in children lt 3 years of age Male to female ratio of 21
location eosinophilic granuloma
commonly presents in the skull ribs clavicle scapula mandible
isolated lesions of the spine (thoracic most common) can also occur in diaphyseal regions of long bones and the
pelvis HSC
multiple bony sites multiple lytic skull lesions visceral involvement of the lungs spleen liver skin lymph
nodes
Genetics no clear genetic pattern of inheritance or locus has
been determined Prognosis
EG isolated involvement generally treatable with local
management spine lesions can spontaneously resolve
HSC prognosis depends on response to chemotherapy worsening prognosis with increasing extraskeletal
involvement LSD
generally fatal in children lt 3 years of age
Symptoms skeletal involvement
pain and swelling at the region of involvement limping can be seen with pelvic or lower extremity
involvement vertebral involvement
localized or diffuse back pain increasingly kyphotic posture radiculopathy can occur with more aggressive lesions
HSC classic triad of
multiple lytic skull lesions diabetes insipidus
increased thirst and water intake exopthalmos
visceral involvement diffuse or nonspecific abdominal or chest pain
Radiographs general
known as the great mimicker as it appears similar to many lesions radiographic differential includes osteomyelitis leukemia lymphoma
fibrous dysplasia or Ewings sarcoma diaphyseal lesions
well defined intramedullary lytic or punched-out lesion cortex may be thinned expanded or destroyed may have periosteal reaction
metaphyseal lesions extend up to but not through the physis less central location than diaphyseal lesions
spinal lesions vertebra plana (flattened vertebrae) in spine increased kyphosis
cranial involvement multiple punched-out lytic lesions
MRI may show a soft tissue mass adjacent to boney lesions
Bone scan generally shows increased uptake in the region of boney lesion
Histology Langerhans cells
mononuclear histiocyte-like cells with oval nuclei with well-defined round or oval cytoplasm
a prominent nuclear groove (coffee bean nuclei) can be seen in most of the nuclei
eosinophilic cytoplasm (pink generally) stain with CD1A electronmicroscopy
birbeck granules seen inside Langerhans cells mixture of inflammatory cells also present giant cells are present lack of nuclear atypia and atypical mitoses
differentiates this condition from malignant conditions such as Ewings sarcoma lymphoma of bone and metastatic neuroblastoma which may look similar based on the round cells alone
eosinophilic cytoplasm (pink generally)
Treatment
bullNonoperative bull observation alone
bull indications bull a self-limited process and it is reasonable to treat with observation alone
bull bracing bull indications
bull to prevent progressive kyphosis of the spinebull outcomes
bull will correct deformity in 90 of patientsbull vertebral lesions generally regain 50 of their height
bull low dose irradiation (600-800 cGy) bull indications
bull indicated for lesions in the spine that compromise stability neurologic statusbull lesions not amenable to injection or open treatment
bull outcomes bull effective for most lesions
bull chemotherapy bull indications
bull diffuse HSCbull outcomes
bull prognosis is improved with less severe extraskeletal involvementbull corticosteroid injection
bull indications bull isolated lesions bull can be performed after curettage as well
Operative curettage and bone grafting
indications for lesions that endanger the articular surface or are a risk for
impending fractures spinal deformity correction
indications progressive spine deformity refractory to bracing
approximately 10 of patients with spine lesion will need operative intervention for deformity correction
Destructive multiple lesion in young patientsAre eosinophilic granuloma lymphoma and leukemiaLymphoma is unlikely to present with exopthalmos diabetes insipidus or vertebra plana Lymphoma bone lesions are lytic and appear moth eatenpermeative on radiographs
Figure A shows a skin lesion typical of eosinophillic granuloma Figure B shows a lytic lesions without significant surrounding sclerosis as is characteristic of eosinophilic granuloma Figure C shows the characteristic histology of multiple eosinophils with their characteristic oval coffee bean nuclei and staining pattern of purpleredpink cytoplasm (depending on the stain) Importantly the histology slide lacks a malignant appearance (no cellular atypia or mytotic complexes and low nuclearcytoplasmic ratio)
Formation of bone in atypical extraskeletal tissues usually occurs
spontaneously or following trauma within 2 months of neurologic injury (brain or spinal cord)
most common location is between muscle and joint capsule Epidemiology
incidence (see table below)
demographics malefemale = 21 especially men with hypertrophic osteoarthritis and women gt65y
location traumatic brain injury or stroke
hip gt elbow gt shoulder gt knee elbow HO more common following brain trauma
occurs on affected (spastic) side rarely in the knee (TBI)
spinal cord injury hip gt knee gt elbow gt shoulder hip flexors and abductors gt extensors or adductors medial aspect of the knee
Heterotopic Ossification
Risk factors
Pathophysiology exact cause of HO is not known but there appears to be a
genetic pre disposition experimental HO associated with
tissue expression of BMP IT IS SAID TO BE CAUSED BY activation and proliferation of
mesenchymal stem cells Associated conditions
orthopaedic manifestations pathologic fractures
from decreased joint ROM and osteoporotic bone nerve impingement soft tissue contractures contributing to the formation of
decubitus ulcers joint ankylosis HO after THA adversely affects outcome of THA
nonorthopaedic conditions skin maceration and hygiene problems
Pathophysiology Early in the formation of HO oedema with exudative
infiltrate is present followed by fibroblastic proliferation and immature connective tissue formation Posteriorly osteoid formation is seen with the subsequent deposition of bone matrix Primitive osteoid is deposited as small masses in the periphery early (within the first two weeks) and osteoblasts are noted located irregularly Osteoblasts produce tropocollagen which polymerizes to form collagen and secrete alkaline phosphatase which allows calcium to precipitate and the mineralization of bone matrix As mineralization progresses amorphous calcium phosphate is progressively replaced by hydroxyapatite crystals During the following weeks the lesion matures with a centripetal pattern and after 6-12 months an appearance of true bone is noted The new bone is always extra-articular and can be contiguous with the skeleton but generally does not involve the periosteum
IN SUMMARY It has been postulated that three conditions
must be met to achieve heterotopic bone formation ---a stimulating event oestrogenic precursor cells and a proper environment LIKE hypercalcaemia tissue hypoxia pH changes (alkalosis) or prolonged immobilization
ClassificationbullSubtypes
bull neurogenic HO bull Four clinical stages of HO in people with spinal cord injury were
described by Nicholas in 1973
bull traumatic myositis ossificans bull fibrodysplasia ossificans progressiva (Munchmeyers Disease)
Neurogenic HO Symptoms
painless loss of ROM interferes with ADL CRPS symptoms fever
Physical exam inspection
warm painful swollen joint may have effusion skin problems
decubitus ulcers from contractures around skin muscles ligaments
skin maceration and hygiene problems motion
decreased joint ROM joint ankylosis with HO after TKA might develop quad muscle snapping or patella
instability neurovascular
peripheral neuropathy HO often impinges on adjacent NV structures
Imaging
bullRadiographs bull findings
bull ossification usually easy to visualize bull maturity of HO
bull the appearance of a bony cortex suggests mature HObull sharp demarcation from surrounding tissue bull trabecular pattern
bull sensitivity and specificity bull not useful for early diagnosisbull only useful at 1 week after onset of symptoms
bull calcium is deposited 7-10 days later than symptom onsetbullUltrasound
bull indications bull for early diagnosis of hip HO
bull findings bull echogenic surfaces with posterior acoustic shadowing
bullCT bull indications
bull useful for preoperative planning bullTriphasic bone scan
bull indications bull best for early diagnosis bull most commonly used diagnostic study
Radiographs are extremely useful in the staging of heterotopic ossification and will show the development of sharp cortical margins once the lesion has reached maturity
Heterotopic bone is a condition in which lamellar bone forms in non-ossified soft tissues In the early stages studies such as MRI and bone scan are more sensitive for diagnosis as radiographs may appear normal for the first three weeks After the appropriate diagnosis is made sequential radiographs are useful for monitoring the progression of the ossification Once it has reached the mature stage sharp cortical margins will appear and surgical resection may be considered
lab
Labs elevated serum alkaline phosphatase (gt250IUL)
ALP removes inhibitors of mineralization nonspecific may be elevated with skeletal trauma cannot determine maturity of HO elevated 12wks after surgery is predictor
elevated CRP correlates with inflammatory activity of HO better than ESR normalization of CRP may correlate with maturity of HO
elevated ESR (gt35mmh) 12wks after THA is predictor
elevated CK correlates with involvement of muscle extent of muscle
involvement Histology
mature fatty bone marrow mature trabecular bone
Heterotopic ossification (HO) most commonly occurs at the amputation site if the amputation was performed thru the zone of injury especially if the injury was a blast mechanism
Symptomatic heterotopic ossification of the quadriceps may occur following placement of a large-diameter Steinmann pin for the purpose of temporary skeletal traction
TreatmentThe prevention of heterotopic ossification is focused on three basic principles disrupting the inductive signalling pathways altering the osteoprogenitor cells or modifying the environment
bullphysiotherapy should involve an assisted range of movement exercises with gentle stretch and terminal resistance trainingbullProphylaxis
bull bisphosphonates amp NSAIDS bull indications
bull although no literature supports are commonly usedbull technique
bull indomethacin is most commonly used bull dose is 75mgday for 10days to 6 weeks
bull perioperative radiation bull indications
bull although no literature supports commonly usedbull is thought to be effective by blocking osteoblast differentiation
bull technique bull a single perioperative dose of 700cGy can be given either 4
hours preop or within 72 hours postoperatively bull lt550cGy not effective
Nonsteroidal anti-inflammatory drugs (NSAIDs) These drugs have demonstrated good results in
preventing heterotopic ossification after total hip arthroplasty
A direct effect of NSAIDs on the formation of heterotopic ossification has been described due to the inhibition of the differentiation of mesenchymal cells into oestrogenic cells There is also an indirect effect which refers to the inhibition of bone remodelling by suppression of the prostagland unmediated inflammatory response (specifically PGE-2)
Indomethacin has been considered a useful medication for heterotopic ossification prophylaxis following total hip replacement
prescribed for three to six weeks in a dose of 75mgday within two months of the injury may reduce the incidence of heterotopic ossification by two to three times
Biphosphonates inhibits precipitation of calcium phosphate and blocks the aggregation and mineralisation of hydroxyapatite crystals In primary prevention Banovac et al [56] have suggested that the treatment should begin as soon as elevated alkaline phosphatase is diagnosed or positive findings in ultrasonography or bone scans are shown In addition disphosphonates could have long-term effects on prevention when the treatment is finished
Posttraumatic wide exposure and surgical resection
indications severe loss of motion and decreased function
technique wide exposure required to identify all neurovascular
structures that may be involved timing of resection (controversial)
marked decrease in bone scan activity AND normalization of ALP
6 months following general trauma 1 year following SCI 15 years following TBI
some data suggests equivalent results when comparing early versus late resection
postop follow with 5 day course of indomethacin early gentle joint mobilization
The surgery is necessary in patients with symptomatic HO and unsuccessful medical treatment such as
Loss of range of motion and ankylosis with associated functional disability such as sitting difficulties
Complications of immobility such as pressure ulcers
Facilitate rehabilitation and recovery of muscular atrophy secondary to prolonged immobilisation
Difficulties of appropriate hygiene because access to the perineum or bladder care is needed
Severe pain refractory to analgesia Vascular andor nerve compression
Advantages to early excision of heterotopic ossification (vs waiting for maturation) include decreased soft tissue contracture better definition between heterotopic and native bone and decreased waiting time for the patient When the soft tissue envelope is benign one may proceed with operative release While waiting for normalization of alkaline phosphatase levels inactivity on bone scan or radiographic maturity may decrease risk of recurrent heterotopic ossification delaying operative release for these reasons has not been shown to improve results of final elbow range of motion after contracture release
Gartland recommended surgery after six months following traumatic heterotopic ossification one year following spinal cord injury and 18 months after head injury
In the past waiting until maturity in order to minimize the rate of recurrence after the surgical treatment was recommended Nevertheless recent studies do not confirm a higher rate of recurrence when the HO is excised in an earlier phase In addition a long delay before surgery leads to ankylosis a high degree of osteoporosis and more extensive intra-articular injuries These findings are associated with bad functional results and potential complications
Should you wait till lesion maturation
Prevention byHandle tissue carefully Avoid excess bleeding Achieve good hemostasis Beware of lesions that span internervous tissue planes
but if it happens resection of a large enough amount of bone to allow improvement of the range of motion and trying to preserve the joint
Our aim must be
A reactive process that is characterized by a well-circumscribed proliferation of fibroblasts cartilage and bone within muscle
A form of heterotopic ossification that is the result direct trauma intramuscular hematoma
most common location is the diaphysis of long bones Must differentiate from tumors Fibrodysplasia ossificans progressiva (FOP) is a rare subtype of heterotopic ossification
involves mutation of the ACVR1 gene (activin A type I receptor gene a BMP type-1 receptor)
Epidemiology demographics
most common in young active males (15 to 35 years old) body locations
quadriceps brachialis and gluteal muscles Genetics
almost always a posttraumatic condition Prognosis
usually self limiting mass usually begins to decrease in size after 1 yea
Myositis ossificans
PresentationbullSymptoms
bull pain tenderness swelling and decreased range of motion that usually presents within days of the injury
bull pain and size of the mass decrease with timebull mass increases in size over several months(usually 3 to 6 cm)
bull after the mass stops growing it becomes firmbullPhysical exam
bull palpable soft tissue massbull restricted range of motion
ImagingbullRadiographs
bull peripheral bone formation with central lucent areabull may appear as dotted veil pattern
bullMRI with gadolinium bull rim enhancement is seen within the first 3 weeks
bullCT scan bull lesion has an eggshell appearance
bullCharacteristic histology shows zonal pattern bull periphery of lesion
bull mature trabeculae of lamellar and woven bonebull calcification seen on xray
bull center of the lesion bull irregular mass of immature fibroblastsbull cartilage component may be presentbull (no calcification seen on xray) bull no cellular atypia seen
Treatment
bullNonoperative bull rest range of motion exercises and activity modification
bull passive stretching is contraindicated (makes it worse)bull physical therapy
bull utilized to maintain range of motionbull radiographic monitoring
bull obtained to confirm maturation of the lesionbullOperative
bull surgical excision bull indicated only if it remains a problem after it maturesbull do not operate in acute phase wait at least six months
bull excision of the lesion within 6 to 12 months predisposes to local recurrence
A 26-year-old man presents with generalized back and joint stiffness and difficulty opening his mouth His elder sister has similar complaints Since childhood he has had 3 surgeries for excision of recurrent bony prominences around his knees He walks with a stooped over posture seen in Figure A Radiographs of his feet knee hip and spine are seen in Figures B-E respectively
fibrodysplasia ossificans progressiva
Stone Man Disease) which involves a mutation of the ACVR1
There are 2 hallmark characteristics progressive heterotopic ossification (muscles fascia tendons ligaments and joint capsules) and congenital malformation of the great toe (hallux valgus malformed first metatarsal and monophalangism) BMP4 which contributes to the formation of the skeleton in the normal embryo is implicated in this disease
Complications
bullHematoma and intraoperative bleedingbullInfection
bull higher rate of infection following joint arthroplasty if HO is present
bullFractures of osteoporotic bone bull osteopenic from disusebull during surgery or physiotherapy
bullRecurrence bull recurrence rate correlates with neurological injury
bull greater recurrence if severe neurological compromisebullAVN
bull if extensive dissection or stripping is required
HTO AND ISS
When ISS is below 25 the mortality risk is minimal and above 25 it is an almost linear increase
When ISS is 50 the mortality is 50 When above 70 it is close to 100 If an injury is assigned an AIS of 6 (unsurvivable injury) the ISS score is
automatically assigned to 75 Highest ISS score obtainable is 75 For trauma patients of vehicular accidents the scoring system is important
for assessing the effectiveness of medical care in reducing morbidity and mortality
Advantages virtually the only anatomical scoring system in use correlates linearly with
mortality morbidity hospital stay other measures of severity
Weaknesses Any error in AIS scoring increases the ISS error Many different injury patterns can yield the same ISS score Injuries to different body regions are not weighted Not a useful triage tool as a full description of patient injuries is not known
prior to full investigation amp operation
risk factors periosteal stripping off anterior femur male gender obesity post traumatic deformity Anterior and anterolateral approach Cementless
Neurogenic HO around the hip due to SCI occurs more often in the medial region than in the lateral region with ossified tissues extending from the pubic symphysis to the anteromedial femoral shaft posterior to the femoral neurovascular structures Ossification is also seen anteriorly involving the iliopsoas and femoral neurovascular structures laterally within gluteus minimus and posteriorly extending from the ilium to the posterior femur encasing the sciatic nerve
HTO AROUND hip and knee
The Brooker Classification of Heterotopic Ossification around the hip joint Class I has islands of bone within the soft tissues Class II has bone spurs from the pelvis or proximal end of the femur leaving at least 1 cm between opposing surfaces Class III has bone spurs from the pelvis andor proximal end of the femur reducing the space between opposing bone surfaces to less than 1 cm Class IV shows apparent bone ankylosis of the hip
Region I - Heterotopic ossifications are strictly below the tip of the greater trochanter
Region II - Heterotopic ossifications are below and above the tip of the greater trochanter
Region III - Heterotopic ossifications are strictly above the tip of the greater trochanter
Grade A - Single or multiple heterotopic ossifications are less than 10 mm in maximal extent without contact with the pelvis or the femur
Grade B - Heterotopic ossifications are greater than 10 mm without contact with the pelvis but with possible contact with the femur there is no bridging from the femur to the proximal part of the greater trochanter and no evidence of ankylosis
Grade C - Ankylosis by means of firm bridging from the femur to the pelvis is present
Shmidt classification
excision may be performed The results of this procedure are varied Patients may find that their range of movement improves but pain relief is likely to be limited
A patient with heterotopic ossification following total hip arthroplasty is thought to have a 90-100 chance of developing it on the contralateral hip if this hip also undergoes total arthroplasty
it would be prudent to minimize the risk of heterotopic ossification developing after arthroplasty by performing surgery whereby the following are ensured
Exposure is meticulous Retraction is performed carefully and soft tissue
is handled carefully Irrigation is adequate Devitalized tissue is excised Hemostasis is adequate Postoperative drains (when used) are not
retained for longer than necessary Perioperative antibiotic prophylaxis is used Postoperative anticoagulation (when used for
deep vein thrombosis prophylaxis) is carefully controlled
sources of knee stiffness 1-extrinsic severe osteoarthritis of the ipsilateral hip neurologic injury leading to muscle rigidity tight quadriceps or hamstring muscles secondary to muscle injury heterotopic ossification or long-standing juvenile inflammatory conditions limiting knee
range of motion prior to the completion of skeletal growth When extrinsic sources are identified revision total knee arthroplasty is unlikely to be associated with a favorable outcome without correction of the extrinsic problem
2-intrinsic (1) overstuffing of the patellofemoral articulation (2) an
excessively tight flexion andor extension gap (3) a tight posterior cruciate ligament (4) femoral andor tibial malrotation (5) arthrofibrosis and (6) limited bearing excursion in association with a highly conforming mobile-bearing prosthetic design
HTO after TKA
Heterotopic Ossification (HO) following primary Total Knee Replacement (TKR)
Occurs in 3-90 of TKRs 3-grade classification system No correlation between HO and component
alignment or component position
Clinical findings similar to early infection Continuing low-grade fever Warm swollen and erythematous knee Normal blood tests Possibly an association with HLA-A2 and B18 HO patients have worse KSS and function
scores
Patients at HIGH risk for developing HO after TKR (Knee Arthroplasty) (5)
Those with limited postoperative knee flexion
Increased lumbar bone mineral density (BMD) on multivariate analysis (3)
Hypertrophic arthrosis Excessive periosteal trauma Notching of the anterior femur Those who require forced manipulation
after TKA 47 in revision TKR surgery (6) Higher rates in revision TKR cases with
infection (up to 76
DaughertyBell classification of HO of the knee 0 No evidence of HO 1 Bone islands in periarticular soft tissue (no
involvement of femur patella or tibia) or HO within quadriceps expansion measuring lt1 cm
2 Spur formation measuring lt5 cm that involves the femur patella or tibia if more than one bone demonstrates HO separation of HO spurs
measure gt1 cm or HO within quadriceps expansion measuring ge1 cm but lt3 cm
3 Spur formation gt5 cm involving femur patella or tibia if more than one bone demonstrates HO separation of HO spurs measure lt1 cm or HO
within quadriceps expansion measuring ge3 cm 4 Extensive HO of the knee causing ankylosis
class 2 HO begins to involve the major bones of the knee joint with spur formation limited to a size of 5 cm
HO class 2 may be observed in select patients with complete ROM and no reported pain Patients with class 3 HO would likely always benefit from surgical excision
followed by RT prophylaxis Certainly patients in either cohort with a subclass ldquoBrdquo assignment (symptomatic) would
benefit from treatment All patients with class 4 HO require
treatment to alleviate ankylosis
treatment
References Whyte ldquoPagetrsquos Disease of Bonerdquo NEMJ vol 355
2006 Klein and Parvizi ldquoSurgical Manifestations of Pagetrsquos
Diseaserdquo JAAOS vol 14 2006 Orthobullets Campbell Apley Emedicinecom
-Chapter 15 Heterotopic Ossification after Traumatic Brain InjuryBy Jesuacutes Moreta and Joseacute Luis Martiacutenez-de los Mozos DOI 10577257343
Questions
Thank You
Hansen et al reviewed the incidence of osteosarcomas complicating Pagets Disease Of the typical sites that are usually involved in Pagets disease (eg spine pelvis femur tibia and humerus) secondary osteosarcoma tends to spare the spine
Shaylor et al reported the mortality rates in 26 patient with osteosarcoma secondary to Paget s disease There was a 47 mortality at 1 year and 75 at 2 years from diagnosis In their series no patient survived for 5 years All patients died of metastatic disease
Langston et al conducted a randomized trial that compared the results of symptomatic treatment versus intensive bisphosphonate therapy in patients with Pagets disease Clinical fractures occurred in 46 of 661 patients (70) in the treatment group compared with 49 of 663 patients (74) in the symptomatic treatment group They concluded that bisphosphonates did not show a significant beneficial impact on pain quality of life or fracture incidence
Hadjipavlou et al reviewed Pagets disease of the bone and its management Farmers have been shown to have an increased incidence of Pagets disease Average age at presentation is in the 5th and 6th decade Symptomatic individuals are recommended to be treated initially with medical management They suggest that bisphosphonates are more effective than calcitonin at suppressing the histological and biochemical activity in Pagetrsquos disease
Summary Epid Very common in elderly Path Abnormal osteoclastshellipuarrbone
turnoverhellipdeposition of abnormal bone SampS Pain deformity fracture arthropathy Labs uarrAlkPhos X-ray Characteristic coarse thickened
trabeculae Bone scan Very hot Rx Bisphosphonates Surgery for arthropathy fracture painful
deformity
A 65-year-old male presents with increasing shoulder pain over the past 9 months He is otherwise healthy and has no other complaints Radiograph of his shoulder is shown in Figure A Whole body bone scan and biopsy photograph are shown in Figures B and C What is the most appropriate treatment for this patient
1 Referral to endocrinology 2 Radiation therapy and chemotherapy 3 Wide resection and reconstruction 4 Radiation therapy wide resection and reconstruction 5 Chemotherapy wide resection and reconstruction
Histiocytosis X or Langerhans cell histiocytosis is a spectrum of diseases of the reticuloendothelial system with one of three general presentations Eosinophilic granuloma (EG)
usually a single self-limited lesion found in younger patients
Hand-Schuller-Christian disease (HSC) chronic disseminated form with bone and visceral lesions also known as Langerhans cell histiocytosis with visceral
involvement Letterer-Siwe disease (LSD)
fatal form that occurs in young children
Eosinophilic granuloma
Epidemiology demographics
most commonly occurs in children (80 of afflicted lt 20 years of age)
HSC disease presents in children gt 3 years of age LSD occurs in children lt 3 years of age Male to female ratio of 21
location eosinophilic granuloma
commonly presents in the skull ribs clavicle scapula mandible
isolated lesions of the spine (thoracic most common) can also occur in diaphyseal regions of long bones and the
pelvis HSC
multiple bony sites multiple lytic skull lesions visceral involvement of the lungs spleen liver skin lymph
nodes
Genetics no clear genetic pattern of inheritance or locus has
been determined Prognosis
EG isolated involvement generally treatable with local
management spine lesions can spontaneously resolve
HSC prognosis depends on response to chemotherapy worsening prognosis with increasing extraskeletal
involvement LSD
generally fatal in children lt 3 years of age
Symptoms skeletal involvement
pain and swelling at the region of involvement limping can be seen with pelvic or lower extremity
involvement vertebral involvement
localized or diffuse back pain increasingly kyphotic posture radiculopathy can occur with more aggressive lesions
HSC classic triad of
multiple lytic skull lesions diabetes insipidus
increased thirst and water intake exopthalmos
visceral involvement diffuse or nonspecific abdominal or chest pain
Radiographs general
known as the great mimicker as it appears similar to many lesions radiographic differential includes osteomyelitis leukemia lymphoma
fibrous dysplasia or Ewings sarcoma diaphyseal lesions
well defined intramedullary lytic or punched-out lesion cortex may be thinned expanded or destroyed may have periosteal reaction
metaphyseal lesions extend up to but not through the physis less central location than diaphyseal lesions
spinal lesions vertebra plana (flattened vertebrae) in spine increased kyphosis
cranial involvement multiple punched-out lytic lesions
MRI may show a soft tissue mass adjacent to boney lesions
Bone scan generally shows increased uptake in the region of boney lesion
Histology Langerhans cells
mononuclear histiocyte-like cells with oval nuclei with well-defined round or oval cytoplasm
a prominent nuclear groove (coffee bean nuclei) can be seen in most of the nuclei
eosinophilic cytoplasm (pink generally) stain with CD1A electronmicroscopy
birbeck granules seen inside Langerhans cells mixture of inflammatory cells also present giant cells are present lack of nuclear atypia and atypical mitoses
differentiates this condition from malignant conditions such as Ewings sarcoma lymphoma of bone and metastatic neuroblastoma which may look similar based on the round cells alone
eosinophilic cytoplasm (pink generally)
Treatment
bullNonoperative bull observation alone
bull indications bull a self-limited process and it is reasonable to treat with observation alone
bull bracing bull indications
bull to prevent progressive kyphosis of the spinebull outcomes
bull will correct deformity in 90 of patientsbull vertebral lesions generally regain 50 of their height
bull low dose irradiation (600-800 cGy) bull indications
bull indicated for lesions in the spine that compromise stability neurologic statusbull lesions not amenable to injection or open treatment
bull outcomes bull effective for most lesions
bull chemotherapy bull indications
bull diffuse HSCbull outcomes
bull prognosis is improved with less severe extraskeletal involvementbull corticosteroid injection
bull indications bull isolated lesions bull can be performed after curettage as well
Operative curettage and bone grafting
indications for lesions that endanger the articular surface or are a risk for
impending fractures spinal deformity correction
indications progressive spine deformity refractory to bracing
approximately 10 of patients with spine lesion will need operative intervention for deformity correction
Destructive multiple lesion in young patientsAre eosinophilic granuloma lymphoma and leukemiaLymphoma is unlikely to present with exopthalmos diabetes insipidus or vertebra plana Lymphoma bone lesions are lytic and appear moth eatenpermeative on radiographs
Figure A shows a skin lesion typical of eosinophillic granuloma Figure B shows a lytic lesions without significant surrounding sclerosis as is characteristic of eosinophilic granuloma Figure C shows the characteristic histology of multiple eosinophils with their characteristic oval coffee bean nuclei and staining pattern of purpleredpink cytoplasm (depending on the stain) Importantly the histology slide lacks a malignant appearance (no cellular atypia or mytotic complexes and low nuclearcytoplasmic ratio)
Formation of bone in atypical extraskeletal tissues usually occurs
spontaneously or following trauma within 2 months of neurologic injury (brain or spinal cord)
most common location is between muscle and joint capsule Epidemiology
incidence (see table below)
demographics malefemale = 21 especially men with hypertrophic osteoarthritis and women gt65y
location traumatic brain injury or stroke
hip gt elbow gt shoulder gt knee elbow HO more common following brain trauma
occurs on affected (spastic) side rarely in the knee (TBI)
spinal cord injury hip gt knee gt elbow gt shoulder hip flexors and abductors gt extensors or adductors medial aspect of the knee
Heterotopic Ossification
Risk factors
Pathophysiology exact cause of HO is not known but there appears to be a
genetic pre disposition experimental HO associated with
tissue expression of BMP IT IS SAID TO BE CAUSED BY activation and proliferation of
mesenchymal stem cells Associated conditions
orthopaedic manifestations pathologic fractures
from decreased joint ROM and osteoporotic bone nerve impingement soft tissue contractures contributing to the formation of
decubitus ulcers joint ankylosis HO after THA adversely affects outcome of THA
nonorthopaedic conditions skin maceration and hygiene problems
Pathophysiology Early in the formation of HO oedema with exudative
infiltrate is present followed by fibroblastic proliferation and immature connective tissue formation Posteriorly osteoid formation is seen with the subsequent deposition of bone matrix Primitive osteoid is deposited as small masses in the periphery early (within the first two weeks) and osteoblasts are noted located irregularly Osteoblasts produce tropocollagen which polymerizes to form collagen and secrete alkaline phosphatase which allows calcium to precipitate and the mineralization of bone matrix As mineralization progresses amorphous calcium phosphate is progressively replaced by hydroxyapatite crystals During the following weeks the lesion matures with a centripetal pattern and after 6-12 months an appearance of true bone is noted The new bone is always extra-articular and can be contiguous with the skeleton but generally does not involve the periosteum
IN SUMMARY It has been postulated that three conditions
must be met to achieve heterotopic bone formation ---a stimulating event oestrogenic precursor cells and a proper environment LIKE hypercalcaemia tissue hypoxia pH changes (alkalosis) or prolonged immobilization
ClassificationbullSubtypes
bull neurogenic HO bull Four clinical stages of HO in people with spinal cord injury were
described by Nicholas in 1973
bull traumatic myositis ossificans bull fibrodysplasia ossificans progressiva (Munchmeyers Disease)
Neurogenic HO Symptoms
painless loss of ROM interferes with ADL CRPS symptoms fever
Physical exam inspection
warm painful swollen joint may have effusion skin problems
decubitus ulcers from contractures around skin muscles ligaments
skin maceration and hygiene problems motion
decreased joint ROM joint ankylosis with HO after TKA might develop quad muscle snapping or patella
instability neurovascular
peripheral neuropathy HO often impinges on adjacent NV structures
Imaging
bullRadiographs bull findings
bull ossification usually easy to visualize bull maturity of HO
bull the appearance of a bony cortex suggests mature HObull sharp demarcation from surrounding tissue bull trabecular pattern
bull sensitivity and specificity bull not useful for early diagnosisbull only useful at 1 week after onset of symptoms
bull calcium is deposited 7-10 days later than symptom onsetbullUltrasound
bull indications bull for early diagnosis of hip HO
bull findings bull echogenic surfaces with posterior acoustic shadowing
bullCT bull indications
bull useful for preoperative planning bullTriphasic bone scan
bull indications bull best for early diagnosis bull most commonly used diagnostic study
Radiographs are extremely useful in the staging of heterotopic ossification and will show the development of sharp cortical margins once the lesion has reached maturity
Heterotopic bone is a condition in which lamellar bone forms in non-ossified soft tissues In the early stages studies such as MRI and bone scan are more sensitive for diagnosis as radiographs may appear normal for the first three weeks After the appropriate diagnosis is made sequential radiographs are useful for monitoring the progression of the ossification Once it has reached the mature stage sharp cortical margins will appear and surgical resection may be considered
lab
Labs elevated serum alkaline phosphatase (gt250IUL)
ALP removes inhibitors of mineralization nonspecific may be elevated with skeletal trauma cannot determine maturity of HO elevated 12wks after surgery is predictor
elevated CRP correlates with inflammatory activity of HO better than ESR normalization of CRP may correlate with maturity of HO
elevated ESR (gt35mmh) 12wks after THA is predictor
elevated CK correlates with involvement of muscle extent of muscle
involvement Histology
mature fatty bone marrow mature trabecular bone
Heterotopic ossification (HO) most commonly occurs at the amputation site if the amputation was performed thru the zone of injury especially if the injury was a blast mechanism
Symptomatic heterotopic ossification of the quadriceps may occur following placement of a large-diameter Steinmann pin for the purpose of temporary skeletal traction
TreatmentThe prevention of heterotopic ossification is focused on three basic principles disrupting the inductive signalling pathways altering the osteoprogenitor cells or modifying the environment
bullphysiotherapy should involve an assisted range of movement exercises with gentle stretch and terminal resistance trainingbullProphylaxis
bull bisphosphonates amp NSAIDS bull indications
bull although no literature supports are commonly usedbull technique
bull indomethacin is most commonly used bull dose is 75mgday for 10days to 6 weeks
bull perioperative radiation bull indications
bull although no literature supports commonly usedbull is thought to be effective by blocking osteoblast differentiation
bull technique bull a single perioperative dose of 700cGy can be given either 4
hours preop or within 72 hours postoperatively bull lt550cGy not effective
Nonsteroidal anti-inflammatory drugs (NSAIDs) These drugs have demonstrated good results in
preventing heterotopic ossification after total hip arthroplasty
A direct effect of NSAIDs on the formation of heterotopic ossification has been described due to the inhibition of the differentiation of mesenchymal cells into oestrogenic cells There is also an indirect effect which refers to the inhibition of bone remodelling by suppression of the prostagland unmediated inflammatory response (specifically PGE-2)
Indomethacin has been considered a useful medication for heterotopic ossification prophylaxis following total hip replacement
prescribed for three to six weeks in a dose of 75mgday within two months of the injury may reduce the incidence of heterotopic ossification by two to three times
Biphosphonates inhibits precipitation of calcium phosphate and blocks the aggregation and mineralisation of hydroxyapatite crystals In primary prevention Banovac et al [56] have suggested that the treatment should begin as soon as elevated alkaline phosphatase is diagnosed or positive findings in ultrasonography or bone scans are shown In addition disphosphonates could have long-term effects on prevention when the treatment is finished
Posttraumatic wide exposure and surgical resection
indications severe loss of motion and decreased function
technique wide exposure required to identify all neurovascular
structures that may be involved timing of resection (controversial)
marked decrease in bone scan activity AND normalization of ALP
6 months following general trauma 1 year following SCI 15 years following TBI
some data suggests equivalent results when comparing early versus late resection
postop follow with 5 day course of indomethacin early gentle joint mobilization
The surgery is necessary in patients with symptomatic HO and unsuccessful medical treatment such as
Loss of range of motion and ankylosis with associated functional disability such as sitting difficulties
Complications of immobility such as pressure ulcers
Facilitate rehabilitation and recovery of muscular atrophy secondary to prolonged immobilisation
Difficulties of appropriate hygiene because access to the perineum or bladder care is needed
Severe pain refractory to analgesia Vascular andor nerve compression
Advantages to early excision of heterotopic ossification (vs waiting for maturation) include decreased soft tissue contracture better definition between heterotopic and native bone and decreased waiting time for the patient When the soft tissue envelope is benign one may proceed with operative release While waiting for normalization of alkaline phosphatase levels inactivity on bone scan or radiographic maturity may decrease risk of recurrent heterotopic ossification delaying operative release for these reasons has not been shown to improve results of final elbow range of motion after contracture release
Gartland recommended surgery after six months following traumatic heterotopic ossification one year following spinal cord injury and 18 months after head injury
In the past waiting until maturity in order to minimize the rate of recurrence after the surgical treatment was recommended Nevertheless recent studies do not confirm a higher rate of recurrence when the HO is excised in an earlier phase In addition a long delay before surgery leads to ankylosis a high degree of osteoporosis and more extensive intra-articular injuries These findings are associated with bad functional results and potential complications
Should you wait till lesion maturation
Prevention byHandle tissue carefully Avoid excess bleeding Achieve good hemostasis Beware of lesions that span internervous tissue planes
but if it happens resection of a large enough amount of bone to allow improvement of the range of motion and trying to preserve the joint
Our aim must be
A reactive process that is characterized by a well-circumscribed proliferation of fibroblasts cartilage and bone within muscle
A form of heterotopic ossification that is the result direct trauma intramuscular hematoma
most common location is the diaphysis of long bones Must differentiate from tumors Fibrodysplasia ossificans progressiva (FOP) is a rare subtype of heterotopic ossification
involves mutation of the ACVR1 gene (activin A type I receptor gene a BMP type-1 receptor)
Epidemiology demographics
most common in young active males (15 to 35 years old) body locations
quadriceps brachialis and gluteal muscles Genetics
almost always a posttraumatic condition Prognosis
usually self limiting mass usually begins to decrease in size after 1 yea
Myositis ossificans
PresentationbullSymptoms
bull pain tenderness swelling and decreased range of motion that usually presents within days of the injury
bull pain and size of the mass decrease with timebull mass increases in size over several months(usually 3 to 6 cm)
bull after the mass stops growing it becomes firmbullPhysical exam
bull palpable soft tissue massbull restricted range of motion
ImagingbullRadiographs
bull peripheral bone formation with central lucent areabull may appear as dotted veil pattern
bullMRI with gadolinium bull rim enhancement is seen within the first 3 weeks
bullCT scan bull lesion has an eggshell appearance
bullCharacteristic histology shows zonal pattern bull periphery of lesion
bull mature trabeculae of lamellar and woven bonebull calcification seen on xray
bull center of the lesion bull irregular mass of immature fibroblastsbull cartilage component may be presentbull (no calcification seen on xray) bull no cellular atypia seen
Treatment
bullNonoperative bull rest range of motion exercises and activity modification
bull passive stretching is contraindicated (makes it worse)bull physical therapy
bull utilized to maintain range of motionbull radiographic monitoring
bull obtained to confirm maturation of the lesionbullOperative
bull surgical excision bull indicated only if it remains a problem after it maturesbull do not operate in acute phase wait at least six months
bull excision of the lesion within 6 to 12 months predisposes to local recurrence
A 26-year-old man presents with generalized back and joint stiffness and difficulty opening his mouth His elder sister has similar complaints Since childhood he has had 3 surgeries for excision of recurrent bony prominences around his knees He walks with a stooped over posture seen in Figure A Radiographs of his feet knee hip and spine are seen in Figures B-E respectively
fibrodysplasia ossificans progressiva
Stone Man Disease) which involves a mutation of the ACVR1
There are 2 hallmark characteristics progressive heterotopic ossification (muscles fascia tendons ligaments and joint capsules) and congenital malformation of the great toe (hallux valgus malformed first metatarsal and monophalangism) BMP4 which contributes to the formation of the skeleton in the normal embryo is implicated in this disease
Complications
bullHematoma and intraoperative bleedingbullInfection
bull higher rate of infection following joint arthroplasty if HO is present
bullFractures of osteoporotic bone bull osteopenic from disusebull during surgery or physiotherapy
bullRecurrence bull recurrence rate correlates with neurological injury
bull greater recurrence if severe neurological compromisebullAVN
bull if extensive dissection or stripping is required
HTO AND ISS
When ISS is below 25 the mortality risk is minimal and above 25 it is an almost linear increase
When ISS is 50 the mortality is 50 When above 70 it is close to 100 If an injury is assigned an AIS of 6 (unsurvivable injury) the ISS score is
automatically assigned to 75 Highest ISS score obtainable is 75 For trauma patients of vehicular accidents the scoring system is important
for assessing the effectiveness of medical care in reducing morbidity and mortality
Advantages virtually the only anatomical scoring system in use correlates linearly with
mortality morbidity hospital stay other measures of severity
Weaknesses Any error in AIS scoring increases the ISS error Many different injury patterns can yield the same ISS score Injuries to different body regions are not weighted Not a useful triage tool as a full description of patient injuries is not known
prior to full investigation amp operation
risk factors periosteal stripping off anterior femur male gender obesity post traumatic deformity Anterior and anterolateral approach Cementless
Neurogenic HO around the hip due to SCI occurs more often in the medial region than in the lateral region with ossified tissues extending from the pubic symphysis to the anteromedial femoral shaft posterior to the femoral neurovascular structures Ossification is also seen anteriorly involving the iliopsoas and femoral neurovascular structures laterally within gluteus minimus and posteriorly extending from the ilium to the posterior femur encasing the sciatic nerve
HTO AROUND hip and knee
The Brooker Classification of Heterotopic Ossification around the hip joint Class I has islands of bone within the soft tissues Class II has bone spurs from the pelvis or proximal end of the femur leaving at least 1 cm between opposing surfaces Class III has bone spurs from the pelvis andor proximal end of the femur reducing the space between opposing bone surfaces to less than 1 cm Class IV shows apparent bone ankylosis of the hip
Region I - Heterotopic ossifications are strictly below the tip of the greater trochanter
Region II - Heterotopic ossifications are below and above the tip of the greater trochanter
Region III - Heterotopic ossifications are strictly above the tip of the greater trochanter
Grade A - Single or multiple heterotopic ossifications are less than 10 mm in maximal extent without contact with the pelvis or the femur
Grade B - Heterotopic ossifications are greater than 10 mm without contact with the pelvis but with possible contact with the femur there is no bridging from the femur to the proximal part of the greater trochanter and no evidence of ankylosis
Grade C - Ankylosis by means of firm bridging from the femur to the pelvis is present
Shmidt classification
excision may be performed The results of this procedure are varied Patients may find that their range of movement improves but pain relief is likely to be limited
A patient with heterotopic ossification following total hip arthroplasty is thought to have a 90-100 chance of developing it on the contralateral hip if this hip also undergoes total arthroplasty
it would be prudent to minimize the risk of heterotopic ossification developing after arthroplasty by performing surgery whereby the following are ensured
Exposure is meticulous Retraction is performed carefully and soft tissue
is handled carefully Irrigation is adequate Devitalized tissue is excised Hemostasis is adequate Postoperative drains (when used) are not
retained for longer than necessary Perioperative antibiotic prophylaxis is used Postoperative anticoagulation (when used for
deep vein thrombosis prophylaxis) is carefully controlled
sources of knee stiffness 1-extrinsic severe osteoarthritis of the ipsilateral hip neurologic injury leading to muscle rigidity tight quadriceps or hamstring muscles secondary to muscle injury heterotopic ossification or long-standing juvenile inflammatory conditions limiting knee
range of motion prior to the completion of skeletal growth When extrinsic sources are identified revision total knee arthroplasty is unlikely to be associated with a favorable outcome without correction of the extrinsic problem
2-intrinsic (1) overstuffing of the patellofemoral articulation (2) an
excessively tight flexion andor extension gap (3) a tight posterior cruciate ligament (4) femoral andor tibial malrotation (5) arthrofibrosis and (6) limited bearing excursion in association with a highly conforming mobile-bearing prosthetic design
HTO after TKA
Heterotopic Ossification (HO) following primary Total Knee Replacement (TKR)
Occurs in 3-90 of TKRs 3-grade classification system No correlation between HO and component
alignment or component position
Clinical findings similar to early infection Continuing low-grade fever Warm swollen and erythematous knee Normal blood tests Possibly an association with HLA-A2 and B18 HO patients have worse KSS and function
scores
Patients at HIGH risk for developing HO after TKR (Knee Arthroplasty) (5)
Those with limited postoperative knee flexion
Increased lumbar bone mineral density (BMD) on multivariate analysis (3)
Hypertrophic arthrosis Excessive periosteal trauma Notching of the anterior femur Those who require forced manipulation
after TKA 47 in revision TKR surgery (6) Higher rates in revision TKR cases with
infection (up to 76
DaughertyBell classification of HO of the knee 0 No evidence of HO 1 Bone islands in periarticular soft tissue (no
involvement of femur patella or tibia) or HO within quadriceps expansion measuring lt1 cm
2 Spur formation measuring lt5 cm that involves the femur patella or tibia if more than one bone demonstrates HO separation of HO spurs
measure gt1 cm or HO within quadriceps expansion measuring ge1 cm but lt3 cm
3 Spur formation gt5 cm involving femur patella or tibia if more than one bone demonstrates HO separation of HO spurs measure lt1 cm or HO
within quadriceps expansion measuring ge3 cm 4 Extensive HO of the knee causing ankylosis
class 2 HO begins to involve the major bones of the knee joint with spur formation limited to a size of 5 cm
HO class 2 may be observed in select patients with complete ROM and no reported pain Patients with class 3 HO would likely always benefit from surgical excision
followed by RT prophylaxis Certainly patients in either cohort with a subclass ldquoBrdquo assignment (symptomatic) would
benefit from treatment All patients with class 4 HO require
treatment to alleviate ankylosis
treatment
References Whyte ldquoPagetrsquos Disease of Bonerdquo NEMJ vol 355
2006 Klein and Parvizi ldquoSurgical Manifestations of Pagetrsquos
Diseaserdquo JAAOS vol 14 2006 Orthobullets Campbell Apley Emedicinecom
-Chapter 15 Heterotopic Ossification after Traumatic Brain InjuryBy Jesuacutes Moreta and Joseacute Luis Martiacutenez-de los Mozos DOI 10577257343
Questions
Thank You
Langston et al conducted a randomized trial that compared the results of symptomatic treatment versus intensive bisphosphonate therapy in patients with Pagets disease Clinical fractures occurred in 46 of 661 patients (70) in the treatment group compared with 49 of 663 patients (74) in the symptomatic treatment group They concluded that bisphosphonates did not show a significant beneficial impact on pain quality of life or fracture incidence
Hadjipavlou et al reviewed Pagets disease of the bone and its management Farmers have been shown to have an increased incidence of Pagets disease Average age at presentation is in the 5th and 6th decade Symptomatic individuals are recommended to be treated initially with medical management They suggest that bisphosphonates are more effective than calcitonin at suppressing the histological and biochemical activity in Pagetrsquos disease
Summary Epid Very common in elderly Path Abnormal osteoclastshellipuarrbone
turnoverhellipdeposition of abnormal bone SampS Pain deformity fracture arthropathy Labs uarrAlkPhos X-ray Characteristic coarse thickened
trabeculae Bone scan Very hot Rx Bisphosphonates Surgery for arthropathy fracture painful
deformity
A 65-year-old male presents with increasing shoulder pain over the past 9 months He is otherwise healthy and has no other complaints Radiograph of his shoulder is shown in Figure A Whole body bone scan and biopsy photograph are shown in Figures B and C What is the most appropriate treatment for this patient
1 Referral to endocrinology 2 Radiation therapy and chemotherapy 3 Wide resection and reconstruction 4 Radiation therapy wide resection and reconstruction 5 Chemotherapy wide resection and reconstruction
Histiocytosis X or Langerhans cell histiocytosis is a spectrum of diseases of the reticuloendothelial system with one of three general presentations Eosinophilic granuloma (EG)
usually a single self-limited lesion found in younger patients
Hand-Schuller-Christian disease (HSC) chronic disseminated form with bone and visceral lesions also known as Langerhans cell histiocytosis with visceral
involvement Letterer-Siwe disease (LSD)
fatal form that occurs in young children
Eosinophilic granuloma
Epidemiology demographics
most commonly occurs in children (80 of afflicted lt 20 years of age)
HSC disease presents in children gt 3 years of age LSD occurs in children lt 3 years of age Male to female ratio of 21
location eosinophilic granuloma
commonly presents in the skull ribs clavicle scapula mandible
isolated lesions of the spine (thoracic most common) can also occur in diaphyseal regions of long bones and the
pelvis HSC
multiple bony sites multiple lytic skull lesions visceral involvement of the lungs spleen liver skin lymph
nodes
Genetics no clear genetic pattern of inheritance or locus has
been determined Prognosis
EG isolated involvement generally treatable with local
management spine lesions can spontaneously resolve
HSC prognosis depends on response to chemotherapy worsening prognosis with increasing extraskeletal
involvement LSD
generally fatal in children lt 3 years of age
Symptoms skeletal involvement
pain and swelling at the region of involvement limping can be seen with pelvic or lower extremity
involvement vertebral involvement
localized or diffuse back pain increasingly kyphotic posture radiculopathy can occur with more aggressive lesions
HSC classic triad of
multiple lytic skull lesions diabetes insipidus
increased thirst and water intake exopthalmos
visceral involvement diffuse or nonspecific abdominal or chest pain
Radiographs general
known as the great mimicker as it appears similar to many lesions radiographic differential includes osteomyelitis leukemia lymphoma
fibrous dysplasia or Ewings sarcoma diaphyseal lesions
well defined intramedullary lytic or punched-out lesion cortex may be thinned expanded or destroyed may have periosteal reaction
metaphyseal lesions extend up to but not through the physis less central location than diaphyseal lesions
spinal lesions vertebra plana (flattened vertebrae) in spine increased kyphosis
cranial involvement multiple punched-out lytic lesions
MRI may show a soft tissue mass adjacent to boney lesions
Bone scan generally shows increased uptake in the region of boney lesion
Histology Langerhans cells
mononuclear histiocyte-like cells with oval nuclei with well-defined round or oval cytoplasm
a prominent nuclear groove (coffee bean nuclei) can be seen in most of the nuclei
eosinophilic cytoplasm (pink generally) stain with CD1A electronmicroscopy
birbeck granules seen inside Langerhans cells mixture of inflammatory cells also present giant cells are present lack of nuclear atypia and atypical mitoses
differentiates this condition from malignant conditions such as Ewings sarcoma lymphoma of bone and metastatic neuroblastoma which may look similar based on the round cells alone
eosinophilic cytoplasm (pink generally)
Treatment
bullNonoperative bull observation alone
bull indications bull a self-limited process and it is reasonable to treat with observation alone
bull bracing bull indications
bull to prevent progressive kyphosis of the spinebull outcomes
bull will correct deformity in 90 of patientsbull vertebral lesions generally regain 50 of their height
bull low dose irradiation (600-800 cGy) bull indications
bull indicated for lesions in the spine that compromise stability neurologic statusbull lesions not amenable to injection or open treatment
bull outcomes bull effective for most lesions
bull chemotherapy bull indications
bull diffuse HSCbull outcomes
bull prognosis is improved with less severe extraskeletal involvementbull corticosteroid injection
bull indications bull isolated lesions bull can be performed after curettage as well
Operative curettage and bone grafting
indications for lesions that endanger the articular surface or are a risk for
impending fractures spinal deformity correction
indications progressive spine deformity refractory to bracing
approximately 10 of patients with spine lesion will need operative intervention for deformity correction
Destructive multiple lesion in young patientsAre eosinophilic granuloma lymphoma and leukemiaLymphoma is unlikely to present with exopthalmos diabetes insipidus or vertebra plana Lymphoma bone lesions are lytic and appear moth eatenpermeative on radiographs
Figure A shows a skin lesion typical of eosinophillic granuloma Figure B shows a lytic lesions without significant surrounding sclerosis as is characteristic of eosinophilic granuloma Figure C shows the characteristic histology of multiple eosinophils with their characteristic oval coffee bean nuclei and staining pattern of purpleredpink cytoplasm (depending on the stain) Importantly the histology slide lacks a malignant appearance (no cellular atypia or mytotic complexes and low nuclearcytoplasmic ratio)
Formation of bone in atypical extraskeletal tissues usually occurs
spontaneously or following trauma within 2 months of neurologic injury (brain or spinal cord)
most common location is between muscle and joint capsule Epidemiology
incidence (see table below)
demographics malefemale = 21 especially men with hypertrophic osteoarthritis and women gt65y
location traumatic brain injury or stroke
hip gt elbow gt shoulder gt knee elbow HO more common following brain trauma
occurs on affected (spastic) side rarely in the knee (TBI)
spinal cord injury hip gt knee gt elbow gt shoulder hip flexors and abductors gt extensors or adductors medial aspect of the knee
Heterotopic Ossification
Risk factors
Pathophysiology exact cause of HO is not known but there appears to be a
genetic pre disposition experimental HO associated with
tissue expression of BMP IT IS SAID TO BE CAUSED BY activation and proliferation of
mesenchymal stem cells Associated conditions
orthopaedic manifestations pathologic fractures
from decreased joint ROM and osteoporotic bone nerve impingement soft tissue contractures contributing to the formation of
decubitus ulcers joint ankylosis HO after THA adversely affects outcome of THA
nonorthopaedic conditions skin maceration and hygiene problems
Pathophysiology Early in the formation of HO oedema with exudative
infiltrate is present followed by fibroblastic proliferation and immature connective tissue formation Posteriorly osteoid formation is seen with the subsequent deposition of bone matrix Primitive osteoid is deposited as small masses in the periphery early (within the first two weeks) and osteoblasts are noted located irregularly Osteoblasts produce tropocollagen which polymerizes to form collagen and secrete alkaline phosphatase which allows calcium to precipitate and the mineralization of bone matrix As mineralization progresses amorphous calcium phosphate is progressively replaced by hydroxyapatite crystals During the following weeks the lesion matures with a centripetal pattern and after 6-12 months an appearance of true bone is noted The new bone is always extra-articular and can be contiguous with the skeleton but generally does not involve the periosteum
IN SUMMARY It has been postulated that three conditions
must be met to achieve heterotopic bone formation ---a stimulating event oestrogenic precursor cells and a proper environment LIKE hypercalcaemia tissue hypoxia pH changes (alkalosis) or prolonged immobilization
ClassificationbullSubtypes
bull neurogenic HO bull Four clinical stages of HO in people with spinal cord injury were
described by Nicholas in 1973
bull traumatic myositis ossificans bull fibrodysplasia ossificans progressiva (Munchmeyers Disease)
Neurogenic HO Symptoms
painless loss of ROM interferes with ADL CRPS symptoms fever
Physical exam inspection
warm painful swollen joint may have effusion skin problems
decubitus ulcers from contractures around skin muscles ligaments
skin maceration and hygiene problems motion
decreased joint ROM joint ankylosis with HO after TKA might develop quad muscle snapping or patella
instability neurovascular
peripheral neuropathy HO often impinges on adjacent NV structures
Imaging
bullRadiographs bull findings
bull ossification usually easy to visualize bull maturity of HO
bull the appearance of a bony cortex suggests mature HObull sharp demarcation from surrounding tissue bull trabecular pattern
bull sensitivity and specificity bull not useful for early diagnosisbull only useful at 1 week after onset of symptoms
bull calcium is deposited 7-10 days later than symptom onsetbullUltrasound
bull indications bull for early diagnosis of hip HO
bull findings bull echogenic surfaces with posterior acoustic shadowing
bullCT bull indications
bull useful for preoperative planning bullTriphasic bone scan
bull indications bull best for early diagnosis bull most commonly used diagnostic study
Radiographs are extremely useful in the staging of heterotopic ossification and will show the development of sharp cortical margins once the lesion has reached maturity
Heterotopic bone is a condition in which lamellar bone forms in non-ossified soft tissues In the early stages studies such as MRI and bone scan are more sensitive for diagnosis as radiographs may appear normal for the first three weeks After the appropriate diagnosis is made sequential radiographs are useful for monitoring the progression of the ossification Once it has reached the mature stage sharp cortical margins will appear and surgical resection may be considered
lab
Labs elevated serum alkaline phosphatase (gt250IUL)
ALP removes inhibitors of mineralization nonspecific may be elevated with skeletal trauma cannot determine maturity of HO elevated 12wks after surgery is predictor
elevated CRP correlates with inflammatory activity of HO better than ESR normalization of CRP may correlate with maturity of HO
elevated ESR (gt35mmh) 12wks after THA is predictor
elevated CK correlates with involvement of muscle extent of muscle
involvement Histology
mature fatty bone marrow mature trabecular bone
Heterotopic ossification (HO) most commonly occurs at the amputation site if the amputation was performed thru the zone of injury especially if the injury was a blast mechanism
Symptomatic heterotopic ossification of the quadriceps may occur following placement of a large-diameter Steinmann pin for the purpose of temporary skeletal traction
TreatmentThe prevention of heterotopic ossification is focused on three basic principles disrupting the inductive signalling pathways altering the osteoprogenitor cells or modifying the environment
bullphysiotherapy should involve an assisted range of movement exercises with gentle stretch and terminal resistance trainingbullProphylaxis
bull bisphosphonates amp NSAIDS bull indications
bull although no literature supports are commonly usedbull technique
bull indomethacin is most commonly used bull dose is 75mgday for 10days to 6 weeks
bull perioperative radiation bull indications
bull although no literature supports commonly usedbull is thought to be effective by blocking osteoblast differentiation
bull technique bull a single perioperative dose of 700cGy can be given either 4
hours preop or within 72 hours postoperatively bull lt550cGy not effective
Nonsteroidal anti-inflammatory drugs (NSAIDs) These drugs have demonstrated good results in
preventing heterotopic ossification after total hip arthroplasty
A direct effect of NSAIDs on the formation of heterotopic ossification has been described due to the inhibition of the differentiation of mesenchymal cells into oestrogenic cells There is also an indirect effect which refers to the inhibition of bone remodelling by suppression of the prostagland unmediated inflammatory response (specifically PGE-2)
Indomethacin has been considered a useful medication for heterotopic ossification prophylaxis following total hip replacement
prescribed for three to six weeks in a dose of 75mgday within two months of the injury may reduce the incidence of heterotopic ossification by two to three times
Biphosphonates inhibits precipitation of calcium phosphate and blocks the aggregation and mineralisation of hydroxyapatite crystals In primary prevention Banovac et al [56] have suggested that the treatment should begin as soon as elevated alkaline phosphatase is diagnosed or positive findings in ultrasonography or bone scans are shown In addition disphosphonates could have long-term effects on prevention when the treatment is finished
Posttraumatic wide exposure and surgical resection
indications severe loss of motion and decreased function
technique wide exposure required to identify all neurovascular
structures that may be involved timing of resection (controversial)
marked decrease in bone scan activity AND normalization of ALP
6 months following general trauma 1 year following SCI 15 years following TBI
some data suggests equivalent results when comparing early versus late resection
postop follow with 5 day course of indomethacin early gentle joint mobilization
The surgery is necessary in patients with symptomatic HO and unsuccessful medical treatment such as
Loss of range of motion and ankylosis with associated functional disability such as sitting difficulties
Complications of immobility such as pressure ulcers
Facilitate rehabilitation and recovery of muscular atrophy secondary to prolonged immobilisation
Difficulties of appropriate hygiene because access to the perineum or bladder care is needed
Severe pain refractory to analgesia Vascular andor nerve compression
Advantages to early excision of heterotopic ossification (vs waiting for maturation) include decreased soft tissue contracture better definition between heterotopic and native bone and decreased waiting time for the patient When the soft tissue envelope is benign one may proceed with operative release While waiting for normalization of alkaline phosphatase levels inactivity on bone scan or radiographic maturity may decrease risk of recurrent heterotopic ossification delaying operative release for these reasons has not been shown to improve results of final elbow range of motion after contracture release
Gartland recommended surgery after six months following traumatic heterotopic ossification one year following spinal cord injury and 18 months after head injury
In the past waiting until maturity in order to minimize the rate of recurrence after the surgical treatment was recommended Nevertheless recent studies do not confirm a higher rate of recurrence when the HO is excised in an earlier phase In addition a long delay before surgery leads to ankylosis a high degree of osteoporosis and more extensive intra-articular injuries These findings are associated with bad functional results and potential complications
Should you wait till lesion maturation
Prevention byHandle tissue carefully Avoid excess bleeding Achieve good hemostasis Beware of lesions that span internervous tissue planes
but if it happens resection of a large enough amount of bone to allow improvement of the range of motion and trying to preserve the joint
Our aim must be
A reactive process that is characterized by a well-circumscribed proliferation of fibroblasts cartilage and bone within muscle
A form of heterotopic ossification that is the result direct trauma intramuscular hematoma
most common location is the diaphysis of long bones Must differentiate from tumors Fibrodysplasia ossificans progressiva (FOP) is a rare subtype of heterotopic ossification
involves mutation of the ACVR1 gene (activin A type I receptor gene a BMP type-1 receptor)
Epidemiology demographics
most common in young active males (15 to 35 years old) body locations
quadriceps brachialis and gluteal muscles Genetics
almost always a posttraumatic condition Prognosis
usually self limiting mass usually begins to decrease in size after 1 yea
Myositis ossificans
PresentationbullSymptoms
bull pain tenderness swelling and decreased range of motion that usually presents within days of the injury
bull pain and size of the mass decrease with timebull mass increases in size over several months(usually 3 to 6 cm)
bull after the mass stops growing it becomes firmbullPhysical exam
bull palpable soft tissue massbull restricted range of motion
ImagingbullRadiographs
bull peripheral bone formation with central lucent areabull may appear as dotted veil pattern
bullMRI with gadolinium bull rim enhancement is seen within the first 3 weeks
bullCT scan bull lesion has an eggshell appearance
bullCharacteristic histology shows zonal pattern bull periphery of lesion
bull mature trabeculae of lamellar and woven bonebull calcification seen on xray
bull center of the lesion bull irregular mass of immature fibroblastsbull cartilage component may be presentbull (no calcification seen on xray) bull no cellular atypia seen
Treatment
bullNonoperative bull rest range of motion exercises and activity modification
bull passive stretching is contraindicated (makes it worse)bull physical therapy
bull utilized to maintain range of motionbull radiographic monitoring
bull obtained to confirm maturation of the lesionbullOperative
bull surgical excision bull indicated only if it remains a problem after it maturesbull do not operate in acute phase wait at least six months
bull excision of the lesion within 6 to 12 months predisposes to local recurrence
A 26-year-old man presents with generalized back and joint stiffness and difficulty opening his mouth His elder sister has similar complaints Since childhood he has had 3 surgeries for excision of recurrent bony prominences around his knees He walks with a stooped over posture seen in Figure A Radiographs of his feet knee hip and spine are seen in Figures B-E respectively
fibrodysplasia ossificans progressiva
Stone Man Disease) which involves a mutation of the ACVR1
There are 2 hallmark characteristics progressive heterotopic ossification (muscles fascia tendons ligaments and joint capsules) and congenital malformation of the great toe (hallux valgus malformed first metatarsal and monophalangism) BMP4 which contributes to the formation of the skeleton in the normal embryo is implicated in this disease
Complications
bullHematoma and intraoperative bleedingbullInfection
bull higher rate of infection following joint arthroplasty if HO is present
bullFractures of osteoporotic bone bull osteopenic from disusebull during surgery or physiotherapy
bullRecurrence bull recurrence rate correlates with neurological injury
bull greater recurrence if severe neurological compromisebullAVN
bull if extensive dissection or stripping is required
HTO AND ISS
When ISS is below 25 the mortality risk is minimal and above 25 it is an almost linear increase
When ISS is 50 the mortality is 50 When above 70 it is close to 100 If an injury is assigned an AIS of 6 (unsurvivable injury) the ISS score is
automatically assigned to 75 Highest ISS score obtainable is 75 For trauma patients of vehicular accidents the scoring system is important
for assessing the effectiveness of medical care in reducing morbidity and mortality
Advantages virtually the only anatomical scoring system in use correlates linearly with
mortality morbidity hospital stay other measures of severity
Weaknesses Any error in AIS scoring increases the ISS error Many different injury patterns can yield the same ISS score Injuries to different body regions are not weighted Not a useful triage tool as a full description of patient injuries is not known
prior to full investigation amp operation
risk factors periosteal stripping off anterior femur male gender obesity post traumatic deformity Anterior and anterolateral approach Cementless
Neurogenic HO around the hip due to SCI occurs more often in the medial region than in the lateral region with ossified tissues extending from the pubic symphysis to the anteromedial femoral shaft posterior to the femoral neurovascular structures Ossification is also seen anteriorly involving the iliopsoas and femoral neurovascular structures laterally within gluteus minimus and posteriorly extending from the ilium to the posterior femur encasing the sciatic nerve
HTO AROUND hip and knee
The Brooker Classification of Heterotopic Ossification around the hip joint Class I has islands of bone within the soft tissues Class II has bone spurs from the pelvis or proximal end of the femur leaving at least 1 cm between opposing surfaces Class III has bone spurs from the pelvis andor proximal end of the femur reducing the space between opposing bone surfaces to less than 1 cm Class IV shows apparent bone ankylosis of the hip
Region I - Heterotopic ossifications are strictly below the tip of the greater trochanter
Region II - Heterotopic ossifications are below and above the tip of the greater trochanter
Region III - Heterotopic ossifications are strictly above the tip of the greater trochanter
Grade A - Single or multiple heterotopic ossifications are less than 10 mm in maximal extent without contact with the pelvis or the femur
Grade B - Heterotopic ossifications are greater than 10 mm without contact with the pelvis but with possible contact with the femur there is no bridging from the femur to the proximal part of the greater trochanter and no evidence of ankylosis
Grade C - Ankylosis by means of firm bridging from the femur to the pelvis is present
Shmidt classification
excision may be performed The results of this procedure are varied Patients may find that their range of movement improves but pain relief is likely to be limited
A patient with heterotopic ossification following total hip arthroplasty is thought to have a 90-100 chance of developing it on the contralateral hip if this hip also undergoes total arthroplasty
it would be prudent to minimize the risk of heterotopic ossification developing after arthroplasty by performing surgery whereby the following are ensured
Exposure is meticulous Retraction is performed carefully and soft tissue
is handled carefully Irrigation is adequate Devitalized tissue is excised Hemostasis is adequate Postoperative drains (when used) are not
retained for longer than necessary Perioperative antibiotic prophylaxis is used Postoperative anticoagulation (when used for
deep vein thrombosis prophylaxis) is carefully controlled
sources of knee stiffness 1-extrinsic severe osteoarthritis of the ipsilateral hip neurologic injury leading to muscle rigidity tight quadriceps or hamstring muscles secondary to muscle injury heterotopic ossification or long-standing juvenile inflammatory conditions limiting knee
range of motion prior to the completion of skeletal growth When extrinsic sources are identified revision total knee arthroplasty is unlikely to be associated with a favorable outcome without correction of the extrinsic problem
2-intrinsic (1) overstuffing of the patellofemoral articulation (2) an
excessively tight flexion andor extension gap (3) a tight posterior cruciate ligament (4) femoral andor tibial malrotation (5) arthrofibrosis and (6) limited bearing excursion in association with a highly conforming mobile-bearing prosthetic design
HTO after TKA
Heterotopic Ossification (HO) following primary Total Knee Replacement (TKR)
Occurs in 3-90 of TKRs 3-grade classification system No correlation between HO and component
alignment or component position
Clinical findings similar to early infection Continuing low-grade fever Warm swollen and erythematous knee Normal blood tests Possibly an association with HLA-A2 and B18 HO patients have worse KSS and function
scores
Patients at HIGH risk for developing HO after TKR (Knee Arthroplasty) (5)
Those with limited postoperative knee flexion
Increased lumbar bone mineral density (BMD) on multivariate analysis (3)
Hypertrophic arthrosis Excessive periosteal trauma Notching of the anterior femur Those who require forced manipulation
after TKA 47 in revision TKR surgery (6) Higher rates in revision TKR cases with
infection (up to 76
DaughertyBell classification of HO of the knee 0 No evidence of HO 1 Bone islands in periarticular soft tissue (no
involvement of femur patella or tibia) or HO within quadriceps expansion measuring lt1 cm
2 Spur formation measuring lt5 cm that involves the femur patella or tibia if more than one bone demonstrates HO separation of HO spurs
measure gt1 cm or HO within quadriceps expansion measuring ge1 cm but lt3 cm
3 Spur formation gt5 cm involving femur patella or tibia if more than one bone demonstrates HO separation of HO spurs measure lt1 cm or HO
within quadriceps expansion measuring ge3 cm 4 Extensive HO of the knee causing ankylosis
class 2 HO begins to involve the major bones of the knee joint with spur formation limited to a size of 5 cm
HO class 2 may be observed in select patients with complete ROM and no reported pain Patients with class 3 HO would likely always benefit from surgical excision
followed by RT prophylaxis Certainly patients in either cohort with a subclass ldquoBrdquo assignment (symptomatic) would
benefit from treatment All patients with class 4 HO require
treatment to alleviate ankylosis
treatment
References Whyte ldquoPagetrsquos Disease of Bonerdquo NEMJ vol 355
2006 Klein and Parvizi ldquoSurgical Manifestations of Pagetrsquos
Diseaserdquo JAAOS vol 14 2006 Orthobullets Campbell Apley Emedicinecom
-Chapter 15 Heterotopic Ossification after Traumatic Brain InjuryBy Jesuacutes Moreta and Joseacute Luis Martiacutenez-de los Mozos DOI 10577257343
Questions
Thank You
Summary Epid Very common in elderly Path Abnormal osteoclastshellipuarrbone
turnoverhellipdeposition of abnormal bone SampS Pain deformity fracture arthropathy Labs uarrAlkPhos X-ray Characteristic coarse thickened
trabeculae Bone scan Very hot Rx Bisphosphonates Surgery for arthropathy fracture painful
deformity
A 65-year-old male presents with increasing shoulder pain over the past 9 months He is otherwise healthy and has no other complaints Radiograph of his shoulder is shown in Figure A Whole body bone scan and biopsy photograph are shown in Figures B and C What is the most appropriate treatment for this patient
1 Referral to endocrinology 2 Radiation therapy and chemotherapy 3 Wide resection and reconstruction 4 Radiation therapy wide resection and reconstruction 5 Chemotherapy wide resection and reconstruction
Histiocytosis X or Langerhans cell histiocytosis is a spectrum of diseases of the reticuloendothelial system with one of three general presentations Eosinophilic granuloma (EG)
usually a single self-limited lesion found in younger patients
Hand-Schuller-Christian disease (HSC) chronic disseminated form with bone and visceral lesions also known as Langerhans cell histiocytosis with visceral
involvement Letterer-Siwe disease (LSD)
fatal form that occurs in young children
Eosinophilic granuloma
Epidemiology demographics
most commonly occurs in children (80 of afflicted lt 20 years of age)
HSC disease presents in children gt 3 years of age LSD occurs in children lt 3 years of age Male to female ratio of 21
location eosinophilic granuloma
commonly presents in the skull ribs clavicle scapula mandible
isolated lesions of the spine (thoracic most common) can also occur in diaphyseal regions of long bones and the
pelvis HSC
multiple bony sites multiple lytic skull lesions visceral involvement of the lungs spleen liver skin lymph
nodes
Genetics no clear genetic pattern of inheritance or locus has
been determined Prognosis
EG isolated involvement generally treatable with local
management spine lesions can spontaneously resolve
HSC prognosis depends on response to chemotherapy worsening prognosis with increasing extraskeletal
involvement LSD
generally fatal in children lt 3 years of age
Symptoms skeletal involvement
pain and swelling at the region of involvement limping can be seen with pelvic or lower extremity
involvement vertebral involvement
localized or diffuse back pain increasingly kyphotic posture radiculopathy can occur with more aggressive lesions
HSC classic triad of
multiple lytic skull lesions diabetes insipidus
increased thirst and water intake exopthalmos
visceral involvement diffuse or nonspecific abdominal or chest pain
Radiographs general
known as the great mimicker as it appears similar to many lesions radiographic differential includes osteomyelitis leukemia lymphoma
fibrous dysplasia or Ewings sarcoma diaphyseal lesions
well defined intramedullary lytic or punched-out lesion cortex may be thinned expanded or destroyed may have periosteal reaction
metaphyseal lesions extend up to but not through the physis less central location than diaphyseal lesions
spinal lesions vertebra plana (flattened vertebrae) in spine increased kyphosis
cranial involvement multiple punched-out lytic lesions
MRI may show a soft tissue mass adjacent to boney lesions
Bone scan generally shows increased uptake in the region of boney lesion
Histology Langerhans cells
mononuclear histiocyte-like cells with oval nuclei with well-defined round or oval cytoplasm
a prominent nuclear groove (coffee bean nuclei) can be seen in most of the nuclei
eosinophilic cytoplasm (pink generally) stain with CD1A electronmicroscopy
birbeck granules seen inside Langerhans cells mixture of inflammatory cells also present giant cells are present lack of nuclear atypia and atypical mitoses
differentiates this condition from malignant conditions such as Ewings sarcoma lymphoma of bone and metastatic neuroblastoma which may look similar based on the round cells alone
eosinophilic cytoplasm (pink generally)
Treatment
bullNonoperative bull observation alone
bull indications bull a self-limited process and it is reasonable to treat with observation alone
bull bracing bull indications
bull to prevent progressive kyphosis of the spinebull outcomes
bull will correct deformity in 90 of patientsbull vertebral lesions generally regain 50 of their height
bull low dose irradiation (600-800 cGy) bull indications
bull indicated for lesions in the spine that compromise stability neurologic statusbull lesions not amenable to injection or open treatment
bull outcomes bull effective for most lesions
bull chemotherapy bull indications
bull diffuse HSCbull outcomes
bull prognosis is improved with less severe extraskeletal involvementbull corticosteroid injection
bull indications bull isolated lesions bull can be performed after curettage as well
Operative curettage and bone grafting
indications for lesions that endanger the articular surface or are a risk for
impending fractures spinal deformity correction
indications progressive spine deformity refractory to bracing
approximately 10 of patients with spine lesion will need operative intervention for deformity correction
Destructive multiple lesion in young patientsAre eosinophilic granuloma lymphoma and leukemiaLymphoma is unlikely to present with exopthalmos diabetes insipidus or vertebra plana Lymphoma bone lesions are lytic and appear moth eatenpermeative on radiographs
Figure A shows a skin lesion typical of eosinophillic granuloma Figure B shows a lytic lesions without significant surrounding sclerosis as is characteristic of eosinophilic granuloma Figure C shows the characteristic histology of multiple eosinophils with their characteristic oval coffee bean nuclei and staining pattern of purpleredpink cytoplasm (depending on the stain) Importantly the histology slide lacks a malignant appearance (no cellular atypia or mytotic complexes and low nuclearcytoplasmic ratio)
Formation of bone in atypical extraskeletal tissues usually occurs
spontaneously or following trauma within 2 months of neurologic injury (brain or spinal cord)
most common location is between muscle and joint capsule Epidemiology
incidence (see table below)
demographics malefemale = 21 especially men with hypertrophic osteoarthritis and women gt65y
location traumatic brain injury or stroke
hip gt elbow gt shoulder gt knee elbow HO more common following brain trauma
occurs on affected (spastic) side rarely in the knee (TBI)
spinal cord injury hip gt knee gt elbow gt shoulder hip flexors and abductors gt extensors or adductors medial aspect of the knee
Heterotopic Ossification
Risk factors
Pathophysiology exact cause of HO is not known but there appears to be a
genetic pre disposition experimental HO associated with
tissue expression of BMP IT IS SAID TO BE CAUSED BY activation and proliferation of
mesenchymal stem cells Associated conditions
orthopaedic manifestations pathologic fractures
from decreased joint ROM and osteoporotic bone nerve impingement soft tissue contractures contributing to the formation of
decubitus ulcers joint ankylosis HO after THA adversely affects outcome of THA
nonorthopaedic conditions skin maceration and hygiene problems
Pathophysiology Early in the formation of HO oedema with exudative
infiltrate is present followed by fibroblastic proliferation and immature connective tissue formation Posteriorly osteoid formation is seen with the subsequent deposition of bone matrix Primitive osteoid is deposited as small masses in the periphery early (within the first two weeks) and osteoblasts are noted located irregularly Osteoblasts produce tropocollagen which polymerizes to form collagen and secrete alkaline phosphatase which allows calcium to precipitate and the mineralization of bone matrix As mineralization progresses amorphous calcium phosphate is progressively replaced by hydroxyapatite crystals During the following weeks the lesion matures with a centripetal pattern and after 6-12 months an appearance of true bone is noted The new bone is always extra-articular and can be contiguous with the skeleton but generally does not involve the periosteum
IN SUMMARY It has been postulated that three conditions
must be met to achieve heterotopic bone formation ---a stimulating event oestrogenic precursor cells and a proper environment LIKE hypercalcaemia tissue hypoxia pH changes (alkalosis) or prolonged immobilization
ClassificationbullSubtypes
bull neurogenic HO bull Four clinical stages of HO in people with spinal cord injury were
described by Nicholas in 1973
bull traumatic myositis ossificans bull fibrodysplasia ossificans progressiva (Munchmeyers Disease)
Neurogenic HO Symptoms
painless loss of ROM interferes with ADL CRPS symptoms fever
Physical exam inspection
warm painful swollen joint may have effusion skin problems
decubitus ulcers from contractures around skin muscles ligaments
skin maceration and hygiene problems motion
decreased joint ROM joint ankylosis with HO after TKA might develop quad muscle snapping or patella
instability neurovascular
peripheral neuropathy HO often impinges on adjacent NV structures
Imaging
bullRadiographs bull findings
bull ossification usually easy to visualize bull maturity of HO
bull the appearance of a bony cortex suggests mature HObull sharp demarcation from surrounding tissue bull trabecular pattern
bull sensitivity and specificity bull not useful for early diagnosisbull only useful at 1 week after onset of symptoms
bull calcium is deposited 7-10 days later than symptom onsetbullUltrasound
bull indications bull for early diagnosis of hip HO
bull findings bull echogenic surfaces with posterior acoustic shadowing
bullCT bull indications
bull useful for preoperative planning bullTriphasic bone scan
bull indications bull best for early diagnosis bull most commonly used diagnostic study
Radiographs are extremely useful in the staging of heterotopic ossification and will show the development of sharp cortical margins once the lesion has reached maturity
Heterotopic bone is a condition in which lamellar bone forms in non-ossified soft tissues In the early stages studies such as MRI and bone scan are more sensitive for diagnosis as radiographs may appear normal for the first three weeks After the appropriate diagnosis is made sequential radiographs are useful for monitoring the progression of the ossification Once it has reached the mature stage sharp cortical margins will appear and surgical resection may be considered
lab
Labs elevated serum alkaline phosphatase (gt250IUL)
ALP removes inhibitors of mineralization nonspecific may be elevated with skeletal trauma cannot determine maturity of HO elevated 12wks after surgery is predictor
elevated CRP correlates with inflammatory activity of HO better than ESR normalization of CRP may correlate with maturity of HO
elevated ESR (gt35mmh) 12wks after THA is predictor
elevated CK correlates with involvement of muscle extent of muscle
involvement Histology
mature fatty bone marrow mature trabecular bone
Heterotopic ossification (HO) most commonly occurs at the amputation site if the amputation was performed thru the zone of injury especially if the injury was a blast mechanism
Symptomatic heterotopic ossification of the quadriceps may occur following placement of a large-diameter Steinmann pin for the purpose of temporary skeletal traction
TreatmentThe prevention of heterotopic ossification is focused on three basic principles disrupting the inductive signalling pathways altering the osteoprogenitor cells or modifying the environment
bullphysiotherapy should involve an assisted range of movement exercises with gentle stretch and terminal resistance trainingbullProphylaxis
bull bisphosphonates amp NSAIDS bull indications
bull although no literature supports are commonly usedbull technique
bull indomethacin is most commonly used bull dose is 75mgday for 10days to 6 weeks
bull perioperative radiation bull indications
bull although no literature supports commonly usedbull is thought to be effective by blocking osteoblast differentiation
bull technique bull a single perioperative dose of 700cGy can be given either 4
hours preop or within 72 hours postoperatively bull lt550cGy not effective
Nonsteroidal anti-inflammatory drugs (NSAIDs) These drugs have demonstrated good results in
preventing heterotopic ossification after total hip arthroplasty
A direct effect of NSAIDs on the formation of heterotopic ossification has been described due to the inhibition of the differentiation of mesenchymal cells into oestrogenic cells There is also an indirect effect which refers to the inhibition of bone remodelling by suppression of the prostagland unmediated inflammatory response (specifically PGE-2)
Indomethacin has been considered a useful medication for heterotopic ossification prophylaxis following total hip replacement
prescribed for three to six weeks in a dose of 75mgday within two months of the injury may reduce the incidence of heterotopic ossification by two to three times
Biphosphonates inhibits precipitation of calcium phosphate and blocks the aggregation and mineralisation of hydroxyapatite crystals In primary prevention Banovac et al [56] have suggested that the treatment should begin as soon as elevated alkaline phosphatase is diagnosed or positive findings in ultrasonography or bone scans are shown In addition disphosphonates could have long-term effects on prevention when the treatment is finished
Posttraumatic wide exposure and surgical resection
indications severe loss of motion and decreased function
technique wide exposure required to identify all neurovascular
structures that may be involved timing of resection (controversial)
marked decrease in bone scan activity AND normalization of ALP
6 months following general trauma 1 year following SCI 15 years following TBI
some data suggests equivalent results when comparing early versus late resection
postop follow with 5 day course of indomethacin early gentle joint mobilization
The surgery is necessary in patients with symptomatic HO and unsuccessful medical treatment such as
Loss of range of motion and ankylosis with associated functional disability such as sitting difficulties
Complications of immobility such as pressure ulcers
Facilitate rehabilitation and recovery of muscular atrophy secondary to prolonged immobilisation
Difficulties of appropriate hygiene because access to the perineum or bladder care is needed
Severe pain refractory to analgesia Vascular andor nerve compression
Advantages to early excision of heterotopic ossification (vs waiting for maturation) include decreased soft tissue contracture better definition between heterotopic and native bone and decreased waiting time for the patient When the soft tissue envelope is benign one may proceed with operative release While waiting for normalization of alkaline phosphatase levels inactivity on bone scan or radiographic maturity may decrease risk of recurrent heterotopic ossification delaying operative release for these reasons has not been shown to improve results of final elbow range of motion after contracture release
Gartland recommended surgery after six months following traumatic heterotopic ossification one year following spinal cord injury and 18 months after head injury
In the past waiting until maturity in order to minimize the rate of recurrence after the surgical treatment was recommended Nevertheless recent studies do not confirm a higher rate of recurrence when the HO is excised in an earlier phase In addition a long delay before surgery leads to ankylosis a high degree of osteoporosis and more extensive intra-articular injuries These findings are associated with bad functional results and potential complications
Should you wait till lesion maturation
Prevention byHandle tissue carefully Avoid excess bleeding Achieve good hemostasis Beware of lesions that span internervous tissue planes
but if it happens resection of a large enough amount of bone to allow improvement of the range of motion and trying to preserve the joint
Our aim must be
A reactive process that is characterized by a well-circumscribed proliferation of fibroblasts cartilage and bone within muscle
A form of heterotopic ossification that is the result direct trauma intramuscular hematoma
most common location is the diaphysis of long bones Must differentiate from tumors Fibrodysplasia ossificans progressiva (FOP) is a rare subtype of heterotopic ossification
involves mutation of the ACVR1 gene (activin A type I receptor gene a BMP type-1 receptor)
Epidemiology demographics
most common in young active males (15 to 35 years old) body locations
quadriceps brachialis and gluteal muscles Genetics
almost always a posttraumatic condition Prognosis
usually self limiting mass usually begins to decrease in size after 1 yea
Myositis ossificans
PresentationbullSymptoms
bull pain tenderness swelling and decreased range of motion that usually presents within days of the injury
bull pain and size of the mass decrease with timebull mass increases in size over several months(usually 3 to 6 cm)
bull after the mass stops growing it becomes firmbullPhysical exam
bull palpable soft tissue massbull restricted range of motion
ImagingbullRadiographs
bull peripheral bone formation with central lucent areabull may appear as dotted veil pattern
bullMRI with gadolinium bull rim enhancement is seen within the first 3 weeks
bullCT scan bull lesion has an eggshell appearance
bullCharacteristic histology shows zonal pattern bull periphery of lesion
bull mature trabeculae of lamellar and woven bonebull calcification seen on xray
bull center of the lesion bull irregular mass of immature fibroblastsbull cartilage component may be presentbull (no calcification seen on xray) bull no cellular atypia seen
Treatment
bullNonoperative bull rest range of motion exercises and activity modification
bull passive stretching is contraindicated (makes it worse)bull physical therapy
bull utilized to maintain range of motionbull radiographic monitoring
bull obtained to confirm maturation of the lesionbullOperative
bull surgical excision bull indicated only if it remains a problem after it maturesbull do not operate in acute phase wait at least six months
bull excision of the lesion within 6 to 12 months predisposes to local recurrence
A 26-year-old man presents with generalized back and joint stiffness and difficulty opening his mouth His elder sister has similar complaints Since childhood he has had 3 surgeries for excision of recurrent bony prominences around his knees He walks with a stooped over posture seen in Figure A Radiographs of his feet knee hip and spine are seen in Figures B-E respectively
fibrodysplasia ossificans progressiva
Stone Man Disease) which involves a mutation of the ACVR1
There are 2 hallmark characteristics progressive heterotopic ossification (muscles fascia tendons ligaments and joint capsules) and congenital malformation of the great toe (hallux valgus malformed first metatarsal and monophalangism) BMP4 which contributes to the formation of the skeleton in the normal embryo is implicated in this disease
Complications
bullHematoma and intraoperative bleedingbullInfection
bull higher rate of infection following joint arthroplasty if HO is present
bullFractures of osteoporotic bone bull osteopenic from disusebull during surgery or physiotherapy
bullRecurrence bull recurrence rate correlates with neurological injury
bull greater recurrence if severe neurological compromisebullAVN
bull if extensive dissection or stripping is required
HTO AND ISS
When ISS is below 25 the mortality risk is minimal and above 25 it is an almost linear increase
When ISS is 50 the mortality is 50 When above 70 it is close to 100 If an injury is assigned an AIS of 6 (unsurvivable injury) the ISS score is
automatically assigned to 75 Highest ISS score obtainable is 75 For trauma patients of vehicular accidents the scoring system is important
for assessing the effectiveness of medical care in reducing morbidity and mortality
Advantages virtually the only anatomical scoring system in use correlates linearly with
mortality morbidity hospital stay other measures of severity
Weaknesses Any error in AIS scoring increases the ISS error Many different injury patterns can yield the same ISS score Injuries to different body regions are not weighted Not a useful triage tool as a full description of patient injuries is not known
prior to full investigation amp operation
risk factors periosteal stripping off anterior femur male gender obesity post traumatic deformity Anterior and anterolateral approach Cementless
Neurogenic HO around the hip due to SCI occurs more often in the medial region than in the lateral region with ossified tissues extending from the pubic symphysis to the anteromedial femoral shaft posterior to the femoral neurovascular structures Ossification is also seen anteriorly involving the iliopsoas and femoral neurovascular structures laterally within gluteus minimus and posteriorly extending from the ilium to the posterior femur encasing the sciatic nerve
HTO AROUND hip and knee
The Brooker Classification of Heterotopic Ossification around the hip joint Class I has islands of bone within the soft tissues Class II has bone spurs from the pelvis or proximal end of the femur leaving at least 1 cm between opposing surfaces Class III has bone spurs from the pelvis andor proximal end of the femur reducing the space between opposing bone surfaces to less than 1 cm Class IV shows apparent bone ankylosis of the hip
Region I - Heterotopic ossifications are strictly below the tip of the greater trochanter
Region II - Heterotopic ossifications are below and above the tip of the greater trochanter
Region III - Heterotopic ossifications are strictly above the tip of the greater trochanter
Grade A - Single or multiple heterotopic ossifications are less than 10 mm in maximal extent without contact with the pelvis or the femur
Grade B - Heterotopic ossifications are greater than 10 mm without contact with the pelvis but with possible contact with the femur there is no bridging from the femur to the proximal part of the greater trochanter and no evidence of ankylosis
Grade C - Ankylosis by means of firm bridging from the femur to the pelvis is present
Shmidt classification
excision may be performed The results of this procedure are varied Patients may find that their range of movement improves but pain relief is likely to be limited
A patient with heterotopic ossification following total hip arthroplasty is thought to have a 90-100 chance of developing it on the contralateral hip if this hip also undergoes total arthroplasty
it would be prudent to minimize the risk of heterotopic ossification developing after arthroplasty by performing surgery whereby the following are ensured
Exposure is meticulous Retraction is performed carefully and soft tissue
is handled carefully Irrigation is adequate Devitalized tissue is excised Hemostasis is adequate Postoperative drains (when used) are not
retained for longer than necessary Perioperative antibiotic prophylaxis is used Postoperative anticoagulation (when used for
deep vein thrombosis prophylaxis) is carefully controlled
sources of knee stiffness 1-extrinsic severe osteoarthritis of the ipsilateral hip neurologic injury leading to muscle rigidity tight quadriceps or hamstring muscles secondary to muscle injury heterotopic ossification or long-standing juvenile inflammatory conditions limiting knee
range of motion prior to the completion of skeletal growth When extrinsic sources are identified revision total knee arthroplasty is unlikely to be associated with a favorable outcome without correction of the extrinsic problem
2-intrinsic (1) overstuffing of the patellofemoral articulation (2) an
excessively tight flexion andor extension gap (3) a tight posterior cruciate ligament (4) femoral andor tibial malrotation (5) arthrofibrosis and (6) limited bearing excursion in association with a highly conforming mobile-bearing prosthetic design
HTO after TKA
Heterotopic Ossification (HO) following primary Total Knee Replacement (TKR)
Occurs in 3-90 of TKRs 3-grade classification system No correlation between HO and component
alignment or component position
Clinical findings similar to early infection Continuing low-grade fever Warm swollen and erythematous knee Normal blood tests Possibly an association with HLA-A2 and B18 HO patients have worse KSS and function
scores
Patients at HIGH risk for developing HO after TKR (Knee Arthroplasty) (5)
Those with limited postoperative knee flexion
Increased lumbar bone mineral density (BMD) on multivariate analysis (3)
Hypertrophic arthrosis Excessive periosteal trauma Notching of the anterior femur Those who require forced manipulation
after TKA 47 in revision TKR surgery (6) Higher rates in revision TKR cases with
infection (up to 76
DaughertyBell classification of HO of the knee 0 No evidence of HO 1 Bone islands in periarticular soft tissue (no
involvement of femur patella or tibia) or HO within quadriceps expansion measuring lt1 cm
2 Spur formation measuring lt5 cm that involves the femur patella or tibia if more than one bone demonstrates HO separation of HO spurs
measure gt1 cm or HO within quadriceps expansion measuring ge1 cm but lt3 cm
3 Spur formation gt5 cm involving femur patella or tibia if more than one bone demonstrates HO separation of HO spurs measure lt1 cm or HO
within quadriceps expansion measuring ge3 cm 4 Extensive HO of the knee causing ankylosis
class 2 HO begins to involve the major bones of the knee joint with spur formation limited to a size of 5 cm
HO class 2 may be observed in select patients with complete ROM and no reported pain Patients with class 3 HO would likely always benefit from surgical excision
followed by RT prophylaxis Certainly patients in either cohort with a subclass ldquoBrdquo assignment (symptomatic) would
benefit from treatment All patients with class 4 HO require
treatment to alleviate ankylosis
treatment
References Whyte ldquoPagetrsquos Disease of Bonerdquo NEMJ vol 355
2006 Klein and Parvizi ldquoSurgical Manifestations of Pagetrsquos
Diseaserdquo JAAOS vol 14 2006 Orthobullets Campbell Apley Emedicinecom
-Chapter 15 Heterotopic Ossification after Traumatic Brain InjuryBy Jesuacutes Moreta and Joseacute Luis Martiacutenez-de los Mozos DOI 10577257343
Questions
Thank You
A 65-year-old male presents with increasing shoulder pain over the past 9 months He is otherwise healthy and has no other complaints Radiograph of his shoulder is shown in Figure A Whole body bone scan and biopsy photograph are shown in Figures B and C What is the most appropriate treatment for this patient
1 Referral to endocrinology 2 Radiation therapy and chemotherapy 3 Wide resection and reconstruction 4 Radiation therapy wide resection and reconstruction 5 Chemotherapy wide resection and reconstruction
Histiocytosis X or Langerhans cell histiocytosis is a spectrum of diseases of the reticuloendothelial system with one of three general presentations Eosinophilic granuloma (EG)
usually a single self-limited lesion found in younger patients
Hand-Schuller-Christian disease (HSC) chronic disseminated form with bone and visceral lesions also known as Langerhans cell histiocytosis with visceral
involvement Letterer-Siwe disease (LSD)
fatal form that occurs in young children
Eosinophilic granuloma
Epidemiology demographics
most commonly occurs in children (80 of afflicted lt 20 years of age)
HSC disease presents in children gt 3 years of age LSD occurs in children lt 3 years of age Male to female ratio of 21
location eosinophilic granuloma
commonly presents in the skull ribs clavicle scapula mandible
isolated lesions of the spine (thoracic most common) can also occur in diaphyseal regions of long bones and the
pelvis HSC
multiple bony sites multiple lytic skull lesions visceral involvement of the lungs spleen liver skin lymph
nodes
Genetics no clear genetic pattern of inheritance or locus has
been determined Prognosis
EG isolated involvement generally treatable with local
management spine lesions can spontaneously resolve
HSC prognosis depends on response to chemotherapy worsening prognosis with increasing extraskeletal
involvement LSD
generally fatal in children lt 3 years of age
Symptoms skeletal involvement
pain and swelling at the region of involvement limping can be seen with pelvic or lower extremity
involvement vertebral involvement
localized or diffuse back pain increasingly kyphotic posture radiculopathy can occur with more aggressive lesions
HSC classic triad of
multiple lytic skull lesions diabetes insipidus
increased thirst and water intake exopthalmos
visceral involvement diffuse or nonspecific abdominal or chest pain
Radiographs general
known as the great mimicker as it appears similar to many lesions radiographic differential includes osteomyelitis leukemia lymphoma
fibrous dysplasia or Ewings sarcoma diaphyseal lesions
well defined intramedullary lytic or punched-out lesion cortex may be thinned expanded or destroyed may have periosteal reaction
metaphyseal lesions extend up to but not through the physis less central location than diaphyseal lesions
spinal lesions vertebra plana (flattened vertebrae) in spine increased kyphosis
cranial involvement multiple punched-out lytic lesions
MRI may show a soft tissue mass adjacent to boney lesions
Bone scan generally shows increased uptake in the region of boney lesion
Histology Langerhans cells
mononuclear histiocyte-like cells with oval nuclei with well-defined round or oval cytoplasm
a prominent nuclear groove (coffee bean nuclei) can be seen in most of the nuclei
eosinophilic cytoplasm (pink generally) stain with CD1A electronmicroscopy
birbeck granules seen inside Langerhans cells mixture of inflammatory cells also present giant cells are present lack of nuclear atypia and atypical mitoses
differentiates this condition from malignant conditions such as Ewings sarcoma lymphoma of bone and metastatic neuroblastoma which may look similar based on the round cells alone
eosinophilic cytoplasm (pink generally)
Treatment
bullNonoperative bull observation alone
bull indications bull a self-limited process and it is reasonable to treat with observation alone
bull bracing bull indications
bull to prevent progressive kyphosis of the spinebull outcomes
bull will correct deformity in 90 of patientsbull vertebral lesions generally regain 50 of their height
bull low dose irradiation (600-800 cGy) bull indications
bull indicated for lesions in the spine that compromise stability neurologic statusbull lesions not amenable to injection or open treatment
bull outcomes bull effective for most lesions
bull chemotherapy bull indications
bull diffuse HSCbull outcomes
bull prognosis is improved with less severe extraskeletal involvementbull corticosteroid injection
bull indications bull isolated lesions bull can be performed after curettage as well
Operative curettage and bone grafting
indications for lesions that endanger the articular surface or are a risk for
impending fractures spinal deformity correction
indications progressive spine deformity refractory to bracing
approximately 10 of patients with spine lesion will need operative intervention for deformity correction
Destructive multiple lesion in young patientsAre eosinophilic granuloma lymphoma and leukemiaLymphoma is unlikely to present with exopthalmos diabetes insipidus or vertebra plana Lymphoma bone lesions are lytic and appear moth eatenpermeative on radiographs
Figure A shows a skin lesion typical of eosinophillic granuloma Figure B shows a lytic lesions without significant surrounding sclerosis as is characteristic of eosinophilic granuloma Figure C shows the characteristic histology of multiple eosinophils with their characteristic oval coffee bean nuclei and staining pattern of purpleredpink cytoplasm (depending on the stain) Importantly the histology slide lacks a malignant appearance (no cellular atypia or mytotic complexes and low nuclearcytoplasmic ratio)
Formation of bone in atypical extraskeletal tissues usually occurs
spontaneously or following trauma within 2 months of neurologic injury (brain or spinal cord)
most common location is between muscle and joint capsule Epidemiology
incidence (see table below)
demographics malefemale = 21 especially men with hypertrophic osteoarthritis and women gt65y
location traumatic brain injury or stroke
hip gt elbow gt shoulder gt knee elbow HO more common following brain trauma
occurs on affected (spastic) side rarely in the knee (TBI)
spinal cord injury hip gt knee gt elbow gt shoulder hip flexors and abductors gt extensors or adductors medial aspect of the knee
Heterotopic Ossification
Risk factors
Pathophysiology exact cause of HO is not known but there appears to be a
genetic pre disposition experimental HO associated with
tissue expression of BMP IT IS SAID TO BE CAUSED BY activation and proliferation of
mesenchymal stem cells Associated conditions
orthopaedic manifestations pathologic fractures
from decreased joint ROM and osteoporotic bone nerve impingement soft tissue contractures contributing to the formation of
decubitus ulcers joint ankylosis HO after THA adversely affects outcome of THA
nonorthopaedic conditions skin maceration and hygiene problems
Pathophysiology Early in the formation of HO oedema with exudative
infiltrate is present followed by fibroblastic proliferation and immature connective tissue formation Posteriorly osteoid formation is seen with the subsequent deposition of bone matrix Primitive osteoid is deposited as small masses in the periphery early (within the first two weeks) and osteoblasts are noted located irregularly Osteoblasts produce tropocollagen which polymerizes to form collagen and secrete alkaline phosphatase which allows calcium to precipitate and the mineralization of bone matrix As mineralization progresses amorphous calcium phosphate is progressively replaced by hydroxyapatite crystals During the following weeks the lesion matures with a centripetal pattern and after 6-12 months an appearance of true bone is noted The new bone is always extra-articular and can be contiguous with the skeleton but generally does not involve the periosteum
IN SUMMARY It has been postulated that three conditions
must be met to achieve heterotopic bone formation ---a stimulating event oestrogenic precursor cells and a proper environment LIKE hypercalcaemia tissue hypoxia pH changes (alkalosis) or prolonged immobilization
ClassificationbullSubtypes
bull neurogenic HO bull Four clinical stages of HO in people with spinal cord injury were
described by Nicholas in 1973
bull traumatic myositis ossificans bull fibrodysplasia ossificans progressiva (Munchmeyers Disease)
Neurogenic HO Symptoms
painless loss of ROM interferes with ADL CRPS symptoms fever
Physical exam inspection
warm painful swollen joint may have effusion skin problems
decubitus ulcers from contractures around skin muscles ligaments
skin maceration and hygiene problems motion
decreased joint ROM joint ankylosis with HO after TKA might develop quad muscle snapping or patella
instability neurovascular
peripheral neuropathy HO often impinges on adjacent NV structures
Imaging
bullRadiographs bull findings
bull ossification usually easy to visualize bull maturity of HO
bull the appearance of a bony cortex suggests mature HObull sharp demarcation from surrounding tissue bull trabecular pattern
bull sensitivity and specificity bull not useful for early diagnosisbull only useful at 1 week after onset of symptoms
bull calcium is deposited 7-10 days later than symptom onsetbullUltrasound
bull indications bull for early diagnosis of hip HO
bull findings bull echogenic surfaces with posterior acoustic shadowing
bullCT bull indications
bull useful for preoperative planning bullTriphasic bone scan
bull indications bull best for early diagnosis bull most commonly used diagnostic study
Radiographs are extremely useful in the staging of heterotopic ossification and will show the development of sharp cortical margins once the lesion has reached maturity
Heterotopic bone is a condition in which lamellar bone forms in non-ossified soft tissues In the early stages studies such as MRI and bone scan are more sensitive for diagnosis as radiographs may appear normal for the first three weeks After the appropriate diagnosis is made sequential radiographs are useful for monitoring the progression of the ossification Once it has reached the mature stage sharp cortical margins will appear and surgical resection may be considered
lab
Labs elevated serum alkaline phosphatase (gt250IUL)
ALP removes inhibitors of mineralization nonspecific may be elevated with skeletal trauma cannot determine maturity of HO elevated 12wks after surgery is predictor
elevated CRP correlates with inflammatory activity of HO better than ESR normalization of CRP may correlate with maturity of HO
elevated ESR (gt35mmh) 12wks after THA is predictor
elevated CK correlates with involvement of muscle extent of muscle
involvement Histology
mature fatty bone marrow mature trabecular bone
Heterotopic ossification (HO) most commonly occurs at the amputation site if the amputation was performed thru the zone of injury especially if the injury was a blast mechanism
Symptomatic heterotopic ossification of the quadriceps may occur following placement of a large-diameter Steinmann pin for the purpose of temporary skeletal traction
TreatmentThe prevention of heterotopic ossification is focused on three basic principles disrupting the inductive signalling pathways altering the osteoprogenitor cells or modifying the environment
bullphysiotherapy should involve an assisted range of movement exercises with gentle stretch and terminal resistance trainingbullProphylaxis
bull bisphosphonates amp NSAIDS bull indications
bull although no literature supports are commonly usedbull technique
bull indomethacin is most commonly used bull dose is 75mgday for 10days to 6 weeks
bull perioperative radiation bull indications
bull although no literature supports commonly usedbull is thought to be effective by blocking osteoblast differentiation
bull technique bull a single perioperative dose of 700cGy can be given either 4
hours preop or within 72 hours postoperatively bull lt550cGy not effective
Nonsteroidal anti-inflammatory drugs (NSAIDs) These drugs have demonstrated good results in
preventing heterotopic ossification after total hip arthroplasty
A direct effect of NSAIDs on the formation of heterotopic ossification has been described due to the inhibition of the differentiation of mesenchymal cells into oestrogenic cells There is also an indirect effect which refers to the inhibition of bone remodelling by suppression of the prostagland unmediated inflammatory response (specifically PGE-2)
Indomethacin has been considered a useful medication for heterotopic ossification prophylaxis following total hip replacement
prescribed for three to six weeks in a dose of 75mgday within two months of the injury may reduce the incidence of heterotopic ossification by two to three times
Biphosphonates inhibits precipitation of calcium phosphate and blocks the aggregation and mineralisation of hydroxyapatite crystals In primary prevention Banovac et al [56] have suggested that the treatment should begin as soon as elevated alkaline phosphatase is diagnosed or positive findings in ultrasonography or bone scans are shown In addition disphosphonates could have long-term effects on prevention when the treatment is finished
Posttraumatic wide exposure and surgical resection
indications severe loss of motion and decreased function
technique wide exposure required to identify all neurovascular
structures that may be involved timing of resection (controversial)
marked decrease in bone scan activity AND normalization of ALP
6 months following general trauma 1 year following SCI 15 years following TBI
some data suggests equivalent results when comparing early versus late resection
postop follow with 5 day course of indomethacin early gentle joint mobilization
The surgery is necessary in patients with symptomatic HO and unsuccessful medical treatment such as
Loss of range of motion and ankylosis with associated functional disability such as sitting difficulties
Complications of immobility such as pressure ulcers
Facilitate rehabilitation and recovery of muscular atrophy secondary to prolonged immobilisation
Difficulties of appropriate hygiene because access to the perineum or bladder care is needed
Severe pain refractory to analgesia Vascular andor nerve compression
Advantages to early excision of heterotopic ossification (vs waiting for maturation) include decreased soft tissue contracture better definition between heterotopic and native bone and decreased waiting time for the patient When the soft tissue envelope is benign one may proceed with operative release While waiting for normalization of alkaline phosphatase levels inactivity on bone scan or radiographic maturity may decrease risk of recurrent heterotopic ossification delaying operative release for these reasons has not been shown to improve results of final elbow range of motion after contracture release
Gartland recommended surgery after six months following traumatic heterotopic ossification one year following spinal cord injury and 18 months after head injury
In the past waiting until maturity in order to minimize the rate of recurrence after the surgical treatment was recommended Nevertheless recent studies do not confirm a higher rate of recurrence when the HO is excised in an earlier phase In addition a long delay before surgery leads to ankylosis a high degree of osteoporosis and more extensive intra-articular injuries These findings are associated with bad functional results and potential complications
Should you wait till lesion maturation
Prevention byHandle tissue carefully Avoid excess bleeding Achieve good hemostasis Beware of lesions that span internervous tissue planes
but if it happens resection of a large enough amount of bone to allow improvement of the range of motion and trying to preserve the joint
Our aim must be
A reactive process that is characterized by a well-circumscribed proliferation of fibroblasts cartilage and bone within muscle
A form of heterotopic ossification that is the result direct trauma intramuscular hematoma
most common location is the diaphysis of long bones Must differentiate from tumors Fibrodysplasia ossificans progressiva (FOP) is a rare subtype of heterotopic ossification
involves mutation of the ACVR1 gene (activin A type I receptor gene a BMP type-1 receptor)
Epidemiology demographics
most common in young active males (15 to 35 years old) body locations
quadriceps brachialis and gluteal muscles Genetics
almost always a posttraumatic condition Prognosis
usually self limiting mass usually begins to decrease in size after 1 yea
Myositis ossificans
PresentationbullSymptoms
bull pain tenderness swelling and decreased range of motion that usually presents within days of the injury
bull pain and size of the mass decrease with timebull mass increases in size over several months(usually 3 to 6 cm)
bull after the mass stops growing it becomes firmbullPhysical exam
bull palpable soft tissue massbull restricted range of motion
ImagingbullRadiographs
bull peripheral bone formation with central lucent areabull may appear as dotted veil pattern
bullMRI with gadolinium bull rim enhancement is seen within the first 3 weeks
bullCT scan bull lesion has an eggshell appearance
bullCharacteristic histology shows zonal pattern bull periphery of lesion
bull mature trabeculae of lamellar and woven bonebull calcification seen on xray
bull center of the lesion bull irregular mass of immature fibroblastsbull cartilage component may be presentbull (no calcification seen on xray) bull no cellular atypia seen
Treatment
bullNonoperative bull rest range of motion exercises and activity modification
bull passive stretching is contraindicated (makes it worse)bull physical therapy
bull utilized to maintain range of motionbull radiographic monitoring
bull obtained to confirm maturation of the lesionbullOperative
bull surgical excision bull indicated only if it remains a problem after it maturesbull do not operate in acute phase wait at least six months
bull excision of the lesion within 6 to 12 months predisposes to local recurrence
A 26-year-old man presents with generalized back and joint stiffness and difficulty opening his mouth His elder sister has similar complaints Since childhood he has had 3 surgeries for excision of recurrent bony prominences around his knees He walks with a stooped over posture seen in Figure A Radiographs of his feet knee hip and spine are seen in Figures B-E respectively
fibrodysplasia ossificans progressiva
Stone Man Disease) which involves a mutation of the ACVR1
There are 2 hallmark characteristics progressive heterotopic ossification (muscles fascia tendons ligaments and joint capsules) and congenital malformation of the great toe (hallux valgus malformed first metatarsal and monophalangism) BMP4 which contributes to the formation of the skeleton in the normal embryo is implicated in this disease
Complications
bullHematoma and intraoperative bleedingbullInfection
bull higher rate of infection following joint arthroplasty if HO is present
bullFractures of osteoporotic bone bull osteopenic from disusebull during surgery or physiotherapy
bullRecurrence bull recurrence rate correlates with neurological injury
bull greater recurrence if severe neurological compromisebullAVN
bull if extensive dissection or stripping is required
HTO AND ISS
When ISS is below 25 the mortality risk is minimal and above 25 it is an almost linear increase
When ISS is 50 the mortality is 50 When above 70 it is close to 100 If an injury is assigned an AIS of 6 (unsurvivable injury) the ISS score is
automatically assigned to 75 Highest ISS score obtainable is 75 For trauma patients of vehicular accidents the scoring system is important
for assessing the effectiveness of medical care in reducing morbidity and mortality
Advantages virtually the only anatomical scoring system in use correlates linearly with
mortality morbidity hospital stay other measures of severity
Weaknesses Any error in AIS scoring increases the ISS error Many different injury patterns can yield the same ISS score Injuries to different body regions are not weighted Not a useful triage tool as a full description of patient injuries is not known
prior to full investigation amp operation
risk factors periosteal stripping off anterior femur male gender obesity post traumatic deformity Anterior and anterolateral approach Cementless
Neurogenic HO around the hip due to SCI occurs more often in the medial region than in the lateral region with ossified tissues extending from the pubic symphysis to the anteromedial femoral shaft posterior to the femoral neurovascular structures Ossification is also seen anteriorly involving the iliopsoas and femoral neurovascular structures laterally within gluteus minimus and posteriorly extending from the ilium to the posterior femur encasing the sciatic nerve
HTO AROUND hip and knee
The Brooker Classification of Heterotopic Ossification around the hip joint Class I has islands of bone within the soft tissues Class II has bone spurs from the pelvis or proximal end of the femur leaving at least 1 cm between opposing surfaces Class III has bone spurs from the pelvis andor proximal end of the femur reducing the space between opposing bone surfaces to less than 1 cm Class IV shows apparent bone ankylosis of the hip
Region I - Heterotopic ossifications are strictly below the tip of the greater trochanter
Region II - Heterotopic ossifications are below and above the tip of the greater trochanter
Region III - Heterotopic ossifications are strictly above the tip of the greater trochanter
Grade A - Single or multiple heterotopic ossifications are less than 10 mm in maximal extent without contact with the pelvis or the femur
Grade B - Heterotopic ossifications are greater than 10 mm without contact with the pelvis but with possible contact with the femur there is no bridging from the femur to the proximal part of the greater trochanter and no evidence of ankylosis
Grade C - Ankylosis by means of firm bridging from the femur to the pelvis is present
Shmidt classification
excision may be performed The results of this procedure are varied Patients may find that their range of movement improves but pain relief is likely to be limited
A patient with heterotopic ossification following total hip arthroplasty is thought to have a 90-100 chance of developing it on the contralateral hip if this hip also undergoes total arthroplasty
it would be prudent to minimize the risk of heterotopic ossification developing after arthroplasty by performing surgery whereby the following are ensured
Exposure is meticulous Retraction is performed carefully and soft tissue
is handled carefully Irrigation is adequate Devitalized tissue is excised Hemostasis is adequate Postoperative drains (when used) are not
retained for longer than necessary Perioperative antibiotic prophylaxis is used Postoperative anticoagulation (when used for
deep vein thrombosis prophylaxis) is carefully controlled
sources of knee stiffness 1-extrinsic severe osteoarthritis of the ipsilateral hip neurologic injury leading to muscle rigidity tight quadriceps or hamstring muscles secondary to muscle injury heterotopic ossification or long-standing juvenile inflammatory conditions limiting knee
range of motion prior to the completion of skeletal growth When extrinsic sources are identified revision total knee arthroplasty is unlikely to be associated with a favorable outcome without correction of the extrinsic problem
2-intrinsic (1) overstuffing of the patellofemoral articulation (2) an
excessively tight flexion andor extension gap (3) a tight posterior cruciate ligament (4) femoral andor tibial malrotation (5) arthrofibrosis and (6) limited bearing excursion in association with a highly conforming mobile-bearing prosthetic design
HTO after TKA
Heterotopic Ossification (HO) following primary Total Knee Replacement (TKR)
Occurs in 3-90 of TKRs 3-grade classification system No correlation between HO and component
alignment or component position
Clinical findings similar to early infection Continuing low-grade fever Warm swollen and erythematous knee Normal blood tests Possibly an association with HLA-A2 and B18 HO patients have worse KSS and function
scores
Patients at HIGH risk for developing HO after TKR (Knee Arthroplasty) (5)
Those with limited postoperative knee flexion
Increased lumbar bone mineral density (BMD) on multivariate analysis (3)
Hypertrophic arthrosis Excessive periosteal trauma Notching of the anterior femur Those who require forced manipulation
after TKA 47 in revision TKR surgery (6) Higher rates in revision TKR cases with
infection (up to 76
DaughertyBell classification of HO of the knee 0 No evidence of HO 1 Bone islands in periarticular soft tissue (no
involvement of femur patella or tibia) or HO within quadriceps expansion measuring lt1 cm
2 Spur formation measuring lt5 cm that involves the femur patella or tibia if more than one bone demonstrates HO separation of HO spurs
measure gt1 cm or HO within quadriceps expansion measuring ge1 cm but lt3 cm
3 Spur formation gt5 cm involving femur patella or tibia if more than one bone demonstrates HO separation of HO spurs measure lt1 cm or HO
within quadriceps expansion measuring ge3 cm 4 Extensive HO of the knee causing ankylosis
class 2 HO begins to involve the major bones of the knee joint with spur formation limited to a size of 5 cm
HO class 2 may be observed in select patients with complete ROM and no reported pain Patients with class 3 HO would likely always benefit from surgical excision
followed by RT prophylaxis Certainly patients in either cohort with a subclass ldquoBrdquo assignment (symptomatic) would
benefit from treatment All patients with class 4 HO require
treatment to alleviate ankylosis
treatment
References Whyte ldquoPagetrsquos Disease of Bonerdquo NEMJ vol 355
2006 Klein and Parvizi ldquoSurgical Manifestations of Pagetrsquos
Diseaserdquo JAAOS vol 14 2006 Orthobullets Campbell Apley Emedicinecom
-Chapter 15 Heterotopic Ossification after Traumatic Brain InjuryBy Jesuacutes Moreta and Joseacute Luis Martiacutenez-de los Mozos DOI 10577257343
Questions
Thank You
1 Referral to endocrinology 2 Radiation therapy and chemotherapy 3 Wide resection and reconstruction 4 Radiation therapy wide resection and reconstruction 5 Chemotherapy wide resection and reconstruction
Histiocytosis X or Langerhans cell histiocytosis is a spectrum of diseases of the reticuloendothelial system with one of three general presentations Eosinophilic granuloma (EG)
usually a single self-limited lesion found in younger patients
Hand-Schuller-Christian disease (HSC) chronic disseminated form with bone and visceral lesions also known as Langerhans cell histiocytosis with visceral
involvement Letterer-Siwe disease (LSD)
fatal form that occurs in young children
Eosinophilic granuloma
Epidemiology demographics
most commonly occurs in children (80 of afflicted lt 20 years of age)
HSC disease presents in children gt 3 years of age LSD occurs in children lt 3 years of age Male to female ratio of 21
location eosinophilic granuloma
commonly presents in the skull ribs clavicle scapula mandible
isolated lesions of the spine (thoracic most common) can also occur in diaphyseal regions of long bones and the
pelvis HSC
multiple bony sites multiple lytic skull lesions visceral involvement of the lungs spleen liver skin lymph
nodes
Genetics no clear genetic pattern of inheritance or locus has
been determined Prognosis
EG isolated involvement generally treatable with local
management spine lesions can spontaneously resolve
HSC prognosis depends on response to chemotherapy worsening prognosis with increasing extraskeletal
involvement LSD
generally fatal in children lt 3 years of age
Symptoms skeletal involvement
pain and swelling at the region of involvement limping can be seen with pelvic or lower extremity
involvement vertebral involvement
localized or diffuse back pain increasingly kyphotic posture radiculopathy can occur with more aggressive lesions
HSC classic triad of
multiple lytic skull lesions diabetes insipidus
increased thirst and water intake exopthalmos
visceral involvement diffuse or nonspecific abdominal or chest pain
Radiographs general
known as the great mimicker as it appears similar to many lesions radiographic differential includes osteomyelitis leukemia lymphoma
fibrous dysplasia or Ewings sarcoma diaphyseal lesions
well defined intramedullary lytic or punched-out lesion cortex may be thinned expanded or destroyed may have periosteal reaction
metaphyseal lesions extend up to but not through the physis less central location than diaphyseal lesions
spinal lesions vertebra plana (flattened vertebrae) in spine increased kyphosis
cranial involvement multiple punched-out lytic lesions
MRI may show a soft tissue mass adjacent to boney lesions
Bone scan generally shows increased uptake in the region of boney lesion
Histology Langerhans cells
mononuclear histiocyte-like cells with oval nuclei with well-defined round or oval cytoplasm
a prominent nuclear groove (coffee bean nuclei) can be seen in most of the nuclei
eosinophilic cytoplasm (pink generally) stain with CD1A electronmicroscopy
birbeck granules seen inside Langerhans cells mixture of inflammatory cells also present giant cells are present lack of nuclear atypia and atypical mitoses
differentiates this condition from malignant conditions such as Ewings sarcoma lymphoma of bone and metastatic neuroblastoma which may look similar based on the round cells alone
eosinophilic cytoplasm (pink generally)
Treatment
bullNonoperative bull observation alone
bull indications bull a self-limited process and it is reasonable to treat with observation alone
bull bracing bull indications
bull to prevent progressive kyphosis of the spinebull outcomes
bull will correct deformity in 90 of patientsbull vertebral lesions generally regain 50 of their height
bull low dose irradiation (600-800 cGy) bull indications
bull indicated for lesions in the spine that compromise stability neurologic statusbull lesions not amenable to injection or open treatment
bull outcomes bull effective for most lesions
bull chemotherapy bull indications
bull diffuse HSCbull outcomes
bull prognosis is improved with less severe extraskeletal involvementbull corticosteroid injection
bull indications bull isolated lesions bull can be performed after curettage as well
Operative curettage and bone grafting
indications for lesions that endanger the articular surface or are a risk for
impending fractures spinal deformity correction
indications progressive spine deformity refractory to bracing
approximately 10 of patients with spine lesion will need operative intervention for deformity correction
Destructive multiple lesion in young patientsAre eosinophilic granuloma lymphoma and leukemiaLymphoma is unlikely to present with exopthalmos diabetes insipidus or vertebra plana Lymphoma bone lesions are lytic and appear moth eatenpermeative on radiographs
Figure A shows a skin lesion typical of eosinophillic granuloma Figure B shows a lytic lesions without significant surrounding sclerosis as is characteristic of eosinophilic granuloma Figure C shows the characteristic histology of multiple eosinophils with their characteristic oval coffee bean nuclei and staining pattern of purpleredpink cytoplasm (depending on the stain) Importantly the histology slide lacks a malignant appearance (no cellular atypia or mytotic complexes and low nuclearcytoplasmic ratio)
Formation of bone in atypical extraskeletal tissues usually occurs
spontaneously or following trauma within 2 months of neurologic injury (brain or spinal cord)
most common location is between muscle and joint capsule Epidemiology
incidence (see table below)
demographics malefemale = 21 especially men with hypertrophic osteoarthritis and women gt65y
location traumatic brain injury or stroke
hip gt elbow gt shoulder gt knee elbow HO more common following brain trauma
occurs on affected (spastic) side rarely in the knee (TBI)
spinal cord injury hip gt knee gt elbow gt shoulder hip flexors and abductors gt extensors or adductors medial aspect of the knee
Heterotopic Ossification
Risk factors
Pathophysiology exact cause of HO is not known but there appears to be a
genetic pre disposition experimental HO associated with
tissue expression of BMP IT IS SAID TO BE CAUSED BY activation and proliferation of
mesenchymal stem cells Associated conditions
orthopaedic manifestations pathologic fractures
from decreased joint ROM and osteoporotic bone nerve impingement soft tissue contractures contributing to the formation of
decubitus ulcers joint ankylosis HO after THA adversely affects outcome of THA
nonorthopaedic conditions skin maceration and hygiene problems
Pathophysiology Early in the formation of HO oedema with exudative
infiltrate is present followed by fibroblastic proliferation and immature connective tissue formation Posteriorly osteoid formation is seen with the subsequent deposition of bone matrix Primitive osteoid is deposited as small masses in the periphery early (within the first two weeks) and osteoblasts are noted located irregularly Osteoblasts produce tropocollagen which polymerizes to form collagen and secrete alkaline phosphatase which allows calcium to precipitate and the mineralization of bone matrix As mineralization progresses amorphous calcium phosphate is progressively replaced by hydroxyapatite crystals During the following weeks the lesion matures with a centripetal pattern and after 6-12 months an appearance of true bone is noted The new bone is always extra-articular and can be contiguous with the skeleton but generally does not involve the periosteum
IN SUMMARY It has been postulated that three conditions
must be met to achieve heterotopic bone formation ---a stimulating event oestrogenic precursor cells and a proper environment LIKE hypercalcaemia tissue hypoxia pH changes (alkalosis) or prolonged immobilization
ClassificationbullSubtypes
bull neurogenic HO bull Four clinical stages of HO in people with spinal cord injury were
described by Nicholas in 1973
bull traumatic myositis ossificans bull fibrodysplasia ossificans progressiva (Munchmeyers Disease)
Neurogenic HO Symptoms
painless loss of ROM interferes with ADL CRPS symptoms fever
Physical exam inspection
warm painful swollen joint may have effusion skin problems
decubitus ulcers from contractures around skin muscles ligaments
skin maceration and hygiene problems motion
decreased joint ROM joint ankylosis with HO after TKA might develop quad muscle snapping or patella
instability neurovascular
peripheral neuropathy HO often impinges on adjacent NV structures
Imaging
bullRadiographs bull findings
bull ossification usually easy to visualize bull maturity of HO
bull the appearance of a bony cortex suggests mature HObull sharp demarcation from surrounding tissue bull trabecular pattern
bull sensitivity and specificity bull not useful for early diagnosisbull only useful at 1 week after onset of symptoms
bull calcium is deposited 7-10 days later than symptom onsetbullUltrasound
bull indications bull for early diagnosis of hip HO
bull findings bull echogenic surfaces with posterior acoustic shadowing
bullCT bull indications
bull useful for preoperative planning bullTriphasic bone scan
bull indications bull best for early diagnosis bull most commonly used diagnostic study
Radiographs are extremely useful in the staging of heterotopic ossification and will show the development of sharp cortical margins once the lesion has reached maturity
Heterotopic bone is a condition in which lamellar bone forms in non-ossified soft tissues In the early stages studies such as MRI and bone scan are more sensitive for diagnosis as radiographs may appear normal for the first three weeks After the appropriate diagnosis is made sequential radiographs are useful for monitoring the progression of the ossification Once it has reached the mature stage sharp cortical margins will appear and surgical resection may be considered
lab
Labs elevated serum alkaline phosphatase (gt250IUL)
ALP removes inhibitors of mineralization nonspecific may be elevated with skeletal trauma cannot determine maturity of HO elevated 12wks after surgery is predictor
elevated CRP correlates with inflammatory activity of HO better than ESR normalization of CRP may correlate with maturity of HO
elevated ESR (gt35mmh) 12wks after THA is predictor
elevated CK correlates with involvement of muscle extent of muscle
involvement Histology
mature fatty bone marrow mature trabecular bone
Heterotopic ossification (HO) most commonly occurs at the amputation site if the amputation was performed thru the zone of injury especially if the injury was a blast mechanism
Symptomatic heterotopic ossification of the quadriceps may occur following placement of a large-diameter Steinmann pin for the purpose of temporary skeletal traction
TreatmentThe prevention of heterotopic ossification is focused on three basic principles disrupting the inductive signalling pathways altering the osteoprogenitor cells or modifying the environment
bullphysiotherapy should involve an assisted range of movement exercises with gentle stretch and terminal resistance trainingbullProphylaxis
bull bisphosphonates amp NSAIDS bull indications
bull although no literature supports are commonly usedbull technique
bull indomethacin is most commonly used bull dose is 75mgday for 10days to 6 weeks
bull perioperative radiation bull indications
bull although no literature supports commonly usedbull is thought to be effective by blocking osteoblast differentiation
bull technique bull a single perioperative dose of 700cGy can be given either 4
hours preop or within 72 hours postoperatively bull lt550cGy not effective
Nonsteroidal anti-inflammatory drugs (NSAIDs) These drugs have demonstrated good results in
preventing heterotopic ossification after total hip arthroplasty
A direct effect of NSAIDs on the formation of heterotopic ossification has been described due to the inhibition of the differentiation of mesenchymal cells into oestrogenic cells There is also an indirect effect which refers to the inhibition of bone remodelling by suppression of the prostagland unmediated inflammatory response (specifically PGE-2)
Indomethacin has been considered a useful medication for heterotopic ossification prophylaxis following total hip replacement
prescribed for three to six weeks in a dose of 75mgday within two months of the injury may reduce the incidence of heterotopic ossification by two to three times
Biphosphonates inhibits precipitation of calcium phosphate and blocks the aggregation and mineralisation of hydroxyapatite crystals In primary prevention Banovac et al [56] have suggested that the treatment should begin as soon as elevated alkaline phosphatase is diagnosed or positive findings in ultrasonography or bone scans are shown In addition disphosphonates could have long-term effects on prevention when the treatment is finished
Posttraumatic wide exposure and surgical resection
indications severe loss of motion and decreased function
technique wide exposure required to identify all neurovascular
structures that may be involved timing of resection (controversial)
marked decrease in bone scan activity AND normalization of ALP
6 months following general trauma 1 year following SCI 15 years following TBI
some data suggests equivalent results when comparing early versus late resection
postop follow with 5 day course of indomethacin early gentle joint mobilization
The surgery is necessary in patients with symptomatic HO and unsuccessful medical treatment such as
Loss of range of motion and ankylosis with associated functional disability such as sitting difficulties
Complications of immobility such as pressure ulcers
Facilitate rehabilitation and recovery of muscular atrophy secondary to prolonged immobilisation
Difficulties of appropriate hygiene because access to the perineum or bladder care is needed
Severe pain refractory to analgesia Vascular andor nerve compression
Advantages to early excision of heterotopic ossification (vs waiting for maturation) include decreased soft tissue contracture better definition between heterotopic and native bone and decreased waiting time for the patient When the soft tissue envelope is benign one may proceed with operative release While waiting for normalization of alkaline phosphatase levels inactivity on bone scan or radiographic maturity may decrease risk of recurrent heterotopic ossification delaying operative release for these reasons has not been shown to improve results of final elbow range of motion after contracture release
Gartland recommended surgery after six months following traumatic heterotopic ossification one year following spinal cord injury and 18 months after head injury
In the past waiting until maturity in order to minimize the rate of recurrence after the surgical treatment was recommended Nevertheless recent studies do not confirm a higher rate of recurrence when the HO is excised in an earlier phase In addition a long delay before surgery leads to ankylosis a high degree of osteoporosis and more extensive intra-articular injuries These findings are associated with bad functional results and potential complications
Should you wait till lesion maturation
Prevention byHandle tissue carefully Avoid excess bleeding Achieve good hemostasis Beware of lesions that span internervous tissue planes
but if it happens resection of a large enough amount of bone to allow improvement of the range of motion and trying to preserve the joint
Our aim must be
A reactive process that is characterized by a well-circumscribed proliferation of fibroblasts cartilage and bone within muscle
A form of heterotopic ossification that is the result direct trauma intramuscular hematoma
most common location is the diaphysis of long bones Must differentiate from tumors Fibrodysplasia ossificans progressiva (FOP) is a rare subtype of heterotopic ossification
involves mutation of the ACVR1 gene (activin A type I receptor gene a BMP type-1 receptor)
Epidemiology demographics
most common in young active males (15 to 35 years old) body locations
quadriceps brachialis and gluteal muscles Genetics
almost always a posttraumatic condition Prognosis
usually self limiting mass usually begins to decrease in size after 1 yea
Myositis ossificans
PresentationbullSymptoms
bull pain tenderness swelling and decreased range of motion that usually presents within days of the injury
bull pain and size of the mass decrease with timebull mass increases in size over several months(usually 3 to 6 cm)
bull after the mass stops growing it becomes firmbullPhysical exam
bull palpable soft tissue massbull restricted range of motion
ImagingbullRadiographs
bull peripheral bone formation with central lucent areabull may appear as dotted veil pattern
bullMRI with gadolinium bull rim enhancement is seen within the first 3 weeks
bullCT scan bull lesion has an eggshell appearance
bullCharacteristic histology shows zonal pattern bull periphery of lesion
bull mature trabeculae of lamellar and woven bonebull calcification seen on xray
bull center of the lesion bull irregular mass of immature fibroblastsbull cartilage component may be presentbull (no calcification seen on xray) bull no cellular atypia seen
Treatment
bullNonoperative bull rest range of motion exercises and activity modification
bull passive stretching is contraindicated (makes it worse)bull physical therapy
bull utilized to maintain range of motionbull radiographic monitoring
bull obtained to confirm maturation of the lesionbullOperative
bull surgical excision bull indicated only if it remains a problem after it maturesbull do not operate in acute phase wait at least six months
bull excision of the lesion within 6 to 12 months predisposes to local recurrence
A 26-year-old man presents with generalized back and joint stiffness and difficulty opening his mouth His elder sister has similar complaints Since childhood he has had 3 surgeries for excision of recurrent bony prominences around his knees He walks with a stooped over posture seen in Figure A Radiographs of his feet knee hip and spine are seen in Figures B-E respectively
fibrodysplasia ossificans progressiva
Stone Man Disease) which involves a mutation of the ACVR1
There are 2 hallmark characteristics progressive heterotopic ossification (muscles fascia tendons ligaments and joint capsules) and congenital malformation of the great toe (hallux valgus malformed first metatarsal and monophalangism) BMP4 which contributes to the formation of the skeleton in the normal embryo is implicated in this disease
Complications
bullHematoma and intraoperative bleedingbullInfection
bull higher rate of infection following joint arthroplasty if HO is present
bullFractures of osteoporotic bone bull osteopenic from disusebull during surgery or physiotherapy
bullRecurrence bull recurrence rate correlates with neurological injury
bull greater recurrence if severe neurological compromisebullAVN
bull if extensive dissection or stripping is required
HTO AND ISS
When ISS is below 25 the mortality risk is minimal and above 25 it is an almost linear increase
When ISS is 50 the mortality is 50 When above 70 it is close to 100 If an injury is assigned an AIS of 6 (unsurvivable injury) the ISS score is
automatically assigned to 75 Highest ISS score obtainable is 75 For trauma patients of vehicular accidents the scoring system is important
for assessing the effectiveness of medical care in reducing morbidity and mortality
Advantages virtually the only anatomical scoring system in use correlates linearly with
mortality morbidity hospital stay other measures of severity
Weaknesses Any error in AIS scoring increases the ISS error Many different injury patterns can yield the same ISS score Injuries to different body regions are not weighted Not a useful triage tool as a full description of patient injuries is not known
prior to full investigation amp operation
risk factors periosteal stripping off anterior femur male gender obesity post traumatic deformity Anterior and anterolateral approach Cementless
Neurogenic HO around the hip due to SCI occurs more often in the medial region than in the lateral region with ossified tissues extending from the pubic symphysis to the anteromedial femoral shaft posterior to the femoral neurovascular structures Ossification is also seen anteriorly involving the iliopsoas and femoral neurovascular structures laterally within gluteus minimus and posteriorly extending from the ilium to the posterior femur encasing the sciatic nerve
HTO AROUND hip and knee
The Brooker Classification of Heterotopic Ossification around the hip joint Class I has islands of bone within the soft tissues Class II has bone spurs from the pelvis or proximal end of the femur leaving at least 1 cm between opposing surfaces Class III has bone spurs from the pelvis andor proximal end of the femur reducing the space between opposing bone surfaces to less than 1 cm Class IV shows apparent bone ankylosis of the hip
Region I - Heterotopic ossifications are strictly below the tip of the greater trochanter
Region II - Heterotopic ossifications are below and above the tip of the greater trochanter
Region III - Heterotopic ossifications are strictly above the tip of the greater trochanter
Grade A - Single or multiple heterotopic ossifications are less than 10 mm in maximal extent without contact with the pelvis or the femur
Grade B - Heterotopic ossifications are greater than 10 mm without contact with the pelvis but with possible contact with the femur there is no bridging from the femur to the proximal part of the greater trochanter and no evidence of ankylosis
Grade C - Ankylosis by means of firm bridging from the femur to the pelvis is present
Shmidt classification
excision may be performed The results of this procedure are varied Patients may find that their range of movement improves but pain relief is likely to be limited
A patient with heterotopic ossification following total hip arthroplasty is thought to have a 90-100 chance of developing it on the contralateral hip if this hip also undergoes total arthroplasty
it would be prudent to minimize the risk of heterotopic ossification developing after arthroplasty by performing surgery whereby the following are ensured
Exposure is meticulous Retraction is performed carefully and soft tissue
is handled carefully Irrigation is adequate Devitalized tissue is excised Hemostasis is adequate Postoperative drains (when used) are not
retained for longer than necessary Perioperative antibiotic prophylaxis is used Postoperative anticoagulation (when used for
deep vein thrombosis prophylaxis) is carefully controlled
sources of knee stiffness 1-extrinsic severe osteoarthritis of the ipsilateral hip neurologic injury leading to muscle rigidity tight quadriceps or hamstring muscles secondary to muscle injury heterotopic ossification or long-standing juvenile inflammatory conditions limiting knee
range of motion prior to the completion of skeletal growth When extrinsic sources are identified revision total knee arthroplasty is unlikely to be associated with a favorable outcome without correction of the extrinsic problem
2-intrinsic (1) overstuffing of the patellofemoral articulation (2) an
excessively tight flexion andor extension gap (3) a tight posterior cruciate ligament (4) femoral andor tibial malrotation (5) arthrofibrosis and (6) limited bearing excursion in association with a highly conforming mobile-bearing prosthetic design
HTO after TKA
Heterotopic Ossification (HO) following primary Total Knee Replacement (TKR)
Occurs in 3-90 of TKRs 3-grade classification system No correlation between HO and component
alignment or component position
Clinical findings similar to early infection Continuing low-grade fever Warm swollen and erythematous knee Normal blood tests Possibly an association with HLA-A2 and B18 HO patients have worse KSS and function
scores
Patients at HIGH risk for developing HO after TKR (Knee Arthroplasty) (5)
Those with limited postoperative knee flexion
Increased lumbar bone mineral density (BMD) on multivariate analysis (3)
Hypertrophic arthrosis Excessive periosteal trauma Notching of the anterior femur Those who require forced manipulation
after TKA 47 in revision TKR surgery (6) Higher rates in revision TKR cases with
infection (up to 76
DaughertyBell classification of HO of the knee 0 No evidence of HO 1 Bone islands in periarticular soft tissue (no
involvement of femur patella or tibia) or HO within quadriceps expansion measuring lt1 cm
2 Spur formation measuring lt5 cm that involves the femur patella or tibia if more than one bone demonstrates HO separation of HO spurs
measure gt1 cm or HO within quadriceps expansion measuring ge1 cm but lt3 cm
3 Spur formation gt5 cm involving femur patella or tibia if more than one bone demonstrates HO separation of HO spurs measure lt1 cm or HO
within quadriceps expansion measuring ge3 cm 4 Extensive HO of the knee causing ankylosis
class 2 HO begins to involve the major bones of the knee joint with spur formation limited to a size of 5 cm
HO class 2 may be observed in select patients with complete ROM and no reported pain Patients with class 3 HO would likely always benefit from surgical excision
followed by RT prophylaxis Certainly patients in either cohort with a subclass ldquoBrdquo assignment (symptomatic) would
benefit from treatment All patients with class 4 HO require
treatment to alleviate ankylosis
treatment
References Whyte ldquoPagetrsquos Disease of Bonerdquo NEMJ vol 355
2006 Klein and Parvizi ldquoSurgical Manifestations of Pagetrsquos
Diseaserdquo JAAOS vol 14 2006 Orthobullets Campbell Apley Emedicinecom
-Chapter 15 Heterotopic Ossification after Traumatic Brain InjuryBy Jesuacutes Moreta and Joseacute Luis Martiacutenez-de los Mozos DOI 10577257343
Questions
Thank You
Histiocytosis X or Langerhans cell histiocytosis is a spectrum of diseases of the reticuloendothelial system with one of three general presentations Eosinophilic granuloma (EG)
usually a single self-limited lesion found in younger patients
Hand-Schuller-Christian disease (HSC) chronic disseminated form with bone and visceral lesions also known as Langerhans cell histiocytosis with visceral
involvement Letterer-Siwe disease (LSD)
fatal form that occurs in young children
Eosinophilic granuloma
Epidemiology demographics
most commonly occurs in children (80 of afflicted lt 20 years of age)
HSC disease presents in children gt 3 years of age LSD occurs in children lt 3 years of age Male to female ratio of 21
location eosinophilic granuloma
commonly presents in the skull ribs clavicle scapula mandible
isolated lesions of the spine (thoracic most common) can also occur in diaphyseal regions of long bones and the
pelvis HSC
multiple bony sites multiple lytic skull lesions visceral involvement of the lungs spleen liver skin lymph
nodes
Genetics no clear genetic pattern of inheritance or locus has
been determined Prognosis
EG isolated involvement generally treatable with local
management spine lesions can spontaneously resolve
HSC prognosis depends on response to chemotherapy worsening prognosis with increasing extraskeletal
involvement LSD
generally fatal in children lt 3 years of age
Symptoms skeletal involvement
pain and swelling at the region of involvement limping can be seen with pelvic or lower extremity
involvement vertebral involvement
localized or diffuse back pain increasingly kyphotic posture radiculopathy can occur with more aggressive lesions
HSC classic triad of
multiple lytic skull lesions diabetes insipidus
increased thirst and water intake exopthalmos
visceral involvement diffuse or nonspecific abdominal or chest pain
Radiographs general
known as the great mimicker as it appears similar to many lesions radiographic differential includes osteomyelitis leukemia lymphoma
fibrous dysplasia or Ewings sarcoma diaphyseal lesions
well defined intramedullary lytic or punched-out lesion cortex may be thinned expanded or destroyed may have periosteal reaction
metaphyseal lesions extend up to but not through the physis less central location than diaphyseal lesions
spinal lesions vertebra plana (flattened vertebrae) in spine increased kyphosis
cranial involvement multiple punched-out lytic lesions
MRI may show a soft tissue mass adjacent to boney lesions
Bone scan generally shows increased uptake in the region of boney lesion
Histology Langerhans cells
mononuclear histiocyte-like cells with oval nuclei with well-defined round or oval cytoplasm
a prominent nuclear groove (coffee bean nuclei) can be seen in most of the nuclei
eosinophilic cytoplasm (pink generally) stain with CD1A electronmicroscopy
birbeck granules seen inside Langerhans cells mixture of inflammatory cells also present giant cells are present lack of nuclear atypia and atypical mitoses
differentiates this condition from malignant conditions such as Ewings sarcoma lymphoma of bone and metastatic neuroblastoma which may look similar based on the round cells alone
eosinophilic cytoplasm (pink generally)
Treatment
bullNonoperative bull observation alone
bull indications bull a self-limited process and it is reasonable to treat with observation alone
bull bracing bull indications
bull to prevent progressive kyphosis of the spinebull outcomes
bull will correct deformity in 90 of patientsbull vertebral lesions generally regain 50 of their height
bull low dose irradiation (600-800 cGy) bull indications
bull indicated for lesions in the spine that compromise stability neurologic statusbull lesions not amenable to injection or open treatment
bull outcomes bull effective for most lesions
bull chemotherapy bull indications
bull diffuse HSCbull outcomes
bull prognosis is improved with less severe extraskeletal involvementbull corticosteroid injection
bull indications bull isolated lesions bull can be performed after curettage as well
Operative curettage and bone grafting
indications for lesions that endanger the articular surface or are a risk for
impending fractures spinal deformity correction
indications progressive spine deformity refractory to bracing
approximately 10 of patients with spine lesion will need operative intervention for deformity correction
Destructive multiple lesion in young patientsAre eosinophilic granuloma lymphoma and leukemiaLymphoma is unlikely to present with exopthalmos diabetes insipidus or vertebra plana Lymphoma bone lesions are lytic and appear moth eatenpermeative on radiographs
Figure A shows a skin lesion typical of eosinophillic granuloma Figure B shows a lytic lesions without significant surrounding sclerosis as is characteristic of eosinophilic granuloma Figure C shows the characteristic histology of multiple eosinophils with their characteristic oval coffee bean nuclei and staining pattern of purpleredpink cytoplasm (depending on the stain) Importantly the histology slide lacks a malignant appearance (no cellular atypia or mytotic complexes and low nuclearcytoplasmic ratio)
Formation of bone in atypical extraskeletal tissues usually occurs
spontaneously or following trauma within 2 months of neurologic injury (brain or spinal cord)
most common location is between muscle and joint capsule Epidemiology
incidence (see table below)
demographics malefemale = 21 especially men with hypertrophic osteoarthritis and women gt65y
location traumatic brain injury or stroke
hip gt elbow gt shoulder gt knee elbow HO more common following brain trauma
occurs on affected (spastic) side rarely in the knee (TBI)
spinal cord injury hip gt knee gt elbow gt shoulder hip flexors and abductors gt extensors or adductors medial aspect of the knee
Heterotopic Ossification
Risk factors
Pathophysiology exact cause of HO is not known but there appears to be a
genetic pre disposition experimental HO associated with
tissue expression of BMP IT IS SAID TO BE CAUSED BY activation and proliferation of
mesenchymal stem cells Associated conditions
orthopaedic manifestations pathologic fractures
from decreased joint ROM and osteoporotic bone nerve impingement soft tissue contractures contributing to the formation of
decubitus ulcers joint ankylosis HO after THA adversely affects outcome of THA
nonorthopaedic conditions skin maceration and hygiene problems
Pathophysiology Early in the formation of HO oedema with exudative
infiltrate is present followed by fibroblastic proliferation and immature connective tissue formation Posteriorly osteoid formation is seen with the subsequent deposition of bone matrix Primitive osteoid is deposited as small masses in the periphery early (within the first two weeks) and osteoblasts are noted located irregularly Osteoblasts produce tropocollagen which polymerizes to form collagen and secrete alkaline phosphatase which allows calcium to precipitate and the mineralization of bone matrix As mineralization progresses amorphous calcium phosphate is progressively replaced by hydroxyapatite crystals During the following weeks the lesion matures with a centripetal pattern and after 6-12 months an appearance of true bone is noted The new bone is always extra-articular and can be contiguous with the skeleton but generally does not involve the periosteum
IN SUMMARY It has been postulated that three conditions
must be met to achieve heterotopic bone formation ---a stimulating event oestrogenic precursor cells and a proper environment LIKE hypercalcaemia tissue hypoxia pH changes (alkalosis) or prolonged immobilization
ClassificationbullSubtypes
bull neurogenic HO bull Four clinical stages of HO in people with spinal cord injury were
described by Nicholas in 1973
bull traumatic myositis ossificans bull fibrodysplasia ossificans progressiva (Munchmeyers Disease)
Neurogenic HO Symptoms
painless loss of ROM interferes with ADL CRPS symptoms fever
Physical exam inspection
warm painful swollen joint may have effusion skin problems
decubitus ulcers from contractures around skin muscles ligaments
skin maceration and hygiene problems motion
decreased joint ROM joint ankylosis with HO after TKA might develop quad muscle snapping or patella
instability neurovascular
peripheral neuropathy HO often impinges on adjacent NV structures
Imaging
bullRadiographs bull findings
bull ossification usually easy to visualize bull maturity of HO
bull the appearance of a bony cortex suggests mature HObull sharp demarcation from surrounding tissue bull trabecular pattern
bull sensitivity and specificity bull not useful for early diagnosisbull only useful at 1 week after onset of symptoms
bull calcium is deposited 7-10 days later than symptom onsetbullUltrasound
bull indications bull for early diagnosis of hip HO
bull findings bull echogenic surfaces with posterior acoustic shadowing
bullCT bull indications
bull useful for preoperative planning bullTriphasic bone scan
bull indications bull best for early diagnosis bull most commonly used diagnostic study
Radiographs are extremely useful in the staging of heterotopic ossification and will show the development of sharp cortical margins once the lesion has reached maturity
Heterotopic bone is a condition in which lamellar bone forms in non-ossified soft tissues In the early stages studies such as MRI and bone scan are more sensitive for diagnosis as radiographs may appear normal for the first three weeks After the appropriate diagnosis is made sequential radiographs are useful for monitoring the progression of the ossification Once it has reached the mature stage sharp cortical margins will appear and surgical resection may be considered
lab
Labs elevated serum alkaline phosphatase (gt250IUL)
ALP removes inhibitors of mineralization nonspecific may be elevated with skeletal trauma cannot determine maturity of HO elevated 12wks after surgery is predictor
elevated CRP correlates with inflammatory activity of HO better than ESR normalization of CRP may correlate with maturity of HO
elevated ESR (gt35mmh) 12wks after THA is predictor
elevated CK correlates with involvement of muscle extent of muscle
involvement Histology
mature fatty bone marrow mature trabecular bone
Heterotopic ossification (HO) most commonly occurs at the amputation site if the amputation was performed thru the zone of injury especially if the injury was a blast mechanism
Symptomatic heterotopic ossification of the quadriceps may occur following placement of a large-diameter Steinmann pin for the purpose of temporary skeletal traction
TreatmentThe prevention of heterotopic ossification is focused on three basic principles disrupting the inductive signalling pathways altering the osteoprogenitor cells or modifying the environment
bullphysiotherapy should involve an assisted range of movement exercises with gentle stretch and terminal resistance trainingbullProphylaxis
bull bisphosphonates amp NSAIDS bull indications
bull although no literature supports are commonly usedbull technique
bull indomethacin is most commonly used bull dose is 75mgday for 10days to 6 weeks
bull perioperative radiation bull indications
bull although no literature supports commonly usedbull is thought to be effective by blocking osteoblast differentiation
bull technique bull a single perioperative dose of 700cGy can be given either 4
hours preop or within 72 hours postoperatively bull lt550cGy not effective
Nonsteroidal anti-inflammatory drugs (NSAIDs) These drugs have demonstrated good results in
preventing heterotopic ossification after total hip arthroplasty
A direct effect of NSAIDs on the formation of heterotopic ossification has been described due to the inhibition of the differentiation of mesenchymal cells into oestrogenic cells There is also an indirect effect which refers to the inhibition of bone remodelling by suppression of the prostagland unmediated inflammatory response (specifically PGE-2)
Indomethacin has been considered a useful medication for heterotopic ossification prophylaxis following total hip replacement
prescribed for three to six weeks in a dose of 75mgday within two months of the injury may reduce the incidence of heterotopic ossification by two to three times
Biphosphonates inhibits precipitation of calcium phosphate and blocks the aggregation and mineralisation of hydroxyapatite crystals In primary prevention Banovac et al [56] have suggested that the treatment should begin as soon as elevated alkaline phosphatase is diagnosed or positive findings in ultrasonography or bone scans are shown In addition disphosphonates could have long-term effects on prevention when the treatment is finished
Posttraumatic wide exposure and surgical resection
indications severe loss of motion and decreased function
technique wide exposure required to identify all neurovascular
structures that may be involved timing of resection (controversial)
marked decrease in bone scan activity AND normalization of ALP
6 months following general trauma 1 year following SCI 15 years following TBI
some data suggests equivalent results when comparing early versus late resection
postop follow with 5 day course of indomethacin early gentle joint mobilization
The surgery is necessary in patients with symptomatic HO and unsuccessful medical treatment such as
Loss of range of motion and ankylosis with associated functional disability such as sitting difficulties
Complications of immobility such as pressure ulcers
Facilitate rehabilitation and recovery of muscular atrophy secondary to prolonged immobilisation
Difficulties of appropriate hygiene because access to the perineum or bladder care is needed
Severe pain refractory to analgesia Vascular andor nerve compression
Advantages to early excision of heterotopic ossification (vs waiting for maturation) include decreased soft tissue contracture better definition between heterotopic and native bone and decreased waiting time for the patient When the soft tissue envelope is benign one may proceed with operative release While waiting for normalization of alkaline phosphatase levels inactivity on bone scan or radiographic maturity may decrease risk of recurrent heterotopic ossification delaying operative release for these reasons has not been shown to improve results of final elbow range of motion after contracture release
Gartland recommended surgery after six months following traumatic heterotopic ossification one year following spinal cord injury and 18 months after head injury
In the past waiting until maturity in order to minimize the rate of recurrence after the surgical treatment was recommended Nevertheless recent studies do not confirm a higher rate of recurrence when the HO is excised in an earlier phase In addition a long delay before surgery leads to ankylosis a high degree of osteoporosis and more extensive intra-articular injuries These findings are associated with bad functional results and potential complications
Should you wait till lesion maturation
Prevention byHandle tissue carefully Avoid excess bleeding Achieve good hemostasis Beware of lesions that span internervous tissue planes
but if it happens resection of a large enough amount of bone to allow improvement of the range of motion and trying to preserve the joint
Our aim must be
A reactive process that is characterized by a well-circumscribed proliferation of fibroblasts cartilage and bone within muscle
A form of heterotopic ossification that is the result direct trauma intramuscular hematoma
most common location is the diaphysis of long bones Must differentiate from tumors Fibrodysplasia ossificans progressiva (FOP) is a rare subtype of heterotopic ossification
involves mutation of the ACVR1 gene (activin A type I receptor gene a BMP type-1 receptor)
Epidemiology demographics
most common in young active males (15 to 35 years old) body locations
quadriceps brachialis and gluteal muscles Genetics
almost always a posttraumatic condition Prognosis
usually self limiting mass usually begins to decrease in size after 1 yea
Myositis ossificans
PresentationbullSymptoms
bull pain tenderness swelling and decreased range of motion that usually presents within days of the injury
bull pain and size of the mass decrease with timebull mass increases in size over several months(usually 3 to 6 cm)
bull after the mass stops growing it becomes firmbullPhysical exam
bull palpable soft tissue massbull restricted range of motion
ImagingbullRadiographs
bull peripheral bone formation with central lucent areabull may appear as dotted veil pattern
bullMRI with gadolinium bull rim enhancement is seen within the first 3 weeks
bullCT scan bull lesion has an eggshell appearance
bullCharacteristic histology shows zonal pattern bull periphery of lesion
bull mature trabeculae of lamellar and woven bonebull calcification seen on xray
bull center of the lesion bull irregular mass of immature fibroblastsbull cartilage component may be presentbull (no calcification seen on xray) bull no cellular atypia seen
Treatment
bullNonoperative bull rest range of motion exercises and activity modification
bull passive stretching is contraindicated (makes it worse)bull physical therapy
bull utilized to maintain range of motionbull radiographic monitoring
bull obtained to confirm maturation of the lesionbullOperative
bull surgical excision bull indicated only if it remains a problem after it maturesbull do not operate in acute phase wait at least six months
bull excision of the lesion within 6 to 12 months predisposes to local recurrence
A 26-year-old man presents with generalized back and joint stiffness and difficulty opening his mouth His elder sister has similar complaints Since childhood he has had 3 surgeries for excision of recurrent bony prominences around his knees He walks with a stooped over posture seen in Figure A Radiographs of his feet knee hip and spine are seen in Figures B-E respectively
fibrodysplasia ossificans progressiva
Stone Man Disease) which involves a mutation of the ACVR1
There are 2 hallmark characteristics progressive heterotopic ossification (muscles fascia tendons ligaments and joint capsules) and congenital malformation of the great toe (hallux valgus malformed first metatarsal and monophalangism) BMP4 which contributes to the formation of the skeleton in the normal embryo is implicated in this disease
Complications
bullHematoma and intraoperative bleedingbullInfection
bull higher rate of infection following joint arthroplasty if HO is present
bullFractures of osteoporotic bone bull osteopenic from disusebull during surgery or physiotherapy
bullRecurrence bull recurrence rate correlates with neurological injury
bull greater recurrence if severe neurological compromisebullAVN
bull if extensive dissection or stripping is required
HTO AND ISS
When ISS is below 25 the mortality risk is minimal and above 25 it is an almost linear increase
When ISS is 50 the mortality is 50 When above 70 it is close to 100 If an injury is assigned an AIS of 6 (unsurvivable injury) the ISS score is
automatically assigned to 75 Highest ISS score obtainable is 75 For trauma patients of vehicular accidents the scoring system is important
for assessing the effectiveness of medical care in reducing morbidity and mortality
Advantages virtually the only anatomical scoring system in use correlates linearly with
mortality morbidity hospital stay other measures of severity
Weaknesses Any error in AIS scoring increases the ISS error Many different injury patterns can yield the same ISS score Injuries to different body regions are not weighted Not a useful triage tool as a full description of patient injuries is not known
prior to full investigation amp operation
risk factors periosteal stripping off anterior femur male gender obesity post traumatic deformity Anterior and anterolateral approach Cementless
Neurogenic HO around the hip due to SCI occurs more often in the medial region than in the lateral region with ossified tissues extending from the pubic symphysis to the anteromedial femoral shaft posterior to the femoral neurovascular structures Ossification is also seen anteriorly involving the iliopsoas and femoral neurovascular structures laterally within gluteus minimus and posteriorly extending from the ilium to the posterior femur encasing the sciatic nerve
HTO AROUND hip and knee
The Brooker Classification of Heterotopic Ossification around the hip joint Class I has islands of bone within the soft tissues Class II has bone spurs from the pelvis or proximal end of the femur leaving at least 1 cm between opposing surfaces Class III has bone spurs from the pelvis andor proximal end of the femur reducing the space between opposing bone surfaces to less than 1 cm Class IV shows apparent bone ankylosis of the hip
Region I - Heterotopic ossifications are strictly below the tip of the greater trochanter
Region II - Heterotopic ossifications are below and above the tip of the greater trochanter
Region III - Heterotopic ossifications are strictly above the tip of the greater trochanter
Grade A - Single or multiple heterotopic ossifications are less than 10 mm in maximal extent without contact with the pelvis or the femur
Grade B - Heterotopic ossifications are greater than 10 mm without contact with the pelvis but with possible contact with the femur there is no bridging from the femur to the proximal part of the greater trochanter and no evidence of ankylosis
Grade C - Ankylosis by means of firm bridging from the femur to the pelvis is present
Shmidt classification
excision may be performed The results of this procedure are varied Patients may find that their range of movement improves but pain relief is likely to be limited
A patient with heterotopic ossification following total hip arthroplasty is thought to have a 90-100 chance of developing it on the contralateral hip if this hip also undergoes total arthroplasty
it would be prudent to minimize the risk of heterotopic ossification developing after arthroplasty by performing surgery whereby the following are ensured
Exposure is meticulous Retraction is performed carefully and soft tissue
is handled carefully Irrigation is adequate Devitalized tissue is excised Hemostasis is adequate Postoperative drains (when used) are not
retained for longer than necessary Perioperative antibiotic prophylaxis is used Postoperative anticoagulation (when used for
deep vein thrombosis prophylaxis) is carefully controlled
sources of knee stiffness 1-extrinsic severe osteoarthritis of the ipsilateral hip neurologic injury leading to muscle rigidity tight quadriceps or hamstring muscles secondary to muscle injury heterotopic ossification or long-standing juvenile inflammatory conditions limiting knee
range of motion prior to the completion of skeletal growth When extrinsic sources are identified revision total knee arthroplasty is unlikely to be associated with a favorable outcome without correction of the extrinsic problem
2-intrinsic (1) overstuffing of the patellofemoral articulation (2) an
excessively tight flexion andor extension gap (3) a tight posterior cruciate ligament (4) femoral andor tibial malrotation (5) arthrofibrosis and (6) limited bearing excursion in association with a highly conforming mobile-bearing prosthetic design
HTO after TKA
Heterotopic Ossification (HO) following primary Total Knee Replacement (TKR)
Occurs in 3-90 of TKRs 3-grade classification system No correlation between HO and component
alignment or component position
Clinical findings similar to early infection Continuing low-grade fever Warm swollen and erythematous knee Normal blood tests Possibly an association with HLA-A2 and B18 HO patients have worse KSS and function
scores
Patients at HIGH risk for developing HO after TKR (Knee Arthroplasty) (5)
Those with limited postoperative knee flexion
Increased lumbar bone mineral density (BMD) on multivariate analysis (3)
Hypertrophic arthrosis Excessive periosteal trauma Notching of the anterior femur Those who require forced manipulation
after TKA 47 in revision TKR surgery (6) Higher rates in revision TKR cases with
infection (up to 76
DaughertyBell classification of HO of the knee 0 No evidence of HO 1 Bone islands in periarticular soft tissue (no
involvement of femur patella or tibia) or HO within quadriceps expansion measuring lt1 cm
2 Spur formation measuring lt5 cm that involves the femur patella or tibia if more than one bone demonstrates HO separation of HO spurs
measure gt1 cm or HO within quadriceps expansion measuring ge1 cm but lt3 cm
3 Spur formation gt5 cm involving femur patella or tibia if more than one bone demonstrates HO separation of HO spurs measure lt1 cm or HO
within quadriceps expansion measuring ge3 cm 4 Extensive HO of the knee causing ankylosis
class 2 HO begins to involve the major bones of the knee joint with spur formation limited to a size of 5 cm
HO class 2 may be observed in select patients with complete ROM and no reported pain Patients with class 3 HO would likely always benefit from surgical excision
followed by RT prophylaxis Certainly patients in either cohort with a subclass ldquoBrdquo assignment (symptomatic) would
benefit from treatment All patients with class 4 HO require
treatment to alleviate ankylosis
treatment
References Whyte ldquoPagetrsquos Disease of Bonerdquo NEMJ vol 355
2006 Klein and Parvizi ldquoSurgical Manifestations of Pagetrsquos
Diseaserdquo JAAOS vol 14 2006 Orthobullets Campbell Apley Emedicinecom
-Chapter 15 Heterotopic Ossification after Traumatic Brain InjuryBy Jesuacutes Moreta and Joseacute Luis Martiacutenez-de los Mozos DOI 10577257343
Questions
Thank You
Epidemiology demographics
most commonly occurs in children (80 of afflicted lt 20 years of age)
HSC disease presents in children gt 3 years of age LSD occurs in children lt 3 years of age Male to female ratio of 21
location eosinophilic granuloma
commonly presents in the skull ribs clavicle scapula mandible
isolated lesions of the spine (thoracic most common) can also occur in diaphyseal regions of long bones and the
pelvis HSC
multiple bony sites multiple lytic skull lesions visceral involvement of the lungs spleen liver skin lymph
nodes
Genetics no clear genetic pattern of inheritance or locus has
been determined Prognosis
EG isolated involvement generally treatable with local
management spine lesions can spontaneously resolve
HSC prognosis depends on response to chemotherapy worsening prognosis with increasing extraskeletal
involvement LSD
generally fatal in children lt 3 years of age
Symptoms skeletal involvement
pain and swelling at the region of involvement limping can be seen with pelvic or lower extremity
involvement vertebral involvement
localized or diffuse back pain increasingly kyphotic posture radiculopathy can occur with more aggressive lesions
HSC classic triad of
multiple lytic skull lesions diabetes insipidus
increased thirst and water intake exopthalmos
visceral involvement diffuse or nonspecific abdominal or chest pain
Radiographs general
known as the great mimicker as it appears similar to many lesions radiographic differential includes osteomyelitis leukemia lymphoma
fibrous dysplasia or Ewings sarcoma diaphyseal lesions
well defined intramedullary lytic or punched-out lesion cortex may be thinned expanded or destroyed may have periosteal reaction
metaphyseal lesions extend up to but not through the physis less central location than diaphyseal lesions
spinal lesions vertebra plana (flattened vertebrae) in spine increased kyphosis
cranial involvement multiple punched-out lytic lesions
MRI may show a soft tissue mass adjacent to boney lesions
Bone scan generally shows increased uptake in the region of boney lesion
Histology Langerhans cells
mononuclear histiocyte-like cells with oval nuclei with well-defined round or oval cytoplasm
a prominent nuclear groove (coffee bean nuclei) can be seen in most of the nuclei
eosinophilic cytoplasm (pink generally) stain with CD1A electronmicroscopy
birbeck granules seen inside Langerhans cells mixture of inflammatory cells also present giant cells are present lack of nuclear atypia and atypical mitoses
differentiates this condition from malignant conditions such as Ewings sarcoma lymphoma of bone and metastatic neuroblastoma which may look similar based on the round cells alone
eosinophilic cytoplasm (pink generally)
Treatment
bullNonoperative bull observation alone
bull indications bull a self-limited process and it is reasonable to treat with observation alone
bull bracing bull indications
bull to prevent progressive kyphosis of the spinebull outcomes
bull will correct deformity in 90 of patientsbull vertebral lesions generally regain 50 of their height
bull low dose irradiation (600-800 cGy) bull indications
bull indicated for lesions in the spine that compromise stability neurologic statusbull lesions not amenable to injection or open treatment
bull outcomes bull effective for most lesions
bull chemotherapy bull indications
bull diffuse HSCbull outcomes
bull prognosis is improved with less severe extraskeletal involvementbull corticosteroid injection
bull indications bull isolated lesions bull can be performed after curettage as well
Operative curettage and bone grafting
indications for lesions that endanger the articular surface or are a risk for
impending fractures spinal deformity correction
indications progressive spine deformity refractory to bracing
approximately 10 of patients with spine lesion will need operative intervention for deformity correction
Destructive multiple lesion in young patientsAre eosinophilic granuloma lymphoma and leukemiaLymphoma is unlikely to present with exopthalmos diabetes insipidus or vertebra plana Lymphoma bone lesions are lytic and appear moth eatenpermeative on radiographs
Figure A shows a skin lesion typical of eosinophillic granuloma Figure B shows a lytic lesions without significant surrounding sclerosis as is characteristic of eosinophilic granuloma Figure C shows the characteristic histology of multiple eosinophils with their characteristic oval coffee bean nuclei and staining pattern of purpleredpink cytoplasm (depending on the stain) Importantly the histology slide lacks a malignant appearance (no cellular atypia or mytotic complexes and low nuclearcytoplasmic ratio)
Formation of bone in atypical extraskeletal tissues usually occurs
spontaneously or following trauma within 2 months of neurologic injury (brain or spinal cord)
most common location is between muscle and joint capsule Epidemiology
incidence (see table below)
demographics malefemale = 21 especially men with hypertrophic osteoarthritis and women gt65y
location traumatic brain injury or stroke
hip gt elbow gt shoulder gt knee elbow HO more common following brain trauma
occurs on affected (spastic) side rarely in the knee (TBI)
spinal cord injury hip gt knee gt elbow gt shoulder hip flexors and abductors gt extensors or adductors medial aspect of the knee
Heterotopic Ossification
Risk factors
Pathophysiology exact cause of HO is not known but there appears to be a
genetic pre disposition experimental HO associated with
tissue expression of BMP IT IS SAID TO BE CAUSED BY activation and proliferation of
mesenchymal stem cells Associated conditions
orthopaedic manifestations pathologic fractures
from decreased joint ROM and osteoporotic bone nerve impingement soft tissue contractures contributing to the formation of
decubitus ulcers joint ankylosis HO after THA adversely affects outcome of THA
nonorthopaedic conditions skin maceration and hygiene problems
Pathophysiology Early in the formation of HO oedema with exudative
infiltrate is present followed by fibroblastic proliferation and immature connective tissue formation Posteriorly osteoid formation is seen with the subsequent deposition of bone matrix Primitive osteoid is deposited as small masses in the periphery early (within the first two weeks) and osteoblasts are noted located irregularly Osteoblasts produce tropocollagen which polymerizes to form collagen and secrete alkaline phosphatase which allows calcium to precipitate and the mineralization of bone matrix As mineralization progresses amorphous calcium phosphate is progressively replaced by hydroxyapatite crystals During the following weeks the lesion matures with a centripetal pattern and after 6-12 months an appearance of true bone is noted The new bone is always extra-articular and can be contiguous with the skeleton but generally does not involve the periosteum
IN SUMMARY It has been postulated that three conditions
must be met to achieve heterotopic bone formation ---a stimulating event oestrogenic precursor cells and a proper environment LIKE hypercalcaemia tissue hypoxia pH changes (alkalosis) or prolonged immobilization
ClassificationbullSubtypes
bull neurogenic HO bull Four clinical stages of HO in people with spinal cord injury were
described by Nicholas in 1973
bull traumatic myositis ossificans bull fibrodysplasia ossificans progressiva (Munchmeyers Disease)
Neurogenic HO Symptoms
painless loss of ROM interferes with ADL CRPS symptoms fever
Physical exam inspection
warm painful swollen joint may have effusion skin problems
decubitus ulcers from contractures around skin muscles ligaments
skin maceration and hygiene problems motion
decreased joint ROM joint ankylosis with HO after TKA might develop quad muscle snapping or patella
instability neurovascular
peripheral neuropathy HO often impinges on adjacent NV structures
Imaging
bullRadiographs bull findings
bull ossification usually easy to visualize bull maturity of HO
bull the appearance of a bony cortex suggests mature HObull sharp demarcation from surrounding tissue bull trabecular pattern
bull sensitivity and specificity bull not useful for early diagnosisbull only useful at 1 week after onset of symptoms
bull calcium is deposited 7-10 days later than symptom onsetbullUltrasound
bull indications bull for early diagnosis of hip HO
bull findings bull echogenic surfaces with posterior acoustic shadowing
bullCT bull indications
bull useful for preoperative planning bullTriphasic bone scan
bull indications bull best for early diagnosis bull most commonly used diagnostic study
Radiographs are extremely useful in the staging of heterotopic ossification and will show the development of sharp cortical margins once the lesion has reached maturity
Heterotopic bone is a condition in which lamellar bone forms in non-ossified soft tissues In the early stages studies such as MRI and bone scan are more sensitive for diagnosis as radiographs may appear normal for the first three weeks After the appropriate diagnosis is made sequential radiographs are useful for monitoring the progression of the ossification Once it has reached the mature stage sharp cortical margins will appear and surgical resection may be considered
lab
Labs elevated serum alkaline phosphatase (gt250IUL)
ALP removes inhibitors of mineralization nonspecific may be elevated with skeletal trauma cannot determine maturity of HO elevated 12wks after surgery is predictor
elevated CRP correlates with inflammatory activity of HO better than ESR normalization of CRP may correlate with maturity of HO
elevated ESR (gt35mmh) 12wks after THA is predictor
elevated CK correlates with involvement of muscle extent of muscle
involvement Histology
mature fatty bone marrow mature trabecular bone
Heterotopic ossification (HO) most commonly occurs at the amputation site if the amputation was performed thru the zone of injury especially if the injury was a blast mechanism
Symptomatic heterotopic ossification of the quadriceps may occur following placement of a large-diameter Steinmann pin for the purpose of temporary skeletal traction
TreatmentThe prevention of heterotopic ossification is focused on three basic principles disrupting the inductive signalling pathways altering the osteoprogenitor cells or modifying the environment
bullphysiotherapy should involve an assisted range of movement exercises with gentle stretch and terminal resistance trainingbullProphylaxis
bull bisphosphonates amp NSAIDS bull indications
bull although no literature supports are commonly usedbull technique
bull indomethacin is most commonly used bull dose is 75mgday for 10days to 6 weeks
bull perioperative radiation bull indications
bull although no literature supports commonly usedbull is thought to be effective by blocking osteoblast differentiation
bull technique bull a single perioperative dose of 700cGy can be given either 4
hours preop or within 72 hours postoperatively bull lt550cGy not effective
Nonsteroidal anti-inflammatory drugs (NSAIDs) These drugs have demonstrated good results in
preventing heterotopic ossification after total hip arthroplasty
A direct effect of NSAIDs on the formation of heterotopic ossification has been described due to the inhibition of the differentiation of mesenchymal cells into oestrogenic cells There is also an indirect effect which refers to the inhibition of bone remodelling by suppression of the prostagland unmediated inflammatory response (specifically PGE-2)
Indomethacin has been considered a useful medication for heterotopic ossification prophylaxis following total hip replacement
prescribed for three to six weeks in a dose of 75mgday within two months of the injury may reduce the incidence of heterotopic ossification by two to three times
Biphosphonates inhibits precipitation of calcium phosphate and blocks the aggregation and mineralisation of hydroxyapatite crystals In primary prevention Banovac et al [56] have suggested that the treatment should begin as soon as elevated alkaline phosphatase is diagnosed or positive findings in ultrasonography or bone scans are shown In addition disphosphonates could have long-term effects on prevention when the treatment is finished
Posttraumatic wide exposure and surgical resection
indications severe loss of motion and decreased function
technique wide exposure required to identify all neurovascular
structures that may be involved timing of resection (controversial)
marked decrease in bone scan activity AND normalization of ALP
6 months following general trauma 1 year following SCI 15 years following TBI
some data suggests equivalent results when comparing early versus late resection
postop follow with 5 day course of indomethacin early gentle joint mobilization
The surgery is necessary in patients with symptomatic HO and unsuccessful medical treatment such as
Loss of range of motion and ankylosis with associated functional disability such as sitting difficulties
Complications of immobility such as pressure ulcers
Facilitate rehabilitation and recovery of muscular atrophy secondary to prolonged immobilisation
Difficulties of appropriate hygiene because access to the perineum or bladder care is needed
Severe pain refractory to analgesia Vascular andor nerve compression
Advantages to early excision of heterotopic ossification (vs waiting for maturation) include decreased soft tissue contracture better definition between heterotopic and native bone and decreased waiting time for the patient When the soft tissue envelope is benign one may proceed with operative release While waiting for normalization of alkaline phosphatase levels inactivity on bone scan or radiographic maturity may decrease risk of recurrent heterotopic ossification delaying operative release for these reasons has not been shown to improve results of final elbow range of motion after contracture release
Gartland recommended surgery after six months following traumatic heterotopic ossification one year following spinal cord injury and 18 months after head injury
In the past waiting until maturity in order to minimize the rate of recurrence after the surgical treatment was recommended Nevertheless recent studies do not confirm a higher rate of recurrence when the HO is excised in an earlier phase In addition a long delay before surgery leads to ankylosis a high degree of osteoporosis and more extensive intra-articular injuries These findings are associated with bad functional results and potential complications
Should you wait till lesion maturation
Prevention byHandle tissue carefully Avoid excess bleeding Achieve good hemostasis Beware of lesions that span internervous tissue planes
but if it happens resection of a large enough amount of bone to allow improvement of the range of motion and trying to preserve the joint
Our aim must be
A reactive process that is characterized by a well-circumscribed proliferation of fibroblasts cartilage and bone within muscle
A form of heterotopic ossification that is the result direct trauma intramuscular hematoma
most common location is the diaphysis of long bones Must differentiate from tumors Fibrodysplasia ossificans progressiva (FOP) is a rare subtype of heterotopic ossification
involves mutation of the ACVR1 gene (activin A type I receptor gene a BMP type-1 receptor)
Epidemiology demographics
most common in young active males (15 to 35 years old) body locations
quadriceps brachialis and gluteal muscles Genetics
almost always a posttraumatic condition Prognosis
usually self limiting mass usually begins to decrease in size after 1 yea
Myositis ossificans
PresentationbullSymptoms
bull pain tenderness swelling and decreased range of motion that usually presents within days of the injury
bull pain and size of the mass decrease with timebull mass increases in size over several months(usually 3 to 6 cm)
bull after the mass stops growing it becomes firmbullPhysical exam
bull palpable soft tissue massbull restricted range of motion
ImagingbullRadiographs
bull peripheral bone formation with central lucent areabull may appear as dotted veil pattern
bullMRI with gadolinium bull rim enhancement is seen within the first 3 weeks
bullCT scan bull lesion has an eggshell appearance
bullCharacteristic histology shows zonal pattern bull periphery of lesion
bull mature trabeculae of lamellar and woven bonebull calcification seen on xray
bull center of the lesion bull irregular mass of immature fibroblastsbull cartilage component may be presentbull (no calcification seen on xray) bull no cellular atypia seen
Treatment
bullNonoperative bull rest range of motion exercises and activity modification
bull passive stretching is contraindicated (makes it worse)bull physical therapy
bull utilized to maintain range of motionbull radiographic monitoring
bull obtained to confirm maturation of the lesionbullOperative
bull surgical excision bull indicated only if it remains a problem after it maturesbull do not operate in acute phase wait at least six months
bull excision of the lesion within 6 to 12 months predisposes to local recurrence
A 26-year-old man presents with generalized back and joint stiffness and difficulty opening his mouth His elder sister has similar complaints Since childhood he has had 3 surgeries for excision of recurrent bony prominences around his knees He walks with a stooped over posture seen in Figure A Radiographs of his feet knee hip and spine are seen in Figures B-E respectively
fibrodysplasia ossificans progressiva
Stone Man Disease) which involves a mutation of the ACVR1
There are 2 hallmark characteristics progressive heterotopic ossification (muscles fascia tendons ligaments and joint capsules) and congenital malformation of the great toe (hallux valgus malformed first metatarsal and monophalangism) BMP4 which contributes to the formation of the skeleton in the normal embryo is implicated in this disease
Complications
bullHematoma and intraoperative bleedingbullInfection
bull higher rate of infection following joint arthroplasty if HO is present
bullFractures of osteoporotic bone bull osteopenic from disusebull during surgery or physiotherapy
bullRecurrence bull recurrence rate correlates with neurological injury
bull greater recurrence if severe neurological compromisebullAVN
bull if extensive dissection or stripping is required
HTO AND ISS
When ISS is below 25 the mortality risk is minimal and above 25 it is an almost linear increase
When ISS is 50 the mortality is 50 When above 70 it is close to 100 If an injury is assigned an AIS of 6 (unsurvivable injury) the ISS score is
automatically assigned to 75 Highest ISS score obtainable is 75 For trauma patients of vehicular accidents the scoring system is important
for assessing the effectiveness of medical care in reducing morbidity and mortality
Advantages virtually the only anatomical scoring system in use correlates linearly with
mortality morbidity hospital stay other measures of severity
Weaknesses Any error in AIS scoring increases the ISS error Many different injury patterns can yield the same ISS score Injuries to different body regions are not weighted Not a useful triage tool as a full description of patient injuries is not known
prior to full investigation amp operation
risk factors periosteal stripping off anterior femur male gender obesity post traumatic deformity Anterior and anterolateral approach Cementless
Neurogenic HO around the hip due to SCI occurs more often in the medial region than in the lateral region with ossified tissues extending from the pubic symphysis to the anteromedial femoral shaft posterior to the femoral neurovascular structures Ossification is also seen anteriorly involving the iliopsoas and femoral neurovascular structures laterally within gluteus minimus and posteriorly extending from the ilium to the posterior femur encasing the sciatic nerve
HTO AROUND hip and knee
The Brooker Classification of Heterotopic Ossification around the hip joint Class I has islands of bone within the soft tissues Class II has bone spurs from the pelvis or proximal end of the femur leaving at least 1 cm between opposing surfaces Class III has bone spurs from the pelvis andor proximal end of the femur reducing the space between opposing bone surfaces to less than 1 cm Class IV shows apparent bone ankylosis of the hip
Region I - Heterotopic ossifications are strictly below the tip of the greater trochanter
Region II - Heterotopic ossifications are below and above the tip of the greater trochanter
Region III - Heterotopic ossifications are strictly above the tip of the greater trochanter
Grade A - Single or multiple heterotopic ossifications are less than 10 mm in maximal extent without contact with the pelvis or the femur
Grade B - Heterotopic ossifications are greater than 10 mm without contact with the pelvis but with possible contact with the femur there is no bridging from the femur to the proximal part of the greater trochanter and no evidence of ankylosis
Grade C - Ankylosis by means of firm bridging from the femur to the pelvis is present
Shmidt classification
excision may be performed The results of this procedure are varied Patients may find that their range of movement improves but pain relief is likely to be limited
A patient with heterotopic ossification following total hip arthroplasty is thought to have a 90-100 chance of developing it on the contralateral hip if this hip also undergoes total arthroplasty
it would be prudent to minimize the risk of heterotopic ossification developing after arthroplasty by performing surgery whereby the following are ensured
Exposure is meticulous Retraction is performed carefully and soft tissue
is handled carefully Irrigation is adequate Devitalized tissue is excised Hemostasis is adequate Postoperative drains (when used) are not
retained for longer than necessary Perioperative antibiotic prophylaxis is used Postoperative anticoagulation (when used for
deep vein thrombosis prophylaxis) is carefully controlled
sources of knee stiffness 1-extrinsic severe osteoarthritis of the ipsilateral hip neurologic injury leading to muscle rigidity tight quadriceps or hamstring muscles secondary to muscle injury heterotopic ossification or long-standing juvenile inflammatory conditions limiting knee
range of motion prior to the completion of skeletal growth When extrinsic sources are identified revision total knee arthroplasty is unlikely to be associated with a favorable outcome without correction of the extrinsic problem
2-intrinsic (1) overstuffing of the patellofemoral articulation (2) an
excessively tight flexion andor extension gap (3) a tight posterior cruciate ligament (4) femoral andor tibial malrotation (5) arthrofibrosis and (6) limited bearing excursion in association with a highly conforming mobile-bearing prosthetic design
HTO after TKA
Heterotopic Ossification (HO) following primary Total Knee Replacement (TKR)
Occurs in 3-90 of TKRs 3-grade classification system No correlation between HO and component
alignment or component position
Clinical findings similar to early infection Continuing low-grade fever Warm swollen and erythematous knee Normal blood tests Possibly an association with HLA-A2 and B18 HO patients have worse KSS and function
scores
Patients at HIGH risk for developing HO after TKR (Knee Arthroplasty) (5)
Those with limited postoperative knee flexion
Increased lumbar bone mineral density (BMD) on multivariate analysis (3)
Hypertrophic arthrosis Excessive periosteal trauma Notching of the anterior femur Those who require forced manipulation
after TKA 47 in revision TKR surgery (6) Higher rates in revision TKR cases with
infection (up to 76
DaughertyBell classification of HO of the knee 0 No evidence of HO 1 Bone islands in periarticular soft tissue (no
involvement of femur patella or tibia) or HO within quadriceps expansion measuring lt1 cm
2 Spur formation measuring lt5 cm that involves the femur patella or tibia if more than one bone demonstrates HO separation of HO spurs
measure gt1 cm or HO within quadriceps expansion measuring ge1 cm but lt3 cm
3 Spur formation gt5 cm involving femur patella or tibia if more than one bone demonstrates HO separation of HO spurs measure lt1 cm or HO
within quadriceps expansion measuring ge3 cm 4 Extensive HO of the knee causing ankylosis
class 2 HO begins to involve the major bones of the knee joint with spur formation limited to a size of 5 cm
HO class 2 may be observed in select patients with complete ROM and no reported pain Patients with class 3 HO would likely always benefit from surgical excision
followed by RT prophylaxis Certainly patients in either cohort with a subclass ldquoBrdquo assignment (symptomatic) would
benefit from treatment All patients with class 4 HO require
treatment to alleviate ankylosis
treatment
References Whyte ldquoPagetrsquos Disease of Bonerdquo NEMJ vol 355
2006 Klein and Parvizi ldquoSurgical Manifestations of Pagetrsquos
Diseaserdquo JAAOS vol 14 2006 Orthobullets Campbell Apley Emedicinecom
-Chapter 15 Heterotopic Ossification after Traumatic Brain InjuryBy Jesuacutes Moreta and Joseacute Luis Martiacutenez-de los Mozos DOI 10577257343
Questions
Thank You
Genetics no clear genetic pattern of inheritance or locus has
been determined Prognosis
EG isolated involvement generally treatable with local
management spine lesions can spontaneously resolve
HSC prognosis depends on response to chemotherapy worsening prognosis with increasing extraskeletal
involvement LSD
generally fatal in children lt 3 years of age
Symptoms skeletal involvement
pain and swelling at the region of involvement limping can be seen with pelvic or lower extremity
involvement vertebral involvement
localized or diffuse back pain increasingly kyphotic posture radiculopathy can occur with more aggressive lesions
HSC classic triad of
multiple lytic skull lesions diabetes insipidus
increased thirst and water intake exopthalmos
visceral involvement diffuse or nonspecific abdominal or chest pain
Radiographs general
known as the great mimicker as it appears similar to many lesions radiographic differential includes osteomyelitis leukemia lymphoma
fibrous dysplasia or Ewings sarcoma diaphyseal lesions
well defined intramedullary lytic or punched-out lesion cortex may be thinned expanded or destroyed may have periosteal reaction
metaphyseal lesions extend up to but not through the physis less central location than diaphyseal lesions
spinal lesions vertebra plana (flattened vertebrae) in spine increased kyphosis
cranial involvement multiple punched-out lytic lesions
MRI may show a soft tissue mass adjacent to boney lesions
Bone scan generally shows increased uptake in the region of boney lesion
Histology Langerhans cells
mononuclear histiocyte-like cells with oval nuclei with well-defined round or oval cytoplasm
a prominent nuclear groove (coffee bean nuclei) can be seen in most of the nuclei
eosinophilic cytoplasm (pink generally) stain with CD1A electronmicroscopy
birbeck granules seen inside Langerhans cells mixture of inflammatory cells also present giant cells are present lack of nuclear atypia and atypical mitoses
differentiates this condition from malignant conditions such as Ewings sarcoma lymphoma of bone and metastatic neuroblastoma which may look similar based on the round cells alone
eosinophilic cytoplasm (pink generally)
Treatment
bullNonoperative bull observation alone
bull indications bull a self-limited process and it is reasonable to treat with observation alone
bull bracing bull indications
bull to prevent progressive kyphosis of the spinebull outcomes
bull will correct deformity in 90 of patientsbull vertebral lesions generally regain 50 of their height
bull low dose irradiation (600-800 cGy) bull indications
bull indicated for lesions in the spine that compromise stability neurologic statusbull lesions not amenable to injection or open treatment
bull outcomes bull effective for most lesions
bull chemotherapy bull indications
bull diffuse HSCbull outcomes
bull prognosis is improved with less severe extraskeletal involvementbull corticosteroid injection
bull indications bull isolated lesions bull can be performed after curettage as well
Operative curettage and bone grafting
indications for lesions that endanger the articular surface or are a risk for
impending fractures spinal deformity correction
indications progressive spine deformity refractory to bracing
approximately 10 of patients with spine lesion will need operative intervention for deformity correction
Destructive multiple lesion in young patientsAre eosinophilic granuloma lymphoma and leukemiaLymphoma is unlikely to present with exopthalmos diabetes insipidus or vertebra plana Lymphoma bone lesions are lytic and appear moth eatenpermeative on radiographs
Figure A shows a skin lesion typical of eosinophillic granuloma Figure B shows a lytic lesions without significant surrounding sclerosis as is characteristic of eosinophilic granuloma Figure C shows the characteristic histology of multiple eosinophils with their characteristic oval coffee bean nuclei and staining pattern of purpleredpink cytoplasm (depending on the stain) Importantly the histology slide lacks a malignant appearance (no cellular atypia or mytotic complexes and low nuclearcytoplasmic ratio)
Formation of bone in atypical extraskeletal tissues usually occurs
spontaneously or following trauma within 2 months of neurologic injury (brain or spinal cord)
most common location is between muscle and joint capsule Epidemiology
incidence (see table below)
demographics malefemale = 21 especially men with hypertrophic osteoarthritis and women gt65y
location traumatic brain injury or stroke
hip gt elbow gt shoulder gt knee elbow HO more common following brain trauma
occurs on affected (spastic) side rarely in the knee (TBI)
spinal cord injury hip gt knee gt elbow gt shoulder hip flexors and abductors gt extensors or adductors medial aspect of the knee
Heterotopic Ossification
Risk factors
Pathophysiology exact cause of HO is not known but there appears to be a
genetic pre disposition experimental HO associated with
tissue expression of BMP IT IS SAID TO BE CAUSED BY activation and proliferation of
mesenchymal stem cells Associated conditions
orthopaedic manifestations pathologic fractures
from decreased joint ROM and osteoporotic bone nerve impingement soft tissue contractures contributing to the formation of
decubitus ulcers joint ankylosis HO after THA adversely affects outcome of THA
nonorthopaedic conditions skin maceration and hygiene problems
Pathophysiology Early in the formation of HO oedema with exudative
infiltrate is present followed by fibroblastic proliferation and immature connective tissue formation Posteriorly osteoid formation is seen with the subsequent deposition of bone matrix Primitive osteoid is deposited as small masses in the periphery early (within the first two weeks) and osteoblasts are noted located irregularly Osteoblasts produce tropocollagen which polymerizes to form collagen and secrete alkaline phosphatase which allows calcium to precipitate and the mineralization of bone matrix As mineralization progresses amorphous calcium phosphate is progressively replaced by hydroxyapatite crystals During the following weeks the lesion matures with a centripetal pattern and after 6-12 months an appearance of true bone is noted The new bone is always extra-articular and can be contiguous with the skeleton but generally does not involve the periosteum
IN SUMMARY It has been postulated that three conditions
must be met to achieve heterotopic bone formation ---a stimulating event oestrogenic precursor cells and a proper environment LIKE hypercalcaemia tissue hypoxia pH changes (alkalosis) or prolonged immobilization
ClassificationbullSubtypes
bull neurogenic HO bull Four clinical stages of HO in people with spinal cord injury were
described by Nicholas in 1973
bull traumatic myositis ossificans bull fibrodysplasia ossificans progressiva (Munchmeyers Disease)
Neurogenic HO Symptoms
painless loss of ROM interferes with ADL CRPS symptoms fever
Physical exam inspection
warm painful swollen joint may have effusion skin problems
decubitus ulcers from contractures around skin muscles ligaments
skin maceration and hygiene problems motion
decreased joint ROM joint ankylosis with HO after TKA might develop quad muscle snapping or patella
instability neurovascular
peripheral neuropathy HO often impinges on adjacent NV structures
Imaging
bullRadiographs bull findings
bull ossification usually easy to visualize bull maturity of HO
bull the appearance of a bony cortex suggests mature HObull sharp demarcation from surrounding tissue bull trabecular pattern
bull sensitivity and specificity bull not useful for early diagnosisbull only useful at 1 week after onset of symptoms
bull calcium is deposited 7-10 days later than symptom onsetbullUltrasound
bull indications bull for early diagnosis of hip HO
bull findings bull echogenic surfaces with posterior acoustic shadowing
bullCT bull indications
bull useful for preoperative planning bullTriphasic bone scan
bull indications bull best for early diagnosis bull most commonly used diagnostic study
Radiographs are extremely useful in the staging of heterotopic ossification and will show the development of sharp cortical margins once the lesion has reached maturity
Heterotopic bone is a condition in which lamellar bone forms in non-ossified soft tissues In the early stages studies such as MRI and bone scan are more sensitive for diagnosis as radiographs may appear normal for the first three weeks After the appropriate diagnosis is made sequential radiographs are useful for monitoring the progression of the ossification Once it has reached the mature stage sharp cortical margins will appear and surgical resection may be considered
lab
Labs elevated serum alkaline phosphatase (gt250IUL)
ALP removes inhibitors of mineralization nonspecific may be elevated with skeletal trauma cannot determine maturity of HO elevated 12wks after surgery is predictor
elevated CRP correlates with inflammatory activity of HO better than ESR normalization of CRP may correlate with maturity of HO
elevated ESR (gt35mmh) 12wks after THA is predictor
elevated CK correlates with involvement of muscle extent of muscle
involvement Histology
mature fatty bone marrow mature trabecular bone
Heterotopic ossification (HO) most commonly occurs at the amputation site if the amputation was performed thru the zone of injury especially if the injury was a blast mechanism
Symptomatic heterotopic ossification of the quadriceps may occur following placement of a large-diameter Steinmann pin for the purpose of temporary skeletal traction
TreatmentThe prevention of heterotopic ossification is focused on three basic principles disrupting the inductive signalling pathways altering the osteoprogenitor cells or modifying the environment
bullphysiotherapy should involve an assisted range of movement exercises with gentle stretch and terminal resistance trainingbullProphylaxis
bull bisphosphonates amp NSAIDS bull indications
bull although no literature supports are commonly usedbull technique
bull indomethacin is most commonly used bull dose is 75mgday for 10days to 6 weeks
bull perioperative radiation bull indications
bull although no literature supports commonly usedbull is thought to be effective by blocking osteoblast differentiation
bull technique bull a single perioperative dose of 700cGy can be given either 4
hours preop or within 72 hours postoperatively bull lt550cGy not effective
Nonsteroidal anti-inflammatory drugs (NSAIDs) These drugs have demonstrated good results in
preventing heterotopic ossification after total hip arthroplasty
A direct effect of NSAIDs on the formation of heterotopic ossification has been described due to the inhibition of the differentiation of mesenchymal cells into oestrogenic cells There is also an indirect effect which refers to the inhibition of bone remodelling by suppression of the prostagland unmediated inflammatory response (specifically PGE-2)
Indomethacin has been considered a useful medication for heterotopic ossification prophylaxis following total hip replacement
prescribed for three to six weeks in a dose of 75mgday within two months of the injury may reduce the incidence of heterotopic ossification by two to three times
Biphosphonates inhibits precipitation of calcium phosphate and blocks the aggregation and mineralisation of hydroxyapatite crystals In primary prevention Banovac et al [56] have suggested that the treatment should begin as soon as elevated alkaline phosphatase is diagnosed or positive findings in ultrasonography or bone scans are shown In addition disphosphonates could have long-term effects on prevention when the treatment is finished
Posttraumatic wide exposure and surgical resection
indications severe loss of motion and decreased function
technique wide exposure required to identify all neurovascular
structures that may be involved timing of resection (controversial)
marked decrease in bone scan activity AND normalization of ALP
6 months following general trauma 1 year following SCI 15 years following TBI
some data suggests equivalent results when comparing early versus late resection
postop follow with 5 day course of indomethacin early gentle joint mobilization
The surgery is necessary in patients with symptomatic HO and unsuccessful medical treatment such as
Loss of range of motion and ankylosis with associated functional disability such as sitting difficulties
Complications of immobility such as pressure ulcers
Facilitate rehabilitation and recovery of muscular atrophy secondary to prolonged immobilisation
Difficulties of appropriate hygiene because access to the perineum or bladder care is needed
Severe pain refractory to analgesia Vascular andor nerve compression
Advantages to early excision of heterotopic ossification (vs waiting for maturation) include decreased soft tissue contracture better definition between heterotopic and native bone and decreased waiting time for the patient When the soft tissue envelope is benign one may proceed with operative release While waiting for normalization of alkaline phosphatase levels inactivity on bone scan or radiographic maturity may decrease risk of recurrent heterotopic ossification delaying operative release for these reasons has not been shown to improve results of final elbow range of motion after contracture release
Gartland recommended surgery after six months following traumatic heterotopic ossification one year following spinal cord injury and 18 months after head injury
In the past waiting until maturity in order to minimize the rate of recurrence after the surgical treatment was recommended Nevertheless recent studies do not confirm a higher rate of recurrence when the HO is excised in an earlier phase In addition a long delay before surgery leads to ankylosis a high degree of osteoporosis and more extensive intra-articular injuries These findings are associated with bad functional results and potential complications
Should you wait till lesion maturation
Prevention byHandle tissue carefully Avoid excess bleeding Achieve good hemostasis Beware of lesions that span internervous tissue planes
but if it happens resection of a large enough amount of bone to allow improvement of the range of motion and trying to preserve the joint
Our aim must be
A reactive process that is characterized by a well-circumscribed proliferation of fibroblasts cartilage and bone within muscle
A form of heterotopic ossification that is the result direct trauma intramuscular hematoma
most common location is the diaphysis of long bones Must differentiate from tumors Fibrodysplasia ossificans progressiva (FOP) is a rare subtype of heterotopic ossification
involves mutation of the ACVR1 gene (activin A type I receptor gene a BMP type-1 receptor)
Epidemiology demographics
most common in young active males (15 to 35 years old) body locations
quadriceps brachialis and gluteal muscles Genetics
almost always a posttraumatic condition Prognosis
usually self limiting mass usually begins to decrease in size after 1 yea
Myositis ossificans
PresentationbullSymptoms
bull pain tenderness swelling and decreased range of motion that usually presents within days of the injury
bull pain and size of the mass decrease with timebull mass increases in size over several months(usually 3 to 6 cm)
bull after the mass stops growing it becomes firmbullPhysical exam
bull palpable soft tissue massbull restricted range of motion
ImagingbullRadiographs
bull peripheral bone formation with central lucent areabull may appear as dotted veil pattern
bullMRI with gadolinium bull rim enhancement is seen within the first 3 weeks
bullCT scan bull lesion has an eggshell appearance
bullCharacteristic histology shows zonal pattern bull periphery of lesion
bull mature trabeculae of lamellar and woven bonebull calcification seen on xray
bull center of the lesion bull irregular mass of immature fibroblastsbull cartilage component may be presentbull (no calcification seen on xray) bull no cellular atypia seen
Treatment
bullNonoperative bull rest range of motion exercises and activity modification
bull passive stretching is contraindicated (makes it worse)bull physical therapy
bull utilized to maintain range of motionbull radiographic monitoring
bull obtained to confirm maturation of the lesionbullOperative
bull surgical excision bull indicated only if it remains a problem after it maturesbull do not operate in acute phase wait at least six months
bull excision of the lesion within 6 to 12 months predisposes to local recurrence
A 26-year-old man presents with generalized back and joint stiffness and difficulty opening his mouth His elder sister has similar complaints Since childhood he has had 3 surgeries for excision of recurrent bony prominences around his knees He walks with a stooped over posture seen in Figure A Radiographs of his feet knee hip and spine are seen in Figures B-E respectively
fibrodysplasia ossificans progressiva
Stone Man Disease) which involves a mutation of the ACVR1
There are 2 hallmark characteristics progressive heterotopic ossification (muscles fascia tendons ligaments and joint capsules) and congenital malformation of the great toe (hallux valgus malformed first metatarsal and monophalangism) BMP4 which contributes to the formation of the skeleton in the normal embryo is implicated in this disease
Complications
bullHematoma and intraoperative bleedingbullInfection
bull higher rate of infection following joint arthroplasty if HO is present
bullFractures of osteoporotic bone bull osteopenic from disusebull during surgery or physiotherapy
bullRecurrence bull recurrence rate correlates with neurological injury
bull greater recurrence if severe neurological compromisebullAVN
bull if extensive dissection or stripping is required
HTO AND ISS
When ISS is below 25 the mortality risk is minimal and above 25 it is an almost linear increase
When ISS is 50 the mortality is 50 When above 70 it is close to 100 If an injury is assigned an AIS of 6 (unsurvivable injury) the ISS score is
automatically assigned to 75 Highest ISS score obtainable is 75 For trauma patients of vehicular accidents the scoring system is important
for assessing the effectiveness of medical care in reducing morbidity and mortality
Advantages virtually the only anatomical scoring system in use correlates linearly with
mortality morbidity hospital stay other measures of severity
Weaknesses Any error in AIS scoring increases the ISS error Many different injury patterns can yield the same ISS score Injuries to different body regions are not weighted Not a useful triage tool as a full description of patient injuries is not known
prior to full investigation amp operation
risk factors periosteal stripping off anterior femur male gender obesity post traumatic deformity Anterior and anterolateral approach Cementless
Neurogenic HO around the hip due to SCI occurs more often in the medial region than in the lateral region with ossified tissues extending from the pubic symphysis to the anteromedial femoral shaft posterior to the femoral neurovascular structures Ossification is also seen anteriorly involving the iliopsoas and femoral neurovascular structures laterally within gluteus minimus and posteriorly extending from the ilium to the posterior femur encasing the sciatic nerve
HTO AROUND hip and knee
The Brooker Classification of Heterotopic Ossification around the hip joint Class I has islands of bone within the soft tissues Class II has bone spurs from the pelvis or proximal end of the femur leaving at least 1 cm between opposing surfaces Class III has bone spurs from the pelvis andor proximal end of the femur reducing the space between opposing bone surfaces to less than 1 cm Class IV shows apparent bone ankylosis of the hip
Region I - Heterotopic ossifications are strictly below the tip of the greater trochanter
Region II - Heterotopic ossifications are below and above the tip of the greater trochanter
Region III - Heterotopic ossifications are strictly above the tip of the greater trochanter
Grade A - Single or multiple heterotopic ossifications are less than 10 mm in maximal extent without contact with the pelvis or the femur
Grade B - Heterotopic ossifications are greater than 10 mm without contact with the pelvis but with possible contact with the femur there is no bridging from the femur to the proximal part of the greater trochanter and no evidence of ankylosis
Grade C - Ankylosis by means of firm bridging from the femur to the pelvis is present
Shmidt classification
excision may be performed The results of this procedure are varied Patients may find that their range of movement improves but pain relief is likely to be limited
A patient with heterotopic ossification following total hip arthroplasty is thought to have a 90-100 chance of developing it on the contralateral hip if this hip also undergoes total arthroplasty
it would be prudent to minimize the risk of heterotopic ossification developing after arthroplasty by performing surgery whereby the following are ensured
Exposure is meticulous Retraction is performed carefully and soft tissue
is handled carefully Irrigation is adequate Devitalized tissue is excised Hemostasis is adequate Postoperative drains (when used) are not
retained for longer than necessary Perioperative antibiotic prophylaxis is used Postoperative anticoagulation (when used for
deep vein thrombosis prophylaxis) is carefully controlled
sources of knee stiffness 1-extrinsic severe osteoarthritis of the ipsilateral hip neurologic injury leading to muscle rigidity tight quadriceps or hamstring muscles secondary to muscle injury heterotopic ossification or long-standing juvenile inflammatory conditions limiting knee
range of motion prior to the completion of skeletal growth When extrinsic sources are identified revision total knee arthroplasty is unlikely to be associated with a favorable outcome without correction of the extrinsic problem
2-intrinsic (1) overstuffing of the patellofemoral articulation (2) an
excessively tight flexion andor extension gap (3) a tight posterior cruciate ligament (4) femoral andor tibial malrotation (5) arthrofibrosis and (6) limited bearing excursion in association with a highly conforming mobile-bearing prosthetic design
HTO after TKA
Heterotopic Ossification (HO) following primary Total Knee Replacement (TKR)
Occurs in 3-90 of TKRs 3-grade classification system No correlation between HO and component
alignment or component position
Clinical findings similar to early infection Continuing low-grade fever Warm swollen and erythematous knee Normal blood tests Possibly an association with HLA-A2 and B18 HO patients have worse KSS and function
scores
Patients at HIGH risk for developing HO after TKR (Knee Arthroplasty) (5)
Those with limited postoperative knee flexion
Increased lumbar bone mineral density (BMD) on multivariate analysis (3)
Hypertrophic arthrosis Excessive periosteal trauma Notching of the anterior femur Those who require forced manipulation
after TKA 47 in revision TKR surgery (6) Higher rates in revision TKR cases with
infection (up to 76
DaughertyBell classification of HO of the knee 0 No evidence of HO 1 Bone islands in periarticular soft tissue (no
involvement of femur patella or tibia) or HO within quadriceps expansion measuring lt1 cm
2 Spur formation measuring lt5 cm that involves the femur patella or tibia if more than one bone demonstrates HO separation of HO spurs
measure gt1 cm or HO within quadriceps expansion measuring ge1 cm but lt3 cm
3 Spur formation gt5 cm involving femur patella or tibia if more than one bone demonstrates HO separation of HO spurs measure lt1 cm or HO
within quadriceps expansion measuring ge3 cm 4 Extensive HO of the knee causing ankylosis
class 2 HO begins to involve the major bones of the knee joint with spur formation limited to a size of 5 cm
HO class 2 may be observed in select patients with complete ROM and no reported pain Patients with class 3 HO would likely always benefit from surgical excision
followed by RT prophylaxis Certainly patients in either cohort with a subclass ldquoBrdquo assignment (symptomatic) would
benefit from treatment All patients with class 4 HO require
treatment to alleviate ankylosis
treatment
References Whyte ldquoPagetrsquos Disease of Bonerdquo NEMJ vol 355
2006 Klein and Parvizi ldquoSurgical Manifestations of Pagetrsquos
Diseaserdquo JAAOS vol 14 2006 Orthobullets Campbell Apley Emedicinecom
-Chapter 15 Heterotopic Ossification after Traumatic Brain InjuryBy Jesuacutes Moreta and Joseacute Luis Martiacutenez-de los Mozos DOI 10577257343
Questions
Thank You
Symptoms skeletal involvement
pain and swelling at the region of involvement limping can be seen with pelvic or lower extremity
involvement vertebral involvement
localized or diffuse back pain increasingly kyphotic posture radiculopathy can occur with more aggressive lesions
HSC classic triad of
multiple lytic skull lesions diabetes insipidus
increased thirst and water intake exopthalmos
visceral involvement diffuse or nonspecific abdominal or chest pain
Radiographs general
known as the great mimicker as it appears similar to many lesions radiographic differential includes osteomyelitis leukemia lymphoma
fibrous dysplasia or Ewings sarcoma diaphyseal lesions
well defined intramedullary lytic or punched-out lesion cortex may be thinned expanded or destroyed may have periosteal reaction
metaphyseal lesions extend up to but not through the physis less central location than diaphyseal lesions
spinal lesions vertebra plana (flattened vertebrae) in spine increased kyphosis
cranial involvement multiple punched-out lytic lesions
MRI may show a soft tissue mass adjacent to boney lesions
Bone scan generally shows increased uptake in the region of boney lesion
Histology Langerhans cells
mononuclear histiocyte-like cells with oval nuclei with well-defined round or oval cytoplasm
a prominent nuclear groove (coffee bean nuclei) can be seen in most of the nuclei
eosinophilic cytoplasm (pink generally) stain with CD1A electronmicroscopy
birbeck granules seen inside Langerhans cells mixture of inflammatory cells also present giant cells are present lack of nuclear atypia and atypical mitoses
differentiates this condition from malignant conditions such as Ewings sarcoma lymphoma of bone and metastatic neuroblastoma which may look similar based on the round cells alone
eosinophilic cytoplasm (pink generally)
Treatment
bullNonoperative bull observation alone
bull indications bull a self-limited process and it is reasonable to treat with observation alone
bull bracing bull indications
bull to prevent progressive kyphosis of the spinebull outcomes
bull will correct deformity in 90 of patientsbull vertebral lesions generally regain 50 of their height
bull low dose irradiation (600-800 cGy) bull indications
bull indicated for lesions in the spine that compromise stability neurologic statusbull lesions not amenable to injection or open treatment
bull outcomes bull effective for most lesions
bull chemotherapy bull indications
bull diffuse HSCbull outcomes
bull prognosis is improved with less severe extraskeletal involvementbull corticosteroid injection
bull indications bull isolated lesions bull can be performed after curettage as well
Operative curettage and bone grafting
indications for lesions that endanger the articular surface or are a risk for
impending fractures spinal deformity correction
indications progressive spine deformity refractory to bracing
approximately 10 of patients with spine lesion will need operative intervention for deformity correction
Destructive multiple lesion in young patientsAre eosinophilic granuloma lymphoma and leukemiaLymphoma is unlikely to present with exopthalmos diabetes insipidus or vertebra plana Lymphoma bone lesions are lytic and appear moth eatenpermeative on radiographs
Figure A shows a skin lesion typical of eosinophillic granuloma Figure B shows a lytic lesions without significant surrounding sclerosis as is characteristic of eosinophilic granuloma Figure C shows the characteristic histology of multiple eosinophils with their characteristic oval coffee bean nuclei and staining pattern of purpleredpink cytoplasm (depending on the stain) Importantly the histology slide lacks a malignant appearance (no cellular atypia or mytotic complexes and low nuclearcytoplasmic ratio)
Formation of bone in atypical extraskeletal tissues usually occurs
spontaneously or following trauma within 2 months of neurologic injury (brain or spinal cord)
most common location is between muscle and joint capsule Epidemiology
incidence (see table below)
demographics malefemale = 21 especially men with hypertrophic osteoarthritis and women gt65y
location traumatic brain injury or stroke
hip gt elbow gt shoulder gt knee elbow HO more common following brain trauma
occurs on affected (spastic) side rarely in the knee (TBI)
spinal cord injury hip gt knee gt elbow gt shoulder hip flexors and abductors gt extensors or adductors medial aspect of the knee
Heterotopic Ossification
Risk factors
Pathophysiology exact cause of HO is not known but there appears to be a
genetic pre disposition experimental HO associated with
tissue expression of BMP IT IS SAID TO BE CAUSED BY activation and proliferation of
mesenchymal stem cells Associated conditions
orthopaedic manifestations pathologic fractures
from decreased joint ROM and osteoporotic bone nerve impingement soft tissue contractures contributing to the formation of
decubitus ulcers joint ankylosis HO after THA adversely affects outcome of THA
nonorthopaedic conditions skin maceration and hygiene problems
Pathophysiology Early in the formation of HO oedema with exudative
infiltrate is present followed by fibroblastic proliferation and immature connective tissue formation Posteriorly osteoid formation is seen with the subsequent deposition of bone matrix Primitive osteoid is deposited as small masses in the periphery early (within the first two weeks) and osteoblasts are noted located irregularly Osteoblasts produce tropocollagen which polymerizes to form collagen and secrete alkaline phosphatase which allows calcium to precipitate and the mineralization of bone matrix As mineralization progresses amorphous calcium phosphate is progressively replaced by hydroxyapatite crystals During the following weeks the lesion matures with a centripetal pattern and after 6-12 months an appearance of true bone is noted The new bone is always extra-articular and can be contiguous with the skeleton but generally does not involve the periosteum
IN SUMMARY It has been postulated that three conditions
must be met to achieve heterotopic bone formation ---a stimulating event oestrogenic precursor cells and a proper environment LIKE hypercalcaemia tissue hypoxia pH changes (alkalosis) or prolonged immobilization
ClassificationbullSubtypes
bull neurogenic HO bull Four clinical stages of HO in people with spinal cord injury were
described by Nicholas in 1973
bull traumatic myositis ossificans bull fibrodysplasia ossificans progressiva (Munchmeyers Disease)
Neurogenic HO Symptoms
painless loss of ROM interferes with ADL CRPS symptoms fever
Physical exam inspection
warm painful swollen joint may have effusion skin problems
decubitus ulcers from contractures around skin muscles ligaments
skin maceration and hygiene problems motion
decreased joint ROM joint ankylosis with HO after TKA might develop quad muscle snapping or patella
instability neurovascular
peripheral neuropathy HO often impinges on adjacent NV structures
Imaging
bullRadiographs bull findings
bull ossification usually easy to visualize bull maturity of HO
bull the appearance of a bony cortex suggests mature HObull sharp demarcation from surrounding tissue bull trabecular pattern
bull sensitivity and specificity bull not useful for early diagnosisbull only useful at 1 week after onset of symptoms
bull calcium is deposited 7-10 days later than symptom onsetbullUltrasound
bull indications bull for early diagnosis of hip HO
bull findings bull echogenic surfaces with posterior acoustic shadowing
bullCT bull indications
bull useful for preoperative planning bullTriphasic bone scan
bull indications bull best for early diagnosis bull most commonly used diagnostic study
Radiographs are extremely useful in the staging of heterotopic ossification and will show the development of sharp cortical margins once the lesion has reached maturity
Heterotopic bone is a condition in which lamellar bone forms in non-ossified soft tissues In the early stages studies such as MRI and bone scan are more sensitive for diagnosis as radiographs may appear normal for the first three weeks After the appropriate diagnosis is made sequential radiographs are useful for monitoring the progression of the ossification Once it has reached the mature stage sharp cortical margins will appear and surgical resection may be considered
lab
Labs elevated serum alkaline phosphatase (gt250IUL)
ALP removes inhibitors of mineralization nonspecific may be elevated with skeletal trauma cannot determine maturity of HO elevated 12wks after surgery is predictor
elevated CRP correlates with inflammatory activity of HO better than ESR normalization of CRP may correlate with maturity of HO
elevated ESR (gt35mmh) 12wks after THA is predictor
elevated CK correlates with involvement of muscle extent of muscle
involvement Histology
mature fatty bone marrow mature trabecular bone
Heterotopic ossification (HO) most commonly occurs at the amputation site if the amputation was performed thru the zone of injury especially if the injury was a blast mechanism
Symptomatic heterotopic ossification of the quadriceps may occur following placement of a large-diameter Steinmann pin for the purpose of temporary skeletal traction
TreatmentThe prevention of heterotopic ossification is focused on three basic principles disrupting the inductive signalling pathways altering the osteoprogenitor cells or modifying the environment
bullphysiotherapy should involve an assisted range of movement exercises with gentle stretch and terminal resistance trainingbullProphylaxis
bull bisphosphonates amp NSAIDS bull indications
bull although no literature supports are commonly usedbull technique
bull indomethacin is most commonly used bull dose is 75mgday for 10days to 6 weeks
bull perioperative radiation bull indications
bull although no literature supports commonly usedbull is thought to be effective by blocking osteoblast differentiation
bull technique bull a single perioperative dose of 700cGy can be given either 4
hours preop or within 72 hours postoperatively bull lt550cGy not effective
Nonsteroidal anti-inflammatory drugs (NSAIDs) These drugs have demonstrated good results in
preventing heterotopic ossification after total hip arthroplasty
A direct effect of NSAIDs on the formation of heterotopic ossification has been described due to the inhibition of the differentiation of mesenchymal cells into oestrogenic cells There is also an indirect effect which refers to the inhibition of bone remodelling by suppression of the prostagland unmediated inflammatory response (specifically PGE-2)
Indomethacin has been considered a useful medication for heterotopic ossification prophylaxis following total hip replacement
prescribed for three to six weeks in a dose of 75mgday within two months of the injury may reduce the incidence of heterotopic ossification by two to three times
Biphosphonates inhibits precipitation of calcium phosphate and blocks the aggregation and mineralisation of hydroxyapatite crystals In primary prevention Banovac et al [56] have suggested that the treatment should begin as soon as elevated alkaline phosphatase is diagnosed or positive findings in ultrasonography or bone scans are shown In addition disphosphonates could have long-term effects on prevention when the treatment is finished
Posttraumatic wide exposure and surgical resection
indications severe loss of motion and decreased function
technique wide exposure required to identify all neurovascular
structures that may be involved timing of resection (controversial)
marked decrease in bone scan activity AND normalization of ALP
6 months following general trauma 1 year following SCI 15 years following TBI
some data suggests equivalent results when comparing early versus late resection
postop follow with 5 day course of indomethacin early gentle joint mobilization
The surgery is necessary in patients with symptomatic HO and unsuccessful medical treatment such as
Loss of range of motion and ankylosis with associated functional disability such as sitting difficulties
Complications of immobility such as pressure ulcers
Facilitate rehabilitation and recovery of muscular atrophy secondary to prolonged immobilisation
Difficulties of appropriate hygiene because access to the perineum or bladder care is needed
Severe pain refractory to analgesia Vascular andor nerve compression
Advantages to early excision of heterotopic ossification (vs waiting for maturation) include decreased soft tissue contracture better definition between heterotopic and native bone and decreased waiting time for the patient When the soft tissue envelope is benign one may proceed with operative release While waiting for normalization of alkaline phosphatase levels inactivity on bone scan or radiographic maturity may decrease risk of recurrent heterotopic ossification delaying operative release for these reasons has not been shown to improve results of final elbow range of motion after contracture release
Gartland recommended surgery after six months following traumatic heterotopic ossification one year following spinal cord injury and 18 months after head injury
In the past waiting until maturity in order to minimize the rate of recurrence after the surgical treatment was recommended Nevertheless recent studies do not confirm a higher rate of recurrence when the HO is excised in an earlier phase In addition a long delay before surgery leads to ankylosis a high degree of osteoporosis and more extensive intra-articular injuries These findings are associated with bad functional results and potential complications
Should you wait till lesion maturation
Prevention byHandle tissue carefully Avoid excess bleeding Achieve good hemostasis Beware of lesions that span internervous tissue planes
but if it happens resection of a large enough amount of bone to allow improvement of the range of motion and trying to preserve the joint
Our aim must be
A reactive process that is characterized by a well-circumscribed proliferation of fibroblasts cartilage and bone within muscle
A form of heterotopic ossification that is the result direct trauma intramuscular hematoma
most common location is the diaphysis of long bones Must differentiate from tumors Fibrodysplasia ossificans progressiva (FOP) is a rare subtype of heterotopic ossification
involves mutation of the ACVR1 gene (activin A type I receptor gene a BMP type-1 receptor)
Epidemiology demographics
most common in young active males (15 to 35 years old) body locations
quadriceps brachialis and gluteal muscles Genetics
almost always a posttraumatic condition Prognosis
usually self limiting mass usually begins to decrease in size after 1 yea
Myositis ossificans
PresentationbullSymptoms
bull pain tenderness swelling and decreased range of motion that usually presents within days of the injury
bull pain and size of the mass decrease with timebull mass increases in size over several months(usually 3 to 6 cm)
bull after the mass stops growing it becomes firmbullPhysical exam
bull palpable soft tissue massbull restricted range of motion
ImagingbullRadiographs
bull peripheral bone formation with central lucent areabull may appear as dotted veil pattern
bullMRI with gadolinium bull rim enhancement is seen within the first 3 weeks
bullCT scan bull lesion has an eggshell appearance
bullCharacteristic histology shows zonal pattern bull periphery of lesion
bull mature trabeculae of lamellar and woven bonebull calcification seen on xray
bull center of the lesion bull irregular mass of immature fibroblastsbull cartilage component may be presentbull (no calcification seen on xray) bull no cellular atypia seen
Treatment
bullNonoperative bull rest range of motion exercises and activity modification
bull passive stretching is contraindicated (makes it worse)bull physical therapy
bull utilized to maintain range of motionbull radiographic monitoring
bull obtained to confirm maturation of the lesionbullOperative
bull surgical excision bull indicated only if it remains a problem after it maturesbull do not operate in acute phase wait at least six months
bull excision of the lesion within 6 to 12 months predisposes to local recurrence
A 26-year-old man presents with generalized back and joint stiffness and difficulty opening his mouth His elder sister has similar complaints Since childhood he has had 3 surgeries for excision of recurrent bony prominences around his knees He walks with a stooped over posture seen in Figure A Radiographs of his feet knee hip and spine are seen in Figures B-E respectively
fibrodysplasia ossificans progressiva
Stone Man Disease) which involves a mutation of the ACVR1
There are 2 hallmark characteristics progressive heterotopic ossification (muscles fascia tendons ligaments and joint capsules) and congenital malformation of the great toe (hallux valgus malformed first metatarsal and monophalangism) BMP4 which contributes to the formation of the skeleton in the normal embryo is implicated in this disease
Complications
bullHematoma and intraoperative bleedingbullInfection
bull higher rate of infection following joint arthroplasty if HO is present
bullFractures of osteoporotic bone bull osteopenic from disusebull during surgery or physiotherapy
bullRecurrence bull recurrence rate correlates with neurological injury
bull greater recurrence if severe neurological compromisebullAVN
bull if extensive dissection or stripping is required
HTO AND ISS
When ISS is below 25 the mortality risk is minimal and above 25 it is an almost linear increase
When ISS is 50 the mortality is 50 When above 70 it is close to 100 If an injury is assigned an AIS of 6 (unsurvivable injury) the ISS score is
automatically assigned to 75 Highest ISS score obtainable is 75 For trauma patients of vehicular accidents the scoring system is important
for assessing the effectiveness of medical care in reducing morbidity and mortality
Advantages virtually the only anatomical scoring system in use correlates linearly with
mortality morbidity hospital stay other measures of severity
Weaknesses Any error in AIS scoring increases the ISS error Many different injury patterns can yield the same ISS score Injuries to different body regions are not weighted Not a useful triage tool as a full description of patient injuries is not known
prior to full investigation amp operation
risk factors periosteal stripping off anterior femur male gender obesity post traumatic deformity Anterior and anterolateral approach Cementless
Neurogenic HO around the hip due to SCI occurs more often in the medial region than in the lateral region with ossified tissues extending from the pubic symphysis to the anteromedial femoral shaft posterior to the femoral neurovascular structures Ossification is also seen anteriorly involving the iliopsoas and femoral neurovascular structures laterally within gluteus minimus and posteriorly extending from the ilium to the posterior femur encasing the sciatic nerve
HTO AROUND hip and knee
The Brooker Classification of Heterotopic Ossification around the hip joint Class I has islands of bone within the soft tissues Class II has bone spurs from the pelvis or proximal end of the femur leaving at least 1 cm between opposing surfaces Class III has bone spurs from the pelvis andor proximal end of the femur reducing the space between opposing bone surfaces to less than 1 cm Class IV shows apparent bone ankylosis of the hip
Region I - Heterotopic ossifications are strictly below the tip of the greater trochanter
Region II - Heterotopic ossifications are below and above the tip of the greater trochanter
Region III - Heterotopic ossifications are strictly above the tip of the greater trochanter
Grade A - Single or multiple heterotopic ossifications are less than 10 mm in maximal extent without contact with the pelvis or the femur
Grade B - Heterotopic ossifications are greater than 10 mm without contact with the pelvis but with possible contact with the femur there is no bridging from the femur to the proximal part of the greater trochanter and no evidence of ankylosis
Grade C - Ankylosis by means of firm bridging from the femur to the pelvis is present
Shmidt classification
excision may be performed The results of this procedure are varied Patients may find that their range of movement improves but pain relief is likely to be limited
A patient with heterotopic ossification following total hip arthroplasty is thought to have a 90-100 chance of developing it on the contralateral hip if this hip also undergoes total arthroplasty
it would be prudent to minimize the risk of heterotopic ossification developing after arthroplasty by performing surgery whereby the following are ensured
Exposure is meticulous Retraction is performed carefully and soft tissue
is handled carefully Irrigation is adequate Devitalized tissue is excised Hemostasis is adequate Postoperative drains (when used) are not
retained for longer than necessary Perioperative antibiotic prophylaxis is used Postoperative anticoagulation (when used for
deep vein thrombosis prophylaxis) is carefully controlled
sources of knee stiffness 1-extrinsic severe osteoarthritis of the ipsilateral hip neurologic injury leading to muscle rigidity tight quadriceps or hamstring muscles secondary to muscle injury heterotopic ossification or long-standing juvenile inflammatory conditions limiting knee
range of motion prior to the completion of skeletal growth When extrinsic sources are identified revision total knee arthroplasty is unlikely to be associated with a favorable outcome without correction of the extrinsic problem
2-intrinsic (1) overstuffing of the patellofemoral articulation (2) an
excessively tight flexion andor extension gap (3) a tight posterior cruciate ligament (4) femoral andor tibial malrotation (5) arthrofibrosis and (6) limited bearing excursion in association with a highly conforming mobile-bearing prosthetic design
HTO after TKA
Heterotopic Ossification (HO) following primary Total Knee Replacement (TKR)
Occurs in 3-90 of TKRs 3-grade classification system No correlation between HO and component
alignment or component position
Clinical findings similar to early infection Continuing low-grade fever Warm swollen and erythematous knee Normal blood tests Possibly an association with HLA-A2 and B18 HO patients have worse KSS and function
scores
Patients at HIGH risk for developing HO after TKR (Knee Arthroplasty) (5)
Those with limited postoperative knee flexion
Increased lumbar bone mineral density (BMD) on multivariate analysis (3)
Hypertrophic arthrosis Excessive periosteal trauma Notching of the anterior femur Those who require forced manipulation
after TKA 47 in revision TKR surgery (6) Higher rates in revision TKR cases with
infection (up to 76
DaughertyBell classification of HO of the knee 0 No evidence of HO 1 Bone islands in periarticular soft tissue (no
involvement of femur patella or tibia) or HO within quadriceps expansion measuring lt1 cm
2 Spur formation measuring lt5 cm that involves the femur patella or tibia if more than one bone demonstrates HO separation of HO spurs
measure gt1 cm or HO within quadriceps expansion measuring ge1 cm but lt3 cm
3 Spur formation gt5 cm involving femur patella or tibia if more than one bone demonstrates HO separation of HO spurs measure lt1 cm or HO
within quadriceps expansion measuring ge3 cm 4 Extensive HO of the knee causing ankylosis
class 2 HO begins to involve the major bones of the knee joint with spur formation limited to a size of 5 cm
HO class 2 may be observed in select patients with complete ROM and no reported pain Patients with class 3 HO would likely always benefit from surgical excision
followed by RT prophylaxis Certainly patients in either cohort with a subclass ldquoBrdquo assignment (symptomatic) would
benefit from treatment All patients with class 4 HO require
treatment to alleviate ankylosis
treatment
References Whyte ldquoPagetrsquos Disease of Bonerdquo NEMJ vol 355
2006 Klein and Parvizi ldquoSurgical Manifestations of Pagetrsquos
Diseaserdquo JAAOS vol 14 2006 Orthobullets Campbell Apley Emedicinecom
-Chapter 15 Heterotopic Ossification after Traumatic Brain InjuryBy Jesuacutes Moreta and Joseacute Luis Martiacutenez-de los Mozos DOI 10577257343
Questions
Thank You
Radiographs general
known as the great mimicker as it appears similar to many lesions radiographic differential includes osteomyelitis leukemia lymphoma
fibrous dysplasia or Ewings sarcoma diaphyseal lesions
well defined intramedullary lytic or punched-out lesion cortex may be thinned expanded or destroyed may have periosteal reaction
metaphyseal lesions extend up to but not through the physis less central location than diaphyseal lesions
spinal lesions vertebra plana (flattened vertebrae) in spine increased kyphosis
cranial involvement multiple punched-out lytic lesions
MRI may show a soft tissue mass adjacent to boney lesions
Bone scan generally shows increased uptake in the region of boney lesion
Histology Langerhans cells
mononuclear histiocyte-like cells with oval nuclei with well-defined round or oval cytoplasm
a prominent nuclear groove (coffee bean nuclei) can be seen in most of the nuclei
eosinophilic cytoplasm (pink generally) stain with CD1A electronmicroscopy
birbeck granules seen inside Langerhans cells mixture of inflammatory cells also present giant cells are present lack of nuclear atypia and atypical mitoses
differentiates this condition from malignant conditions such as Ewings sarcoma lymphoma of bone and metastatic neuroblastoma which may look similar based on the round cells alone
eosinophilic cytoplasm (pink generally)
Treatment
bullNonoperative bull observation alone
bull indications bull a self-limited process and it is reasonable to treat with observation alone
bull bracing bull indications
bull to prevent progressive kyphosis of the spinebull outcomes
bull will correct deformity in 90 of patientsbull vertebral lesions generally regain 50 of their height
bull low dose irradiation (600-800 cGy) bull indications
bull indicated for lesions in the spine that compromise stability neurologic statusbull lesions not amenable to injection or open treatment
bull outcomes bull effective for most lesions
bull chemotherapy bull indications
bull diffuse HSCbull outcomes
bull prognosis is improved with less severe extraskeletal involvementbull corticosteroid injection
bull indications bull isolated lesions bull can be performed after curettage as well
Operative curettage and bone grafting
indications for lesions that endanger the articular surface or are a risk for
impending fractures spinal deformity correction
indications progressive spine deformity refractory to bracing
approximately 10 of patients with spine lesion will need operative intervention for deformity correction
Destructive multiple lesion in young patientsAre eosinophilic granuloma lymphoma and leukemiaLymphoma is unlikely to present with exopthalmos diabetes insipidus or vertebra plana Lymphoma bone lesions are lytic and appear moth eatenpermeative on radiographs
Figure A shows a skin lesion typical of eosinophillic granuloma Figure B shows a lytic lesions without significant surrounding sclerosis as is characteristic of eosinophilic granuloma Figure C shows the characteristic histology of multiple eosinophils with their characteristic oval coffee bean nuclei and staining pattern of purpleredpink cytoplasm (depending on the stain) Importantly the histology slide lacks a malignant appearance (no cellular atypia or mytotic complexes and low nuclearcytoplasmic ratio)
Formation of bone in atypical extraskeletal tissues usually occurs
spontaneously or following trauma within 2 months of neurologic injury (brain or spinal cord)
most common location is between muscle and joint capsule Epidemiology
incidence (see table below)
demographics malefemale = 21 especially men with hypertrophic osteoarthritis and women gt65y
location traumatic brain injury or stroke
hip gt elbow gt shoulder gt knee elbow HO more common following brain trauma
occurs on affected (spastic) side rarely in the knee (TBI)
spinal cord injury hip gt knee gt elbow gt shoulder hip flexors and abductors gt extensors or adductors medial aspect of the knee
Heterotopic Ossification
Risk factors
Pathophysiology exact cause of HO is not known but there appears to be a
genetic pre disposition experimental HO associated with
tissue expression of BMP IT IS SAID TO BE CAUSED BY activation and proliferation of
mesenchymal stem cells Associated conditions
orthopaedic manifestations pathologic fractures
from decreased joint ROM and osteoporotic bone nerve impingement soft tissue contractures contributing to the formation of
decubitus ulcers joint ankylosis HO after THA adversely affects outcome of THA
nonorthopaedic conditions skin maceration and hygiene problems
Pathophysiology Early in the formation of HO oedema with exudative
infiltrate is present followed by fibroblastic proliferation and immature connective tissue formation Posteriorly osteoid formation is seen with the subsequent deposition of bone matrix Primitive osteoid is deposited as small masses in the periphery early (within the first two weeks) and osteoblasts are noted located irregularly Osteoblasts produce tropocollagen which polymerizes to form collagen and secrete alkaline phosphatase which allows calcium to precipitate and the mineralization of bone matrix As mineralization progresses amorphous calcium phosphate is progressively replaced by hydroxyapatite crystals During the following weeks the lesion matures with a centripetal pattern and after 6-12 months an appearance of true bone is noted The new bone is always extra-articular and can be contiguous with the skeleton but generally does not involve the periosteum
IN SUMMARY It has been postulated that three conditions
must be met to achieve heterotopic bone formation ---a stimulating event oestrogenic precursor cells and a proper environment LIKE hypercalcaemia tissue hypoxia pH changes (alkalosis) or prolonged immobilization
ClassificationbullSubtypes
bull neurogenic HO bull Four clinical stages of HO in people with spinal cord injury were
described by Nicholas in 1973
bull traumatic myositis ossificans bull fibrodysplasia ossificans progressiva (Munchmeyers Disease)
Neurogenic HO Symptoms
painless loss of ROM interferes with ADL CRPS symptoms fever
Physical exam inspection
warm painful swollen joint may have effusion skin problems
decubitus ulcers from contractures around skin muscles ligaments
skin maceration and hygiene problems motion
decreased joint ROM joint ankylosis with HO after TKA might develop quad muscle snapping or patella
instability neurovascular
peripheral neuropathy HO often impinges on adjacent NV structures
Imaging
bullRadiographs bull findings
bull ossification usually easy to visualize bull maturity of HO
bull the appearance of a bony cortex suggests mature HObull sharp demarcation from surrounding tissue bull trabecular pattern
bull sensitivity and specificity bull not useful for early diagnosisbull only useful at 1 week after onset of symptoms
bull calcium is deposited 7-10 days later than symptom onsetbullUltrasound
bull indications bull for early diagnosis of hip HO
bull findings bull echogenic surfaces with posterior acoustic shadowing
bullCT bull indications
bull useful for preoperative planning bullTriphasic bone scan
bull indications bull best for early diagnosis bull most commonly used diagnostic study
Radiographs are extremely useful in the staging of heterotopic ossification and will show the development of sharp cortical margins once the lesion has reached maturity
Heterotopic bone is a condition in which lamellar bone forms in non-ossified soft tissues In the early stages studies such as MRI and bone scan are more sensitive for diagnosis as radiographs may appear normal for the first three weeks After the appropriate diagnosis is made sequential radiographs are useful for monitoring the progression of the ossification Once it has reached the mature stage sharp cortical margins will appear and surgical resection may be considered
lab
Labs elevated serum alkaline phosphatase (gt250IUL)
ALP removes inhibitors of mineralization nonspecific may be elevated with skeletal trauma cannot determine maturity of HO elevated 12wks after surgery is predictor
elevated CRP correlates with inflammatory activity of HO better than ESR normalization of CRP may correlate with maturity of HO
elevated ESR (gt35mmh) 12wks after THA is predictor
elevated CK correlates with involvement of muscle extent of muscle
involvement Histology
mature fatty bone marrow mature trabecular bone
Heterotopic ossification (HO) most commonly occurs at the amputation site if the amputation was performed thru the zone of injury especially if the injury was a blast mechanism
Symptomatic heterotopic ossification of the quadriceps may occur following placement of a large-diameter Steinmann pin for the purpose of temporary skeletal traction
TreatmentThe prevention of heterotopic ossification is focused on three basic principles disrupting the inductive signalling pathways altering the osteoprogenitor cells or modifying the environment
bullphysiotherapy should involve an assisted range of movement exercises with gentle stretch and terminal resistance trainingbullProphylaxis
bull bisphosphonates amp NSAIDS bull indications
bull although no literature supports are commonly usedbull technique
bull indomethacin is most commonly used bull dose is 75mgday for 10days to 6 weeks
bull perioperative radiation bull indications
bull although no literature supports commonly usedbull is thought to be effective by blocking osteoblast differentiation
bull technique bull a single perioperative dose of 700cGy can be given either 4
hours preop or within 72 hours postoperatively bull lt550cGy not effective
Nonsteroidal anti-inflammatory drugs (NSAIDs) These drugs have demonstrated good results in
preventing heterotopic ossification after total hip arthroplasty
A direct effect of NSAIDs on the formation of heterotopic ossification has been described due to the inhibition of the differentiation of mesenchymal cells into oestrogenic cells There is also an indirect effect which refers to the inhibition of bone remodelling by suppression of the prostagland unmediated inflammatory response (specifically PGE-2)
Indomethacin has been considered a useful medication for heterotopic ossification prophylaxis following total hip replacement
prescribed for three to six weeks in a dose of 75mgday within two months of the injury may reduce the incidence of heterotopic ossification by two to three times
Biphosphonates inhibits precipitation of calcium phosphate and blocks the aggregation and mineralisation of hydroxyapatite crystals In primary prevention Banovac et al [56] have suggested that the treatment should begin as soon as elevated alkaline phosphatase is diagnosed or positive findings in ultrasonography or bone scans are shown In addition disphosphonates could have long-term effects on prevention when the treatment is finished
Posttraumatic wide exposure and surgical resection
indications severe loss of motion and decreased function
technique wide exposure required to identify all neurovascular
structures that may be involved timing of resection (controversial)
marked decrease in bone scan activity AND normalization of ALP
6 months following general trauma 1 year following SCI 15 years following TBI
some data suggests equivalent results when comparing early versus late resection
postop follow with 5 day course of indomethacin early gentle joint mobilization
The surgery is necessary in patients with symptomatic HO and unsuccessful medical treatment such as
Loss of range of motion and ankylosis with associated functional disability such as sitting difficulties
Complications of immobility such as pressure ulcers
Facilitate rehabilitation and recovery of muscular atrophy secondary to prolonged immobilisation
Difficulties of appropriate hygiene because access to the perineum or bladder care is needed
Severe pain refractory to analgesia Vascular andor nerve compression
Advantages to early excision of heterotopic ossification (vs waiting for maturation) include decreased soft tissue contracture better definition between heterotopic and native bone and decreased waiting time for the patient When the soft tissue envelope is benign one may proceed with operative release While waiting for normalization of alkaline phosphatase levels inactivity on bone scan or radiographic maturity may decrease risk of recurrent heterotopic ossification delaying operative release for these reasons has not been shown to improve results of final elbow range of motion after contracture release
Gartland recommended surgery after six months following traumatic heterotopic ossification one year following spinal cord injury and 18 months after head injury
In the past waiting until maturity in order to minimize the rate of recurrence after the surgical treatment was recommended Nevertheless recent studies do not confirm a higher rate of recurrence when the HO is excised in an earlier phase In addition a long delay before surgery leads to ankylosis a high degree of osteoporosis and more extensive intra-articular injuries These findings are associated with bad functional results and potential complications
Should you wait till lesion maturation
Prevention byHandle tissue carefully Avoid excess bleeding Achieve good hemostasis Beware of lesions that span internervous tissue planes
but if it happens resection of a large enough amount of bone to allow improvement of the range of motion and trying to preserve the joint
Our aim must be
A reactive process that is characterized by a well-circumscribed proliferation of fibroblasts cartilage and bone within muscle
A form of heterotopic ossification that is the result direct trauma intramuscular hematoma
most common location is the diaphysis of long bones Must differentiate from tumors Fibrodysplasia ossificans progressiva (FOP) is a rare subtype of heterotopic ossification
involves mutation of the ACVR1 gene (activin A type I receptor gene a BMP type-1 receptor)
Epidemiology demographics
most common in young active males (15 to 35 years old) body locations
quadriceps brachialis and gluteal muscles Genetics
almost always a posttraumatic condition Prognosis
usually self limiting mass usually begins to decrease in size after 1 yea
Myositis ossificans
PresentationbullSymptoms
bull pain tenderness swelling and decreased range of motion that usually presents within days of the injury
bull pain and size of the mass decrease with timebull mass increases in size over several months(usually 3 to 6 cm)
bull after the mass stops growing it becomes firmbullPhysical exam
bull palpable soft tissue massbull restricted range of motion
ImagingbullRadiographs
bull peripheral bone formation with central lucent areabull may appear as dotted veil pattern
bullMRI with gadolinium bull rim enhancement is seen within the first 3 weeks
bullCT scan bull lesion has an eggshell appearance
bullCharacteristic histology shows zonal pattern bull periphery of lesion
bull mature trabeculae of lamellar and woven bonebull calcification seen on xray
bull center of the lesion bull irregular mass of immature fibroblastsbull cartilage component may be presentbull (no calcification seen on xray) bull no cellular atypia seen
Treatment
bullNonoperative bull rest range of motion exercises and activity modification
bull passive stretching is contraindicated (makes it worse)bull physical therapy
bull utilized to maintain range of motionbull radiographic monitoring
bull obtained to confirm maturation of the lesionbullOperative
bull surgical excision bull indicated only if it remains a problem after it maturesbull do not operate in acute phase wait at least six months
bull excision of the lesion within 6 to 12 months predisposes to local recurrence
A 26-year-old man presents with generalized back and joint stiffness and difficulty opening his mouth His elder sister has similar complaints Since childhood he has had 3 surgeries for excision of recurrent bony prominences around his knees He walks with a stooped over posture seen in Figure A Radiographs of his feet knee hip and spine are seen in Figures B-E respectively
fibrodysplasia ossificans progressiva
Stone Man Disease) which involves a mutation of the ACVR1
There are 2 hallmark characteristics progressive heterotopic ossification (muscles fascia tendons ligaments and joint capsules) and congenital malformation of the great toe (hallux valgus malformed first metatarsal and monophalangism) BMP4 which contributes to the formation of the skeleton in the normal embryo is implicated in this disease
Complications
bullHematoma and intraoperative bleedingbullInfection
bull higher rate of infection following joint arthroplasty if HO is present
bullFractures of osteoporotic bone bull osteopenic from disusebull during surgery or physiotherapy
bullRecurrence bull recurrence rate correlates with neurological injury
bull greater recurrence if severe neurological compromisebullAVN
bull if extensive dissection or stripping is required
HTO AND ISS
When ISS is below 25 the mortality risk is minimal and above 25 it is an almost linear increase
When ISS is 50 the mortality is 50 When above 70 it is close to 100 If an injury is assigned an AIS of 6 (unsurvivable injury) the ISS score is
automatically assigned to 75 Highest ISS score obtainable is 75 For trauma patients of vehicular accidents the scoring system is important
for assessing the effectiveness of medical care in reducing morbidity and mortality
Advantages virtually the only anatomical scoring system in use correlates linearly with
mortality morbidity hospital stay other measures of severity
Weaknesses Any error in AIS scoring increases the ISS error Many different injury patterns can yield the same ISS score Injuries to different body regions are not weighted Not a useful triage tool as a full description of patient injuries is not known
prior to full investigation amp operation
risk factors periosteal stripping off anterior femur male gender obesity post traumatic deformity Anterior and anterolateral approach Cementless
Neurogenic HO around the hip due to SCI occurs more often in the medial region than in the lateral region with ossified tissues extending from the pubic symphysis to the anteromedial femoral shaft posterior to the femoral neurovascular structures Ossification is also seen anteriorly involving the iliopsoas and femoral neurovascular structures laterally within gluteus minimus and posteriorly extending from the ilium to the posterior femur encasing the sciatic nerve
HTO AROUND hip and knee
The Brooker Classification of Heterotopic Ossification around the hip joint Class I has islands of bone within the soft tissues Class II has bone spurs from the pelvis or proximal end of the femur leaving at least 1 cm between opposing surfaces Class III has bone spurs from the pelvis andor proximal end of the femur reducing the space between opposing bone surfaces to less than 1 cm Class IV shows apparent bone ankylosis of the hip
Region I - Heterotopic ossifications are strictly below the tip of the greater trochanter
Region II - Heterotopic ossifications are below and above the tip of the greater trochanter
Region III - Heterotopic ossifications are strictly above the tip of the greater trochanter
Grade A - Single or multiple heterotopic ossifications are less than 10 mm in maximal extent without contact with the pelvis or the femur
Grade B - Heterotopic ossifications are greater than 10 mm without contact with the pelvis but with possible contact with the femur there is no bridging from the femur to the proximal part of the greater trochanter and no evidence of ankylosis
Grade C - Ankylosis by means of firm bridging from the femur to the pelvis is present
Shmidt classification
excision may be performed The results of this procedure are varied Patients may find that their range of movement improves but pain relief is likely to be limited
A patient with heterotopic ossification following total hip arthroplasty is thought to have a 90-100 chance of developing it on the contralateral hip if this hip also undergoes total arthroplasty
it would be prudent to minimize the risk of heterotopic ossification developing after arthroplasty by performing surgery whereby the following are ensured
Exposure is meticulous Retraction is performed carefully and soft tissue
is handled carefully Irrigation is adequate Devitalized tissue is excised Hemostasis is adequate Postoperative drains (when used) are not
retained for longer than necessary Perioperative antibiotic prophylaxis is used Postoperative anticoagulation (when used for
deep vein thrombosis prophylaxis) is carefully controlled
sources of knee stiffness 1-extrinsic severe osteoarthritis of the ipsilateral hip neurologic injury leading to muscle rigidity tight quadriceps or hamstring muscles secondary to muscle injury heterotopic ossification or long-standing juvenile inflammatory conditions limiting knee
range of motion prior to the completion of skeletal growth When extrinsic sources are identified revision total knee arthroplasty is unlikely to be associated with a favorable outcome without correction of the extrinsic problem
2-intrinsic (1) overstuffing of the patellofemoral articulation (2) an
excessively tight flexion andor extension gap (3) a tight posterior cruciate ligament (4) femoral andor tibial malrotation (5) arthrofibrosis and (6) limited bearing excursion in association with a highly conforming mobile-bearing prosthetic design
HTO after TKA
Heterotopic Ossification (HO) following primary Total Knee Replacement (TKR)
Occurs in 3-90 of TKRs 3-grade classification system No correlation between HO and component
alignment or component position
Clinical findings similar to early infection Continuing low-grade fever Warm swollen and erythematous knee Normal blood tests Possibly an association with HLA-A2 and B18 HO patients have worse KSS and function
scores
Patients at HIGH risk for developing HO after TKR (Knee Arthroplasty) (5)
Those with limited postoperative knee flexion
Increased lumbar bone mineral density (BMD) on multivariate analysis (3)
Hypertrophic arthrosis Excessive periosteal trauma Notching of the anterior femur Those who require forced manipulation
after TKA 47 in revision TKR surgery (6) Higher rates in revision TKR cases with
infection (up to 76
DaughertyBell classification of HO of the knee 0 No evidence of HO 1 Bone islands in periarticular soft tissue (no
involvement of femur patella or tibia) or HO within quadriceps expansion measuring lt1 cm
2 Spur formation measuring lt5 cm that involves the femur patella or tibia if more than one bone demonstrates HO separation of HO spurs
measure gt1 cm or HO within quadriceps expansion measuring ge1 cm but lt3 cm
3 Spur formation gt5 cm involving femur patella or tibia if more than one bone demonstrates HO separation of HO spurs measure lt1 cm or HO
within quadriceps expansion measuring ge3 cm 4 Extensive HO of the knee causing ankylosis
class 2 HO begins to involve the major bones of the knee joint with spur formation limited to a size of 5 cm
HO class 2 may be observed in select patients with complete ROM and no reported pain Patients with class 3 HO would likely always benefit from surgical excision
followed by RT prophylaxis Certainly patients in either cohort with a subclass ldquoBrdquo assignment (symptomatic) would
benefit from treatment All patients with class 4 HO require
treatment to alleviate ankylosis
treatment
References Whyte ldquoPagetrsquos Disease of Bonerdquo NEMJ vol 355
2006 Klein and Parvizi ldquoSurgical Manifestations of Pagetrsquos
Diseaserdquo JAAOS vol 14 2006 Orthobullets Campbell Apley Emedicinecom
-Chapter 15 Heterotopic Ossification after Traumatic Brain InjuryBy Jesuacutes Moreta and Joseacute Luis Martiacutenez-de los Mozos DOI 10577257343
Questions
Thank You
Histology Langerhans cells
mononuclear histiocyte-like cells with oval nuclei with well-defined round or oval cytoplasm
a prominent nuclear groove (coffee bean nuclei) can be seen in most of the nuclei
eosinophilic cytoplasm (pink generally) stain with CD1A electronmicroscopy
birbeck granules seen inside Langerhans cells mixture of inflammatory cells also present giant cells are present lack of nuclear atypia and atypical mitoses
differentiates this condition from malignant conditions such as Ewings sarcoma lymphoma of bone and metastatic neuroblastoma which may look similar based on the round cells alone
eosinophilic cytoplasm (pink generally)
Treatment
bullNonoperative bull observation alone
bull indications bull a self-limited process and it is reasonable to treat with observation alone
bull bracing bull indications
bull to prevent progressive kyphosis of the spinebull outcomes
bull will correct deformity in 90 of patientsbull vertebral lesions generally regain 50 of their height
bull low dose irradiation (600-800 cGy) bull indications
bull indicated for lesions in the spine that compromise stability neurologic statusbull lesions not amenable to injection or open treatment
bull outcomes bull effective for most lesions
bull chemotherapy bull indications
bull diffuse HSCbull outcomes
bull prognosis is improved with less severe extraskeletal involvementbull corticosteroid injection
bull indications bull isolated lesions bull can be performed after curettage as well
Operative curettage and bone grafting
indications for lesions that endanger the articular surface or are a risk for
impending fractures spinal deformity correction
indications progressive spine deformity refractory to bracing
approximately 10 of patients with spine lesion will need operative intervention for deformity correction
Destructive multiple lesion in young patientsAre eosinophilic granuloma lymphoma and leukemiaLymphoma is unlikely to present with exopthalmos diabetes insipidus or vertebra plana Lymphoma bone lesions are lytic and appear moth eatenpermeative on radiographs
Figure A shows a skin lesion typical of eosinophillic granuloma Figure B shows a lytic lesions without significant surrounding sclerosis as is characteristic of eosinophilic granuloma Figure C shows the characteristic histology of multiple eosinophils with their characteristic oval coffee bean nuclei and staining pattern of purpleredpink cytoplasm (depending on the stain) Importantly the histology slide lacks a malignant appearance (no cellular atypia or mytotic complexes and low nuclearcytoplasmic ratio)
Formation of bone in atypical extraskeletal tissues usually occurs
spontaneously or following trauma within 2 months of neurologic injury (brain or spinal cord)
most common location is between muscle and joint capsule Epidemiology
incidence (see table below)
demographics malefemale = 21 especially men with hypertrophic osteoarthritis and women gt65y
location traumatic brain injury or stroke
hip gt elbow gt shoulder gt knee elbow HO more common following brain trauma
occurs on affected (spastic) side rarely in the knee (TBI)
spinal cord injury hip gt knee gt elbow gt shoulder hip flexors and abductors gt extensors or adductors medial aspect of the knee
Heterotopic Ossification
Risk factors
Pathophysiology exact cause of HO is not known but there appears to be a
genetic pre disposition experimental HO associated with
tissue expression of BMP IT IS SAID TO BE CAUSED BY activation and proliferation of
mesenchymal stem cells Associated conditions
orthopaedic manifestations pathologic fractures
from decreased joint ROM and osteoporotic bone nerve impingement soft tissue contractures contributing to the formation of
decubitus ulcers joint ankylosis HO after THA adversely affects outcome of THA
nonorthopaedic conditions skin maceration and hygiene problems
Pathophysiology Early in the formation of HO oedema with exudative
infiltrate is present followed by fibroblastic proliferation and immature connective tissue formation Posteriorly osteoid formation is seen with the subsequent deposition of bone matrix Primitive osteoid is deposited as small masses in the periphery early (within the first two weeks) and osteoblasts are noted located irregularly Osteoblasts produce tropocollagen which polymerizes to form collagen and secrete alkaline phosphatase which allows calcium to precipitate and the mineralization of bone matrix As mineralization progresses amorphous calcium phosphate is progressively replaced by hydroxyapatite crystals During the following weeks the lesion matures with a centripetal pattern and after 6-12 months an appearance of true bone is noted The new bone is always extra-articular and can be contiguous with the skeleton but generally does not involve the periosteum
IN SUMMARY It has been postulated that three conditions
must be met to achieve heterotopic bone formation ---a stimulating event oestrogenic precursor cells and a proper environment LIKE hypercalcaemia tissue hypoxia pH changes (alkalosis) or prolonged immobilization
ClassificationbullSubtypes
bull neurogenic HO bull Four clinical stages of HO in people with spinal cord injury were
described by Nicholas in 1973
bull traumatic myositis ossificans bull fibrodysplasia ossificans progressiva (Munchmeyers Disease)
Neurogenic HO Symptoms
painless loss of ROM interferes with ADL CRPS symptoms fever
Physical exam inspection
warm painful swollen joint may have effusion skin problems
decubitus ulcers from contractures around skin muscles ligaments
skin maceration and hygiene problems motion
decreased joint ROM joint ankylosis with HO after TKA might develop quad muscle snapping or patella
instability neurovascular
peripheral neuropathy HO often impinges on adjacent NV structures
Imaging
bullRadiographs bull findings
bull ossification usually easy to visualize bull maturity of HO
bull the appearance of a bony cortex suggests mature HObull sharp demarcation from surrounding tissue bull trabecular pattern
bull sensitivity and specificity bull not useful for early diagnosisbull only useful at 1 week after onset of symptoms
bull calcium is deposited 7-10 days later than symptom onsetbullUltrasound
bull indications bull for early diagnosis of hip HO
bull findings bull echogenic surfaces with posterior acoustic shadowing
bullCT bull indications
bull useful for preoperative planning bullTriphasic bone scan
bull indications bull best for early diagnosis bull most commonly used diagnostic study
Radiographs are extremely useful in the staging of heterotopic ossification and will show the development of sharp cortical margins once the lesion has reached maturity
Heterotopic bone is a condition in which lamellar bone forms in non-ossified soft tissues In the early stages studies such as MRI and bone scan are more sensitive for diagnosis as radiographs may appear normal for the first three weeks After the appropriate diagnosis is made sequential radiographs are useful for monitoring the progression of the ossification Once it has reached the mature stage sharp cortical margins will appear and surgical resection may be considered
lab
Labs elevated serum alkaline phosphatase (gt250IUL)
ALP removes inhibitors of mineralization nonspecific may be elevated with skeletal trauma cannot determine maturity of HO elevated 12wks after surgery is predictor
elevated CRP correlates with inflammatory activity of HO better than ESR normalization of CRP may correlate with maturity of HO
elevated ESR (gt35mmh) 12wks after THA is predictor
elevated CK correlates with involvement of muscle extent of muscle
involvement Histology
mature fatty bone marrow mature trabecular bone
Heterotopic ossification (HO) most commonly occurs at the amputation site if the amputation was performed thru the zone of injury especially if the injury was a blast mechanism
Symptomatic heterotopic ossification of the quadriceps may occur following placement of a large-diameter Steinmann pin for the purpose of temporary skeletal traction
TreatmentThe prevention of heterotopic ossification is focused on three basic principles disrupting the inductive signalling pathways altering the osteoprogenitor cells or modifying the environment
bullphysiotherapy should involve an assisted range of movement exercises with gentle stretch and terminal resistance trainingbullProphylaxis
bull bisphosphonates amp NSAIDS bull indications
bull although no literature supports are commonly usedbull technique
bull indomethacin is most commonly used bull dose is 75mgday for 10days to 6 weeks
bull perioperative radiation bull indications
bull although no literature supports commonly usedbull is thought to be effective by blocking osteoblast differentiation
bull technique bull a single perioperative dose of 700cGy can be given either 4
hours preop or within 72 hours postoperatively bull lt550cGy not effective
Nonsteroidal anti-inflammatory drugs (NSAIDs) These drugs have demonstrated good results in
preventing heterotopic ossification after total hip arthroplasty
A direct effect of NSAIDs on the formation of heterotopic ossification has been described due to the inhibition of the differentiation of mesenchymal cells into oestrogenic cells There is also an indirect effect which refers to the inhibition of bone remodelling by suppression of the prostagland unmediated inflammatory response (specifically PGE-2)
Indomethacin has been considered a useful medication for heterotopic ossification prophylaxis following total hip replacement
prescribed for three to six weeks in a dose of 75mgday within two months of the injury may reduce the incidence of heterotopic ossification by two to three times
Biphosphonates inhibits precipitation of calcium phosphate and blocks the aggregation and mineralisation of hydroxyapatite crystals In primary prevention Banovac et al [56] have suggested that the treatment should begin as soon as elevated alkaline phosphatase is diagnosed or positive findings in ultrasonography or bone scans are shown In addition disphosphonates could have long-term effects on prevention when the treatment is finished
Posttraumatic wide exposure and surgical resection
indications severe loss of motion and decreased function
technique wide exposure required to identify all neurovascular
structures that may be involved timing of resection (controversial)
marked decrease in bone scan activity AND normalization of ALP
6 months following general trauma 1 year following SCI 15 years following TBI
some data suggests equivalent results when comparing early versus late resection
postop follow with 5 day course of indomethacin early gentle joint mobilization
The surgery is necessary in patients with symptomatic HO and unsuccessful medical treatment such as
Loss of range of motion and ankylosis with associated functional disability such as sitting difficulties
Complications of immobility such as pressure ulcers
Facilitate rehabilitation and recovery of muscular atrophy secondary to prolonged immobilisation
Difficulties of appropriate hygiene because access to the perineum or bladder care is needed
Severe pain refractory to analgesia Vascular andor nerve compression
Advantages to early excision of heterotopic ossification (vs waiting for maturation) include decreased soft tissue contracture better definition between heterotopic and native bone and decreased waiting time for the patient When the soft tissue envelope is benign one may proceed with operative release While waiting for normalization of alkaline phosphatase levels inactivity on bone scan or radiographic maturity may decrease risk of recurrent heterotopic ossification delaying operative release for these reasons has not been shown to improve results of final elbow range of motion after contracture release
Gartland recommended surgery after six months following traumatic heterotopic ossification one year following spinal cord injury and 18 months after head injury
In the past waiting until maturity in order to minimize the rate of recurrence after the surgical treatment was recommended Nevertheless recent studies do not confirm a higher rate of recurrence when the HO is excised in an earlier phase In addition a long delay before surgery leads to ankylosis a high degree of osteoporosis and more extensive intra-articular injuries These findings are associated with bad functional results and potential complications
Should you wait till lesion maturation
Prevention byHandle tissue carefully Avoid excess bleeding Achieve good hemostasis Beware of lesions that span internervous tissue planes
but if it happens resection of a large enough amount of bone to allow improvement of the range of motion and trying to preserve the joint
Our aim must be
A reactive process that is characterized by a well-circumscribed proliferation of fibroblasts cartilage and bone within muscle
A form of heterotopic ossification that is the result direct trauma intramuscular hematoma
most common location is the diaphysis of long bones Must differentiate from tumors Fibrodysplasia ossificans progressiva (FOP) is a rare subtype of heterotopic ossification
involves mutation of the ACVR1 gene (activin A type I receptor gene a BMP type-1 receptor)
Epidemiology demographics
most common in young active males (15 to 35 years old) body locations
quadriceps brachialis and gluteal muscles Genetics
almost always a posttraumatic condition Prognosis
usually self limiting mass usually begins to decrease in size after 1 yea
Myositis ossificans
PresentationbullSymptoms
bull pain tenderness swelling and decreased range of motion that usually presents within days of the injury
bull pain and size of the mass decrease with timebull mass increases in size over several months(usually 3 to 6 cm)
bull after the mass stops growing it becomes firmbullPhysical exam
bull palpable soft tissue massbull restricted range of motion
ImagingbullRadiographs
bull peripheral bone formation with central lucent areabull may appear as dotted veil pattern
bullMRI with gadolinium bull rim enhancement is seen within the first 3 weeks
bullCT scan bull lesion has an eggshell appearance
bullCharacteristic histology shows zonal pattern bull periphery of lesion
bull mature trabeculae of lamellar and woven bonebull calcification seen on xray
bull center of the lesion bull irregular mass of immature fibroblastsbull cartilage component may be presentbull (no calcification seen on xray) bull no cellular atypia seen
Treatment
bullNonoperative bull rest range of motion exercises and activity modification
bull passive stretching is contraindicated (makes it worse)bull physical therapy
bull utilized to maintain range of motionbull radiographic monitoring
bull obtained to confirm maturation of the lesionbullOperative
bull surgical excision bull indicated only if it remains a problem after it maturesbull do not operate in acute phase wait at least six months
bull excision of the lesion within 6 to 12 months predisposes to local recurrence
A 26-year-old man presents with generalized back and joint stiffness and difficulty opening his mouth His elder sister has similar complaints Since childhood he has had 3 surgeries for excision of recurrent bony prominences around his knees He walks with a stooped over posture seen in Figure A Radiographs of his feet knee hip and spine are seen in Figures B-E respectively
fibrodysplasia ossificans progressiva
Stone Man Disease) which involves a mutation of the ACVR1
There are 2 hallmark characteristics progressive heterotopic ossification (muscles fascia tendons ligaments and joint capsules) and congenital malformation of the great toe (hallux valgus malformed first metatarsal and monophalangism) BMP4 which contributes to the formation of the skeleton in the normal embryo is implicated in this disease
Complications
bullHematoma and intraoperative bleedingbullInfection
bull higher rate of infection following joint arthroplasty if HO is present
bullFractures of osteoporotic bone bull osteopenic from disusebull during surgery or physiotherapy
bullRecurrence bull recurrence rate correlates with neurological injury
bull greater recurrence if severe neurological compromisebullAVN
bull if extensive dissection or stripping is required
HTO AND ISS
When ISS is below 25 the mortality risk is minimal and above 25 it is an almost linear increase
When ISS is 50 the mortality is 50 When above 70 it is close to 100 If an injury is assigned an AIS of 6 (unsurvivable injury) the ISS score is
automatically assigned to 75 Highest ISS score obtainable is 75 For trauma patients of vehicular accidents the scoring system is important
for assessing the effectiveness of medical care in reducing morbidity and mortality
Advantages virtually the only anatomical scoring system in use correlates linearly with
mortality morbidity hospital stay other measures of severity
Weaknesses Any error in AIS scoring increases the ISS error Many different injury patterns can yield the same ISS score Injuries to different body regions are not weighted Not a useful triage tool as a full description of patient injuries is not known
prior to full investigation amp operation
risk factors periosteal stripping off anterior femur male gender obesity post traumatic deformity Anterior and anterolateral approach Cementless
Neurogenic HO around the hip due to SCI occurs more often in the medial region than in the lateral region with ossified tissues extending from the pubic symphysis to the anteromedial femoral shaft posterior to the femoral neurovascular structures Ossification is also seen anteriorly involving the iliopsoas and femoral neurovascular structures laterally within gluteus minimus and posteriorly extending from the ilium to the posterior femur encasing the sciatic nerve
HTO AROUND hip and knee
The Brooker Classification of Heterotopic Ossification around the hip joint Class I has islands of bone within the soft tissues Class II has bone spurs from the pelvis or proximal end of the femur leaving at least 1 cm between opposing surfaces Class III has bone spurs from the pelvis andor proximal end of the femur reducing the space between opposing bone surfaces to less than 1 cm Class IV shows apparent bone ankylosis of the hip
Region I - Heterotopic ossifications are strictly below the tip of the greater trochanter
Region II - Heterotopic ossifications are below and above the tip of the greater trochanter
Region III - Heterotopic ossifications are strictly above the tip of the greater trochanter
Grade A - Single or multiple heterotopic ossifications are less than 10 mm in maximal extent without contact with the pelvis or the femur
Grade B - Heterotopic ossifications are greater than 10 mm without contact with the pelvis but with possible contact with the femur there is no bridging from the femur to the proximal part of the greater trochanter and no evidence of ankylosis
Grade C - Ankylosis by means of firm bridging from the femur to the pelvis is present
Shmidt classification
excision may be performed The results of this procedure are varied Patients may find that their range of movement improves but pain relief is likely to be limited
A patient with heterotopic ossification following total hip arthroplasty is thought to have a 90-100 chance of developing it on the contralateral hip if this hip also undergoes total arthroplasty
it would be prudent to minimize the risk of heterotopic ossification developing after arthroplasty by performing surgery whereby the following are ensured
Exposure is meticulous Retraction is performed carefully and soft tissue
is handled carefully Irrigation is adequate Devitalized tissue is excised Hemostasis is adequate Postoperative drains (when used) are not
retained for longer than necessary Perioperative antibiotic prophylaxis is used Postoperative anticoagulation (when used for
deep vein thrombosis prophylaxis) is carefully controlled
sources of knee stiffness 1-extrinsic severe osteoarthritis of the ipsilateral hip neurologic injury leading to muscle rigidity tight quadriceps or hamstring muscles secondary to muscle injury heterotopic ossification or long-standing juvenile inflammatory conditions limiting knee
range of motion prior to the completion of skeletal growth When extrinsic sources are identified revision total knee arthroplasty is unlikely to be associated with a favorable outcome without correction of the extrinsic problem
2-intrinsic (1) overstuffing of the patellofemoral articulation (2) an
excessively tight flexion andor extension gap (3) a tight posterior cruciate ligament (4) femoral andor tibial malrotation (5) arthrofibrosis and (6) limited bearing excursion in association with a highly conforming mobile-bearing prosthetic design
HTO after TKA
Heterotopic Ossification (HO) following primary Total Knee Replacement (TKR)
Occurs in 3-90 of TKRs 3-grade classification system No correlation between HO and component
alignment or component position
Clinical findings similar to early infection Continuing low-grade fever Warm swollen and erythematous knee Normal blood tests Possibly an association with HLA-A2 and B18 HO patients have worse KSS and function
scores
Patients at HIGH risk for developing HO after TKR (Knee Arthroplasty) (5)
Those with limited postoperative knee flexion
Increased lumbar bone mineral density (BMD) on multivariate analysis (3)
Hypertrophic arthrosis Excessive periosteal trauma Notching of the anterior femur Those who require forced manipulation
after TKA 47 in revision TKR surgery (6) Higher rates in revision TKR cases with
infection (up to 76
DaughertyBell classification of HO of the knee 0 No evidence of HO 1 Bone islands in periarticular soft tissue (no
involvement of femur patella or tibia) or HO within quadriceps expansion measuring lt1 cm
2 Spur formation measuring lt5 cm that involves the femur patella or tibia if more than one bone demonstrates HO separation of HO spurs
measure gt1 cm or HO within quadriceps expansion measuring ge1 cm but lt3 cm
3 Spur formation gt5 cm involving femur patella or tibia if more than one bone demonstrates HO separation of HO spurs measure lt1 cm or HO
within quadriceps expansion measuring ge3 cm 4 Extensive HO of the knee causing ankylosis
class 2 HO begins to involve the major bones of the knee joint with spur formation limited to a size of 5 cm
HO class 2 may be observed in select patients with complete ROM and no reported pain Patients with class 3 HO would likely always benefit from surgical excision
followed by RT prophylaxis Certainly patients in either cohort with a subclass ldquoBrdquo assignment (symptomatic) would
benefit from treatment All patients with class 4 HO require
treatment to alleviate ankylosis
treatment
References Whyte ldquoPagetrsquos Disease of Bonerdquo NEMJ vol 355
2006 Klein and Parvizi ldquoSurgical Manifestations of Pagetrsquos
Diseaserdquo JAAOS vol 14 2006 Orthobullets Campbell Apley Emedicinecom
-Chapter 15 Heterotopic Ossification after Traumatic Brain InjuryBy Jesuacutes Moreta and Joseacute Luis Martiacutenez-de los Mozos DOI 10577257343
Questions
Thank You
eosinophilic cytoplasm (pink generally)
Treatment
bullNonoperative bull observation alone
bull indications bull a self-limited process and it is reasonable to treat with observation alone
bull bracing bull indications
bull to prevent progressive kyphosis of the spinebull outcomes
bull will correct deformity in 90 of patientsbull vertebral lesions generally regain 50 of their height
bull low dose irradiation (600-800 cGy) bull indications
bull indicated for lesions in the spine that compromise stability neurologic statusbull lesions not amenable to injection or open treatment
bull outcomes bull effective for most lesions
bull chemotherapy bull indications
bull diffuse HSCbull outcomes
bull prognosis is improved with less severe extraskeletal involvementbull corticosteroid injection
bull indications bull isolated lesions bull can be performed after curettage as well
Operative curettage and bone grafting
indications for lesions that endanger the articular surface or are a risk for
impending fractures spinal deformity correction
indications progressive spine deformity refractory to bracing
approximately 10 of patients with spine lesion will need operative intervention for deformity correction
Destructive multiple lesion in young patientsAre eosinophilic granuloma lymphoma and leukemiaLymphoma is unlikely to present with exopthalmos diabetes insipidus or vertebra plana Lymphoma bone lesions are lytic and appear moth eatenpermeative on radiographs
Figure A shows a skin lesion typical of eosinophillic granuloma Figure B shows a lytic lesions without significant surrounding sclerosis as is characteristic of eosinophilic granuloma Figure C shows the characteristic histology of multiple eosinophils with their characteristic oval coffee bean nuclei and staining pattern of purpleredpink cytoplasm (depending on the stain) Importantly the histology slide lacks a malignant appearance (no cellular atypia or mytotic complexes and low nuclearcytoplasmic ratio)
Formation of bone in atypical extraskeletal tissues usually occurs
spontaneously or following trauma within 2 months of neurologic injury (brain or spinal cord)
most common location is between muscle and joint capsule Epidemiology
incidence (see table below)
demographics malefemale = 21 especially men with hypertrophic osteoarthritis and women gt65y
location traumatic brain injury or stroke
hip gt elbow gt shoulder gt knee elbow HO more common following brain trauma
occurs on affected (spastic) side rarely in the knee (TBI)
spinal cord injury hip gt knee gt elbow gt shoulder hip flexors and abductors gt extensors or adductors medial aspect of the knee
Heterotopic Ossification
Risk factors
Pathophysiology exact cause of HO is not known but there appears to be a
genetic pre disposition experimental HO associated with
tissue expression of BMP IT IS SAID TO BE CAUSED BY activation and proliferation of
mesenchymal stem cells Associated conditions
orthopaedic manifestations pathologic fractures
from decreased joint ROM and osteoporotic bone nerve impingement soft tissue contractures contributing to the formation of
decubitus ulcers joint ankylosis HO after THA adversely affects outcome of THA
nonorthopaedic conditions skin maceration and hygiene problems
Pathophysiology Early in the formation of HO oedema with exudative
infiltrate is present followed by fibroblastic proliferation and immature connective tissue formation Posteriorly osteoid formation is seen with the subsequent deposition of bone matrix Primitive osteoid is deposited as small masses in the periphery early (within the first two weeks) and osteoblasts are noted located irregularly Osteoblasts produce tropocollagen which polymerizes to form collagen and secrete alkaline phosphatase which allows calcium to precipitate and the mineralization of bone matrix As mineralization progresses amorphous calcium phosphate is progressively replaced by hydroxyapatite crystals During the following weeks the lesion matures with a centripetal pattern and after 6-12 months an appearance of true bone is noted The new bone is always extra-articular and can be contiguous with the skeleton but generally does not involve the periosteum
IN SUMMARY It has been postulated that three conditions
must be met to achieve heterotopic bone formation ---a stimulating event oestrogenic precursor cells and a proper environment LIKE hypercalcaemia tissue hypoxia pH changes (alkalosis) or prolonged immobilization
ClassificationbullSubtypes
bull neurogenic HO bull Four clinical stages of HO in people with spinal cord injury were
described by Nicholas in 1973
bull traumatic myositis ossificans bull fibrodysplasia ossificans progressiva (Munchmeyers Disease)
Neurogenic HO Symptoms
painless loss of ROM interferes with ADL CRPS symptoms fever
Physical exam inspection
warm painful swollen joint may have effusion skin problems
decubitus ulcers from contractures around skin muscles ligaments
skin maceration and hygiene problems motion
decreased joint ROM joint ankylosis with HO after TKA might develop quad muscle snapping or patella
instability neurovascular
peripheral neuropathy HO often impinges on adjacent NV structures
Imaging
bullRadiographs bull findings
bull ossification usually easy to visualize bull maturity of HO
bull the appearance of a bony cortex suggests mature HObull sharp demarcation from surrounding tissue bull trabecular pattern
bull sensitivity and specificity bull not useful for early diagnosisbull only useful at 1 week after onset of symptoms
bull calcium is deposited 7-10 days later than symptom onsetbullUltrasound
bull indications bull for early diagnosis of hip HO
bull findings bull echogenic surfaces with posterior acoustic shadowing
bullCT bull indications
bull useful for preoperative planning bullTriphasic bone scan
bull indications bull best for early diagnosis bull most commonly used diagnostic study
Radiographs are extremely useful in the staging of heterotopic ossification and will show the development of sharp cortical margins once the lesion has reached maturity
Heterotopic bone is a condition in which lamellar bone forms in non-ossified soft tissues In the early stages studies such as MRI and bone scan are more sensitive for diagnosis as radiographs may appear normal for the first three weeks After the appropriate diagnosis is made sequential radiographs are useful for monitoring the progression of the ossification Once it has reached the mature stage sharp cortical margins will appear and surgical resection may be considered
lab
Labs elevated serum alkaline phosphatase (gt250IUL)
ALP removes inhibitors of mineralization nonspecific may be elevated with skeletal trauma cannot determine maturity of HO elevated 12wks after surgery is predictor
elevated CRP correlates with inflammatory activity of HO better than ESR normalization of CRP may correlate with maturity of HO
elevated ESR (gt35mmh) 12wks after THA is predictor
elevated CK correlates with involvement of muscle extent of muscle
involvement Histology
mature fatty bone marrow mature trabecular bone
Heterotopic ossification (HO) most commonly occurs at the amputation site if the amputation was performed thru the zone of injury especially if the injury was a blast mechanism
Symptomatic heterotopic ossification of the quadriceps may occur following placement of a large-diameter Steinmann pin for the purpose of temporary skeletal traction
TreatmentThe prevention of heterotopic ossification is focused on three basic principles disrupting the inductive signalling pathways altering the osteoprogenitor cells or modifying the environment
bullphysiotherapy should involve an assisted range of movement exercises with gentle stretch and terminal resistance trainingbullProphylaxis
bull bisphosphonates amp NSAIDS bull indications
bull although no literature supports are commonly usedbull technique
bull indomethacin is most commonly used bull dose is 75mgday for 10days to 6 weeks
bull perioperative radiation bull indications
bull although no literature supports commonly usedbull is thought to be effective by blocking osteoblast differentiation
bull technique bull a single perioperative dose of 700cGy can be given either 4
hours preop or within 72 hours postoperatively bull lt550cGy not effective
Nonsteroidal anti-inflammatory drugs (NSAIDs) These drugs have demonstrated good results in
preventing heterotopic ossification after total hip arthroplasty
A direct effect of NSAIDs on the formation of heterotopic ossification has been described due to the inhibition of the differentiation of mesenchymal cells into oestrogenic cells There is also an indirect effect which refers to the inhibition of bone remodelling by suppression of the prostagland unmediated inflammatory response (specifically PGE-2)
Indomethacin has been considered a useful medication for heterotopic ossification prophylaxis following total hip replacement
prescribed for three to six weeks in a dose of 75mgday within two months of the injury may reduce the incidence of heterotopic ossification by two to three times
Biphosphonates inhibits precipitation of calcium phosphate and blocks the aggregation and mineralisation of hydroxyapatite crystals In primary prevention Banovac et al [56] have suggested that the treatment should begin as soon as elevated alkaline phosphatase is diagnosed or positive findings in ultrasonography or bone scans are shown In addition disphosphonates could have long-term effects on prevention when the treatment is finished
Posttraumatic wide exposure and surgical resection
indications severe loss of motion and decreased function
technique wide exposure required to identify all neurovascular
structures that may be involved timing of resection (controversial)
marked decrease in bone scan activity AND normalization of ALP
6 months following general trauma 1 year following SCI 15 years following TBI
some data suggests equivalent results when comparing early versus late resection
postop follow with 5 day course of indomethacin early gentle joint mobilization
The surgery is necessary in patients with symptomatic HO and unsuccessful medical treatment such as
Loss of range of motion and ankylosis with associated functional disability such as sitting difficulties
Complications of immobility such as pressure ulcers
Facilitate rehabilitation and recovery of muscular atrophy secondary to prolonged immobilisation
Difficulties of appropriate hygiene because access to the perineum or bladder care is needed
Severe pain refractory to analgesia Vascular andor nerve compression
Advantages to early excision of heterotopic ossification (vs waiting for maturation) include decreased soft tissue contracture better definition between heterotopic and native bone and decreased waiting time for the patient When the soft tissue envelope is benign one may proceed with operative release While waiting for normalization of alkaline phosphatase levels inactivity on bone scan or radiographic maturity may decrease risk of recurrent heterotopic ossification delaying operative release for these reasons has not been shown to improve results of final elbow range of motion after contracture release
Gartland recommended surgery after six months following traumatic heterotopic ossification one year following spinal cord injury and 18 months after head injury
In the past waiting until maturity in order to minimize the rate of recurrence after the surgical treatment was recommended Nevertheless recent studies do not confirm a higher rate of recurrence when the HO is excised in an earlier phase In addition a long delay before surgery leads to ankylosis a high degree of osteoporosis and more extensive intra-articular injuries These findings are associated with bad functional results and potential complications
Should you wait till lesion maturation
Prevention byHandle tissue carefully Avoid excess bleeding Achieve good hemostasis Beware of lesions that span internervous tissue planes
but if it happens resection of a large enough amount of bone to allow improvement of the range of motion and trying to preserve the joint
Our aim must be
A reactive process that is characterized by a well-circumscribed proliferation of fibroblasts cartilage and bone within muscle
A form of heterotopic ossification that is the result direct trauma intramuscular hematoma
most common location is the diaphysis of long bones Must differentiate from tumors Fibrodysplasia ossificans progressiva (FOP) is a rare subtype of heterotopic ossification
involves mutation of the ACVR1 gene (activin A type I receptor gene a BMP type-1 receptor)
Epidemiology demographics
most common in young active males (15 to 35 years old) body locations
quadriceps brachialis and gluteal muscles Genetics
almost always a posttraumatic condition Prognosis
usually self limiting mass usually begins to decrease in size after 1 yea
Myositis ossificans
PresentationbullSymptoms
bull pain tenderness swelling and decreased range of motion that usually presents within days of the injury
bull pain and size of the mass decrease with timebull mass increases in size over several months(usually 3 to 6 cm)
bull after the mass stops growing it becomes firmbullPhysical exam
bull palpable soft tissue massbull restricted range of motion
ImagingbullRadiographs
bull peripheral bone formation with central lucent areabull may appear as dotted veil pattern
bullMRI with gadolinium bull rim enhancement is seen within the first 3 weeks
bullCT scan bull lesion has an eggshell appearance
bullCharacteristic histology shows zonal pattern bull periphery of lesion
bull mature trabeculae of lamellar and woven bonebull calcification seen on xray
bull center of the lesion bull irregular mass of immature fibroblastsbull cartilage component may be presentbull (no calcification seen on xray) bull no cellular atypia seen
Treatment
bullNonoperative bull rest range of motion exercises and activity modification
bull passive stretching is contraindicated (makes it worse)bull physical therapy
bull utilized to maintain range of motionbull radiographic monitoring
bull obtained to confirm maturation of the lesionbullOperative
bull surgical excision bull indicated only if it remains a problem after it maturesbull do not operate in acute phase wait at least six months
bull excision of the lesion within 6 to 12 months predisposes to local recurrence
A 26-year-old man presents with generalized back and joint stiffness and difficulty opening his mouth His elder sister has similar complaints Since childhood he has had 3 surgeries for excision of recurrent bony prominences around his knees He walks with a stooped over posture seen in Figure A Radiographs of his feet knee hip and spine are seen in Figures B-E respectively
fibrodysplasia ossificans progressiva
Stone Man Disease) which involves a mutation of the ACVR1
There are 2 hallmark characteristics progressive heterotopic ossification (muscles fascia tendons ligaments and joint capsules) and congenital malformation of the great toe (hallux valgus malformed first metatarsal and monophalangism) BMP4 which contributes to the formation of the skeleton in the normal embryo is implicated in this disease
Complications
bullHematoma and intraoperative bleedingbullInfection
bull higher rate of infection following joint arthroplasty if HO is present
bullFractures of osteoporotic bone bull osteopenic from disusebull during surgery or physiotherapy
bullRecurrence bull recurrence rate correlates with neurological injury
bull greater recurrence if severe neurological compromisebullAVN
bull if extensive dissection or stripping is required
HTO AND ISS
When ISS is below 25 the mortality risk is minimal and above 25 it is an almost linear increase
When ISS is 50 the mortality is 50 When above 70 it is close to 100 If an injury is assigned an AIS of 6 (unsurvivable injury) the ISS score is
automatically assigned to 75 Highest ISS score obtainable is 75 For trauma patients of vehicular accidents the scoring system is important
for assessing the effectiveness of medical care in reducing morbidity and mortality
Advantages virtually the only anatomical scoring system in use correlates linearly with
mortality morbidity hospital stay other measures of severity
Weaknesses Any error in AIS scoring increases the ISS error Many different injury patterns can yield the same ISS score Injuries to different body regions are not weighted Not a useful triage tool as a full description of patient injuries is not known
prior to full investigation amp operation
risk factors periosteal stripping off anterior femur male gender obesity post traumatic deformity Anterior and anterolateral approach Cementless
Neurogenic HO around the hip due to SCI occurs more often in the medial region than in the lateral region with ossified tissues extending from the pubic symphysis to the anteromedial femoral shaft posterior to the femoral neurovascular structures Ossification is also seen anteriorly involving the iliopsoas and femoral neurovascular structures laterally within gluteus minimus and posteriorly extending from the ilium to the posterior femur encasing the sciatic nerve
HTO AROUND hip and knee
The Brooker Classification of Heterotopic Ossification around the hip joint Class I has islands of bone within the soft tissues Class II has bone spurs from the pelvis or proximal end of the femur leaving at least 1 cm between opposing surfaces Class III has bone spurs from the pelvis andor proximal end of the femur reducing the space between opposing bone surfaces to less than 1 cm Class IV shows apparent bone ankylosis of the hip
Region I - Heterotopic ossifications are strictly below the tip of the greater trochanter
Region II - Heterotopic ossifications are below and above the tip of the greater trochanter
Region III - Heterotopic ossifications are strictly above the tip of the greater trochanter
Grade A - Single or multiple heterotopic ossifications are less than 10 mm in maximal extent without contact with the pelvis or the femur
Grade B - Heterotopic ossifications are greater than 10 mm without contact with the pelvis but with possible contact with the femur there is no bridging from the femur to the proximal part of the greater trochanter and no evidence of ankylosis
Grade C - Ankylosis by means of firm bridging from the femur to the pelvis is present
Shmidt classification
excision may be performed The results of this procedure are varied Patients may find that their range of movement improves but pain relief is likely to be limited
A patient with heterotopic ossification following total hip arthroplasty is thought to have a 90-100 chance of developing it on the contralateral hip if this hip also undergoes total arthroplasty
it would be prudent to minimize the risk of heterotopic ossification developing after arthroplasty by performing surgery whereby the following are ensured
Exposure is meticulous Retraction is performed carefully and soft tissue
is handled carefully Irrigation is adequate Devitalized tissue is excised Hemostasis is adequate Postoperative drains (when used) are not
retained for longer than necessary Perioperative antibiotic prophylaxis is used Postoperative anticoagulation (when used for
deep vein thrombosis prophylaxis) is carefully controlled
sources of knee stiffness 1-extrinsic severe osteoarthritis of the ipsilateral hip neurologic injury leading to muscle rigidity tight quadriceps or hamstring muscles secondary to muscle injury heterotopic ossification or long-standing juvenile inflammatory conditions limiting knee
range of motion prior to the completion of skeletal growth When extrinsic sources are identified revision total knee arthroplasty is unlikely to be associated with a favorable outcome without correction of the extrinsic problem
2-intrinsic (1) overstuffing of the patellofemoral articulation (2) an
excessively tight flexion andor extension gap (3) a tight posterior cruciate ligament (4) femoral andor tibial malrotation (5) arthrofibrosis and (6) limited bearing excursion in association with a highly conforming mobile-bearing prosthetic design
HTO after TKA
Heterotopic Ossification (HO) following primary Total Knee Replacement (TKR)
Occurs in 3-90 of TKRs 3-grade classification system No correlation between HO and component
alignment or component position
Clinical findings similar to early infection Continuing low-grade fever Warm swollen and erythematous knee Normal blood tests Possibly an association with HLA-A2 and B18 HO patients have worse KSS and function
scores
Patients at HIGH risk for developing HO after TKR (Knee Arthroplasty) (5)
Those with limited postoperative knee flexion
Increased lumbar bone mineral density (BMD) on multivariate analysis (3)
Hypertrophic arthrosis Excessive periosteal trauma Notching of the anterior femur Those who require forced manipulation
after TKA 47 in revision TKR surgery (6) Higher rates in revision TKR cases with
infection (up to 76
DaughertyBell classification of HO of the knee 0 No evidence of HO 1 Bone islands in periarticular soft tissue (no
involvement of femur patella or tibia) or HO within quadriceps expansion measuring lt1 cm
2 Spur formation measuring lt5 cm that involves the femur patella or tibia if more than one bone demonstrates HO separation of HO spurs
measure gt1 cm or HO within quadriceps expansion measuring ge1 cm but lt3 cm
3 Spur formation gt5 cm involving femur patella or tibia if more than one bone demonstrates HO separation of HO spurs measure lt1 cm or HO
within quadriceps expansion measuring ge3 cm 4 Extensive HO of the knee causing ankylosis
class 2 HO begins to involve the major bones of the knee joint with spur formation limited to a size of 5 cm
HO class 2 may be observed in select patients with complete ROM and no reported pain Patients with class 3 HO would likely always benefit from surgical excision
followed by RT prophylaxis Certainly patients in either cohort with a subclass ldquoBrdquo assignment (symptomatic) would
benefit from treatment All patients with class 4 HO require
treatment to alleviate ankylosis
treatment
References Whyte ldquoPagetrsquos Disease of Bonerdquo NEMJ vol 355
2006 Klein and Parvizi ldquoSurgical Manifestations of Pagetrsquos
Diseaserdquo JAAOS vol 14 2006 Orthobullets Campbell Apley Emedicinecom
-Chapter 15 Heterotopic Ossification after Traumatic Brain InjuryBy Jesuacutes Moreta and Joseacute Luis Martiacutenez-de los Mozos DOI 10577257343
Questions
Thank You
Treatment
bullNonoperative bull observation alone
bull indications bull a self-limited process and it is reasonable to treat with observation alone
bull bracing bull indications
bull to prevent progressive kyphosis of the spinebull outcomes
bull will correct deformity in 90 of patientsbull vertebral lesions generally regain 50 of their height
bull low dose irradiation (600-800 cGy) bull indications
bull indicated for lesions in the spine that compromise stability neurologic statusbull lesions not amenable to injection or open treatment
bull outcomes bull effective for most lesions
bull chemotherapy bull indications
bull diffuse HSCbull outcomes
bull prognosis is improved with less severe extraskeletal involvementbull corticosteroid injection
bull indications bull isolated lesions bull can be performed after curettage as well
Operative curettage and bone grafting
indications for lesions that endanger the articular surface or are a risk for
impending fractures spinal deformity correction
indications progressive spine deformity refractory to bracing
approximately 10 of patients with spine lesion will need operative intervention for deformity correction
Destructive multiple lesion in young patientsAre eosinophilic granuloma lymphoma and leukemiaLymphoma is unlikely to present with exopthalmos diabetes insipidus or vertebra plana Lymphoma bone lesions are lytic and appear moth eatenpermeative on radiographs
Figure A shows a skin lesion typical of eosinophillic granuloma Figure B shows a lytic lesions without significant surrounding sclerosis as is characteristic of eosinophilic granuloma Figure C shows the characteristic histology of multiple eosinophils with their characteristic oval coffee bean nuclei and staining pattern of purpleredpink cytoplasm (depending on the stain) Importantly the histology slide lacks a malignant appearance (no cellular atypia or mytotic complexes and low nuclearcytoplasmic ratio)
Formation of bone in atypical extraskeletal tissues usually occurs
spontaneously or following trauma within 2 months of neurologic injury (brain or spinal cord)
most common location is between muscle and joint capsule Epidemiology
incidence (see table below)
demographics malefemale = 21 especially men with hypertrophic osteoarthritis and women gt65y
location traumatic brain injury or stroke
hip gt elbow gt shoulder gt knee elbow HO more common following brain trauma
occurs on affected (spastic) side rarely in the knee (TBI)
spinal cord injury hip gt knee gt elbow gt shoulder hip flexors and abductors gt extensors or adductors medial aspect of the knee
Heterotopic Ossification
Risk factors
Pathophysiology exact cause of HO is not known but there appears to be a
genetic pre disposition experimental HO associated with
tissue expression of BMP IT IS SAID TO BE CAUSED BY activation and proliferation of
mesenchymal stem cells Associated conditions
orthopaedic manifestations pathologic fractures
from decreased joint ROM and osteoporotic bone nerve impingement soft tissue contractures contributing to the formation of
decubitus ulcers joint ankylosis HO after THA adversely affects outcome of THA
nonorthopaedic conditions skin maceration and hygiene problems
Pathophysiology Early in the formation of HO oedema with exudative
infiltrate is present followed by fibroblastic proliferation and immature connective tissue formation Posteriorly osteoid formation is seen with the subsequent deposition of bone matrix Primitive osteoid is deposited as small masses in the periphery early (within the first two weeks) and osteoblasts are noted located irregularly Osteoblasts produce tropocollagen which polymerizes to form collagen and secrete alkaline phosphatase which allows calcium to precipitate and the mineralization of bone matrix As mineralization progresses amorphous calcium phosphate is progressively replaced by hydroxyapatite crystals During the following weeks the lesion matures with a centripetal pattern and after 6-12 months an appearance of true bone is noted The new bone is always extra-articular and can be contiguous with the skeleton but generally does not involve the periosteum
IN SUMMARY It has been postulated that three conditions
must be met to achieve heterotopic bone formation ---a stimulating event oestrogenic precursor cells and a proper environment LIKE hypercalcaemia tissue hypoxia pH changes (alkalosis) or prolonged immobilization
ClassificationbullSubtypes
bull neurogenic HO bull Four clinical stages of HO in people with spinal cord injury were
described by Nicholas in 1973
bull traumatic myositis ossificans bull fibrodysplasia ossificans progressiva (Munchmeyers Disease)
Neurogenic HO Symptoms
painless loss of ROM interferes with ADL CRPS symptoms fever
Physical exam inspection
warm painful swollen joint may have effusion skin problems
decubitus ulcers from contractures around skin muscles ligaments
skin maceration and hygiene problems motion
decreased joint ROM joint ankylosis with HO after TKA might develop quad muscle snapping or patella
instability neurovascular
peripheral neuropathy HO often impinges on adjacent NV structures
Imaging
bullRadiographs bull findings
bull ossification usually easy to visualize bull maturity of HO
bull the appearance of a bony cortex suggests mature HObull sharp demarcation from surrounding tissue bull trabecular pattern
bull sensitivity and specificity bull not useful for early diagnosisbull only useful at 1 week after onset of symptoms
bull calcium is deposited 7-10 days later than symptom onsetbullUltrasound
bull indications bull for early diagnosis of hip HO
bull findings bull echogenic surfaces with posterior acoustic shadowing
bullCT bull indications
bull useful for preoperative planning bullTriphasic bone scan
bull indications bull best for early diagnosis bull most commonly used diagnostic study
Radiographs are extremely useful in the staging of heterotopic ossification and will show the development of sharp cortical margins once the lesion has reached maturity
Heterotopic bone is a condition in which lamellar bone forms in non-ossified soft tissues In the early stages studies such as MRI and bone scan are more sensitive for diagnosis as radiographs may appear normal for the first three weeks After the appropriate diagnosis is made sequential radiographs are useful for monitoring the progression of the ossification Once it has reached the mature stage sharp cortical margins will appear and surgical resection may be considered
lab
Labs elevated serum alkaline phosphatase (gt250IUL)
ALP removes inhibitors of mineralization nonspecific may be elevated with skeletal trauma cannot determine maturity of HO elevated 12wks after surgery is predictor
elevated CRP correlates with inflammatory activity of HO better than ESR normalization of CRP may correlate with maturity of HO
elevated ESR (gt35mmh) 12wks after THA is predictor
elevated CK correlates with involvement of muscle extent of muscle
involvement Histology
mature fatty bone marrow mature trabecular bone
Heterotopic ossification (HO) most commonly occurs at the amputation site if the amputation was performed thru the zone of injury especially if the injury was a blast mechanism
Symptomatic heterotopic ossification of the quadriceps may occur following placement of a large-diameter Steinmann pin for the purpose of temporary skeletal traction
TreatmentThe prevention of heterotopic ossification is focused on three basic principles disrupting the inductive signalling pathways altering the osteoprogenitor cells or modifying the environment
bullphysiotherapy should involve an assisted range of movement exercises with gentle stretch and terminal resistance trainingbullProphylaxis
bull bisphosphonates amp NSAIDS bull indications
bull although no literature supports are commonly usedbull technique
bull indomethacin is most commonly used bull dose is 75mgday for 10days to 6 weeks
bull perioperative radiation bull indications
bull although no literature supports commonly usedbull is thought to be effective by blocking osteoblast differentiation
bull technique bull a single perioperative dose of 700cGy can be given either 4
hours preop or within 72 hours postoperatively bull lt550cGy not effective
Nonsteroidal anti-inflammatory drugs (NSAIDs) These drugs have demonstrated good results in
preventing heterotopic ossification after total hip arthroplasty
A direct effect of NSAIDs on the formation of heterotopic ossification has been described due to the inhibition of the differentiation of mesenchymal cells into oestrogenic cells There is also an indirect effect which refers to the inhibition of bone remodelling by suppression of the prostagland unmediated inflammatory response (specifically PGE-2)
Indomethacin has been considered a useful medication for heterotopic ossification prophylaxis following total hip replacement
prescribed for three to six weeks in a dose of 75mgday within two months of the injury may reduce the incidence of heterotopic ossification by two to three times
Biphosphonates inhibits precipitation of calcium phosphate and blocks the aggregation and mineralisation of hydroxyapatite crystals In primary prevention Banovac et al [56] have suggested that the treatment should begin as soon as elevated alkaline phosphatase is diagnosed or positive findings in ultrasonography or bone scans are shown In addition disphosphonates could have long-term effects on prevention when the treatment is finished
Posttraumatic wide exposure and surgical resection
indications severe loss of motion and decreased function
technique wide exposure required to identify all neurovascular
structures that may be involved timing of resection (controversial)
marked decrease in bone scan activity AND normalization of ALP
6 months following general trauma 1 year following SCI 15 years following TBI
some data suggests equivalent results when comparing early versus late resection
postop follow with 5 day course of indomethacin early gentle joint mobilization
The surgery is necessary in patients with symptomatic HO and unsuccessful medical treatment such as
Loss of range of motion and ankylosis with associated functional disability such as sitting difficulties
Complications of immobility such as pressure ulcers
Facilitate rehabilitation and recovery of muscular atrophy secondary to prolonged immobilisation
Difficulties of appropriate hygiene because access to the perineum or bladder care is needed
Severe pain refractory to analgesia Vascular andor nerve compression
Advantages to early excision of heterotopic ossification (vs waiting for maturation) include decreased soft tissue contracture better definition between heterotopic and native bone and decreased waiting time for the patient When the soft tissue envelope is benign one may proceed with operative release While waiting for normalization of alkaline phosphatase levels inactivity on bone scan or radiographic maturity may decrease risk of recurrent heterotopic ossification delaying operative release for these reasons has not been shown to improve results of final elbow range of motion after contracture release
Gartland recommended surgery after six months following traumatic heterotopic ossification one year following spinal cord injury and 18 months after head injury
In the past waiting until maturity in order to minimize the rate of recurrence after the surgical treatment was recommended Nevertheless recent studies do not confirm a higher rate of recurrence when the HO is excised in an earlier phase In addition a long delay before surgery leads to ankylosis a high degree of osteoporosis and more extensive intra-articular injuries These findings are associated with bad functional results and potential complications
Should you wait till lesion maturation
Prevention byHandle tissue carefully Avoid excess bleeding Achieve good hemostasis Beware of lesions that span internervous tissue planes
but if it happens resection of a large enough amount of bone to allow improvement of the range of motion and trying to preserve the joint
Our aim must be
A reactive process that is characterized by a well-circumscribed proliferation of fibroblasts cartilage and bone within muscle
A form of heterotopic ossification that is the result direct trauma intramuscular hematoma
most common location is the diaphysis of long bones Must differentiate from tumors Fibrodysplasia ossificans progressiva (FOP) is a rare subtype of heterotopic ossification
involves mutation of the ACVR1 gene (activin A type I receptor gene a BMP type-1 receptor)
Epidemiology demographics
most common in young active males (15 to 35 years old) body locations
quadriceps brachialis and gluteal muscles Genetics
almost always a posttraumatic condition Prognosis
usually self limiting mass usually begins to decrease in size after 1 yea
Myositis ossificans
PresentationbullSymptoms
bull pain tenderness swelling and decreased range of motion that usually presents within days of the injury
bull pain and size of the mass decrease with timebull mass increases in size over several months(usually 3 to 6 cm)
bull after the mass stops growing it becomes firmbullPhysical exam
bull palpable soft tissue massbull restricted range of motion
ImagingbullRadiographs
bull peripheral bone formation with central lucent areabull may appear as dotted veil pattern
bullMRI with gadolinium bull rim enhancement is seen within the first 3 weeks
bullCT scan bull lesion has an eggshell appearance
bullCharacteristic histology shows zonal pattern bull periphery of lesion
bull mature trabeculae of lamellar and woven bonebull calcification seen on xray
bull center of the lesion bull irregular mass of immature fibroblastsbull cartilage component may be presentbull (no calcification seen on xray) bull no cellular atypia seen
Treatment
bullNonoperative bull rest range of motion exercises and activity modification
bull passive stretching is contraindicated (makes it worse)bull physical therapy
bull utilized to maintain range of motionbull radiographic monitoring
bull obtained to confirm maturation of the lesionbullOperative
bull surgical excision bull indicated only if it remains a problem after it maturesbull do not operate in acute phase wait at least six months
bull excision of the lesion within 6 to 12 months predisposes to local recurrence
A 26-year-old man presents with generalized back and joint stiffness and difficulty opening his mouth His elder sister has similar complaints Since childhood he has had 3 surgeries for excision of recurrent bony prominences around his knees He walks with a stooped over posture seen in Figure A Radiographs of his feet knee hip and spine are seen in Figures B-E respectively
fibrodysplasia ossificans progressiva
Stone Man Disease) which involves a mutation of the ACVR1
There are 2 hallmark characteristics progressive heterotopic ossification (muscles fascia tendons ligaments and joint capsules) and congenital malformation of the great toe (hallux valgus malformed first metatarsal and monophalangism) BMP4 which contributes to the formation of the skeleton in the normal embryo is implicated in this disease
Complications
bullHematoma and intraoperative bleedingbullInfection
bull higher rate of infection following joint arthroplasty if HO is present
bullFractures of osteoporotic bone bull osteopenic from disusebull during surgery or physiotherapy
bullRecurrence bull recurrence rate correlates with neurological injury
bull greater recurrence if severe neurological compromisebullAVN
bull if extensive dissection or stripping is required
HTO AND ISS
When ISS is below 25 the mortality risk is minimal and above 25 it is an almost linear increase
When ISS is 50 the mortality is 50 When above 70 it is close to 100 If an injury is assigned an AIS of 6 (unsurvivable injury) the ISS score is
automatically assigned to 75 Highest ISS score obtainable is 75 For trauma patients of vehicular accidents the scoring system is important
for assessing the effectiveness of medical care in reducing morbidity and mortality
Advantages virtually the only anatomical scoring system in use correlates linearly with
mortality morbidity hospital stay other measures of severity
Weaknesses Any error in AIS scoring increases the ISS error Many different injury patterns can yield the same ISS score Injuries to different body regions are not weighted Not a useful triage tool as a full description of patient injuries is not known
prior to full investigation amp operation
risk factors periosteal stripping off anterior femur male gender obesity post traumatic deformity Anterior and anterolateral approach Cementless
Neurogenic HO around the hip due to SCI occurs more often in the medial region than in the lateral region with ossified tissues extending from the pubic symphysis to the anteromedial femoral shaft posterior to the femoral neurovascular structures Ossification is also seen anteriorly involving the iliopsoas and femoral neurovascular structures laterally within gluteus minimus and posteriorly extending from the ilium to the posterior femur encasing the sciatic nerve
HTO AROUND hip and knee
The Brooker Classification of Heterotopic Ossification around the hip joint Class I has islands of bone within the soft tissues Class II has bone spurs from the pelvis or proximal end of the femur leaving at least 1 cm between opposing surfaces Class III has bone spurs from the pelvis andor proximal end of the femur reducing the space between opposing bone surfaces to less than 1 cm Class IV shows apparent bone ankylosis of the hip
Region I - Heterotopic ossifications are strictly below the tip of the greater trochanter
Region II - Heterotopic ossifications are below and above the tip of the greater trochanter
Region III - Heterotopic ossifications are strictly above the tip of the greater trochanter
Grade A - Single or multiple heterotopic ossifications are less than 10 mm in maximal extent without contact with the pelvis or the femur
Grade B - Heterotopic ossifications are greater than 10 mm without contact with the pelvis but with possible contact with the femur there is no bridging from the femur to the proximal part of the greater trochanter and no evidence of ankylosis
Grade C - Ankylosis by means of firm bridging from the femur to the pelvis is present
Shmidt classification
excision may be performed The results of this procedure are varied Patients may find that their range of movement improves but pain relief is likely to be limited
A patient with heterotopic ossification following total hip arthroplasty is thought to have a 90-100 chance of developing it on the contralateral hip if this hip also undergoes total arthroplasty
it would be prudent to minimize the risk of heterotopic ossification developing after arthroplasty by performing surgery whereby the following are ensured
Exposure is meticulous Retraction is performed carefully and soft tissue
is handled carefully Irrigation is adequate Devitalized tissue is excised Hemostasis is adequate Postoperative drains (when used) are not
retained for longer than necessary Perioperative antibiotic prophylaxis is used Postoperative anticoagulation (when used for
deep vein thrombosis prophylaxis) is carefully controlled
sources of knee stiffness 1-extrinsic severe osteoarthritis of the ipsilateral hip neurologic injury leading to muscle rigidity tight quadriceps or hamstring muscles secondary to muscle injury heterotopic ossification or long-standing juvenile inflammatory conditions limiting knee
range of motion prior to the completion of skeletal growth When extrinsic sources are identified revision total knee arthroplasty is unlikely to be associated with a favorable outcome without correction of the extrinsic problem
2-intrinsic (1) overstuffing of the patellofemoral articulation (2) an
excessively tight flexion andor extension gap (3) a tight posterior cruciate ligament (4) femoral andor tibial malrotation (5) arthrofibrosis and (6) limited bearing excursion in association with a highly conforming mobile-bearing prosthetic design
HTO after TKA
Heterotopic Ossification (HO) following primary Total Knee Replacement (TKR)
Occurs in 3-90 of TKRs 3-grade classification system No correlation between HO and component
alignment or component position
Clinical findings similar to early infection Continuing low-grade fever Warm swollen and erythematous knee Normal blood tests Possibly an association with HLA-A2 and B18 HO patients have worse KSS and function
scores
Patients at HIGH risk for developing HO after TKR (Knee Arthroplasty) (5)
Those with limited postoperative knee flexion
Increased lumbar bone mineral density (BMD) on multivariate analysis (3)
Hypertrophic arthrosis Excessive periosteal trauma Notching of the anterior femur Those who require forced manipulation
after TKA 47 in revision TKR surgery (6) Higher rates in revision TKR cases with
infection (up to 76
DaughertyBell classification of HO of the knee 0 No evidence of HO 1 Bone islands in periarticular soft tissue (no
involvement of femur patella or tibia) or HO within quadriceps expansion measuring lt1 cm
2 Spur formation measuring lt5 cm that involves the femur patella or tibia if more than one bone demonstrates HO separation of HO spurs
measure gt1 cm or HO within quadriceps expansion measuring ge1 cm but lt3 cm
3 Spur formation gt5 cm involving femur patella or tibia if more than one bone demonstrates HO separation of HO spurs measure lt1 cm or HO
within quadriceps expansion measuring ge3 cm 4 Extensive HO of the knee causing ankylosis
class 2 HO begins to involve the major bones of the knee joint with spur formation limited to a size of 5 cm
HO class 2 may be observed in select patients with complete ROM and no reported pain Patients with class 3 HO would likely always benefit from surgical excision
followed by RT prophylaxis Certainly patients in either cohort with a subclass ldquoBrdquo assignment (symptomatic) would
benefit from treatment All patients with class 4 HO require
treatment to alleviate ankylosis
treatment
References Whyte ldquoPagetrsquos Disease of Bonerdquo NEMJ vol 355
2006 Klein and Parvizi ldquoSurgical Manifestations of Pagetrsquos
Diseaserdquo JAAOS vol 14 2006 Orthobullets Campbell Apley Emedicinecom
-Chapter 15 Heterotopic Ossification after Traumatic Brain InjuryBy Jesuacutes Moreta and Joseacute Luis Martiacutenez-de los Mozos DOI 10577257343
Questions
Thank You
Operative curettage and bone grafting
indications for lesions that endanger the articular surface or are a risk for
impending fractures spinal deformity correction
indications progressive spine deformity refractory to bracing
approximately 10 of patients with spine lesion will need operative intervention for deformity correction
Destructive multiple lesion in young patientsAre eosinophilic granuloma lymphoma and leukemiaLymphoma is unlikely to present with exopthalmos diabetes insipidus or vertebra plana Lymphoma bone lesions are lytic and appear moth eatenpermeative on radiographs
Figure A shows a skin lesion typical of eosinophillic granuloma Figure B shows a lytic lesions without significant surrounding sclerosis as is characteristic of eosinophilic granuloma Figure C shows the characteristic histology of multiple eosinophils with their characteristic oval coffee bean nuclei and staining pattern of purpleredpink cytoplasm (depending on the stain) Importantly the histology slide lacks a malignant appearance (no cellular atypia or mytotic complexes and low nuclearcytoplasmic ratio)
Formation of bone in atypical extraskeletal tissues usually occurs
spontaneously or following trauma within 2 months of neurologic injury (brain or spinal cord)
most common location is between muscle and joint capsule Epidemiology
incidence (see table below)
demographics malefemale = 21 especially men with hypertrophic osteoarthritis and women gt65y
location traumatic brain injury or stroke
hip gt elbow gt shoulder gt knee elbow HO more common following brain trauma
occurs on affected (spastic) side rarely in the knee (TBI)
spinal cord injury hip gt knee gt elbow gt shoulder hip flexors and abductors gt extensors or adductors medial aspect of the knee
Heterotopic Ossification
Risk factors
Pathophysiology exact cause of HO is not known but there appears to be a
genetic pre disposition experimental HO associated with
tissue expression of BMP IT IS SAID TO BE CAUSED BY activation and proliferation of
mesenchymal stem cells Associated conditions
orthopaedic manifestations pathologic fractures
from decreased joint ROM and osteoporotic bone nerve impingement soft tissue contractures contributing to the formation of
decubitus ulcers joint ankylosis HO after THA adversely affects outcome of THA
nonorthopaedic conditions skin maceration and hygiene problems
Pathophysiology Early in the formation of HO oedema with exudative
infiltrate is present followed by fibroblastic proliferation and immature connective tissue formation Posteriorly osteoid formation is seen with the subsequent deposition of bone matrix Primitive osteoid is deposited as small masses in the periphery early (within the first two weeks) and osteoblasts are noted located irregularly Osteoblasts produce tropocollagen which polymerizes to form collagen and secrete alkaline phosphatase which allows calcium to precipitate and the mineralization of bone matrix As mineralization progresses amorphous calcium phosphate is progressively replaced by hydroxyapatite crystals During the following weeks the lesion matures with a centripetal pattern and after 6-12 months an appearance of true bone is noted The new bone is always extra-articular and can be contiguous with the skeleton but generally does not involve the periosteum
IN SUMMARY It has been postulated that three conditions
must be met to achieve heterotopic bone formation ---a stimulating event oestrogenic precursor cells and a proper environment LIKE hypercalcaemia tissue hypoxia pH changes (alkalosis) or prolonged immobilization
ClassificationbullSubtypes
bull neurogenic HO bull Four clinical stages of HO in people with spinal cord injury were
described by Nicholas in 1973
bull traumatic myositis ossificans bull fibrodysplasia ossificans progressiva (Munchmeyers Disease)
Neurogenic HO Symptoms
painless loss of ROM interferes with ADL CRPS symptoms fever
Physical exam inspection
warm painful swollen joint may have effusion skin problems
decubitus ulcers from contractures around skin muscles ligaments
skin maceration and hygiene problems motion
decreased joint ROM joint ankylosis with HO after TKA might develop quad muscle snapping or patella
instability neurovascular
peripheral neuropathy HO often impinges on adjacent NV structures
Imaging
bullRadiographs bull findings
bull ossification usually easy to visualize bull maturity of HO
bull the appearance of a bony cortex suggests mature HObull sharp demarcation from surrounding tissue bull trabecular pattern
bull sensitivity and specificity bull not useful for early diagnosisbull only useful at 1 week after onset of symptoms
bull calcium is deposited 7-10 days later than symptom onsetbullUltrasound
bull indications bull for early diagnosis of hip HO
bull findings bull echogenic surfaces with posterior acoustic shadowing
bullCT bull indications
bull useful for preoperative planning bullTriphasic bone scan
bull indications bull best for early diagnosis bull most commonly used diagnostic study
Radiographs are extremely useful in the staging of heterotopic ossification and will show the development of sharp cortical margins once the lesion has reached maturity
Heterotopic bone is a condition in which lamellar bone forms in non-ossified soft tissues In the early stages studies such as MRI and bone scan are more sensitive for diagnosis as radiographs may appear normal for the first three weeks After the appropriate diagnosis is made sequential radiographs are useful for monitoring the progression of the ossification Once it has reached the mature stage sharp cortical margins will appear and surgical resection may be considered
lab
Labs elevated serum alkaline phosphatase (gt250IUL)
ALP removes inhibitors of mineralization nonspecific may be elevated with skeletal trauma cannot determine maturity of HO elevated 12wks after surgery is predictor
elevated CRP correlates with inflammatory activity of HO better than ESR normalization of CRP may correlate with maturity of HO
elevated ESR (gt35mmh) 12wks after THA is predictor
elevated CK correlates with involvement of muscle extent of muscle
involvement Histology
mature fatty bone marrow mature trabecular bone
Heterotopic ossification (HO) most commonly occurs at the amputation site if the amputation was performed thru the zone of injury especially if the injury was a blast mechanism
Symptomatic heterotopic ossification of the quadriceps may occur following placement of a large-diameter Steinmann pin for the purpose of temporary skeletal traction
TreatmentThe prevention of heterotopic ossification is focused on three basic principles disrupting the inductive signalling pathways altering the osteoprogenitor cells or modifying the environment
bullphysiotherapy should involve an assisted range of movement exercises with gentle stretch and terminal resistance trainingbullProphylaxis
bull bisphosphonates amp NSAIDS bull indications
bull although no literature supports are commonly usedbull technique
bull indomethacin is most commonly used bull dose is 75mgday for 10days to 6 weeks
bull perioperative radiation bull indications
bull although no literature supports commonly usedbull is thought to be effective by blocking osteoblast differentiation
bull technique bull a single perioperative dose of 700cGy can be given either 4
hours preop or within 72 hours postoperatively bull lt550cGy not effective
Nonsteroidal anti-inflammatory drugs (NSAIDs) These drugs have demonstrated good results in
preventing heterotopic ossification after total hip arthroplasty
A direct effect of NSAIDs on the formation of heterotopic ossification has been described due to the inhibition of the differentiation of mesenchymal cells into oestrogenic cells There is also an indirect effect which refers to the inhibition of bone remodelling by suppression of the prostagland unmediated inflammatory response (specifically PGE-2)
Indomethacin has been considered a useful medication for heterotopic ossification prophylaxis following total hip replacement
prescribed for three to six weeks in a dose of 75mgday within two months of the injury may reduce the incidence of heterotopic ossification by two to three times
Biphosphonates inhibits precipitation of calcium phosphate and blocks the aggregation and mineralisation of hydroxyapatite crystals In primary prevention Banovac et al [56] have suggested that the treatment should begin as soon as elevated alkaline phosphatase is diagnosed or positive findings in ultrasonography or bone scans are shown In addition disphosphonates could have long-term effects on prevention when the treatment is finished
Posttraumatic wide exposure and surgical resection
indications severe loss of motion and decreased function
technique wide exposure required to identify all neurovascular
structures that may be involved timing of resection (controversial)
marked decrease in bone scan activity AND normalization of ALP
6 months following general trauma 1 year following SCI 15 years following TBI
some data suggests equivalent results when comparing early versus late resection
postop follow with 5 day course of indomethacin early gentle joint mobilization
The surgery is necessary in patients with symptomatic HO and unsuccessful medical treatment such as
Loss of range of motion and ankylosis with associated functional disability such as sitting difficulties
Complications of immobility such as pressure ulcers
Facilitate rehabilitation and recovery of muscular atrophy secondary to prolonged immobilisation
Difficulties of appropriate hygiene because access to the perineum or bladder care is needed
Severe pain refractory to analgesia Vascular andor nerve compression
Advantages to early excision of heterotopic ossification (vs waiting for maturation) include decreased soft tissue contracture better definition between heterotopic and native bone and decreased waiting time for the patient When the soft tissue envelope is benign one may proceed with operative release While waiting for normalization of alkaline phosphatase levels inactivity on bone scan or radiographic maturity may decrease risk of recurrent heterotopic ossification delaying operative release for these reasons has not been shown to improve results of final elbow range of motion after contracture release
Gartland recommended surgery after six months following traumatic heterotopic ossification one year following spinal cord injury and 18 months after head injury
In the past waiting until maturity in order to minimize the rate of recurrence after the surgical treatment was recommended Nevertheless recent studies do not confirm a higher rate of recurrence when the HO is excised in an earlier phase In addition a long delay before surgery leads to ankylosis a high degree of osteoporosis and more extensive intra-articular injuries These findings are associated with bad functional results and potential complications
Should you wait till lesion maturation
Prevention byHandle tissue carefully Avoid excess bleeding Achieve good hemostasis Beware of lesions that span internervous tissue planes
but if it happens resection of a large enough amount of bone to allow improvement of the range of motion and trying to preserve the joint
Our aim must be
A reactive process that is characterized by a well-circumscribed proliferation of fibroblasts cartilage and bone within muscle
A form of heterotopic ossification that is the result direct trauma intramuscular hematoma
most common location is the diaphysis of long bones Must differentiate from tumors Fibrodysplasia ossificans progressiva (FOP) is a rare subtype of heterotopic ossification
involves mutation of the ACVR1 gene (activin A type I receptor gene a BMP type-1 receptor)
Epidemiology demographics
most common in young active males (15 to 35 years old) body locations
quadriceps brachialis and gluteal muscles Genetics
almost always a posttraumatic condition Prognosis
usually self limiting mass usually begins to decrease in size after 1 yea
Myositis ossificans
PresentationbullSymptoms
bull pain tenderness swelling and decreased range of motion that usually presents within days of the injury
bull pain and size of the mass decrease with timebull mass increases in size over several months(usually 3 to 6 cm)
bull after the mass stops growing it becomes firmbullPhysical exam
bull palpable soft tissue massbull restricted range of motion
ImagingbullRadiographs
bull peripheral bone formation with central lucent areabull may appear as dotted veil pattern
bullMRI with gadolinium bull rim enhancement is seen within the first 3 weeks
bullCT scan bull lesion has an eggshell appearance
bullCharacteristic histology shows zonal pattern bull periphery of lesion
bull mature trabeculae of lamellar and woven bonebull calcification seen on xray
bull center of the lesion bull irregular mass of immature fibroblastsbull cartilage component may be presentbull (no calcification seen on xray) bull no cellular atypia seen
Treatment
bullNonoperative bull rest range of motion exercises and activity modification
bull passive stretching is contraindicated (makes it worse)bull physical therapy
bull utilized to maintain range of motionbull radiographic monitoring
bull obtained to confirm maturation of the lesionbullOperative
bull surgical excision bull indicated only if it remains a problem after it maturesbull do not operate in acute phase wait at least six months
bull excision of the lesion within 6 to 12 months predisposes to local recurrence
A 26-year-old man presents with generalized back and joint stiffness and difficulty opening his mouth His elder sister has similar complaints Since childhood he has had 3 surgeries for excision of recurrent bony prominences around his knees He walks with a stooped over posture seen in Figure A Radiographs of his feet knee hip and spine are seen in Figures B-E respectively
fibrodysplasia ossificans progressiva
Stone Man Disease) which involves a mutation of the ACVR1
There are 2 hallmark characteristics progressive heterotopic ossification (muscles fascia tendons ligaments and joint capsules) and congenital malformation of the great toe (hallux valgus malformed first metatarsal and monophalangism) BMP4 which contributes to the formation of the skeleton in the normal embryo is implicated in this disease
Complications
bullHematoma and intraoperative bleedingbullInfection
bull higher rate of infection following joint arthroplasty if HO is present
bullFractures of osteoporotic bone bull osteopenic from disusebull during surgery or physiotherapy
bullRecurrence bull recurrence rate correlates with neurological injury
bull greater recurrence if severe neurological compromisebullAVN
bull if extensive dissection or stripping is required
HTO AND ISS
When ISS is below 25 the mortality risk is minimal and above 25 it is an almost linear increase
When ISS is 50 the mortality is 50 When above 70 it is close to 100 If an injury is assigned an AIS of 6 (unsurvivable injury) the ISS score is
automatically assigned to 75 Highest ISS score obtainable is 75 For trauma patients of vehicular accidents the scoring system is important
for assessing the effectiveness of medical care in reducing morbidity and mortality
Advantages virtually the only anatomical scoring system in use correlates linearly with
mortality morbidity hospital stay other measures of severity
Weaknesses Any error in AIS scoring increases the ISS error Many different injury patterns can yield the same ISS score Injuries to different body regions are not weighted Not a useful triage tool as a full description of patient injuries is not known
prior to full investigation amp operation
risk factors periosteal stripping off anterior femur male gender obesity post traumatic deformity Anterior and anterolateral approach Cementless
Neurogenic HO around the hip due to SCI occurs more often in the medial region than in the lateral region with ossified tissues extending from the pubic symphysis to the anteromedial femoral shaft posterior to the femoral neurovascular structures Ossification is also seen anteriorly involving the iliopsoas and femoral neurovascular structures laterally within gluteus minimus and posteriorly extending from the ilium to the posterior femur encasing the sciatic nerve
HTO AROUND hip and knee
The Brooker Classification of Heterotopic Ossification around the hip joint Class I has islands of bone within the soft tissues Class II has bone spurs from the pelvis or proximal end of the femur leaving at least 1 cm between opposing surfaces Class III has bone spurs from the pelvis andor proximal end of the femur reducing the space between opposing bone surfaces to less than 1 cm Class IV shows apparent bone ankylosis of the hip
Region I - Heterotopic ossifications are strictly below the tip of the greater trochanter
Region II - Heterotopic ossifications are below and above the tip of the greater trochanter
Region III - Heterotopic ossifications are strictly above the tip of the greater trochanter
Grade A - Single or multiple heterotopic ossifications are less than 10 mm in maximal extent without contact with the pelvis or the femur
Grade B - Heterotopic ossifications are greater than 10 mm without contact with the pelvis but with possible contact with the femur there is no bridging from the femur to the proximal part of the greater trochanter and no evidence of ankylosis
Grade C - Ankylosis by means of firm bridging from the femur to the pelvis is present
Shmidt classification
excision may be performed The results of this procedure are varied Patients may find that their range of movement improves but pain relief is likely to be limited
A patient with heterotopic ossification following total hip arthroplasty is thought to have a 90-100 chance of developing it on the contralateral hip if this hip also undergoes total arthroplasty
it would be prudent to minimize the risk of heterotopic ossification developing after arthroplasty by performing surgery whereby the following are ensured
Exposure is meticulous Retraction is performed carefully and soft tissue
is handled carefully Irrigation is adequate Devitalized tissue is excised Hemostasis is adequate Postoperative drains (when used) are not
retained for longer than necessary Perioperative antibiotic prophylaxis is used Postoperative anticoagulation (when used for
deep vein thrombosis prophylaxis) is carefully controlled
sources of knee stiffness 1-extrinsic severe osteoarthritis of the ipsilateral hip neurologic injury leading to muscle rigidity tight quadriceps or hamstring muscles secondary to muscle injury heterotopic ossification or long-standing juvenile inflammatory conditions limiting knee
range of motion prior to the completion of skeletal growth When extrinsic sources are identified revision total knee arthroplasty is unlikely to be associated with a favorable outcome without correction of the extrinsic problem
2-intrinsic (1) overstuffing of the patellofemoral articulation (2) an
excessively tight flexion andor extension gap (3) a tight posterior cruciate ligament (4) femoral andor tibial malrotation (5) arthrofibrosis and (6) limited bearing excursion in association with a highly conforming mobile-bearing prosthetic design
HTO after TKA
Heterotopic Ossification (HO) following primary Total Knee Replacement (TKR)
Occurs in 3-90 of TKRs 3-grade classification system No correlation between HO and component
alignment or component position
Clinical findings similar to early infection Continuing low-grade fever Warm swollen and erythematous knee Normal blood tests Possibly an association with HLA-A2 and B18 HO patients have worse KSS and function
scores
Patients at HIGH risk for developing HO after TKR (Knee Arthroplasty) (5)
Those with limited postoperative knee flexion
Increased lumbar bone mineral density (BMD) on multivariate analysis (3)
Hypertrophic arthrosis Excessive periosteal trauma Notching of the anterior femur Those who require forced manipulation
after TKA 47 in revision TKR surgery (6) Higher rates in revision TKR cases with
infection (up to 76
DaughertyBell classification of HO of the knee 0 No evidence of HO 1 Bone islands in periarticular soft tissue (no
involvement of femur patella or tibia) or HO within quadriceps expansion measuring lt1 cm
2 Spur formation measuring lt5 cm that involves the femur patella or tibia if more than one bone demonstrates HO separation of HO spurs
measure gt1 cm or HO within quadriceps expansion measuring ge1 cm but lt3 cm
3 Spur formation gt5 cm involving femur patella or tibia if more than one bone demonstrates HO separation of HO spurs measure lt1 cm or HO
within quadriceps expansion measuring ge3 cm 4 Extensive HO of the knee causing ankylosis
class 2 HO begins to involve the major bones of the knee joint with spur formation limited to a size of 5 cm
HO class 2 may be observed in select patients with complete ROM and no reported pain Patients with class 3 HO would likely always benefit from surgical excision
followed by RT prophylaxis Certainly patients in either cohort with a subclass ldquoBrdquo assignment (symptomatic) would
benefit from treatment All patients with class 4 HO require
treatment to alleviate ankylosis
treatment
References Whyte ldquoPagetrsquos Disease of Bonerdquo NEMJ vol 355
2006 Klein and Parvizi ldquoSurgical Manifestations of Pagetrsquos
Diseaserdquo JAAOS vol 14 2006 Orthobullets Campbell Apley Emedicinecom
-Chapter 15 Heterotopic Ossification after Traumatic Brain InjuryBy Jesuacutes Moreta and Joseacute Luis Martiacutenez-de los Mozos DOI 10577257343
Questions
Thank You
Figure A shows a skin lesion typical of eosinophillic granuloma Figure B shows a lytic lesions without significant surrounding sclerosis as is characteristic of eosinophilic granuloma Figure C shows the characteristic histology of multiple eosinophils with their characteristic oval coffee bean nuclei and staining pattern of purpleredpink cytoplasm (depending on the stain) Importantly the histology slide lacks a malignant appearance (no cellular atypia or mytotic complexes and low nuclearcytoplasmic ratio)
Formation of bone in atypical extraskeletal tissues usually occurs
spontaneously or following trauma within 2 months of neurologic injury (brain or spinal cord)
most common location is between muscle and joint capsule Epidemiology
incidence (see table below)
demographics malefemale = 21 especially men with hypertrophic osteoarthritis and women gt65y
location traumatic brain injury or stroke
hip gt elbow gt shoulder gt knee elbow HO more common following brain trauma
occurs on affected (spastic) side rarely in the knee (TBI)
spinal cord injury hip gt knee gt elbow gt shoulder hip flexors and abductors gt extensors or adductors medial aspect of the knee
Heterotopic Ossification
Risk factors
Pathophysiology exact cause of HO is not known but there appears to be a
genetic pre disposition experimental HO associated with
tissue expression of BMP IT IS SAID TO BE CAUSED BY activation and proliferation of
mesenchymal stem cells Associated conditions
orthopaedic manifestations pathologic fractures
from decreased joint ROM and osteoporotic bone nerve impingement soft tissue contractures contributing to the formation of
decubitus ulcers joint ankylosis HO after THA adversely affects outcome of THA
nonorthopaedic conditions skin maceration and hygiene problems
Pathophysiology Early in the formation of HO oedema with exudative
infiltrate is present followed by fibroblastic proliferation and immature connective tissue formation Posteriorly osteoid formation is seen with the subsequent deposition of bone matrix Primitive osteoid is deposited as small masses in the periphery early (within the first two weeks) and osteoblasts are noted located irregularly Osteoblasts produce tropocollagen which polymerizes to form collagen and secrete alkaline phosphatase which allows calcium to precipitate and the mineralization of bone matrix As mineralization progresses amorphous calcium phosphate is progressively replaced by hydroxyapatite crystals During the following weeks the lesion matures with a centripetal pattern and after 6-12 months an appearance of true bone is noted The new bone is always extra-articular and can be contiguous with the skeleton but generally does not involve the periosteum
IN SUMMARY It has been postulated that three conditions
must be met to achieve heterotopic bone formation ---a stimulating event oestrogenic precursor cells and a proper environment LIKE hypercalcaemia tissue hypoxia pH changes (alkalosis) or prolonged immobilization
ClassificationbullSubtypes
bull neurogenic HO bull Four clinical stages of HO in people with spinal cord injury were
described by Nicholas in 1973
bull traumatic myositis ossificans bull fibrodysplasia ossificans progressiva (Munchmeyers Disease)
Neurogenic HO Symptoms
painless loss of ROM interferes with ADL CRPS symptoms fever
Physical exam inspection
warm painful swollen joint may have effusion skin problems
decubitus ulcers from contractures around skin muscles ligaments
skin maceration and hygiene problems motion
decreased joint ROM joint ankylosis with HO after TKA might develop quad muscle snapping or patella
instability neurovascular
peripheral neuropathy HO often impinges on adjacent NV structures
Imaging
bullRadiographs bull findings
bull ossification usually easy to visualize bull maturity of HO
bull the appearance of a bony cortex suggests mature HObull sharp demarcation from surrounding tissue bull trabecular pattern
bull sensitivity and specificity bull not useful for early diagnosisbull only useful at 1 week after onset of symptoms
bull calcium is deposited 7-10 days later than symptom onsetbullUltrasound
bull indications bull for early diagnosis of hip HO
bull findings bull echogenic surfaces with posterior acoustic shadowing
bullCT bull indications
bull useful for preoperative planning bullTriphasic bone scan
bull indications bull best for early diagnosis bull most commonly used diagnostic study
Radiographs are extremely useful in the staging of heterotopic ossification and will show the development of sharp cortical margins once the lesion has reached maturity
Heterotopic bone is a condition in which lamellar bone forms in non-ossified soft tissues In the early stages studies such as MRI and bone scan are more sensitive for diagnosis as radiographs may appear normal for the first three weeks After the appropriate diagnosis is made sequential radiographs are useful for monitoring the progression of the ossification Once it has reached the mature stage sharp cortical margins will appear and surgical resection may be considered
lab
Labs elevated serum alkaline phosphatase (gt250IUL)
ALP removes inhibitors of mineralization nonspecific may be elevated with skeletal trauma cannot determine maturity of HO elevated 12wks after surgery is predictor
elevated CRP correlates with inflammatory activity of HO better than ESR normalization of CRP may correlate with maturity of HO
elevated ESR (gt35mmh) 12wks after THA is predictor
elevated CK correlates with involvement of muscle extent of muscle
involvement Histology
mature fatty bone marrow mature trabecular bone
Heterotopic ossification (HO) most commonly occurs at the amputation site if the amputation was performed thru the zone of injury especially if the injury was a blast mechanism
Symptomatic heterotopic ossification of the quadriceps may occur following placement of a large-diameter Steinmann pin for the purpose of temporary skeletal traction
TreatmentThe prevention of heterotopic ossification is focused on three basic principles disrupting the inductive signalling pathways altering the osteoprogenitor cells or modifying the environment
bullphysiotherapy should involve an assisted range of movement exercises with gentle stretch and terminal resistance trainingbullProphylaxis
bull bisphosphonates amp NSAIDS bull indications
bull although no literature supports are commonly usedbull technique
bull indomethacin is most commonly used bull dose is 75mgday for 10days to 6 weeks
bull perioperative radiation bull indications
bull although no literature supports commonly usedbull is thought to be effective by blocking osteoblast differentiation
bull technique bull a single perioperative dose of 700cGy can be given either 4
hours preop or within 72 hours postoperatively bull lt550cGy not effective
Nonsteroidal anti-inflammatory drugs (NSAIDs) These drugs have demonstrated good results in
preventing heterotopic ossification after total hip arthroplasty
A direct effect of NSAIDs on the formation of heterotopic ossification has been described due to the inhibition of the differentiation of mesenchymal cells into oestrogenic cells There is also an indirect effect which refers to the inhibition of bone remodelling by suppression of the prostagland unmediated inflammatory response (specifically PGE-2)
Indomethacin has been considered a useful medication for heterotopic ossification prophylaxis following total hip replacement
prescribed for three to six weeks in a dose of 75mgday within two months of the injury may reduce the incidence of heterotopic ossification by two to three times
Biphosphonates inhibits precipitation of calcium phosphate and blocks the aggregation and mineralisation of hydroxyapatite crystals In primary prevention Banovac et al [56] have suggested that the treatment should begin as soon as elevated alkaline phosphatase is diagnosed or positive findings in ultrasonography or bone scans are shown In addition disphosphonates could have long-term effects on prevention when the treatment is finished
Posttraumatic wide exposure and surgical resection
indications severe loss of motion and decreased function
technique wide exposure required to identify all neurovascular
structures that may be involved timing of resection (controversial)
marked decrease in bone scan activity AND normalization of ALP
6 months following general trauma 1 year following SCI 15 years following TBI
some data suggests equivalent results when comparing early versus late resection
postop follow with 5 day course of indomethacin early gentle joint mobilization
The surgery is necessary in patients with symptomatic HO and unsuccessful medical treatment such as
Loss of range of motion and ankylosis with associated functional disability such as sitting difficulties
Complications of immobility such as pressure ulcers
Facilitate rehabilitation and recovery of muscular atrophy secondary to prolonged immobilisation
Difficulties of appropriate hygiene because access to the perineum or bladder care is needed
Severe pain refractory to analgesia Vascular andor nerve compression
Advantages to early excision of heterotopic ossification (vs waiting for maturation) include decreased soft tissue contracture better definition between heterotopic and native bone and decreased waiting time for the patient When the soft tissue envelope is benign one may proceed with operative release While waiting for normalization of alkaline phosphatase levels inactivity on bone scan or radiographic maturity may decrease risk of recurrent heterotopic ossification delaying operative release for these reasons has not been shown to improve results of final elbow range of motion after contracture release
Gartland recommended surgery after six months following traumatic heterotopic ossification one year following spinal cord injury and 18 months after head injury
In the past waiting until maturity in order to minimize the rate of recurrence after the surgical treatment was recommended Nevertheless recent studies do not confirm a higher rate of recurrence when the HO is excised in an earlier phase In addition a long delay before surgery leads to ankylosis a high degree of osteoporosis and more extensive intra-articular injuries These findings are associated with bad functional results and potential complications
Should you wait till lesion maturation
Prevention byHandle tissue carefully Avoid excess bleeding Achieve good hemostasis Beware of lesions that span internervous tissue planes
but if it happens resection of a large enough amount of bone to allow improvement of the range of motion and trying to preserve the joint
Our aim must be
A reactive process that is characterized by a well-circumscribed proliferation of fibroblasts cartilage and bone within muscle
A form of heterotopic ossification that is the result direct trauma intramuscular hematoma
most common location is the diaphysis of long bones Must differentiate from tumors Fibrodysplasia ossificans progressiva (FOP) is a rare subtype of heterotopic ossification
involves mutation of the ACVR1 gene (activin A type I receptor gene a BMP type-1 receptor)
Epidemiology demographics
most common in young active males (15 to 35 years old) body locations
quadriceps brachialis and gluteal muscles Genetics
almost always a posttraumatic condition Prognosis
usually self limiting mass usually begins to decrease in size after 1 yea
Myositis ossificans
PresentationbullSymptoms
bull pain tenderness swelling and decreased range of motion that usually presents within days of the injury
bull pain and size of the mass decrease with timebull mass increases in size over several months(usually 3 to 6 cm)
bull after the mass stops growing it becomes firmbullPhysical exam
bull palpable soft tissue massbull restricted range of motion
ImagingbullRadiographs
bull peripheral bone formation with central lucent areabull may appear as dotted veil pattern
bullMRI with gadolinium bull rim enhancement is seen within the first 3 weeks
bullCT scan bull lesion has an eggshell appearance
bullCharacteristic histology shows zonal pattern bull periphery of lesion
bull mature trabeculae of lamellar and woven bonebull calcification seen on xray
bull center of the lesion bull irregular mass of immature fibroblastsbull cartilage component may be presentbull (no calcification seen on xray) bull no cellular atypia seen
Treatment
bullNonoperative bull rest range of motion exercises and activity modification
bull passive stretching is contraindicated (makes it worse)bull physical therapy
bull utilized to maintain range of motionbull radiographic monitoring
bull obtained to confirm maturation of the lesionbullOperative
bull surgical excision bull indicated only if it remains a problem after it maturesbull do not operate in acute phase wait at least six months
bull excision of the lesion within 6 to 12 months predisposes to local recurrence
A 26-year-old man presents with generalized back and joint stiffness and difficulty opening his mouth His elder sister has similar complaints Since childhood he has had 3 surgeries for excision of recurrent bony prominences around his knees He walks with a stooped over posture seen in Figure A Radiographs of his feet knee hip and spine are seen in Figures B-E respectively
fibrodysplasia ossificans progressiva
Stone Man Disease) which involves a mutation of the ACVR1
There are 2 hallmark characteristics progressive heterotopic ossification (muscles fascia tendons ligaments and joint capsules) and congenital malformation of the great toe (hallux valgus malformed first metatarsal and monophalangism) BMP4 which contributes to the formation of the skeleton in the normal embryo is implicated in this disease
Complications
bullHematoma and intraoperative bleedingbullInfection
bull higher rate of infection following joint arthroplasty if HO is present
bullFractures of osteoporotic bone bull osteopenic from disusebull during surgery or physiotherapy
bullRecurrence bull recurrence rate correlates with neurological injury
bull greater recurrence if severe neurological compromisebullAVN
bull if extensive dissection or stripping is required
HTO AND ISS
When ISS is below 25 the mortality risk is minimal and above 25 it is an almost linear increase
When ISS is 50 the mortality is 50 When above 70 it is close to 100 If an injury is assigned an AIS of 6 (unsurvivable injury) the ISS score is
automatically assigned to 75 Highest ISS score obtainable is 75 For trauma patients of vehicular accidents the scoring system is important
for assessing the effectiveness of medical care in reducing morbidity and mortality
Advantages virtually the only anatomical scoring system in use correlates linearly with
mortality morbidity hospital stay other measures of severity
Weaknesses Any error in AIS scoring increases the ISS error Many different injury patterns can yield the same ISS score Injuries to different body regions are not weighted Not a useful triage tool as a full description of patient injuries is not known
prior to full investigation amp operation
risk factors periosteal stripping off anterior femur male gender obesity post traumatic deformity Anterior and anterolateral approach Cementless
Neurogenic HO around the hip due to SCI occurs more often in the medial region than in the lateral region with ossified tissues extending from the pubic symphysis to the anteromedial femoral shaft posterior to the femoral neurovascular structures Ossification is also seen anteriorly involving the iliopsoas and femoral neurovascular structures laterally within gluteus minimus and posteriorly extending from the ilium to the posterior femur encasing the sciatic nerve
HTO AROUND hip and knee
The Brooker Classification of Heterotopic Ossification around the hip joint Class I has islands of bone within the soft tissues Class II has bone spurs from the pelvis or proximal end of the femur leaving at least 1 cm between opposing surfaces Class III has bone spurs from the pelvis andor proximal end of the femur reducing the space between opposing bone surfaces to less than 1 cm Class IV shows apparent bone ankylosis of the hip
Region I - Heterotopic ossifications are strictly below the tip of the greater trochanter
Region II - Heterotopic ossifications are below and above the tip of the greater trochanter
Region III - Heterotopic ossifications are strictly above the tip of the greater trochanter
Grade A - Single or multiple heterotopic ossifications are less than 10 mm in maximal extent without contact with the pelvis or the femur
Grade B - Heterotopic ossifications are greater than 10 mm without contact with the pelvis but with possible contact with the femur there is no bridging from the femur to the proximal part of the greater trochanter and no evidence of ankylosis
Grade C - Ankylosis by means of firm bridging from the femur to the pelvis is present
Shmidt classification
excision may be performed The results of this procedure are varied Patients may find that their range of movement improves but pain relief is likely to be limited
A patient with heterotopic ossification following total hip arthroplasty is thought to have a 90-100 chance of developing it on the contralateral hip if this hip also undergoes total arthroplasty
it would be prudent to minimize the risk of heterotopic ossification developing after arthroplasty by performing surgery whereby the following are ensured
Exposure is meticulous Retraction is performed carefully and soft tissue
is handled carefully Irrigation is adequate Devitalized tissue is excised Hemostasis is adequate Postoperative drains (when used) are not
retained for longer than necessary Perioperative antibiotic prophylaxis is used Postoperative anticoagulation (when used for
deep vein thrombosis prophylaxis) is carefully controlled
sources of knee stiffness 1-extrinsic severe osteoarthritis of the ipsilateral hip neurologic injury leading to muscle rigidity tight quadriceps or hamstring muscles secondary to muscle injury heterotopic ossification or long-standing juvenile inflammatory conditions limiting knee
range of motion prior to the completion of skeletal growth When extrinsic sources are identified revision total knee arthroplasty is unlikely to be associated with a favorable outcome without correction of the extrinsic problem
2-intrinsic (1) overstuffing of the patellofemoral articulation (2) an
excessively tight flexion andor extension gap (3) a tight posterior cruciate ligament (4) femoral andor tibial malrotation (5) arthrofibrosis and (6) limited bearing excursion in association with a highly conforming mobile-bearing prosthetic design
HTO after TKA
Heterotopic Ossification (HO) following primary Total Knee Replacement (TKR)
Occurs in 3-90 of TKRs 3-grade classification system No correlation between HO and component
alignment or component position
Clinical findings similar to early infection Continuing low-grade fever Warm swollen and erythematous knee Normal blood tests Possibly an association with HLA-A2 and B18 HO patients have worse KSS and function
scores
Patients at HIGH risk for developing HO after TKR (Knee Arthroplasty) (5)
Those with limited postoperative knee flexion
Increased lumbar bone mineral density (BMD) on multivariate analysis (3)
Hypertrophic arthrosis Excessive periosteal trauma Notching of the anterior femur Those who require forced manipulation
after TKA 47 in revision TKR surgery (6) Higher rates in revision TKR cases with
infection (up to 76
DaughertyBell classification of HO of the knee 0 No evidence of HO 1 Bone islands in periarticular soft tissue (no
involvement of femur patella or tibia) or HO within quadriceps expansion measuring lt1 cm
2 Spur formation measuring lt5 cm that involves the femur patella or tibia if more than one bone demonstrates HO separation of HO spurs
measure gt1 cm or HO within quadriceps expansion measuring ge1 cm but lt3 cm
3 Spur formation gt5 cm involving femur patella or tibia if more than one bone demonstrates HO separation of HO spurs measure lt1 cm or HO
within quadriceps expansion measuring ge3 cm 4 Extensive HO of the knee causing ankylosis
class 2 HO begins to involve the major bones of the knee joint with spur formation limited to a size of 5 cm
HO class 2 may be observed in select patients with complete ROM and no reported pain Patients with class 3 HO would likely always benefit from surgical excision
followed by RT prophylaxis Certainly patients in either cohort with a subclass ldquoBrdquo assignment (symptomatic) would
benefit from treatment All patients with class 4 HO require
treatment to alleviate ankylosis
treatment
References Whyte ldquoPagetrsquos Disease of Bonerdquo NEMJ vol 355
2006 Klein and Parvizi ldquoSurgical Manifestations of Pagetrsquos
Diseaserdquo JAAOS vol 14 2006 Orthobullets Campbell Apley Emedicinecom
-Chapter 15 Heterotopic Ossification after Traumatic Brain InjuryBy Jesuacutes Moreta and Joseacute Luis Martiacutenez-de los Mozos DOI 10577257343
Questions
Thank You
Formation of bone in atypical extraskeletal tissues usually occurs
spontaneously or following trauma within 2 months of neurologic injury (brain or spinal cord)
most common location is between muscle and joint capsule Epidemiology
incidence (see table below)
demographics malefemale = 21 especially men with hypertrophic osteoarthritis and women gt65y
location traumatic brain injury or stroke
hip gt elbow gt shoulder gt knee elbow HO more common following brain trauma
occurs on affected (spastic) side rarely in the knee (TBI)
spinal cord injury hip gt knee gt elbow gt shoulder hip flexors and abductors gt extensors or adductors medial aspect of the knee
Heterotopic Ossification
Risk factors
Pathophysiology exact cause of HO is not known but there appears to be a
genetic pre disposition experimental HO associated with
tissue expression of BMP IT IS SAID TO BE CAUSED BY activation and proliferation of
mesenchymal stem cells Associated conditions
orthopaedic manifestations pathologic fractures
from decreased joint ROM and osteoporotic bone nerve impingement soft tissue contractures contributing to the formation of
decubitus ulcers joint ankylosis HO after THA adversely affects outcome of THA
nonorthopaedic conditions skin maceration and hygiene problems
Pathophysiology Early in the formation of HO oedema with exudative
infiltrate is present followed by fibroblastic proliferation and immature connective tissue formation Posteriorly osteoid formation is seen with the subsequent deposition of bone matrix Primitive osteoid is deposited as small masses in the periphery early (within the first two weeks) and osteoblasts are noted located irregularly Osteoblasts produce tropocollagen which polymerizes to form collagen and secrete alkaline phosphatase which allows calcium to precipitate and the mineralization of bone matrix As mineralization progresses amorphous calcium phosphate is progressively replaced by hydroxyapatite crystals During the following weeks the lesion matures with a centripetal pattern and after 6-12 months an appearance of true bone is noted The new bone is always extra-articular and can be contiguous with the skeleton but generally does not involve the periosteum
IN SUMMARY It has been postulated that three conditions
must be met to achieve heterotopic bone formation ---a stimulating event oestrogenic precursor cells and a proper environment LIKE hypercalcaemia tissue hypoxia pH changes (alkalosis) or prolonged immobilization
ClassificationbullSubtypes
bull neurogenic HO bull Four clinical stages of HO in people with spinal cord injury were
described by Nicholas in 1973
bull traumatic myositis ossificans bull fibrodysplasia ossificans progressiva (Munchmeyers Disease)
Neurogenic HO Symptoms
painless loss of ROM interferes with ADL CRPS symptoms fever
Physical exam inspection
warm painful swollen joint may have effusion skin problems
decubitus ulcers from contractures around skin muscles ligaments
skin maceration and hygiene problems motion
decreased joint ROM joint ankylosis with HO after TKA might develop quad muscle snapping or patella
instability neurovascular
peripheral neuropathy HO often impinges on adjacent NV structures
Imaging
bullRadiographs bull findings
bull ossification usually easy to visualize bull maturity of HO
bull the appearance of a bony cortex suggests mature HObull sharp demarcation from surrounding tissue bull trabecular pattern
bull sensitivity and specificity bull not useful for early diagnosisbull only useful at 1 week after onset of symptoms
bull calcium is deposited 7-10 days later than symptom onsetbullUltrasound
bull indications bull for early diagnosis of hip HO
bull findings bull echogenic surfaces with posterior acoustic shadowing
bullCT bull indications
bull useful for preoperative planning bullTriphasic bone scan
bull indications bull best for early diagnosis bull most commonly used diagnostic study
Radiographs are extremely useful in the staging of heterotopic ossification and will show the development of sharp cortical margins once the lesion has reached maturity
Heterotopic bone is a condition in which lamellar bone forms in non-ossified soft tissues In the early stages studies such as MRI and bone scan are more sensitive for diagnosis as radiographs may appear normal for the first three weeks After the appropriate diagnosis is made sequential radiographs are useful for monitoring the progression of the ossification Once it has reached the mature stage sharp cortical margins will appear and surgical resection may be considered
lab
Labs elevated serum alkaline phosphatase (gt250IUL)
ALP removes inhibitors of mineralization nonspecific may be elevated with skeletal trauma cannot determine maturity of HO elevated 12wks after surgery is predictor
elevated CRP correlates with inflammatory activity of HO better than ESR normalization of CRP may correlate with maturity of HO
elevated ESR (gt35mmh) 12wks after THA is predictor
elevated CK correlates with involvement of muscle extent of muscle
involvement Histology
mature fatty bone marrow mature trabecular bone
Heterotopic ossification (HO) most commonly occurs at the amputation site if the amputation was performed thru the zone of injury especially if the injury was a blast mechanism
Symptomatic heterotopic ossification of the quadriceps may occur following placement of a large-diameter Steinmann pin for the purpose of temporary skeletal traction
TreatmentThe prevention of heterotopic ossification is focused on three basic principles disrupting the inductive signalling pathways altering the osteoprogenitor cells or modifying the environment
bullphysiotherapy should involve an assisted range of movement exercises with gentle stretch and terminal resistance trainingbullProphylaxis
bull bisphosphonates amp NSAIDS bull indications
bull although no literature supports are commonly usedbull technique
bull indomethacin is most commonly used bull dose is 75mgday for 10days to 6 weeks
bull perioperative radiation bull indications
bull although no literature supports commonly usedbull is thought to be effective by blocking osteoblast differentiation
bull technique bull a single perioperative dose of 700cGy can be given either 4
hours preop or within 72 hours postoperatively bull lt550cGy not effective
Nonsteroidal anti-inflammatory drugs (NSAIDs) These drugs have demonstrated good results in
preventing heterotopic ossification after total hip arthroplasty
A direct effect of NSAIDs on the formation of heterotopic ossification has been described due to the inhibition of the differentiation of mesenchymal cells into oestrogenic cells There is also an indirect effect which refers to the inhibition of bone remodelling by suppression of the prostagland unmediated inflammatory response (specifically PGE-2)
Indomethacin has been considered a useful medication for heterotopic ossification prophylaxis following total hip replacement
prescribed for three to six weeks in a dose of 75mgday within two months of the injury may reduce the incidence of heterotopic ossification by two to three times
Biphosphonates inhibits precipitation of calcium phosphate and blocks the aggregation and mineralisation of hydroxyapatite crystals In primary prevention Banovac et al [56] have suggested that the treatment should begin as soon as elevated alkaline phosphatase is diagnosed or positive findings in ultrasonography or bone scans are shown In addition disphosphonates could have long-term effects on prevention when the treatment is finished
Posttraumatic wide exposure and surgical resection
indications severe loss of motion and decreased function
technique wide exposure required to identify all neurovascular
structures that may be involved timing of resection (controversial)
marked decrease in bone scan activity AND normalization of ALP
6 months following general trauma 1 year following SCI 15 years following TBI
some data suggests equivalent results when comparing early versus late resection
postop follow with 5 day course of indomethacin early gentle joint mobilization
The surgery is necessary in patients with symptomatic HO and unsuccessful medical treatment such as
Loss of range of motion and ankylosis with associated functional disability such as sitting difficulties
Complications of immobility such as pressure ulcers
Facilitate rehabilitation and recovery of muscular atrophy secondary to prolonged immobilisation
Difficulties of appropriate hygiene because access to the perineum or bladder care is needed
Severe pain refractory to analgesia Vascular andor nerve compression
Advantages to early excision of heterotopic ossification (vs waiting for maturation) include decreased soft tissue contracture better definition between heterotopic and native bone and decreased waiting time for the patient When the soft tissue envelope is benign one may proceed with operative release While waiting for normalization of alkaline phosphatase levels inactivity on bone scan or radiographic maturity may decrease risk of recurrent heterotopic ossification delaying operative release for these reasons has not been shown to improve results of final elbow range of motion after contracture release
Gartland recommended surgery after six months following traumatic heterotopic ossification one year following spinal cord injury and 18 months after head injury
In the past waiting until maturity in order to minimize the rate of recurrence after the surgical treatment was recommended Nevertheless recent studies do not confirm a higher rate of recurrence when the HO is excised in an earlier phase In addition a long delay before surgery leads to ankylosis a high degree of osteoporosis and more extensive intra-articular injuries These findings are associated with bad functional results and potential complications
Should you wait till lesion maturation
Prevention byHandle tissue carefully Avoid excess bleeding Achieve good hemostasis Beware of lesions that span internervous tissue planes
but if it happens resection of a large enough amount of bone to allow improvement of the range of motion and trying to preserve the joint
Our aim must be
A reactive process that is characterized by a well-circumscribed proliferation of fibroblasts cartilage and bone within muscle
A form of heterotopic ossification that is the result direct trauma intramuscular hematoma
most common location is the diaphysis of long bones Must differentiate from tumors Fibrodysplasia ossificans progressiva (FOP) is a rare subtype of heterotopic ossification
involves mutation of the ACVR1 gene (activin A type I receptor gene a BMP type-1 receptor)
Epidemiology demographics
most common in young active males (15 to 35 years old) body locations
quadriceps brachialis and gluteal muscles Genetics
almost always a posttraumatic condition Prognosis
usually self limiting mass usually begins to decrease in size after 1 yea
Myositis ossificans
PresentationbullSymptoms
bull pain tenderness swelling and decreased range of motion that usually presents within days of the injury
bull pain and size of the mass decrease with timebull mass increases in size over several months(usually 3 to 6 cm)
bull after the mass stops growing it becomes firmbullPhysical exam
bull palpable soft tissue massbull restricted range of motion
ImagingbullRadiographs
bull peripheral bone formation with central lucent areabull may appear as dotted veil pattern
bullMRI with gadolinium bull rim enhancement is seen within the first 3 weeks
bullCT scan bull lesion has an eggshell appearance
bullCharacteristic histology shows zonal pattern bull periphery of lesion
bull mature trabeculae of lamellar and woven bonebull calcification seen on xray
bull center of the lesion bull irregular mass of immature fibroblastsbull cartilage component may be presentbull (no calcification seen on xray) bull no cellular atypia seen
Treatment
bullNonoperative bull rest range of motion exercises and activity modification
bull passive stretching is contraindicated (makes it worse)bull physical therapy
bull utilized to maintain range of motionbull radiographic monitoring
bull obtained to confirm maturation of the lesionbullOperative
bull surgical excision bull indicated only if it remains a problem after it maturesbull do not operate in acute phase wait at least six months
bull excision of the lesion within 6 to 12 months predisposes to local recurrence
A 26-year-old man presents with generalized back and joint stiffness and difficulty opening his mouth His elder sister has similar complaints Since childhood he has had 3 surgeries for excision of recurrent bony prominences around his knees He walks with a stooped over posture seen in Figure A Radiographs of his feet knee hip and spine are seen in Figures B-E respectively
fibrodysplasia ossificans progressiva
Stone Man Disease) which involves a mutation of the ACVR1
There are 2 hallmark characteristics progressive heterotopic ossification (muscles fascia tendons ligaments and joint capsules) and congenital malformation of the great toe (hallux valgus malformed first metatarsal and monophalangism) BMP4 which contributes to the formation of the skeleton in the normal embryo is implicated in this disease
Complications
bullHematoma and intraoperative bleedingbullInfection
bull higher rate of infection following joint arthroplasty if HO is present
bullFractures of osteoporotic bone bull osteopenic from disusebull during surgery or physiotherapy
bullRecurrence bull recurrence rate correlates with neurological injury
bull greater recurrence if severe neurological compromisebullAVN
bull if extensive dissection or stripping is required
HTO AND ISS
When ISS is below 25 the mortality risk is minimal and above 25 it is an almost linear increase
When ISS is 50 the mortality is 50 When above 70 it is close to 100 If an injury is assigned an AIS of 6 (unsurvivable injury) the ISS score is
automatically assigned to 75 Highest ISS score obtainable is 75 For trauma patients of vehicular accidents the scoring system is important
for assessing the effectiveness of medical care in reducing morbidity and mortality
Advantages virtually the only anatomical scoring system in use correlates linearly with
mortality morbidity hospital stay other measures of severity
Weaknesses Any error in AIS scoring increases the ISS error Many different injury patterns can yield the same ISS score Injuries to different body regions are not weighted Not a useful triage tool as a full description of patient injuries is not known
prior to full investigation amp operation
risk factors periosteal stripping off anterior femur male gender obesity post traumatic deformity Anterior and anterolateral approach Cementless
Neurogenic HO around the hip due to SCI occurs more often in the medial region than in the lateral region with ossified tissues extending from the pubic symphysis to the anteromedial femoral shaft posterior to the femoral neurovascular structures Ossification is also seen anteriorly involving the iliopsoas and femoral neurovascular structures laterally within gluteus minimus and posteriorly extending from the ilium to the posterior femur encasing the sciatic nerve
HTO AROUND hip and knee
The Brooker Classification of Heterotopic Ossification around the hip joint Class I has islands of bone within the soft tissues Class II has bone spurs from the pelvis or proximal end of the femur leaving at least 1 cm between opposing surfaces Class III has bone spurs from the pelvis andor proximal end of the femur reducing the space between opposing bone surfaces to less than 1 cm Class IV shows apparent bone ankylosis of the hip
Region I - Heterotopic ossifications are strictly below the tip of the greater trochanter
Region II - Heterotopic ossifications are below and above the tip of the greater trochanter
Region III - Heterotopic ossifications are strictly above the tip of the greater trochanter
Grade A - Single or multiple heterotopic ossifications are less than 10 mm in maximal extent without contact with the pelvis or the femur
Grade B - Heterotopic ossifications are greater than 10 mm without contact with the pelvis but with possible contact with the femur there is no bridging from the femur to the proximal part of the greater trochanter and no evidence of ankylosis
Grade C - Ankylosis by means of firm bridging from the femur to the pelvis is present
Shmidt classification
excision may be performed The results of this procedure are varied Patients may find that their range of movement improves but pain relief is likely to be limited
A patient with heterotopic ossification following total hip arthroplasty is thought to have a 90-100 chance of developing it on the contralateral hip if this hip also undergoes total arthroplasty
it would be prudent to minimize the risk of heterotopic ossification developing after arthroplasty by performing surgery whereby the following are ensured
Exposure is meticulous Retraction is performed carefully and soft tissue
is handled carefully Irrigation is adequate Devitalized tissue is excised Hemostasis is adequate Postoperative drains (when used) are not
retained for longer than necessary Perioperative antibiotic prophylaxis is used Postoperative anticoagulation (when used for
deep vein thrombosis prophylaxis) is carefully controlled
sources of knee stiffness 1-extrinsic severe osteoarthritis of the ipsilateral hip neurologic injury leading to muscle rigidity tight quadriceps or hamstring muscles secondary to muscle injury heterotopic ossification or long-standing juvenile inflammatory conditions limiting knee
range of motion prior to the completion of skeletal growth When extrinsic sources are identified revision total knee arthroplasty is unlikely to be associated with a favorable outcome without correction of the extrinsic problem
2-intrinsic (1) overstuffing of the patellofemoral articulation (2) an
excessively tight flexion andor extension gap (3) a tight posterior cruciate ligament (4) femoral andor tibial malrotation (5) arthrofibrosis and (6) limited bearing excursion in association with a highly conforming mobile-bearing prosthetic design
HTO after TKA
Heterotopic Ossification (HO) following primary Total Knee Replacement (TKR)
Occurs in 3-90 of TKRs 3-grade classification system No correlation between HO and component
alignment or component position
Clinical findings similar to early infection Continuing low-grade fever Warm swollen and erythematous knee Normal blood tests Possibly an association with HLA-A2 and B18 HO patients have worse KSS and function
scores
Patients at HIGH risk for developing HO after TKR (Knee Arthroplasty) (5)
Those with limited postoperative knee flexion
Increased lumbar bone mineral density (BMD) on multivariate analysis (3)
Hypertrophic arthrosis Excessive periosteal trauma Notching of the anterior femur Those who require forced manipulation
after TKA 47 in revision TKR surgery (6) Higher rates in revision TKR cases with
infection (up to 76
DaughertyBell classification of HO of the knee 0 No evidence of HO 1 Bone islands in periarticular soft tissue (no
involvement of femur patella or tibia) or HO within quadriceps expansion measuring lt1 cm
2 Spur formation measuring lt5 cm that involves the femur patella or tibia if more than one bone demonstrates HO separation of HO spurs
measure gt1 cm or HO within quadriceps expansion measuring ge1 cm but lt3 cm
3 Spur formation gt5 cm involving femur patella or tibia if more than one bone demonstrates HO separation of HO spurs measure lt1 cm or HO
within quadriceps expansion measuring ge3 cm 4 Extensive HO of the knee causing ankylosis
class 2 HO begins to involve the major bones of the knee joint with spur formation limited to a size of 5 cm
HO class 2 may be observed in select patients with complete ROM and no reported pain Patients with class 3 HO would likely always benefit from surgical excision
followed by RT prophylaxis Certainly patients in either cohort with a subclass ldquoBrdquo assignment (symptomatic) would
benefit from treatment All patients with class 4 HO require
treatment to alleviate ankylosis
treatment
References Whyte ldquoPagetrsquos Disease of Bonerdquo NEMJ vol 355
2006 Klein and Parvizi ldquoSurgical Manifestations of Pagetrsquos
Diseaserdquo JAAOS vol 14 2006 Orthobullets Campbell Apley Emedicinecom
-Chapter 15 Heterotopic Ossification after Traumatic Brain InjuryBy Jesuacutes Moreta and Joseacute Luis Martiacutenez-de los Mozos DOI 10577257343
Questions
Thank You
Risk factors
Pathophysiology exact cause of HO is not known but there appears to be a
genetic pre disposition experimental HO associated with
tissue expression of BMP IT IS SAID TO BE CAUSED BY activation and proliferation of
mesenchymal stem cells Associated conditions
orthopaedic manifestations pathologic fractures
from decreased joint ROM and osteoporotic bone nerve impingement soft tissue contractures contributing to the formation of
decubitus ulcers joint ankylosis HO after THA adversely affects outcome of THA
nonorthopaedic conditions skin maceration and hygiene problems
Pathophysiology Early in the formation of HO oedema with exudative
infiltrate is present followed by fibroblastic proliferation and immature connective tissue formation Posteriorly osteoid formation is seen with the subsequent deposition of bone matrix Primitive osteoid is deposited as small masses in the periphery early (within the first two weeks) and osteoblasts are noted located irregularly Osteoblasts produce tropocollagen which polymerizes to form collagen and secrete alkaline phosphatase which allows calcium to precipitate and the mineralization of bone matrix As mineralization progresses amorphous calcium phosphate is progressively replaced by hydroxyapatite crystals During the following weeks the lesion matures with a centripetal pattern and after 6-12 months an appearance of true bone is noted The new bone is always extra-articular and can be contiguous with the skeleton but generally does not involve the periosteum
IN SUMMARY It has been postulated that three conditions
must be met to achieve heterotopic bone formation ---a stimulating event oestrogenic precursor cells and a proper environment LIKE hypercalcaemia tissue hypoxia pH changes (alkalosis) or prolonged immobilization
ClassificationbullSubtypes
bull neurogenic HO bull Four clinical stages of HO in people with spinal cord injury were
described by Nicholas in 1973
bull traumatic myositis ossificans bull fibrodysplasia ossificans progressiva (Munchmeyers Disease)
Neurogenic HO Symptoms
painless loss of ROM interferes with ADL CRPS symptoms fever
Physical exam inspection
warm painful swollen joint may have effusion skin problems
decubitus ulcers from contractures around skin muscles ligaments
skin maceration and hygiene problems motion
decreased joint ROM joint ankylosis with HO after TKA might develop quad muscle snapping or patella
instability neurovascular
peripheral neuropathy HO often impinges on adjacent NV structures
Imaging
bullRadiographs bull findings
bull ossification usually easy to visualize bull maturity of HO
bull the appearance of a bony cortex suggests mature HObull sharp demarcation from surrounding tissue bull trabecular pattern
bull sensitivity and specificity bull not useful for early diagnosisbull only useful at 1 week after onset of symptoms
bull calcium is deposited 7-10 days later than symptom onsetbullUltrasound
bull indications bull for early diagnosis of hip HO
bull findings bull echogenic surfaces with posterior acoustic shadowing
bullCT bull indications
bull useful for preoperative planning bullTriphasic bone scan
bull indications bull best for early diagnosis bull most commonly used diagnostic study
Radiographs are extremely useful in the staging of heterotopic ossification and will show the development of sharp cortical margins once the lesion has reached maturity
Heterotopic bone is a condition in which lamellar bone forms in non-ossified soft tissues In the early stages studies such as MRI and bone scan are more sensitive for diagnosis as radiographs may appear normal for the first three weeks After the appropriate diagnosis is made sequential radiographs are useful for monitoring the progression of the ossification Once it has reached the mature stage sharp cortical margins will appear and surgical resection may be considered
lab
Labs elevated serum alkaline phosphatase (gt250IUL)
ALP removes inhibitors of mineralization nonspecific may be elevated with skeletal trauma cannot determine maturity of HO elevated 12wks after surgery is predictor
elevated CRP correlates with inflammatory activity of HO better than ESR normalization of CRP may correlate with maturity of HO
elevated ESR (gt35mmh) 12wks after THA is predictor
elevated CK correlates with involvement of muscle extent of muscle
involvement Histology
mature fatty bone marrow mature trabecular bone
Heterotopic ossification (HO) most commonly occurs at the amputation site if the amputation was performed thru the zone of injury especially if the injury was a blast mechanism
Symptomatic heterotopic ossification of the quadriceps may occur following placement of a large-diameter Steinmann pin for the purpose of temporary skeletal traction
TreatmentThe prevention of heterotopic ossification is focused on three basic principles disrupting the inductive signalling pathways altering the osteoprogenitor cells or modifying the environment
bullphysiotherapy should involve an assisted range of movement exercises with gentle stretch and terminal resistance trainingbullProphylaxis
bull bisphosphonates amp NSAIDS bull indications
bull although no literature supports are commonly usedbull technique
bull indomethacin is most commonly used bull dose is 75mgday for 10days to 6 weeks
bull perioperative radiation bull indications
bull although no literature supports commonly usedbull is thought to be effective by blocking osteoblast differentiation
bull technique bull a single perioperative dose of 700cGy can be given either 4
hours preop or within 72 hours postoperatively bull lt550cGy not effective
Nonsteroidal anti-inflammatory drugs (NSAIDs) These drugs have demonstrated good results in
preventing heterotopic ossification after total hip arthroplasty
A direct effect of NSAIDs on the formation of heterotopic ossification has been described due to the inhibition of the differentiation of mesenchymal cells into oestrogenic cells There is also an indirect effect which refers to the inhibition of bone remodelling by suppression of the prostagland unmediated inflammatory response (specifically PGE-2)
Indomethacin has been considered a useful medication for heterotopic ossification prophylaxis following total hip replacement
prescribed for three to six weeks in a dose of 75mgday within two months of the injury may reduce the incidence of heterotopic ossification by two to three times
Biphosphonates inhibits precipitation of calcium phosphate and blocks the aggregation and mineralisation of hydroxyapatite crystals In primary prevention Banovac et al [56] have suggested that the treatment should begin as soon as elevated alkaline phosphatase is diagnosed or positive findings in ultrasonography or bone scans are shown In addition disphosphonates could have long-term effects on prevention when the treatment is finished
Posttraumatic wide exposure and surgical resection
indications severe loss of motion and decreased function
technique wide exposure required to identify all neurovascular
structures that may be involved timing of resection (controversial)
marked decrease in bone scan activity AND normalization of ALP
6 months following general trauma 1 year following SCI 15 years following TBI
some data suggests equivalent results when comparing early versus late resection
postop follow with 5 day course of indomethacin early gentle joint mobilization
The surgery is necessary in patients with symptomatic HO and unsuccessful medical treatment such as
Loss of range of motion and ankylosis with associated functional disability such as sitting difficulties
Complications of immobility such as pressure ulcers
Facilitate rehabilitation and recovery of muscular atrophy secondary to prolonged immobilisation
Difficulties of appropriate hygiene because access to the perineum or bladder care is needed
Severe pain refractory to analgesia Vascular andor nerve compression
Advantages to early excision of heterotopic ossification (vs waiting for maturation) include decreased soft tissue contracture better definition between heterotopic and native bone and decreased waiting time for the patient When the soft tissue envelope is benign one may proceed with operative release While waiting for normalization of alkaline phosphatase levels inactivity on bone scan or radiographic maturity may decrease risk of recurrent heterotopic ossification delaying operative release for these reasons has not been shown to improve results of final elbow range of motion after contracture release
Gartland recommended surgery after six months following traumatic heterotopic ossification one year following spinal cord injury and 18 months after head injury
In the past waiting until maturity in order to minimize the rate of recurrence after the surgical treatment was recommended Nevertheless recent studies do not confirm a higher rate of recurrence when the HO is excised in an earlier phase In addition a long delay before surgery leads to ankylosis a high degree of osteoporosis and more extensive intra-articular injuries These findings are associated with bad functional results and potential complications
Should you wait till lesion maturation
Prevention byHandle tissue carefully Avoid excess bleeding Achieve good hemostasis Beware of lesions that span internervous tissue planes
but if it happens resection of a large enough amount of bone to allow improvement of the range of motion and trying to preserve the joint
Our aim must be
A reactive process that is characterized by a well-circumscribed proliferation of fibroblasts cartilage and bone within muscle
A form of heterotopic ossification that is the result direct trauma intramuscular hematoma
most common location is the diaphysis of long bones Must differentiate from tumors Fibrodysplasia ossificans progressiva (FOP) is a rare subtype of heterotopic ossification
involves mutation of the ACVR1 gene (activin A type I receptor gene a BMP type-1 receptor)
Epidemiology demographics
most common in young active males (15 to 35 years old) body locations
quadriceps brachialis and gluteal muscles Genetics
almost always a posttraumatic condition Prognosis
usually self limiting mass usually begins to decrease in size after 1 yea
Myositis ossificans
PresentationbullSymptoms
bull pain tenderness swelling and decreased range of motion that usually presents within days of the injury
bull pain and size of the mass decrease with timebull mass increases in size over several months(usually 3 to 6 cm)
bull after the mass stops growing it becomes firmbullPhysical exam
bull palpable soft tissue massbull restricted range of motion
ImagingbullRadiographs
bull peripheral bone formation with central lucent areabull may appear as dotted veil pattern
bullMRI with gadolinium bull rim enhancement is seen within the first 3 weeks
bullCT scan bull lesion has an eggshell appearance
bullCharacteristic histology shows zonal pattern bull periphery of lesion
bull mature trabeculae of lamellar and woven bonebull calcification seen on xray
bull center of the lesion bull irregular mass of immature fibroblastsbull cartilage component may be presentbull (no calcification seen on xray) bull no cellular atypia seen
Treatment
bullNonoperative bull rest range of motion exercises and activity modification
bull passive stretching is contraindicated (makes it worse)bull physical therapy
bull utilized to maintain range of motionbull radiographic monitoring
bull obtained to confirm maturation of the lesionbullOperative
bull surgical excision bull indicated only if it remains a problem after it maturesbull do not operate in acute phase wait at least six months
bull excision of the lesion within 6 to 12 months predisposes to local recurrence
A 26-year-old man presents with generalized back and joint stiffness and difficulty opening his mouth His elder sister has similar complaints Since childhood he has had 3 surgeries for excision of recurrent bony prominences around his knees He walks with a stooped over posture seen in Figure A Radiographs of his feet knee hip and spine are seen in Figures B-E respectively
fibrodysplasia ossificans progressiva
Stone Man Disease) which involves a mutation of the ACVR1
There are 2 hallmark characteristics progressive heterotopic ossification (muscles fascia tendons ligaments and joint capsules) and congenital malformation of the great toe (hallux valgus malformed first metatarsal and monophalangism) BMP4 which contributes to the formation of the skeleton in the normal embryo is implicated in this disease
Complications
bullHematoma and intraoperative bleedingbullInfection
bull higher rate of infection following joint arthroplasty if HO is present
bullFractures of osteoporotic bone bull osteopenic from disusebull during surgery or physiotherapy
bullRecurrence bull recurrence rate correlates with neurological injury
bull greater recurrence if severe neurological compromisebullAVN
bull if extensive dissection or stripping is required
HTO AND ISS
When ISS is below 25 the mortality risk is minimal and above 25 it is an almost linear increase
When ISS is 50 the mortality is 50 When above 70 it is close to 100 If an injury is assigned an AIS of 6 (unsurvivable injury) the ISS score is
automatically assigned to 75 Highest ISS score obtainable is 75 For trauma patients of vehicular accidents the scoring system is important
for assessing the effectiveness of medical care in reducing morbidity and mortality
Advantages virtually the only anatomical scoring system in use correlates linearly with
mortality morbidity hospital stay other measures of severity
Weaknesses Any error in AIS scoring increases the ISS error Many different injury patterns can yield the same ISS score Injuries to different body regions are not weighted Not a useful triage tool as a full description of patient injuries is not known
prior to full investigation amp operation
risk factors periosteal stripping off anterior femur male gender obesity post traumatic deformity Anterior and anterolateral approach Cementless
Neurogenic HO around the hip due to SCI occurs more often in the medial region than in the lateral region with ossified tissues extending from the pubic symphysis to the anteromedial femoral shaft posterior to the femoral neurovascular structures Ossification is also seen anteriorly involving the iliopsoas and femoral neurovascular structures laterally within gluteus minimus and posteriorly extending from the ilium to the posterior femur encasing the sciatic nerve
HTO AROUND hip and knee
The Brooker Classification of Heterotopic Ossification around the hip joint Class I has islands of bone within the soft tissues Class II has bone spurs from the pelvis or proximal end of the femur leaving at least 1 cm between opposing surfaces Class III has bone spurs from the pelvis andor proximal end of the femur reducing the space between opposing bone surfaces to less than 1 cm Class IV shows apparent bone ankylosis of the hip
Region I - Heterotopic ossifications are strictly below the tip of the greater trochanter
Region II - Heterotopic ossifications are below and above the tip of the greater trochanter
Region III - Heterotopic ossifications are strictly above the tip of the greater trochanter
Grade A - Single or multiple heterotopic ossifications are less than 10 mm in maximal extent without contact with the pelvis or the femur
Grade B - Heterotopic ossifications are greater than 10 mm without contact with the pelvis but with possible contact with the femur there is no bridging from the femur to the proximal part of the greater trochanter and no evidence of ankylosis
Grade C - Ankylosis by means of firm bridging from the femur to the pelvis is present
Shmidt classification
excision may be performed The results of this procedure are varied Patients may find that their range of movement improves but pain relief is likely to be limited
A patient with heterotopic ossification following total hip arthroplasty is thought to have a 90-100 chance of developing it on the contralateral hip if this hip also undergoes total arthroplasty
it would be prudent to minimize the risk of heterotopic ossification developing after arthroplasty by performing surgery whereby the following are ensured
Exposure is meticulous Retraction is performed carefully and soft tissue
is handled carefully Irrigation is adequate Devitalized tissue is excised Hemostasis is adequate Postoperative drains (when used) are not
retained for longer than necessary Perioperative antibiotic prophylaxis is used Postoperative anticoagulation (when used for
deep vein thrombosis prophylaxis) is carefully controlled
sources of knee stiffness 1-extrinsic severe osteoarthritis of the ipsilateral hip neurologic injury leading to muscle rigidity tight quadriceps or hamstring muscles secondary to muscle injury heterotopic ossification or long-standing juvenile inflammatory conditions limiting knee
range of motion prior to the completion of skeletal growth When extrinsic sources are identified revision total knee arthroplasty is unlikely to be associated with a favorable outcome without correction of the extrinsic problem
2-intrinsic (1) overstuffing of the patellofemoral articulation (2) an
excessively tight flexion andor extension gap (3) a tight posterior cruciate ligament (4) femoral andor tibial malrotation (5) arthrofibrosis and (6) limited bearing excursion in association with a highly conforming mobile-bearing prosthetic design
HTO after TKA
Heterotopic Ossification (HO) following primary Total Knee Replacement (TKR)
Occurs in 3-90 of TKRs 3-grade classification system No correlation between HO and component
alignment or component position
Clinical findings similar to early infection Continuing low-grade fever Warm swollen and erythematous knee Normal blood tests Possibly an association with HLA-A2 and B18 HO patients have worse KSS and function
scores
Patients at HIGH risk for developing HO after TKR (Knee Arthroplasty) (5)
Those with limited postoperative knee flexion
Increased lumbar bone mineral density (BMD) on multivariate analysis (3)
Hypertrophic arthrosis Excessive periosteal trauma Notching of the anterior femur Those who require forced manipulation
after TKA 47 in revision TKR surgery (6) Higher rates in revision TKR cases with
infection (up to 76
DaughertyBell classification of HO of the knee 0 No evidence of HO 1 Bone islands in periarticular soft tissue (no
involvement of femur patella or tibia) or HO within quadriceps expansion measuring lt1 cm
2 Spur formation measuring lt5 cm that involves the femur patella or tibia if more than one bone demonstrates HO separation of HO spurs
measure gt1 cm or HO within quadriceps expansion measuring ge1 cm but lt3 cm
3 Spur formation gt5 cm involving femur patella or tibia if more than one bone demonstrates HO separation of HO spurs measure lt1 cm or HO
within quadriceps expansion measuring ge3 cm 4 Extensive HO of the knee causing ankylosis
class 2 HO begins to involve the major bones of the knee joint with spur formation limited to a size of 5 cm
HO class 2 may be observed in select patients with complete ROM and no reported pain Patients with class 3 HO would likely always benefit from surgical excision
followed by RT prophylaxis Certainly patients in either cohort with a subclass ldquoBrdquo assignment (symptomatic) would
benefit from treatment All patients with class 4 HO require
treatment to alleviate ankylosis
treatment
References Whyte ldquoPagetrsquos Disease of Bonerdquo NEMJ vol 355
2006 Klein and Parvizi ldquoSurgical Manifestations of Pagetrsquos
Diseaserdquo JAAOS vol 14 2006 Orthobullets Campbell Apley Emedicinecom
-Chapter 15 Heterotopic Ossification after Traumatic Brain InjuryBy Jesuacutes Moreta and Joseacute Luis Martiacutenez-de los Mozos DOI 10577257343
Questions
Thank You
Pathophysiology exact cause of HO is not known but there appears to be a
genetic pre disposition experimental HO associated with
tissue expression of BMP IT IS SAID TO BE CAUSED BY activation and proliferation of
mesenchymal stem cells Associated conditions
orthopaedic manifestations pathologic fractures
from decreased joint ROM and osteoporotic bone nerve impingement soft tissue contractures contributing to the formation of
decubitus ulcers joint ankylosis HO after THA adversely affects outcome of THA
nonorthopaedic conditions skin maceration and hygiene problems
Pathophysiology Early in the formation of HO oedema with exudative
infiltrate is present followed by fibroblastic proliferation and immature connective tissue formation Posteriorly osteoid formation is seen with the subsequent deposition of bone matrix Primitive osteoid is deposited as small masses in the periphery early (within the first two weeks) and osteoblasts are noted located irregularly Osteoblasts produce tropocollagen which polymerizes to form collagen and secrete alkaline phosphatase which allows calcium to precipitate and the mineralization of bone matrix As mineralization progresses amorphous calcium phosphate is progressively replaced by hydroxyapatite crystals During the following weeks the lesion matures with a centripetal pattern and after 6-12 months an appearance of true bone is noted The new bone is always extra-articular and can be contiguous with the skeleton but generally does not involve the periosteum
IN SUMMARY It has been postulated that three conditions
must be met to achieve heterotopic bone formation ---a stimulating event oestrogenic precursor cells and a proper environment LIKE hypercalcaemia tissue hypoxia pH changes (alkalosis) or prolonged immobilization
ClassificationbullSubtypes
bull neurogenic HO bull Four clinical stages of HO in people with spinal cord injury were
described by Nicholas in 1973
bull traumatic myositis ossificans bull fibrodysplasia ossificans progressiva (Munchmeyers Disease)
Neurogenic HO Symptoms
painless loss of ROM interferes with ADL CRPS symptoms fever
Physical exam inspection
warm painful swollen joint may have effusion skin problems
decubitus ulcers from contractures around skin muscles ligaments
skin maceration and hygiene problems motion
decreased joint ROM joint ankylosis with HO after TKA might develop quad muscle snapping or patella
instability neurovascular
peripheral neuropathy HO often impinges on adjacent NV structures
Imaging
bullRadiographs bull findings
bull ossification usually easy to visualize bull maturity of HO
bull the appearance of a bony cortex suggests mature HObull sharp demarcation from surrounding tissue bull trabecular pattern
bull sensitivity and specificity bull not useful for early diagnosisbull only useful at 1 week after onset of symptoms
bull calcium is deposited 7-10 days later than symptom onsetbullUltrasound
bull indications bull for early diagnosis of hip HO
bull findings bull echogenic surfaces with posterior acoustic shadowing
bullCT bull indications
bull useful for preoperative planning bullTriphasic bone scan
bull indications bull best for early diagnosis bull most commonly used diagnostic study
Radiographs are extremely useful in the staging of heterotopic ossification and will show the development of sharp cortical margins once the lesion has reached maturity
Heterotopic bone is a condition in which lamellar bone forms in non-ossified soft tissues In the early stages studies such as MRI and bone scan are more sensitive for diagnosis as radiographs may appear normal for the first three weeks After the appropriate diagnosis is made sequential radiographs are useful for monitoring the progression of the ossification Once it has reached the mature stage sharp cortical margins will appear and surgical resection may be considered
lab
Labs elevated serum alkaline phosphatase (gt250IUL)
ALP removes inhibitors of mineralization nonspecific may be elevated with skeletal trauma cannot determine maturity of HO elevated 12wks after surgery is predictor
elevated CRP correlates with inflammatory activity of HO better than ESR normalization of CRP may correlate with maturity of HO
elevated ESR (gt35mmh) 12wks after THA is predictor
elevated CK correlates with involvement of muscle extent of muscle
involvement Histology
mature fatty bone marrow mature trabecular bone
Heterotopic ossification (HO) most commonly occurs at the amputation site if the amputation was performed thru the zone of injury especially if the injury was a blast mechanism
Symptomatic heterotopic ossification of the quadriceps may occur following placement of a large-diameter Steinmann pin for the purpose of temporary skeletal traction
TreatmentThe prevention of heterotopic ossification is focused on three basic principles disrupting the inductive signalling pathways altering the osteoprogenitor cells or modifying the environment
bullphysiotherapy should involve an assisted range of movement exercises with gentle stretch and terminal resistance trainingbullProphylaxis
bull bisphosphonates amp NSAIDS bull indications
bull although no literature supports are commonly usedbull technique
bull indomethacin is most commonly used bull dose is 75mgday for 10days to 6 weeks
bull perioperative radiation bull indications
bull although no literature supports commonly usedbull is thought to be effective by blocking osteoblast differentiation
bull technique bull a single perioperative dose of 700cGy can be given either 4
hours preop or within 72 hours postoperatively bull lt550cGy not effective
Nonsteroidal anti-inflammatory drugs (NSAIDs) These drugs have demonstrated good results in
preventing heterotopic ossification after total hip arthroplasty
A direct effect of NSAIDs on the formation of heterotopic ossification has been described due to the inhibition of the differentiation of mesenchymal cells into oestrogenic cells There is also an indirect effect which refers to the inhibition of bone remodelling by suppression of the prostagland unmediated inflammatory response (specifically PGE-2)
Indomethacin has been considered a useful medication for heterotopic ossification prophylaxis following total hip replacement
prescribed for three to six weeks in a dose of 75mgday within two months of the injury may reduce the incidence of heterotopic ossification by two to three times
Biphosphonates inhibits precipitation of calcium phosphate and blocks the aggregation and mineralisation of hydroxyapatite crystals In primary prevention Banovac et al [56] have suggested that the treatment should begin as soon as elevated alkaline phosphatase is diagnosed or positive findings in ultrasonography or bone scans are shown In addition disphosphonates could have long-term effects on prevention when the treatment is finished
Posttraumatic wide exposure and surgical resection
indications severe loss of motion and decreased function
technique wide exposure required to identify all neurovascular
structures that may be involved timing of resection (controversial)
marked decrease in bone scan activity AND normalization of ALP
6 months following general trauma 1 year following SCI 15 years following TBI
some data suggests equivalent results when comparing early versus late resection
postop follow with 5 day course of indomethacin early gentle joint mobilization
The surgery is necessary in patients with symptomatic HO and unsuccessful medical treatment such as
Loss of range of motion and ankylosis with associated functional disability such as sitting difficulties
Complications of immobility such as pressure ulcers
Facilitate rehabilitation and recovery of muscular atrophy secondary to prolonged immobilisation
Difficulties of appropriate hygiene because access to the perineum or bladder care is needed
Severe pain refractory to analgesia Vascular andor nerve compression
Advantages to early excision of heterotopic ossification (vs waiting for maturation) include decreased soft tissue contracture better definition between heterotopic and native bone and decreased waiting time for the patient When the soft tissue envelope is benign one may proceed with operative release While waiting for normalization of alkaline phosphatase levels inactivity on bone scan or radiographic maturity may decrease risk of recurrent heterotopic ossification delaying operative release for these reasons has not been shown to improve results of final elbow range of motion after contracture release
Gartland recommended surgery after six months following traumatic heterotopic ossification one year following spinal cord injury and 18 months after head injury
In the past waiting until maturity in order to minimize the rate of recurrence after the surgical treatment was recommended Nevertheless recent studies do not confirm a higher rate of recurrence when the HO is excised in an earlier phase In addition a long delay before surgery leads to ankylosis a high degree of osteoporosis and more extensive intra-articular injuries These findings are associated with bad functional results and potential complications
Should you wait till lesion maturation
Prevention byHandle tissue carefully Avoid excess bleeding Achieve good hemostasis Beware of lesions that span internervous tissue planes
but if it happens resection of a large enough amount of bone to allow improvement of the range of motion and trying to preserve the joint
Our aim must be
A reactive process that is characterized by a well-circumscribed proliferation of fibroblasts cartilage and bone within muscle
A form of heterotopic ossification that is the result direct trauma intramuscular hematoma
most common location is the diaphysis of long bones Must differentiate from tumors Fibrodysplasia ossificans progressiva (FOP) is a rare subtype of heterotopic ossification
involves mutation of the ACVR1 gene (activin A type I receptor gene a BMP type-1 receptor)
Epidemiology demographics
most common in young active males (15 to 35 years old) body locations
quadriceps brachialis and gluteal muscles Genetics
almost always a posttraumatic condition Prognosis
usually self limiting mass usually begins to decrease in size after 1 yea
Myositis ossificans
PresentationbullSymptoms
bull pain tenderness swelling and decreased range of motion that usually presents within days of the injury
bull pain and size of the mass decrease with timebull mass increases in size over several months(usually 3 to 6 cm)
bull after the mass stops growing it becomes firmbullPhysical exam
bull palpable soft tissue massbull restricted range of motion
ImagingbullRadiographs
bull peripheral bone formation with central lucent areabull may appear as dotted veil pattern
bullMRI with gadolinium bull rim enhancement is seen within the first 3 weeks
bullCT scan bull lesion has an eggshell appearance
bullCharacteristic histology shows zonal pattern bull periphery of lesion
bull mature trabeculae of lamellar and woven bonebull calcification seen on xray
bull center of the lesion bull irregular mass of immature fibroblastsbull cartilage component may be presentbull (no calcification seen on xray) bull no cellular atypia seen
Treatment
bullNonoperative bull rest range of motion exercises and activity modification
bull passive stretching is contraindicated (makes it worse)bull physical therapy
bull utilized to maintain range of motionbull radiographic monitoring
bull obtained to confirm maturation of the lesionbullOperative
bull surgical excision bull indicated only if it remains a problem after it maturesbull do not operate in acute phase wait at least six months
bull excision of the lesion within 6 to 12 months predisposes to local recurrence
A 26-year-old man presents with generalized back and joint stiffness and difficulty opening his mouth His elder sister has similar complaints Since childhood he has had 3 surgeries for excision of recurrent bony prominences around his knees He walks with a stooped over posture seen in Figure A Radiographs of his feet knee hip and spine are seen in Figures B-E respectively
fibrodysplasia ossificans progressiva
Stone Man Disease) which involves a mutation of the ACVR1
There are 2 hallmark characteristics progressive heterotopic ossification (muscles fascia tendons ligaments and joint capsules) and congenital malformation of the great toe (hallux valgus malformed first metatarsal and monophalangism) BMP4 which contributes to the formation of the skeleton in the normal embryo is implicated in this disease
Complications
bullHematoma and intraoperative bleedingbullInfection
bull higher rate of infection following joint arthroplasty if HO is present
bullFractures of osteoporotic bone bull osteopenic from disusebull during surgery or physiotherapy
bullRecurrence bull recurrence rate correlates with neurological injury
bull greater recurrence if severe neurological compromisebullAVN
bull if extensive dissection or stripping is required
HTO AND ISS
When ISS is below 25 the mortality risk is minimal and above 25 it is an almost linear increase
When ISS is 50 the mortality is 50 When above 70 it is close to 100 If an injury is assigned an AIS of 6 (unsurvivable injury) the ISS score is
automatically assigned to 75 Highest ISS score obtainable is 75 For trauma patients of vehicular accidents the scoring system is important
for assessing the effectiveness of medical care in reducing morbidity and mortality
Advantages virtually the only anatomical scoring system in use correlates linearly with
mortality morbidity hospital stay other measures of severity
Weaknesses Any error in AIS scoring increases the ISS error Many different injury patterns can yield the same ISS score Injuries to different body regions are not weighted Not a useful triage tool as a full description of patient injuries is not known
prior to full investigation amp operation
risk factors periosteal stripping off anterior femur male gender obesity post traumatic deformity Anterior and anterolateral approach Cementless
Neurogenic HO around the hip due to SCI occurs more often in the medial region than in the lateral region with ossified tissues extending from the pubic symphysis to the anteromedial femoral shaft posterior to the femoral neurovascular structures Ossification is also seen anteriorly involving the iliopsoas and femoral neurovascular structures laterally within gluteus minimus and posteriorly extending from the ilium to the posterior femur encasing the sciatic nerve
HTO AROUND hip and knee
The Brooker Classification of Heterotopic Ossification around the hip joint Class I has islands of bone within the soft tissues Class II has bone spurs from the pelvis or proximal end of the femur leaving at least 1 cm between opposing surfaces Class III has bone spurs from the pelvis andor proximal end of the femur reducing the space between opposing bone surfaces to less than 1 cm Class IV shows apparent bone ankylosis of the hip
Region I - Heterotopic ossifications are strictly below the tip of the greater trochanter
Region II - Heterotopic ossifications are below and above the tip of the greater trochanter
Region III - Heterotopic ossifications are strictly above the tip of the greater trochanter
Grade A - Single or multiple heterotopic ossifications are less than 10 mm in maximal extent without contact with the pelvis or the femur
Grade B - Heterotopic ossifications are greater than 10 mm without contact with the pelvis but with possible contact with the femur there is no bridging from the femur to the proximal part of the greater trochanter and no evidence of ankylosis
Grade C - Ankylosis by means of firm bridging from the femur to the pelvis is present
Shmidt classification
excision may be performed The results of this procedure are varied Patients may find that their range of movement improves but pain relief is likely to be limited
A patient with heterotopic ossification following total hip arthroplasty is thought to have a 90-100 chance of developing it on the contralateral hip if this hip also undergoes total arthroplasty
it would be prudent to minimize the risk of heterotopic ossification developing after arthroplasty by performing surgery whereby the following are ensured
Exposure is meticulous Retraction is performed carefully and soft tissue
is handled carefully Irrigation is adequate Devitalized tissue is excised Hemostasis is adequate Postoperative drains (when used) are not
retained for longer than necessary Perioperative antibiotic prophylaxis is used Postoperative anticoagulation (when used for
deep vein thrombosis prophylaxis) is carefully controlled
sources of knee stiffness 1-extrinsic severe osteoarthritis of the ipsilateral hip neurologic injury leading to muscle rigidity tight quadriceps or hamstring muscles secondary to muscle injury heterotopic ossification or long-standing juvenile inflammatory conditions limiting knee
range of motion prior to the completion of skeletal growth When extrinsic sources are identified revision total knee arthroplasty is unlikely to be associated with a favorable outcome without correction of the extrinsic problem
2-intrinsic (1) overstuffing of the patellofemoral articulation (2) an
excessively tight flexion andor extension gap (3) a tight posterior cruciate ligament (4) femoral andor tibial malrotation (5) arthrofibrosis and (6) limited bearing excursion in association with a highly conforming mobile-bearing prosthetic design
HTO after TKA
Heterotopic Ossification (HO) following primary Total Knee Replacement (TKR)
Occurs in 3-90 of TKRs 3-grade classification system No correlation between HO and component
alignment or component position
Clinical findings similar to early infection Continuing low-grade fever Warm swollen and erythematous knee Normal blood tests Possibly an association with HLA-A2 and B18 HO patients have worse KSS and function
scores
Patients at HIGH risk for developing HO after TKR (Knee Arthroplasty) (5)
Those with limited postoperative knee flexion
Increased lumbar bone mineral density (BMD) on multivariate analysis (3)
Hypertrophic arthrosis Excessive periosteal trauma Notching of the anterior femur Those who require forced manipulation
after TKA 47 in revision TKR surgery (6) Higher rates in revision TKR cases with
infection (up to 76
DaughertyBell classification of HO of the knee 0 No evidence of HO 1 Bone islands in periarticular soft tissue (no
involvement of femur patella or tibia) or HO within quadriceps expansion measuring lt1 cm
2 Spur formation measuring lt5 cm that involves the femur patella or tibia if more than one bone demonstrates HO separation of HO spurs
measure gt1 cm or HO within quadriceps expansion measuring ge1 cm but lt3 cm
3 Spur formation gt5 cm involving femur patella or tibia if more than one bone demonstrates HO separation of HO spurs measure lt1 cm or HO
within quadriceps expansion measuring ge3 cm 4 Extensive HO of the knee causing ankylosis
class 2 HO begins to involve the major bones of the knee joint with spur formation limited to a size of 5 cm
HO class 2 may be observed in select patients with complete ROM and no reported pain Patients with class 3 HO would likely always benefit from surgical excision
followed by RT prophylaxis Certainly patients in either cohort with a subclass ldquoBrdquo assignment (symptomatic) would
benefit from treatment All patients with class 4 HO require
treatment to alleviate ankylosis
treatment
References Whyte ldquoPagetrsquos Disease of Bonerdquo NEMJ vol 355
2006 Klein and Parvizi ldquoSurgical Manifestations of Pagetrsquos
Diseaserdquo JAAOS vol 14 2006 Orthobullets Campbell Apley Emedicinecom
-Chapter 15 Heterotopic Ossification after Traumatic Brain InjuryBy Jesuacutes Moreta and Joseacute Luis Martiacutenez-de los Mozos DOI 10577257343
Questions
Thank You
Pathophysiology Early in the formation of HO oedema with exudative
infiltrate is present followed by fibroblastic proliferation and immature connective tissue formation Posteriorly osteoid formation is seen with the subsequent deposition of bone matrix Primitive osteoid is deposited as small masses in the periphery early (within the first two weeks) and osteoblasts are noted located irregularly Osteoblasts produce tropocollagen which polymerizes to form collagen and secrete alkaline phosphatase which allows calcium to precipitate and the mineralization of bone matrix As mineralization progresses amorphous calcium phosphate is progressively replaced by hydroxyapatite crystals During the following weeks the lesion matures with a centripetal pattern and after 6-12 months an appearance of true bone is noted The new bone is always extra-articular and can be contiguous with the skeleton but generally does not involve the periosteum
IN SUMMARY It has been postulated that three conditions
must be met to achieve heterotopic bone formation ---a stimulating event oestrogenic precursor cells and a proper environment LIKE hypercalcaemia tissue hypoxia pH changes (alkalosis) or prolonged immobilization
ClassificationbullSubtypes
bull neurogenic HO bull Four clinical stages of HO in people with spinal cord injury were
described by Nicholas in 1973
bull traumatic myositis ossificans bull fibrodysplasia ossificans progressiva (Munchmeyers Disease)
Neurogenic HO Symptoms
painless loss of ROM interferes with ADL CRPS symptoms fever
Physical exam inspection
warm painful swollen joint may have effusion skin problems
decubitus ulcers from contractures around skin muscles ligaments
skin maceration and hygiene problems motion
decreased joint ROM joint ankylosis with HO after TKA might develop quad muscle snapping or patella
instability neurovascular
peripheral neuropathy HO often impinges on adjacent NV structures
Imaging
bullRadiographs bull findings
bull ossification usually easy to visualize bull maturity of HO
bull the appearance of a bony cortex suggests mature HObull sharp demarcation from surrounding tissue bull trabecular pattern
bull sensitivity and specificity bull not useful for early diagnosisbull only useful at 1 week after onset of symptoms
bull calcium is deposited 7-10 days later than symptom onsetbullUltrasound
bull indications bull for early diagnosis of hip HO
bull findings bull echogenic surfaces with posterior acoustic shadowing
bullCT bull indications
bull useful for preoperative planning bullTriphasic bone scan
bull indications bull best for early diagnosis bull most commonly used diagnostic study
Radiographs are extremely useful in the staging of heterotopic ossification and will show the development of sharp cortical margins once the lesion has reached maturity
Heterotopic bone is a condition in which lamellar bone forms in non-ossified soft tissues In the early stages studies such as MRI and bone scan are more sensitive for diagnosis as radiographs may appear normal for the first three weeks After the appropriate diagnosis is made sequential radiographs are useful for monitoring the progression of the ossification Once it has reached the mature stage sharp cortical margins will appear and surgical resection may be considered
lab
Labs elevated serum alkaline phosphatase (gt250IUL)
ALP removes inhibitors of mineralization nonspecific may be elevated with skeletal trauma cannot determine maturity of HO elevated 12wks after surgery is predictor
elevated CRP correlates with inflammatory activity of HO better than ESR normalization of CRP may correlate with maturity of HO
elevated ESR (gt35mmh) 12wks after THA is predictor
elevated CK correlates with involvement of muscle extent of muscle
involvement Histology
mature fatty bone marrow mature trabecular bone
Heterotopic ossification (HO) most commonly occurs at the amputation site if the amputation was performed thru the zone of injury especially if the injury was a blast mechanism
Symptomatic heterotopic ossification of the quadriceps may occur following placement of a large-diameter Steinmann pin for the purpose of temporary skeletal traction
TreatmentThe prevention of heterotopic ossification is focused on three basic principles disrupting the inductive signalling pathways altering the osteoprogenitor cells or modifying the environment
bullphysiotherapy should involve an assisted range of movement exercises with gentle stretch and terminal resistance trainingbullProphylaxis
bull bisphosphonates amp NSAIDS bull indications
bull although no literature supports are commonly usedbull technique
bull indomethacin is most commonly used bull dose is 75mgday for 10days to 6 weeks
bull perioperative radiation bull indications
bull although no literature supports commonly usedbull is thought to be effective by blocking osteoblast differentiation
bull technique bull a single perioperative dose of 700cGy can be given either 4
hours preop or within 72 hours postoperatively bull lt550cGy not effective
Nonsteroidal anti-inflammatory drugs (NSAIDs) These drugs have demonstrated good results in
preventing heterotopic ossification after total hip arthroplasty
A direct effect of NSAIDs on the formation of heterotopic ossification has been described due to the inhibition of the differentiation of mesenchymal cells into oestrogenic cells There is also an indirect effect which refers to the inhibition of bone remodelling by suppression of the prostagland unmediated inflammatory response (specifically PGE-2)
Indomethacin has been considered a useful medication for heterotopic ossification prophylaxis following total hip replacement
prescribed for three to six weeks in a dose of 75mgday within two months of the injury may reduce the incidence of heterotopic ossification by two to three times
Biphosphonates inhibits precipitation of calcium phosphate and blocks the aggregation and mineralisation of hydroxyapatite crystals In primary prevention Banovac et al [56] have suggested that the treatment should begin as soon as elevated alkaline phosphatase is diagnosed or positive findings in ultrasonography or bone scans are shown In addition disphosphonates could have long-term effects on prevention when the treatment is finished
Posttraumatic wide exposure and surgical resection
indications severe loss of motion and decreased function
technique wide exposure required to identify all neurovascular
structures that may be involved timing of resection (controversial)
marked decrease in bone scan activity AND normalization of ALP
6 months following general trauma 1 year following SCI 15 years following TBI
some data suggests equivalent results when comparing early versus late resection
postop follow with 5 day course of indomethacin early gentle joint mobilization
The surgery is necessary in patients with symptomatic HO and unsuccessful medical treatment such as
Loss of range of motion and ankylosis with associated functional disability such as sitting difficulties
Complications of immobility such as pressure ulcers
Facilitate rehabilitation and recovery of muscular atrophy secondary to prolonged immobilisation
Difficulties of appropriate hygiene because access to the perineum or bladder care is needed
Severe pain refractory to analgesia Vascular andor nerve compression
Advantages to early excision of heterotopic ossification (vs waiting for maturation) include decreased soft tissue contracture better definition between heterotopic and native bone and decreased waiting time for the patient When the soft tissue envelope is benign one may proceed with operative release While waiting for normalization of alkaline phosphatase levels inactivity on bone scan or radiographic maturity may decrease risk of recurrent heterotopic ossification delaying operative release for these reasons has not been shown to improve results of final elbow range of motion after contracture release
Gartland recommended surgery after six months following traumatic heterotopic ossification one year following spinal cord injury and 18 months after head injury
In the past waiting until maturity in order to minimize the rate of recurrence after the surgical treatment was recommended Nevertheless recent studies do not confirm a higher rate of recurrence when the HO is excised in an earlier phase In addition a long delay before surgery leads to ankylosis a high degree of osteoporosis and more extensive intra-articular injuries These findings are associated with bad functional results and potential complications
Should you wait till lesion maturation
Prevention byHandle tissue carefully Avoid excess bleeding Achieve good hemostasis Beware of lesions that span internervous tissue planes
but if it happens resection of a large enough amount of bone to allow improvement of the range of motion and trying to preserve the joint
Our aim must be
A reactive process that is characterized by a well-circumscribed proliferation of fibroblasts cartilage and bone within muscle
A form of heterotopic ossification that is the result direct trauma intramuscular hematoma
most common location is the diaphysis of long bones Must differentiate from tumors Fibrodysplasia ossificans progressiva (FOP) is a rare subtype of heterotopic ossification
involves mutation of the ACVR1 gene (activin A type I receptor gene a BMP type-1 receptor)
Epidemiology demographics
most common in young active males (15 to 35 years old) body locations
quadriceps brachialis and gluteal muscles Genetics
almost always a posttraumatic condition Prognosis
usually self limiting mass usually begins to decrease in size after 1 yea
Myositis ossificans
PresentationbullSymptoms
bull pain tenderness swelling and decreased range of motion that usually presents within days of the injury
bull pain and size of the mass decrease with timebull mass increases in size over several months(usually 3 to 6 cm)
bull after the mass stops growing it becomes firmbullPhysical exam
bull palpable soft tissue massbull restricted range of motion
ImagingbullRadiographs
bull peripheral bone formation with central lucent areabull may appear as dotted veil pattern
bullMRI with gadolinium bull rim enhancement is seen within the first 3 weeks
bullCT scan bull lesion has an eggshell appearance
bullCharacteristic histology shows zonal pattern bull periphery of lesion
bull mature trabeculae of lamellar and woven bonebull calcification seen on xray
bull center of the lesion bull irregular mass of immature fibroblastsbull cartilage component may be presentbull (no calcification seen on xray) bull no cellular atypia seen
Treatment
bullNonoperative bull rest range of motion exercises and activity modification
bull passive stretching is contraindicated (makes it worse)bull physical therapy
bull utilized to maintain range of motionbull radiographic monitoring
bull obtained to confirm maturation of the lesionbullOperative
bull surgical excision bull indicated only if it remains a problem after it maturesbull do not operate in acute phase wait at least six months
bull excision of the lesion within 6 to 12 months predisposes to local recurrence
A 26-year-old man presents with generalized back and joint stiffness and difficulty opening his mouth His elder sister has similar complaints Since childhood he has had 3 surgeries for excision of recurrent bony prominences around his knees He walks with a stooped over posture seen in Figure A Radiographs of his feet knee hip and spine are seen in Figures B-E respectively
fibrodysplasia ossificans progressiva
Stone Man Disease) which involves a mutation of the ACVR1
There are 2 hallmark characteristics progressive heterotopic ossification (muscles fascia tendons ligaments and joint capsules) and congenital malformation of the great toe (hallux valgus malformed first metatarsal and monophalangism) BMP4 which contributes to the formation of the skeleton in the normal embryo is implicated in this disease
Complications
bullHematoma and intraoperative bleedingbullInfection
bull higher rate of infection following joint arthroplasty if HO is present
bullFractures of osteoporotic bone bull osteopenic from disusebull during surgery or physiotherapy
bullRecurrence bull recurrence rate correlates with neurological injury
bull greater recurrence if severe neurological compromisebullAVN
bull if extensive dissection or stripping is required
HTO AND ISS
When ISS is below 25 the mortality risk is minimal and above 25 it is an almost linear increase
When ISS is 50 the mortality is 50 When above 70 it is close to 100 If an injury is assigned an AIS of 6 (unsurvivable injury) the ISS score is
automatically assigned to 75 Highest ISS score obtainable is 75 For trauma patients of vehicular accidents the scoring system is important
for assessing the effectiveness of medical care in reducing morbidity and mortality
Advantages virtually the only anatomical scoring system in use correlates linearly with
mortality morbidity hospital stay other measures of severity
Weaknesses Any error in AIS scoring increases the ISS error Many different injury patterns can yield the same ISS score Injuries to different body regions are not weighted Not a useful triage tool as a full description of patient injuries is not known
prior to full investigation amp operation
risk factors periosteal stripping off anterior femur male gender obesity post traumatic deformity Anterior and anterolateral approach Cementless
Neurogenic HO around the hip due to SCI occurs more often in the medial region than in the lateral region with ossified tissues extending from the pubic symphysis to the anteromedial femoral shaft posterior to the femoral neurovascular structures Ossification is also seen anteriorly involving the iliopsoas and femoral neurovascular structures laterally within gluteus minimus and posteriorly extending from the ilium to the posterior femur encasing the sciatic nerve
HTO AROUND hip and knee
The Brooker Classification of Heterotopic Ossification around the hip joint Class I has islands of bone within the soft tissues Class II has bone spurs from the pelvis or proximal end of the femur leaving at least 1 cm between opposing surfaces Class III has bone spurs from the pelvis andor proximal end of the femur reducing the space between opposing bone surfaces to less than 1 cm Class IV shows apparent bone ankylosis of the hip
Region I - Heterotopic ossifications are strictly below the tip of the greater trochanter
Region II - Heterotopic ossifications are below and above the tip of the greater trochanter
Region III - Heterotopic ossifications are strictly above the tip of the greater trochanter
Grade A - Single or multiple heterotopic ossifications are less than 10 mm in maximal extent without contact with the pelvis or the femur
Grade B - Heterotopic ossifications are greater than 10 mm without contact with the pelvis but with possible contact with the femur there is no bridging from the femur to the proximal part of the greater trochanter and no evidence of ankylosis
Grade C - Ankylosis by means of firm bridging from the femur to the pelvis is present
Shmidt classification
excision may be performed The results of this procedure are varied Patients may find that their range of movement improves but pain relief is likely to be limited
A patient with heterotopic ossification following total hip arthroplasty is thought to have a 90-100 chance of developing it on the contralateral hip if this hip also undergoes total arthroplasty
it would be prudent to minimize the risk of heterotopic ossification developing after arthroplasty by performing surgery whereby the following are ensured
Exposure is meticulous Retraction is performed carefully and soft tissue
is handled carefully Irrigation is adequate Devitalized tissue is excised Hemostasis is adequate Postoperative drains (when used) are not
retained for longer than necessary Perioperative antibiotic prophylaxis is used Postoperative anticoagulation (when used for
deep vein thrombosis prophylaxis) is carefully controlled
sources of knee stiffness 1-extrinsic severe osteoarthritis of the ipsilateral hip neurologic injury leading to muscle rigidity tight quadriceps or hamstring muscles secondary to muscle injury heterotopic ossification or long-standing juvenile inflammatory conditions limiting knee
range of motion prior to the completion of skeletal growth When extrinsic sources are identified revision total knee arthroplasty is unlikely to be associated with a favorable outcome without correction of the extrinsic problem
2-intrinsic (1) overstuffing of the patellofemoral articulation (2) an
excessively tight flexion andor extension gap (3) a tight posterior cruciate ligament (4) femoral andor tibial malrotation (5) arthrofibrosis and (6) limited bearing excursion in association with a highly conforming mobile-bearing prosthetic design
HTO after TKA
Heterotopic Ossification (HO) following primary Total Knee Replacement (TKR)
Occurs in 3-90 of TKRs 3-grade classification system No correlation between HO and component
alignment or component position
Clinical findings similar to early infection Continuing low-grade fever Warm swollen and erythematous knee Normal blood tests Possibly an association with HLA-A2 and B18 HO patients have worse KSS and function
scores
Patients at HIGH risk for developing HO after TKR (Knee Arthroplasty) (5)
Those with limited postoperative knee flexion
Increased lumbar bone mineral density (BMD) on multivariate analysis (3)
Hypertrophic arthrosis Excessive periosteal trauma Notching of the anterior femur Those who require forced manipulation
after TKA 47 in revision TKR surgery (6) Higher rates in revision TKR cases with
infection (up to 76
DaughertyBell classification of HO of the knee 0 No evidence of HO 1 Bone islands in periarticular soft tissue (no
involvement of femur patella or tibia) or HO within quadriceps expansion measuring lt1 cm
2 Spur formation measuring lt5 cm that involves the femur patella or tibia if more than one bone demonstrates HO separation of HO spurs
measure gt1 cm or HO within quadriceps expansion measuring ge1 cm but lt3 cm
3 Spur formation gt5 cm involving femur patella or tibia if more than one bone demonstrates HO separation of HO spurs measure lt1 cm or HO
within quadriceps expansion measuring ge3 cm 4 Extensive HO of the knee causing ankylosis
class 2 HO begins to involve the major bones of the knee joint with spur formation limited to a size of 5 cm
HO class 2 may be observed in select patients with complete ROM and no reported pain Patients with class 3 HO would likely always benefit from surgical excision
followed by RT prophylaxis Certainly patients in either cohort with a subclass ldquoBrdquo assignment (symptomatic) would
benefit from treatment All patients with class 4 HO require
treatment to alleviate ankylosis
treatment
References Whyte ldquoPagetrsquos Disease of Bonerdquo NEMJ vol 355
2006 Klein and Parvizi ldquoSurgical Manifestations of Pagetrsquos
Diseaserdquo JAAOS vol 14 2006 Orthobullets Campbell Apley Emedicinecom
-Chapter 15 Heterotopic Ossification after Traumatic Brain InjuryBy Jesuacutes Moreta and Joseacute Luis Martiacutenez-de los Mozos DOI 10577257343
Questions
Thank You
IN SUMMARY It has been postulated that three conditions
must be met to achieve heterotopic bone formation ---a stimulating event oestrogenic precursor cells and a proper environment LIKE hypercalcaemia tissue hypoxia pH changes (alkalosis) or prolonged immobilization
ClassificationbullSubtypes
bull neurogenic HO bull Four clinical stages of HO in people with spinal cord injury were
described by Nicholas in 1973
bull traumatic myositis ossificans bull fibrodysplasia ossificans progressiva (Munchmeyers Disease)
Neurogenic HO Symptoms
painless loss of ROM interferes with ADL CRPS symptoms fever
Physical exam inspection
warm painful swollen joint may have effusion skin problems
decubitus ulcers from contractures around skin muscles ligaments
skin maceration and hygiene problems motion
decreased joint ROM joint ankylosis with HO after TKA might develop quad muscle snapping or patella
instability neurovascular
peripheral neuropathy HO often impinges on adjacent NV structures
Imaging
bullRadiographs bull findings
bull ossification usually easy to visualize bull maturity of HO
bull the appearance of a bony cortex suggests mature HObull sharp demarcation from surrounding tissue bull trabecular pattern
bull sensitivity and specificity bull not useful for early diagnosisbull only useful at 1 week after onset of symptoms
bull calcium is deposited 7-10 days later than symptom onsetbullUltrasound
bull indications bull for early diagnosis of hip HO
bull findings bull echogenic surfaces with posterior acoustic shadowing
bullCT bull indications
bull useful for preoperative planning bullTriphasic bone scan
bull indications bull best for early diagnosis bull most commonly used diagnostic study
Radiographs are extremely useful in the staging of heterotopic ossification and will show the development of sharp cortical margins once the lesion has reached maturity
Heterotopic bone is a condition in which lamellar bone forms in non-ossified soft tissues In the early stages studies such as MRI and bone scan are more sensitive for diagnosis as radiographs may appear normal for the first three weeks After the appropriate diagnosis is made sequential radiographs are useful for monitoring the progression of the ossification Once it has reached the mature stage sharp cortical margins will appear and surgical resection may be considered
lab
Labs elevated serum alkaline phosphatase (gt250IUL)
ALP removes inhibitors of mineralization nonspecific may be elevated with skeletal trauma cannot determine maturity of HO elevated 12wks after surgery is predictor
elevated CRP correlates with inflammatory activity of HO better than ESR normalization of CRP may correlate with maturity of HO
elevated ESR (gt35mmh) 12wks after THA is predictor
elevated CK correlates with involvement of muscle extent of muscle
involvement Histology
mature fatty bone marrow mature trabecular bone
Heterotopic ossification (HO) most commonly occurs at the amputation site if the amputation was performed thru the zone of injury especially if the injury was a blast mechanism
Symptomatic heterotopic ossification of the quadriceps may occur following placement of a large-diameter Steinmann pin for the purpose of temporary skeletal traction
TreatmentThe prevention of heterotopic ossification is focused on three basic principles disrupting the inductive signalling pathways altering the osteoprogenitor cells or modifying the environment
bullphysiotherapy should involve an assisted range of movement exercises with gentle stretch and terminal resistance trainingbullProphylaxis
bull bisphosphonates amp NSAIDS bull indications
bull although no literature supports are commonly usedbull technique
bull indomethacin is most commonly used bull dose is 75mgday for 10days to 6 weeks
bull perioperative radiation bull indications
bull although no literature supports commonly usedbull is thought to be effective by blocking osteoblast differentiation
bull technique bull a single perioperative dose of 700cGy can be given either 4
hours preop or within 72 hours postoperatively bull lt550cGy not effective
Nonsteroidal anti-inflammatory drugs (NSAIDs) These drugs have demonstrated good results in
preventing heterotopic ossification after total hip arthroplasty
A direct effect of NSAIDs on the formation of heterotopic ossification has been described due to the inhibition of the differentiation of mesenchymal cells into oestrogenic cells There is also an indirect effect which refers to the inhibition of bone remodelling by suppression of the prostagland unmediated inflammatory response (specifically PGE-2)
Indomethacin has been considered a useful medication for heterotopic ossification prophylaxis following total hip replacement
prescribed for three to six weeks in a dose of 75mgday within two months of the injury may reduce the incidence of heterotopic ossification by two to three times
Biphosphonates inhibits precipitation of calcium phosphate and blocks the aggregation and mineralisation of hydroxyapatite crystals In primary prevention Banovac et al [56] have suggested that the treatment should begin as soon as elevated alkaline phosphatase is diagnosed or positive findings in ultrasonography or bone scans are shown In addition disphosphonates could have long-term effects on prevention when the treatment is finished
Posttraumatic wide exposure and surgical resection
indications severe loss of motion and decreased function
technique wide exposure required to identify all neurovascular
structures that may be involved timing of resection (controversial)
marked decrease in bone scan activity AND normalization of ALP
6 months following general trauma 1 year following SCI 15 years following TBI
some data suggests equivalent results when comparing early versus late resection
postop follow with 5 day course of indomethacin early gentle joint mobilization
The surgery is necessary in patients with symptomatic HO and unsuccessful medical treatment such as
Loss of range of motion and ankylosis with associated functional disability such as sitting difficulties
Complications of immobility such as pressure ulcers
Facilitate rehabilitation and recovery of muscular atrophy secondary to prolonged immobilisation
Difficulties of appropriate hygiene because access to the perineum or bladder care is needed
Severe pain refractory to analgesia Vascular andor nerve compression
Advantages to early excision of heterotopic ossification (vs waiting for maturation) include decreased soft tissue contracture better definition between heterotopic and native bone and decreased waiting time for the patient When the soft tissue envelope is benign one may proceed with operative release While waiting for normalization of alkaline phosphatase levels inactivity on bone scan or radiographic maturity may decrease risk of recurrent heterotopic ossification delaying operative release for these reasons has not been shown to improve results of final elbow range of motion after contracture release
Gartland recommended surgery after six months following traumatic heterotopic ossification one year following spinal cord injury and 18 months after head injury
In the past waiting until maturity in order to minimize the rate of recurrence after the surgical treatment was recommended Nevertheless recent studies do not confirm a higher rate of recurrence when the HO is excised in an earlier phase In addition a long delay before surgery leads to ankylosis a high degree of osteoporosis and more extensive intra-articular injuries These findings are associated with bad functional results and potential complications
Should you wait till lesion maturation
Prevention byHandle tissue carefully Avoid excess bleeding Achieve good hemostasis Beware of lesions that span internervous tissue planes
but if it happens resection of a large enough amount of bone to allow improvement of the range of motion and trying to preserve the joint
Our aim must be
A reactive process that is characterized by a well-circumscribed proliferation of fibroblasts cartilage and bone within muscle
A form of heterotopic ossification that is the result direct trauma intramuscular hematoma
most common location is the diaphysis of long bones Must differentiate from tumors Fibrodysplasia ossificans progressiva (FOP) is a rare subtype of heterotopic ossification
involves mutation of the ACVR1 gene (activin A type I receptor gene a BMP type-1 receptor)
Epidemiology demographics
most common in young active males (15 to 35 years old) body locations
quadriceps brachialis and gluteal muscles Genetics
almost always a posttraumatic condition Prognosis
usually self limiting mass usually begins to decrease in size after 1 yea
Myositis ossificans
PresentationbullSymptoms
bull pain tenderness swelling and decreased range of motion that usually presents within days of the injury
bull pain and size of the mass decrease with timebull mass increases in size over several months(usually 3 to 6 cm)
bull after the mass stops growing it becomes firmbullPhysical exam
bull palpable soft tissue massbull restricted range of motion
ImagingbullRadiographs
bull peripheral bone formation with central lucent areabull may appear as dotted veil pattern
bullMRI with gadolinium bull rim enhancement is seen within the first 3 weeks
bullCT scan bull lesion has an eggshell appearance
bullCharacteristic histology shows zonal pattern bull periphery of lesion
bull mature trabeculae of lamellar and woven bonebull calcification seen on xray
bull center of the lesion bull irregular mass of immature fibroblastsbull cartilage component may be presentbull (no calcification seen on xray) bull no cellular atypia seen
Treatment
bullNonoperative bull rest range of motion exercises and activity modification
bull passive stretching is contraindicated (makes it worse)bull physical therapy
bull utilized to maintain range of motionbull radiographic monitoring
bull obtained to confirm maturation of the lesionbullOperative
bull surgical excision bull indicated only if it remains a problem after it maturesbull do not operate in acute phase wait at least six months
bull excision of the lesion within 6 to 12 months predisposes to local recurrence
A 26-year-old man presents with generalized back and joint stiffness and difficulty opening his mouth His elder sister has similar complaints Since childhood he has had 3 surgeries for excision of recurrent bony prominences around his knees He walks with a stooped over posture seen in Figure A Radiographs of his feet knee hip and spine are seen in Figures B-E respectively
fibrodysplasia ossificans progressiva
Stone Man Disease) which involves a mutation of the ACVR1
There are 2 hallmark characteristics progressive heterotopic ossification (muscles fascia tendons ligaments and joint capsules) and congenital malformation of the great toe (hallux valgus malformed first metatarsal and monophalangism) BMP4 which contributes to the formation of the skeleton in the normal embryo is implicated in this disease
Complications
bullHematoma and intraoperative bleedingbullInfection
bull higher rate of infection following joint arthroplasty if HO is present
bullFractures of osteoporotic bone bull osteopenic from disusebull during surgery or physiotherapy
bullRecurrence bull recurrence rate correlates with neurological injury
bull greater recurrence if severe neurological compromisebullAVN
bull if extensive dissection or stripping is required
HTO AND ISS
When ISS is below 25 the mortality risk is minimal and above 25 it is an almost linear increase
When ISS is 50 the mortality is 50 When above 70 it is close to 100 If an injury is assigned an AIS of 6 (unsurvivable injury) the ISS score is
automatically assigned to 75 Highest ISS score obtainable is 75 For trauma patients of vehicular accidents the scoring system is important
for assessing the effectiveness of medical care in reducing morbidity and mortality
Advantages virtually the only anatomical scoring system in use correlates linearly with
mortality morbidity hospital stay other measures of severity
Weaknesses Any error in AIS scoring increases the ISS error Many different injury patterns can yield the same ISS score Injuries to different body regions are not weighted Not a useful triage tool as a full description of patient injuries is not known
prior to full investigation amp operation
risk factors periosteal stripping off anterior femur male gender obesity post traumatic deformity Anterior and anterolateral approach Cementless
Neurogenic HO around the hip due to SCI occurs more often in the medial region than in the lateral region with ossified tissues extending from the pubic symphysis to the anteromedial femoral shaft posterior to the femoral neurovascular structures Ossification is also seen anteriorly involving the iliopsoas and femoral neurovascular structures laterally within gluteus minimus and posteriorly extending from the ilium to the posterior femur encasing the sciatic nerve
HTO AROUND hip and knee
The Brooker Classification of Heterotopic Ossification around the hip joint Class I has islands of bone within the soft tissues Class II has bone spurs from the pelvis or proximal end of the femur leaving at least 1 cm between opposing surfaces Class III has bone spurs from the pelvis andor proximal end of the femur reducing the space between opposing bone surfaces to less than 1 cm Class IV shows apparent bone ankylosis of the hip
Region I - Heterotopic ossifications are strictly below the tip of the greater trochanter
Region II - Heterotopic ossifications are below and above the tip of the greater trochanter
Region III - Heterotopic ossifications are strictly above the tip of the greater trochanter
Grade A - Single or multiple heterotopic ossifications are less than 10 mm in maximal extent without contact with the pelvis or the femur
Grade B - Heterotopic ossifications are greater than 10 mm without contact with the pelvis but with possible contact with the femur there is no bridging from the femur to the proximal part of the greater trochanter and no evidence of ankylosis
Grade C - Ankylosis by means of firm bridging from the femur to the pelvis is present
Shmidt classification
excision may be performed The results of this procedure are varied Patients may find that their range of movement improves but pain relief is likely to be limited
A patient with heterotopic ossification following total hip arthroplasty is thought to have a 90-100 chance of developing it on the contralateral hip if this hip also undergoes total arthroplasty
it would be prudent to minimize the risk of heterotopic ossification developing after arthroplasty by performing surgery whereby the following are ensured
Exposure is meticulous Retraction is performed carefully and soft tissue
is handled carefully Irrigation is adequate Devitalized tissue is excised Hemostasis is adequate Postoperative drains (when used) are not
retained for longer than necessary Perioperative antibiotic prophylaxis is used Postoperative anticoagulation (when used for
deep vein thrombosis prophylaxis) is carefully controlled
sources of knee stiffness 1-extrinsic severe osteoarthritis of the ipsilateral hip neurologic injury leading to muscle rigidity tight quadriceps or hamstring muscles secondary to muscle injury heterotopic ossification or long-standing juvenile inflammatory conditions limiting knee
range of motion prior to the completion of skeletal growth When extrinsic sources are identified revision total knee arthroplasty is unlikely to be associated with a favorable outcome without correction of the extrinsic problem
2-intrinsic (1) overstuffing of the patellofemoral articulation (2) an
excessively tight flexion andor extension gap (3) a tight posterior cruciate ligament (4) femoral andor tibial malrotation (5) arthrofibrosis and (6) limited bearing excursion in association with a highly conforming mobile-bearing prosthetic design
HTO after TKA
Heterotopic Ossification (HO) following primary Total Knee Replacement (TKR)
Occurs in 3-90 of TKRs 3-grade classification system No correlation between HO and component
alignment or component position
Clinical findings similar to early infection Continuing low-grade fever Warm swollen and erythematous knee Normal blood tests Possibly an association with HLA-A2 and B18 HO patients have worse KSS and function
scores
Patients at HIGH risk for developing HO after TKR (Knee Arthroplasty) (5)
Those with limited postoperative knee flexion
Increased lumbar bone mineral density (BMD) on multivariate analysis (3)
Hypertrophic arthrosis Excessive periosteal trauma Notching of the anterior femur Those who require forced manipulation
after TKA 47 in revision TKR surgery (6) Higher rates in revision TKR cases with
infection (up to 76
DaughertyBell classification of HO of the knee 0 No evidence of HO 1 Bone islands in periarticular soft tissue (no
involvement of femur patella or tibia) or HO within quadriceps expansion measuring lt1 cm
2 Spur formation measuring lt5 cm that involves the femur patella or tibia if more than one bone demonstrates HO separation of HO spurs
measure gt1 cm or HO within quadriceps expansion measuring ge1 cm but lt3 cm
3 Spur formation gt5 cm involving femur patella or tibia if more than one bone demonstrates HO separation of HO spurs measure lt1 cm or HO
within quadriceps expansion measuring ge3 cm 4 Extensive HO of the knee causing ankylosis
class 2 HO begins to involve the major bones of the knee joint with spur formation limited to a size of 5 cm
HO class 2 may be observed in select patients with complete ROM and no reported pain Patients with class 3 HO would likely always benefit from surgical excision
followed by RT prophylaxis Certainly patients in either cohort with a subclass ldquoBrdquo assignment (symptomatic) would
benefit from treatment All patients with class 4 HO require
treatment to alleviate ankylosis
treatment
References Whyte ldquoPagetrsquos Disease of Bonerdquo NEMJ vol 355
2006 Klein and Parvizi ldquoSurgical Manifestations of Pagetrsquos
Diseaserdquo JAAOS vol 14 2006 Orthobullets Campbell Apley Emedicinecom
-Chapter 15 Heterotopic Ossification after Traumatic Brain InjuryBy Jesuacutes Moreta and Joseacute Luis Martiacutenez-de los Mozos DOI 10577257343
Questions
Thank You
ClassificationbullSubtypes
bull neurogenic HO bull Four clinical stages of HO in people with spinal cord injury were
described by Nicholas in 1973
bull traumatic myositis ossificans bull fibrodysplasia ossificans progressiva (Munchmeyers Disease)
Neurogenic HO Symptoms
painless loss of ROM interferes with ADL CRPS symptoms fever
Physical exam inspection
warm painful swollen joint may have effusion skin problems
decubitus ulcers from contractures around skin muscles ligaments
skin maceration and hygiene problems motion
decreased joint ROM joint ankylosis with HO after TKA might develop quad muscle snapping or patella
instability neurovascular
peripheral neuropathy HO often impinges on adjacent NV structures
Imaging
bullRadiographs bull findings
bull ossification usually easy to visualize bull maturity of HO
bull the appearance of a bony cortex suggests mature HObull sharp demarcation from surrounding tissue bull trabecular pattern
bull sensitivity and specificity bull not useful for early diagnosisbull only useful at 1 week after onset of symptoms
bull calcium is deposited 7-10 days later than symptom onsetbullUltrasound
bull indications bull for early diagnosis of hip HO
bull findings bull echogenic surfaces with posterior acoustic shadowing
bullCT bull indications
bull useful for preoperative planning bullTriphasic bone scan
bull indications bull best for early diagnosis bull most commonly used diagnostic study
Radiographs are extremely useful in the staging of heterotopic ossification and will show the development of sharp cortical margins once the lesion has reached maturity
Heterotopic bone is a condition in which lamellar bone forms in non-ossified soft tissues In the early stages studies such as MRI and bone scan are more sensitive for diagnosis as radiographs may appear normal for the first three weeks After the appropriate diagnosis is made sequential radiographs are useful for monitoring the progression of the ossification Once it has reached the mature stage sharp cortical margins will appear and surgical resection may be considered
lab
Labs elevated serum alkaline phosphatase (gt250IUL)
ALP removes inhibitors of mineralization nonspecific may be elevated with skeletal trauma cannot determine maturity of HO elevated 12wks after surgery is predictor
elevated CRP correlates with inflammatory activity of HO better than ESR normalization of CRP may correlate with maturity of HO
elevated ESR (gt35mmh) 12wks after THA is predictor
elevated CK correlates with involvement of muscle extent of muscle
involvement Histology
mature fatty bone marrow mature trabecular bone
Heterotopic ossification (HO) most commonly occurs at the amputation site if the amputation was performed thru the zone of injury especially if the injury was a blast mechanism
Symptomatic heterotopic ossification of the quadriceps may occur following placement of a large-diameter Steinmann pin for the purpose of temporary skeletal traction
TreatmentThe prevention of heterotopic ossification is focused on three basic principles disrupting the inductive signalling pathways altering the osteoprogenitor cells or modifying the environment
bullphysiotherapy should involve an assisted range of movement exercises with gentle stretch and terminal resistance trainingbullProphylaxis
bull bisphosphonates amp NSAIDS bull indications
bull although no literature supports are commonly usedbull technique
bull indomethacin is most commonly used bull dose is 75mgday for 10days to 6 weeks
bull perioperative radiation bull indications
bull although no literature supports commonly usedbull is thought to be effective by blocking osteoblast differentiation
bull technique bull a single perioperative dose of 700cGy can be given either 4
hours preop or within 72 hours postoperatively bull lt550cGy not effective
Nonsteroidal anti-inflammatory drugs (NSAIDs) These drugs have demonstrated good results in
preventing heterotopic ossification after total hip arthroplasty
A direct effect of NSAIDs on the formation of heterotopic ossification has been described due to the inhibition of the differentiation of mesenchymal cells into oestrogenic cells There is also an indirect effect which refers to the inhibition of bone remodelling by suppression of the prostagland unmediated inflammatory response (specifically PGE-2)
Indomethacin has been considered a useful medication for heterotopic ossification prophylaxis following total hip replacement
prescribed for three to six weeks in a dose of 75mgday within two months of the injury may reduce the incidence of heterotopic ossification by two to three times
Biphosphonates inhibits precipitation of calcium phosphate and blocks the aggregation and mineralisation of hydroxyapatite crystals In primary prevention Banovac et al [56] have suggested that the treatment should begin as soon as elevated alkaline phosphatase is diagnosed or positive findings in ultrasonography or bone scans are shown In addition disphosphonates could have long-term effects on prevention when the treatment is finished
Posttraumatic wide exposure and surgical resection
indications severe loss of motion and decreased function
technique wide exposure required to identify all neurovascular
structures that may be involved timing of resection (controversial)
marked decrease in bone scan activity AND normalization of ALP
6 months following general trauma 1 year following SCI 15 years following TBI
some data suggests equivalent results when comparing early versus late resection
postop follow with 5 day course of indomethacin early gentle joint mobilization
The surgery is necessary in patients with symptomatic HO and unsuccessful medical treatment such as
Loss of range of motion and ankylosis with associated functional disability such as sitting difficulties
Complications of immobility such as pressure ulcers
Facilitate rehabilitation and recovery of muscular atrophy secondary to prolonged immobilisation
Difficulties of appropriate hygiene because access to the perineum or bladder care is needed
Severe pain refractory to analgesia Vascular andor nerve compression
Advantages to early excision of heterotopic ossification (vs waiting for maturation) include decreased soft tissue contracture better definition between heterotopic and native bone and decreased waiting time for the patient When the soft tissue envelope is benign one may proceed with operative release While waiting for normalization of alkaline phosphatase levels inactivity on bone scan or radiographic maturity may decrease risk of recurrent heterotopic ossification delaying operative release for these reasons has not been shown to improve results of final elbow range of motion after contracture release
Gartland recommended surgery after six months following traumatic heterotopic ossification one year following spinal cord injury and 18 months after head injury
In the past waiting until maturity in order to minimize the rate of recurrence after the surgical treatment was recommended Nevertheless recent studies do not confirm a higher rate of recurrence when the HO is excised in an earlier phase In addition a long delay before surgery leads to ankylosis a high degree of osteoporosis and more extensive intra-articular injuries These findings are associated with bad functional results and potential complications
Should you wait till lesion maturation
Prevention byHandle tissue carefully Avoid excess bleeding Achieve good hemostasis Beware of lesions that span internervous tissue planes
but if it happens resection of a large enough amount of bone to allow improvement of the range of motion and trying to preserve the joint
Our aim must be
A reactive process that is characterized by a well-circumscribed proliferation of fibroblasts cartilage and bone within muscle
A form of heterotopic ossification that is the result direct trauma intramuscular hematoma
most common location is the diaphysis of long bones Must differentiate from tumors Fibrodysplasia ossificans progressiva (FOP) is a rare subtype of heterotopic ossification
involves mutation of the ACVR1 gene (activin A type I receptor gene a BMP type-1 receptor)
Epidemiology demographics
most common in young active males (15 to 35 years old) body locations
quadriceps brachialis and gluteal muscles Genetics
almost always a posttraumatic condition Prognosis
usually self limiting mass usually begins to decrease in size after 1 yea
Myositis ossificans
PresentationbullSymptoms
bull pain tenderness swelling and decreased range of motion that usually presents within days of the injury
bull pain and size of the mass decrease with timebull mass increases in size over several months(usually 3 to 6 cm)
bull after the mass stops growing it becomes firmbullPhysical exam
bull palpable soft tissue massbull restricted range of motion
ImagingbullRadiographs
bull peripheral bone formation with central lucent areabull may appear as dotted veil pattern
bullMRI with gadolinium bull rim enhancement is seen within the first 3 weeks
bullCT scan bull lesion has an eggshell appearance
bullCharacteristic histology shows zonal pattern bull periphery of lesion
bull mature trabeculae of lamellar and woven bonebull calcification seen on xray
bull center of the lesion bull irregular mass of immature fibroblastsbull cartilage component may be presentbull (no calcification seen on xray) bull no cellular atypia seen
Treatment
bullNonoperative bull rest range of motion exercises and activity modification
bull passive stretching is contraindicated (makes it worse)bull physical therapy
bull utilized to maintain range of motionbull radiographic monitoring
bull obtained to confirm maturation of the lesionbullOperative
bull surgical excision bull indicated only if it remains a problem after it maturesbull do not operate in acute phase wait at least six months
bull excision of the lesion within 6 to 12 months predisposes to local recurrence
A 26-year-old man presents with generalized back and joint stiffness and difficulty opening his mouth His elder sister has similar complaints Since childhood he has had 3 surgeries for excision of recurrent bony prominences around his knees He walks with a stooped over posture seen in Figure A Radiographs of his feet knee hip and spine are seen in Figures B-E respectively
fibrodysplasia ossificans progressiva
Stone Man Disease) which involves a mutation of the ACVR1
There are 2 hallmark characteristics progressive heterotopic ossification (muscles fascia tendons ligaments and joint capsules) and congenital malformation of the great toe (hallux valgus malformed first metatarsal and monophalangism) BMP4 which contributes to the formation of the skeleton in the normal embryo is implicated in this disease
Complications
bullHematoma and intraoperative bleedingbullInfection
bull higher rate of infection following joint arthroplasty if HO is present
bullFractures of osteoporotic bone bull osteopenic from disusebull during surgery or physiotherapy
bullRecurrence bull recurrence rate correlates with neurological injury
bull greater recurrence if severe neurological compromisebullAVN
bull if extensive dissection or stripping is required
HTO AND ISS
When ISS is below 25 the mortality risk is minimal and above 25 it is an almost linear increase
When ISS is 50 the mortality is 50 When above 70 it is close to 100 If an injury is assigned an AIS of 6 (unsurvivable injury) the ISS score is
automatically assigned to 75 Highest ISS score obtainable is 75 For trauma patients of vehicular accidents the scoring system is important
for assessing the effectiveness of medical care in reducing morbidity and mortality
Advantages virtually the only anatomical scoring system in use correlates linearly with
mortality morbidity hospital stay other measures of severity
Weaknesses Any error in AIS scoring increases the ISS error Many different injury patterns can yield the same ISS score Injuries to different body regions are not weighted Not a useful triage tool as a full description of patient injuries is not known
prior to full investigation amp operation
risk factors periosteal stripping off anterior femur male gender obesity post traumatic deformity Anterior and anterolateral approach Cementless
Neurogenic HO around the hip due to SCI occurs more often in the medial region than in the lateral region with ossified tissues extending from the pubic symphysis to the anteromedial femoral shaft posterior to the femoral neurovascular structures Ossification is also seen anteriorly involving the iliopsoas and femoral neurovascular structures laterally within gluteus minimus and posteriorly extending from the ilium to the posterior femur encasing the sciatic nerve
HTO AROUND hip and knee
The Brooker Classification of Heterotopic Ossification around the hip joint Class I has islands of bone within the soft tissues Class II has bone spurs from the pelvis or proximal end of the femur leaving at least 1 cm between opposing surfaces Class III has bone spurs from the pelvis andor proximal end of the femur reducing the space between opposing bone surfaces to less than 1 cm Class IV shows apparent bone ankylosis of the hip
Region I - Heterotopic ossifications are strictly below the tip of the greater trochanter
Region II - Heterotopic ossifications are below and above the tip of the greater trochanter
Region III - Heterotopic ossifications are strictly above the tip of the greater trochanter
Grade A - Single or multiple heterotopic ossifications are less than 10 mm in maximal extent without contact with the pelvis or the femur
Grade B - Heterotopic ossifications are greater than 10 mm without contact with the pelvis but with possible contact with the femur there is no bridging from the femur to the proximal part of the greater trochanter and no evidence of ankylosis
Grade C - Ankylosis by means of firm bridging from the femur to the pelvis is present
Shmidt classification
excision may be performed The results of this procedure are varied Patients may find that their range of movement improves but pain relief is likely to be limited
A patient with heterotopic ossification following total hip arthroplasty is thought to have a 90-100 chance of developing it on the contralateral hip if this hip also undergoes total arthroplasty
it would be prudent to minimize the risk of heterotopic ossification developing after arthroplasty by performing surgery whereby the following are ensured
Exposure is meticulous Retraction is performed carefully and soft tissue
is handled carefully Irrigation is adequate Devitalized tissue is excised Hemostasis is adequate Postoperative drains (when used) are not
retained for longer than necessary Perioperative antibiotic prophylaxis is used Postoperative anticoagulation (when used for
deep vein thrombosis prophylaxis) is carefully controlled
sources of knee stiffness 1-extrinsic severe osteoarthritis of the ipsilateral hip neurologic injury leading to muscle rigidity tight quadriceps or hamstring muscles secondary to muscle injury heterotopic ossification or long-standing juvenile inflammatory conditions limiting knee
range of motion prior to the completion of skeletal growth When extrinsic sources are identified revision total knee arthroplasty is unlikely to be associated with a favorable outcome without correction of the extrinsic problem
2-intrinsic (1) overstuffing of the patellofemoral articulation (2) an
excessively tight flexion andor extension gap (3) a tight posterior cruciate ligament (4) femoral andor tibial malrotation (5) arthrofibrosis and (6) limited bearing excursion in association with a highly conforming mobile-bearing prosthetic design
HTO after TKA
Heterotopic Ossification (HO) following primary Total Knee Replacement (TKR)
Occurs in 3-90 of TKRs 3-grade classification system No correlation between HO and component
alignment or component position
Clinical findings similar to early infection Continuing low-grade fever Warm swollen and erythematous knee Normal blood tests Possibly an association with HLA-A2 and B18 HO patients have worse KSS and function
scores
Patients at HIGH risk for developing HO after TKR (Knee Arthroplasty) (5)
Those with limited postoperative knee flexion
Increased lumbar bone mineral density (BMD) on multivariate analysis (3)
Hypertrophic arthrosis Excessive periosteal trauma Notching of the anterior femur Those who require forced manipulation
after TKA 47 in revision TKR surgery (6) Higher rates in revision TKR cases with
infection (up to 76
DaughertyBell classification of HO of the knee 0 No evidence of HO 1 Bone islands in periarticular soft tissue (no
involvement of femur patella or tibia) or HO within quadriceps expansion measuring lt1 cm
2 Spur formation measuring lt5 cm that involves the femur patella or tibia if more than one bone demonstrates HO separation of HO spurs
measure gt1 cm or HO within quadriceps expansion measuring ge1 cm but lt3 cm
3 Spur formation gt5 cm involving femur patella or tibia if more than one bone demonstrates HO separation of HO spurs measure lt1 cm or HO
within quadriceps expansion measuring ge3 cm 4 Extensive HO of the knee causing ankylosis
class 2 HO begins to involve the major bones of the knee joint with spur formation limited to a size of 5 cm
HO class 2 may be observed in select patients with complete ROM and no reported pain Patients with class 3 HO would likely always benefit from surgical excision
followed by RT prophylaxis Certainly patients in either cohort with a subclass ldquoBrdquo assignment (symptomatic) would
benefit from treatment All patients with class 4 HO require
treatment to alleviate ankylosis
treatment
References Whyte ldquoPagetrsquos Disease of Bonerdquo NEMJ vol 355
2006 Klein and Parvizi ldquoSurgical Manifestations of Pagetrsquos
Diseaserdquo JAAOS vol 14 2006 Orthobullets Campbell Apley Emedicinecom
-Chapter 15 Heterotopic Ossification after Traumatic Brain InjuryBy Jesuacutes Moreta and Joseacute Luis Martiacutenez-de los Mozos DOI 10577257343
Questions
Thank You
Neurogenic HO Symptoms
painless loss of ROM interferes with ADL CRPS symptoms fever
Physical exam inspection
warm painful swollen joint may have effusion skin problems
decubitus ulcers from contractures around skin muscles ligaments
skin maceration and hygiene problems motion
decreased joint ROM joint ankylosis with HO after TKA might develop quad muscle snapping or patella
instability neurovascular
peripheral neuropathy HO often impinges on adjacent NV structures
Imaging
bullRadiographs bull findings
bull ossification usually easy to visualize bull maturity of HO
bull the appearance of a bony cortex suggests mature HObull sharp demarcation from surrounding tissue bull trabecular pattern
bull sensitivity and specificity bull not useful for early diagnosisbull only useful at 1 week after onset of symptoms
bull calcium is deposited 7-10 days later than symptom onsetbullUltrasound
bull indications bull for early diagnosis of hip HO
bull findings bull echogenic surfaces with posterior acoustic shadowing
bullCT bull indications
bull useful for preoperative planning bullTriphasic bone scan
bull indications bull best for early diagnosis bull most commonly used diagnostic study
Radiographs are extremely useful in the staging of heterotopic ossification and will show the development of sharp cortical margins once the lesion has reached maturity
Heterotopic bone is a condition in which lamellar bone forms in non-ossified soft tissues In the early stages studies such as MRI and bone scan are more sensitive for diagnosis as radiographs may appear normal for the first three weeks After the appropriate diagnosis is made sequential radiographs are useful for monitoring the progression of the ossification Once it has reached the mature stage sharp cortical margins will appear and surgical resection may be considered
lab
Labs elevated serum alkaline phosphatase (gt250IUL)
ALP removes inhibitors of mineralization nonspecific may be elevated with skeletal trauma cannot determine maturity of HO elevated 12wks after surgery is predictor
elevated CRP correlates with inflammatory activity of HO better than ESR normalization of CRP may correlate with maturity of HO
elevated ESR (gt35mmh) 12wks after THA is predictor
elevated CK correlates with involvement of muscle extent of muscle
involvement Histology
mature fatty bone marrow mature trabecular bone
Heterotopic ossification (HO) most commonly occurs at the amputation site if the amputation was performed thru the zone of injury especially if the injury was a blast mechanism
Symptomatic heterotopic ossification of the quadriceps may occur following placement of a large-diameter Steinmann pin for the purpose of temporary skeletal traction
TreatmentThe prevention of heterotopic ossification is focused on three basic principles disrupting the inductive signalling pathways altering the osteoprogenitor cells or modifying the environment
bullphysiotherapy should involve an assisted range of movement exercises with gentle stretch and terminal resistance trainingbullProphylaxis
bull bisphosphonates amp NSAIDS bull indications
bull although no literature supports are commonly usedbull technique
bull indomethacin is most commonly used bull dose is 75mgday for 10days to 6 weeks
bull perioperative radiation bull indications
bull although no literature supports commonly usedbull is thought to be effective by blocking osteoblast differentiation
bull technique bull a single perioperative dose of 700cGy can be given either 4
hours preop or within 72 hours postoperatively bull lt550cGy not effective
Nonsteroidal anti-inflammatory drugs (NSAIDs) These drugs have demonstrated good results in
preventing heterotopic ossification after total hip arthroplasty
A direct effect of NSAIDs on the formation of heterotopic ossification has been described due to the inhibition of the differentiation of mesenchymal cells into oestrogenic cells There is also an indirect effect which refers to the inhibition of bone remodelling by suppression of the prostagland unmediated inflammatory response (specifically PGE-2)
Indomethacin has been considered a useful medication for heterotopic ossification prophylaxis following total hip replacement
prescribed for three to six weeks in a dose of 75mgday within two months of the injury may reduce the incidence of heterotopic ossification by two to three times
Biphosphonates inhibits precipitation of calcium phosphate and blocks the aggregation and mineralisation of hydroxyapatite crystals In primary prevention Banovac et al [56] have suggested that the treatment should begin as soon as elevated alkaline phosphatase is diagnosed or positive findings in ultrasonography or bone scans are shown In addition disphosphonates could have long-term effects on prevention when the treatment is finished
Posttraumatic wide exposure and surgical resection
indications severe loss of motion and decreased function
technique wide exposure required to identify all neurovascular
structures that may be involved timing of resection (controversial)
marked decrease in bone scan activity AND normalization of ALP
6 months following general trauma 1 year following SCI 15 years following TBI
some data suggests equivalent results when comparing early versus late resection
postop follow with 5 day course of indomethacin early gentle joint mobilization
The surgery is necessary in patients with symptomatic HO and unsuccessful medical treatment such as
Loss of range of motion and ankylosis with associated functional disability such as sitting difficulties
Complications of immobility such as pressure ulcers
Facilitate rehabilitation and recovery of muscular atrophy secondary to prolonged immobilisation
Difficulties of appropriate hygiene because access to the perineum or bladder care is needed
Severe pain refractory to analgesia Vascular andor nerve compression
Advantages to early excision of heterotopic ossification (vs waiting for maturation) include decreased soft tissue contracture better definition between heterotopic and native bone and decreased waiting time for the patient When the soft tissue envelope is benign one may proceed with operative release While waiting for normalization of alkaline phosphatase levels inactivity on bone scan or radiographic maturity may decrease risk of recurrent heterotopic ossification delaying operative release for these reasons has not been shown to improve results of final elbow range of motion after contracture release
Gartland recommended surgery after six months following traumatic heterotopic ossification one year following spinal cord injury and 18 months after head injury
In the past waiting until maturity in order to minimize the rate of recurrence after the surgical treatment was recommended Nevertheless recent studies do not confirm a higher rate of recurrence when the HO is excised in an earlier phase In addition a long delay before surgery leads to ankylosis a high degree of osteoporosis and more extensive intra-articular injuries These findings are associated with bad functional results and potential complications
Should you wait till lesion maturation
Prevention byHandle tissue carefully Avoid excess bleeding Achieve good hemostasis Beware of lesions that span internervous tissue planes
but if it happens resection of a large enough amount of bone to allow improvement of the range of motion and trying to preserve the joint
Our aim must be
A reactive process that is characterized by a well-circumscribed proliferation of fibroblasts cartilage and bone within muscle
A form of heterotopic ossification that is the result direct trauma intramuscular hematoma
most common location is the diaphysis of long bones Must differentiate from tumors Fibrodysplasia ossificans progressiva (FOP) is a rare subtype of heterotopic ossification
involves mutation of the ACVR1 gene (activin A type I receptor gene a BMP type-1 receptor)
Epidemiology demographics
most common in young active males (15 to 35 years old) body locations
quadriceps brachialis and gluteal muscles Genetics
almost always a posttraumatic condition Prognosis
usually self limiting mass usually begins to decrease in size after 1 yea
Myositis ossificans
PresentationbullSymptoms
bull pain tenderness swelling and decreased range of motion that usually presents within days of the injury
bull pain and size of the mass decrease with timebull mass increases in size over several months(usually 3 to 6 cm)
bull after the mass stops growing it becomes firmbullPhysical exam
bull palpable soft tissue massbull restricted range of motion
ImagingbullRadiographs
bull peripheral bone formation with central lucent areabull may appear as dotted veil pattern
bullMRI with gadolinium bull rim enhancement is seen within the first 3 weeks
bullCT scan bull lesion has an eggshell appearance
bullCharacteristic histology shows zonal pattern bull periphery of lesion
bull mature trabeculae of lamellar and woven bonebull calcification seen on xray
bull center of the lesion bull irregular mass of immature fibroblastsbull cartilage component may be presentbull (no calcification seen on xray) bull no cellular atypia seen
Treatment
bullNonoperative bull rest range of motion exercises and activity modification
bull passive stretching is contraindicated (makes it worse)bull physical therapy
bull utilized to maintain range of motionbull radiographic monitoring
bull obtained to confirm maturation of the lesionbullOperative
bull surgical excision bull indicated only if it remains a problem after it maturesbull do not operate in acute phase wait at least six months
bull excision of the lesion within 6 to 12 months predisposes to local recurrence
A 26-year-old man presents with generalized back and joint stiffness and difficulty opening his mouth His elder sister has similar complaints Since childhood he has had 3 surgeries for excision of recurrent bony prominences around his knees He walks with a stooped over posture seen in Figure A Radiographs of his feet knee hip and spine are seen in Figures B-E respectively
fibrodysplasia ossificans progressiva
Stone Man Disease) which involves a mutation of the ACVR1
There are 2 hallmark characteristics progressive heterotopic ossification (muscles fascia tendons ligaments and joint capsules) and congenital malformation of the great toe (hallux valgus malformed first metatarsal and monophalangism) BMP4 which contributes to the formation of the skeleton in the normal embryo is implicated in this disease
Complications
bullHematoma and intraoperative bleedingbullInfection
bull higher rate of infection following joint arthroplasty if HO is present
bullFractures of osteoporotic bone bull osteopenic from disusebull during surgery or physiotherapy
bullRecurrence bull recurrence rate correlates with neurological injury
bull greater recurrence if severe neurological compromisebullAVN
bull if extensive dissection or stripping is required
HTO AND ISS
When ISS is below 25 the mortality risk is minimal and above 25 it is an almost linear increase
When ISS is 50 the mortality is 50 When above 70 it is close to 100 If an injury is assigned an AIS of 6 (unsurvivable injury) the ISS score is
automatically assigned to 75 Highest ISS score obtainable is 75 For trauma patients of vehicular accidents the scoring system is important
for assessing the effectiveness of medical care in reducing morbidity and mortality
Advantages virtually the only anatomical scoring system in use correlates linearly with
mortality morbidity hospital stay other measures of severity
Weaknesses Any error in AIS scoring increases the ISS error Many different injury patterns can yield the same ISS score Injuries to different body regions are not weighted Not a useful triage tool as a full description of patient injuries is not known
prior to full investigation amp operation
risk factors periosteal stripping off anterior femur male gender obesity post traumatic deformity Anterior and anterolateral approach Cementless
Neurogenic HO around the hip due to SCI occurs more often in the medial region than in the lateral region with ossified tissues extending from the pubic symphysis to the anteromedial femoral shaft posterior to the femoral neurovascular structures Ossification is also seen anteriorly involving the iliopsoas and femoral neurovascular structures laterally within gluteus minimus and posteriorly extending from the ilium to the posterior femur encasing the sciatic nerve
HTO AROUND hip and knee
The Brooker Classification of Heterotopic Ossification around the hip joint Class I has islands of bone within the soft tissues Class II has bone spurs from the pelvis or proximal end of the femur leaving at least 1 cm between opposing surfaces Class III has bone spurs from the pelvis andor proximal end of the femur reducing the space between opposing bone surfaces to less than 1 cm Class IV shows apparent bone ankylosis of the hip
Region I - Heterotopic ossifications are strictly below the tip of the greater trochanter
Region II - Heterotopic ossifications are below and above the tip of the greater trochanter
Region III - Heterotopic ossifications are strictly above the tip of the greater trochanter
Grade A - Single or multiple heterotopic ossifications are less than 10 mm in maximal extent without contact with the pelvis or the femur
Grade B - Heterotopic ossifications are greater than 10 mm without contact with the pelvis but with possible contact with the femur there is no bridging from the femur to the proximal part of the greater trochanter and no evidence of ankylosis
Grade C - Ankylosis by means of firm bridging from the femur to the pelvis is present
Shmidt classification
excision may be performed The results of this procedure are varied Patients may find that their range of movement improves but pain relief is likely to be limited
A patient with heterotopic ossification following total hip arthroplasty is thought to have a 90-100 chance of developing it on the contralateral hip if this hip also undergoes total arthroplasty
it would be prudent to minimize the risk of heterotopic ossification developing after arthroplasty by performing surgery whereby the following are ensured
Exposure is meticulous Retraction is performed carefully and soft tissue
is handled carefully Irrigation is adequate Devitalized tissue is excised Hemostasis is adequate Postoperative drains (when used) are not
retained for longer than necessary Perioperative antibiotic prophylaxis is used Postoperative anticoagulation (when used for
deep vein thrombosis prophylaxis) is carefully controlled
sources of knee stiffness 1-extrinsic severe osteoarthritis of the ipsilateral hip neurologic injury leading to muscle rigidity tight quadriceps or hamstring muscles secondary to muscle injury heterotopic ossification or long-standing juvenile inflammatory conditions limiting knee
range of motion prior to the completion of skeletal growth When extrinsic sources are identified revision total knee arthroplasty is unlikely to be associated with a favorable outcome without correction of the extrinsic problem
2-intrinsic (1) overstuffing of the patellofemoral articulation (2) an
excessively tight flexion andor extension gap (3) a tight posterior cruciate ligament (4) femoral andor tibial malrotation (5) arthrofibrosis and (6) limited bearing excursion in association with a highly conforming mobile-bearing prosthetic design
HTO after TKA
Heterotopic Ossification (HO) following primary Total Knee Replacement (TKR)
Occurs in 3-90 of TKRs 3-grade classification system No correlation between HO and component
alignment or component position
Clinical findings similar to early infection Continuing low-grade fever Warm swollen and erythematous knee Normal blood tests Possibly an association with HLA-A2 and B18 HO patients have worse KSS and function
scores
Patients at HIGH risk for developing HO after TKR (Knee Arthroplasty) (5)
Those with limited postoperative knee flexion
Increased lumbar bone mineral density (BMD) on multivariate analysis (3)
Hypertrophic arthrosis Excessive periosteal trauma Notching of the anterior femur Those who require forced manipulation
after TKA 47 in revision TKR surgery (6) Higher rates in revision TKR cases with
infection (up to 76
DaughertyBell classification of HO of the knee 0 No evidence of HO 1 Bone islands in periarticular soft tissue (no
involvement of femur patella or tibia) or HO within quadriceps expansion measuring lt1 cm
2 Spur formation measuring lt5 cm that involves the femur patella or tibia if more than one bone demonstrates HO separation of HO spurs
measure gt1 cm or HO within quadriceps expansion measuring ge1 cm but lt3 cm
3 Spur formation gt5 cm involving femur patella or tibia if more than one bone demonstrates HO separation of HO spurs measure lt1 cm or HO
within quadriceps expansion measuring ge3 cm 4 Extensive HO of the knee causing ankylosis
class 2 HO begins to involve the major bones of the knee joint with spur formation limited to a size of 5 cm
HO class 2 may be observed in select patients with complete ROM and no reported pain Patients with class 3 HO would likely always benefit from surgical excision
followed by RT prophylaxis Certainly patients in either cohort with a subclass ldquoBrdquo assignment (symptomatic) would
benefit from treatment All patients with class 4 HO require
treatment to alleviate ankylosis
treatment
References Whyte ldquoPagetrsquos Disease of Bonerdquo NEMJ vol 355
2006 Klein and Parvizi ldquoSurgical Manifestations of Pagetrsquos
Diseaserdquo JAAOS vol 14 2006 Orthobullets Campbell Apley Emedicinecom
-Chapter 15 Heterotopic Ossification after Traumatic Brain InjuryBy Jesuacutes Moreta and Joseacute Luis Martiacutenez-de los Mozos DOI 10577257343
Questions
Thank You
Imaging
bullRadiographs bull findings
bull ossification usually easy to visualize bull maturity of HO
bull the appearance of a bony cortex suggests mature HObull sharp demarcation from surrounding tissue bull trabecular pattern
bull sensitivity and specificity bull not useful for early diagnosisbull only useful at 1 week after onset of symptoms
bull calcium is deposited 7-10 days later than symptom onsetbullUltrasound
bull indications bull for early diagnosis of hip HO
bull findings bull echogenic surfaces with posterior acoustic shadowing
bullCT bull indications
bull useful for preoperative planning bullTriphasic bone scan
bull indications bull best for early diagnosis bull most commonly used diagnostic study
Radiographs are extremely useful in the staging of heterotopic ossification and will show the development of sharp cortical margins once the lesion has reached maturity
Heterotopic bone is a condition in which lamellar bone forms in non-ossified soft tissues In the early stages studies such as MRI and bone scan are more sensitive for diagnosis as radiographs may appear normal for the first three weeks After the appropriate diagnosis is made sequential radiographs are useful for monitoring the progression of the ossification Once it has reached the mature stage sharp cortical margins will appear and surgical resection may be considered
lab
Labs elevated serum alkaline phosphatase (gt250IUL)
ALP removes inhibitors of mineralization nonspecific may be elevated with skeletal trauma cannot determine maturity of HO elevated 12wks after surgery is predictor
elevated CRP correlates with inflammatory activity of HO better than ESR normalization of CRP may correlate with maturity of HO
elevated ESR (gt35mmh) 12wks after THA is predictor
elevated CK correlates with involvement of muscle extent of muscle
involvement Histology
mature fatty bone marrow mature trabecular bone
Heterotopic ossification (HO) most commonly occurs at the amputation site if the amputation was performed thru the zone of injury especially if the injury was a blast mechanism
Symptomatic heterotopic ossification of the quadriceps may occur following placement of a large-diameter Steinmann pin for the purpose of temporary skeletal traction
TreatmentThe prevention of heterotopic ossification is focused on three basic principles disrupting the inductive signalling pathways altering the osteoprogenitor cells or modifying the environment
bullphysiotherapy should involve an assisted range of movement exercises with gentle stretch and terminal resistance trainingbullProphylaxis
bull bisphosphonates amp NSAIDS bull indications
bull although no literature supports are commonly usedbull technique
bull indomethacin is most commonly used bull dose is 75mgday for 10days to 6 weeks
bull perioperative radiation bull indications
bull although no literature supports commonly usedbull is thought to be effective by blocking osteoblast differentiation
bull technique bull a single perioperative dose of 700cGy can be given either 4
hours preop or within 72 hours postoperatively bull lt550cGy not effective
Nonsteroidal anti-inflammatory drugs (NSAIDs) These drugs have demonstrated good results in
preventing heterotopic ossification after total hip arthroplasty
A direct effect of NSAIDs on the formation of heterotopic ossification has been described due to the inhibition of the differentiation of mesenchymal cells into oestrogenic cells There is also an indirect effect which refers to the inhibition of bone remodelling by suppression of the prostagland unmediated inflammatory response (specifically PGE-2)
Indomethacin has been considered a useful medication for heterotopic ossification prophylaxis following total hip replacement
prescribed for three to six weeks in a dose of 75mgday within two months of the injury may reduce the incidence of heterotopic ossification by two to three times
Biphosphonates inhibits precipitation of calcium phosphate and blocks the aggregation and mineralisation of hydroxyapatite crystals In primary prevention Banovac et al [56] have suggested that the treatment should begin as soon as elevated alkaline phosphatase is diagnosed or positive findings in ultrasonography or bone scans are shown In addition disphosphonates could have long-term effects on prevention when the treatment is finished
Posttraumatic wide exposure and surgical resection
indications severe loss of motion and decreased function
technique wide exposure required to identify all neurovascular
structures that may be involved timing of resection (controversial)
marked decrease in bone scan activity AND normalization of ALP
6 months following general trauma 1 year following SCI 15 years following TBI
some data suggests equivalent results when comparing early versus late resection
postop follow with 5 day course of indomethacin early gentle joint mobilization
The surgery is necessary in patients with symptomatic HO and unsuccessful medical treatment such as
Loss of range of motion and ankylosis with associated functional disability such as sitting difficulties
Complications of immobility such as pressure ulcers
Facilitate rehabilitation and recovery of muscular atrophy secondary to prolonged immobilisation
Difficulties of appropriate hygiene because access to the perineum or bladder care is needed
Severe pain refractory to analgesia Vascular andor nerve compression
Advantages to early excision of heterotopic ossification (vs waiting for maturation) include decreased soft tissue contracture better definition between heterotopic and native bone and decreased waiting time for the patient When the soft tissue envelope is benign one may proceed with operative release While waiting for normalization of alkaline phosphatase levels inactivity on bone scan or radiographic maturity may decrease risk of recurrent heterotopic ossification delaying operative release for these reasons has not been shown to improve results of final elbow range of motion after contracture release
Gartland recommended surgery after six months following traumatic heterotopic ossification one year following spinal cord injury and 18 months after head injury
In the past waiting until maturity in order to minimize the rate of recurrence after the surgical treatment was recommended Nevertheless recent studies do not confirm a higher rate of recurrence when the HO is excised in an earlier phase In addition a long delay before surgery leads to ankylosis a high degree of osteoporosis and more extensive intra-articular injuries These findings are associated with bad functional results and potential complications
Should you wait till lesion maturation
Prevention byHandle tissue carefully Avoid excess bleeding Achieve good hemostasis Beware of lesions that span internervous tissue planes
but if it happens resection of a large enough amount of bone to allow improvement of the range of motion and trying to preserve the joint
Our aim must be
A reactive process that is characterized by a well-circumscribed proliferation of fibroblasts cartilage and bone within muscle
A form of heterotopic ossification that is the result direct trauma intramuscular hematoma
most common location is the diaphysis of long bones Must differentiate from tumors Fibrodysplasia ossificans progressiva (FOP) is a rare subtype of heterotopic ossification
involves mutation of the ACVR1 gene (activin A type I receptor gene a BMP type-1 receptor)
Epidemiology demographics
most common in young active males (15 to 35 years old) body locations
quadriceps brachialis and gluteal muscles Genetics
almost always a posttraumatic condition Prognosis
usually self limiting mass usually begins to decrease in size after 1 yea
Myositis ossificans
PresentationbullSymptoms
bull pain tenderness swelling and decreased range of motion that usually presents within days of the injury
bull pain and size of the mass decrease with timebull mass increases in size over several months(usually 3 to 6 cm)
bull after the mass stops growing it becomes firmbullPhysical exam
bull palpable soft tissue massbull restricted range of motion
ImagingbullRadiographs
bull peripheral bone formation with central lucent areabull may appear as dotted veil pattern
bullMRI with gadolinium bull rim enhancement is seen within the first 3 weeks
bullCT scan bull lesion has an eggshell appearance
bullCharacteristic histology shows zonal pattern bull periphery of lesion
bull mature trabeculae of lamellar and woven bonebull calcification seen on xray
bull center of the lesion bull irregular mass of immature fibroblastsbull cartilage component may be presentbull (no calcification seen on xray) bull no cellular atypia seen
Treatment
bullNonoperative bull rest range of motion exercises and activity modification
bull passive stretching is contraindicated (makes it worse)bull physical therapy
bull utilized to maintain range of motionbull radiographic monitoring
bull obtained to confirm maturation of the lesionbullOperative
bull surgical excision bull indicated only if it remains a problem after it maturesbull do not operate in acute phase wait at least six months
bull excision of the lesion within 6 to 12 months predisposes to local recurrence
A 26-year-old man presents with generalized back and joint stiffness and difficulty opening his mouth His elder sister has similar complaints Since childhood he has had 3 surgeries for excision of recurrent bony prominences around his knees He walks with a stooped over posture seen in Figure A Radiographs of his feet knee hip and spine are seen in Figures B-E respectively
fibrodysplasia ossificans progressiva
Stone Man Disease) which involves a mutation of the ACVR1
There are 2 hallmark characteristics progressive heterotopic ossification (muscles fascia tendons ligaments and joint capsules) and congenital malformation of the great toe (hallux valgus malformed first metatarsal and monophalangism) BMP4 which contributes to the formation of the skeleton in the normal embryo is implicated in this disease
Complications
bullHematoma and intraoperative bleedingbullInfection
bull higher rate of infection following joint arthroplasty if HO is present
bullFractures of osteoporotic bone bull osteopenic from disusebull during surgery or physiotherapy
bullRecurrence bull recurrence rate correlates with neurological injury
bull greater recurrence if severe neurological compromisebullAVN
bull if extensive dissection or stripping is required
HTO AND ISS
When ISS is below 25 the mortality risk is minimal and above 25 it is an almost linear increase
When ISS is 50 the mortality is 50 When above 70 it is close to 100 If an injury is assigned an AIS of 6 (unsurvivable injury) the ISS score is
automatically assigned to 75 Highest ISS score obtainable is 75 For trauma patients of vehicular accidents the scoring system is important
for assessing the effectiveness of medical care in reducing morbidity and mortality
Advantages virtually the only anatomical scoring system in use correlates linearly with
mortality morbidity hospital stay other measures of severity
Weaknesses Any error in AIS scoring increases the ISS error Many different injury patterns can yield the same ISS score Injuries to different body regions are not weighted Not a useful triage tool as a full description of patient injuries is not known
prior to full investigation amp operation
risk factors periosteal stripping off anterior femur male gender obesity post traumatic deformity Anterior and anterolateral approach Cementless
Neurogenic HO around the hip due to SCI occurs more often in the medial region than in the lateral region with ossified tissues extending from the pubic symphysis to the anteromedial femoral shaft posterior to the femoral neurovascular structures Ossification is also seen anteriorly involving the iliopsoas and femoral neurovascular structures laterally within gluteus minimus and posteriorly extending from the ilium to the posterior femur encasing the sciatic nerve
HTO AROUND hip and knee
The Brooker Classification of Heterotopic Ossification around the hip joint Class I has islands of bone within the soft tissues Class II has bone spurs from the pelvis or proximal end of the femur leaving at least 1 cm between opposing surfaces Class III has bone spurs from the pelvis andor proximal end of the femur reducing the space between opposing bone surfaces to less than 1 cm Class IV shows apparent bone ankylosis of the hip
Region I - Heterotopic ossifications are strictly below the tip of the greater trochanter
Region II - Heterotopic ossifications are below and above the tip of the greater trochanter
Region III - Heterotopic ossifications are strictly above the tip of the greater trochanter
Grade A - Single or multiple heterotopic ossifications are less than 10 mm in maximal extent without contact with the pelvis or the femur
Grade B - Heterotopic ossifications are greater than 10 mm without contact with the pelvis but with possible contact with the femur there is no bridging from the femur to the proximal part of the greater trochanter and no evidence of ankylosis
Grade C - Ankylosis by means of firm bridging from the femur to the pelvis is present
Shmidt classification
excision may be performed The results of this procedure are varied Patients may find that their range of movement improves but pain relief is likely to be limited
A patient with heterotopic ossification following total hip arthroplasty is thought to have a 90-100 chance of developing it on the contralateral hip if this hip also undergoes total arthroplasty
it would be prudent to minimize the risk of heterotopic ossification developing after arthroplasty by performing surgery whereby the following are ensured
Exposure is meticulous Retraction is performed carefully and soft tissue
is handled carefully Irrigation is adequate Devitalized tissue is excised Hemostasis is adequate Postoperative drains (when used) are not
retained for longer than necessary Perioperative antibiotic prophylaxis is used Postoperative anticoagulation (when used for
deep vein thrombosis prophylaxis) is carefully controlled
sources of knee stiffness 1-extrinsic severe osteoarthritis of the ipsilateral hip neurologic injury leading to muscle rigidity tight quadriceps or hamstring muscles secondary to muscle injury heterotopic ossification or long-standing juvenile inflammatory conditions limiting knee
range of motion prior to the completion of skeletal growth When extrinsic sources are identified revision total knee arthroplasty is unlikely to be associated with a favorable outcome without correction of the extrinsic problem
2-intrinsic (1) overstuffing of the patellofemoral articulation (2) an
excessively tight flexion andor extension gap (3) a tight posterior cruciate ligament (4) femoral andor tibial malrotation (5) arthrofibrosis and (6) limited bearing excursion in association with a highly conforming mobile-bearing prosthetic design
HTO after TKA
Heterotopic Ossification (HO) following primary Total Knee Replacement (TKR)
Occurs in 3-90 of TKRs 3-grade classification system No correlation between HO and component
alignment or component position
Clinical findings similar to early infection Continuing low-grade fever Warm swollen and erythematous knee Normal blood tests Possibly an association with HLA-A2 and B18 HO patients have worse KSS and function
scores
Patients at HIGH risk for developing HO after TKR (Knee Arthroplasty) (5)
Those with limited postoperative knee flexion
Increased lumbar bone mineral density (BMD) on multivariate analysis (3)
Hypertrophic arthrosis Excessive periosteal trauma Notching of the anterior femur Those who require forced manipulation
after TKA 47 in revision TKR surgery (6) Higher rates in revision TKR cases with
infection (up to 76
DaughertyBell classification of HO of the knee 0 No evidence of HO 1 Bone islands in periarticular soft tissue (no
involvement of femur patella or tibia) or HO within quadriceps expansion measuring lt1 cm
2 Spur formation measuring lt5 cm that involves the femur patella or tibia if more than one bone demonstrates HO separation of HO spurs
measure gt1 cm or HO within quadriceps expansion measuring ge1 cm but lt3 cm
3 Spur formation gt5 cm involving femur patella or tibia if more than one bone demonstrates HO separation of HO spurs measure lt1 cm or HO
within quadriceps expansion measuring ge3 cm 4 Extensive HO of the knee causing ankylosis
class 2 HO begins to involve the major bones of the knee joint with spur formation limited to a size of 5 cm
HO class 2 may be observed in select patients with complete ROM and no reported pain Patients with class 3 HO would likely always benefit from surgical excision
followed by RT prophylaxis Certainly patients in either cohort with a subclass ldquoBrdquo assignment (symptomatic) would
benefit from treatment All patients with class 4 HO require
treatment to alleviate ankylosis
treatment
References Whyte ldquoPagetrsquos Disease of Bonerdquo NEMJ vol 355
2006 Klein and Parvizi ldquoSurgical Manifestations of Pagetrsquos
Diseaserdquo JAAOS vol 14 2006 Orthobullets Campbell Apley Emedicinecom
-Chapter 15 Heterotopic Ossification after Traumatic Brain InjuryBy Jesuacutes Moreta and Joseacute Luis Martiacutenez-de los Mozos DOI 10577257343
Questions
Thank You
Radiographs are extremely useful in the staging of heterotopic ossification and will show the development of sharp cortical margins once the lesion has reached maturity
Heterotopic bone is a condition in which lamellar bone forms in non-ossified soft tissues In the early stages studies such as MRI and bone scan are more sensitive for diagnosis as radiographs may appear normal for the first three weeks After the appropriate diagnosis is made sequential radiographs are useful for monitoring the progression of the ossification Once it has reached the mature stage sharp cortical margins will appear and surgical resection may be considered
lab
Labs elevated serum alkaline phosphatase (gt250IUL)
ALP removes inhibitors of mineralization nonspecific may be elevated with skeletal trauma cannot determine maturity of HO elevated 12wks after surgery is predictor
elevated CRP correlates with inflammatory activity of HO better than ESR normalization of CRP may correlate with maturity of HO
elevated ESR (gt35mmh) 12wks after THA is predictor
elevated CK correlates with involvement of muscle extent of muscle
involvement Histology
mature fatty bone marrow mature trabecular bone
Heterotopic ossification (HO) most commonly occurs at the amputation site if the amputation was performed thru the zone of injury especially if the injury was a blast mechanism
Symptomatic heterotopic ossification of the quadriceps may occur following placement of a large-diameter Steinmann pin for the purpose of temporary skeletal traction
TreatmentThe prevention of heterotopic ossification is focused on three basic principles disrupting the inductive signalling pathways altering the osteoprogenitor cells or modifying the environment
bullphysiotherapy should involve an assisted range of movement exercises with gentle stretch and terminal resistance trainingbullProphylaxis
bull bisphosphonates amp NSAIDS bull indications
bull although no literature supports are commonly usedbull technique
bull indomethacin is most commonly used bull dose is 75mgday for 10days to 6 weeks
bull perioperative radiation bull indications
bull although no literature supports commonly usedbull is thought to be effective by blocking osteoblast differentiation
bull technique bull a single perioperative dose of 700cGy can be given either 4
hours preop or within 72 hours postoperatively bull lt550cGy not effective
Nonsteroidal anti-inflammatory drugs (NSAIDs) These drugs have demonstrated good results in
preventing heterotopic ossification after total hip arthroplasty
A direct effect of NSAIDs on the formation of heterotopic ossification has been described due to the inhibition of the differentiation of mesenchymal cells into oestrogenic cells There is also an indirect effect which refers to the inhibition of bone remodelling by suppression of the prostagland unmediated inflammatory response (specifically PGE-2)
Indomethacin has been considered a useful medication for heterotopic ossification prophylaxis following total hip replacement
prescribed for three to six weeks in a dose of 75mgday within two months of the injury may reduce the incidence of heterotopic ossification by two to three times
Biphosphonates inhibits precipitation of calcium phosphate and blocks the aggregation and mineralisation of hydroxyapatite crystals In primary prevention Banovac et al [56] have suggested that the treatment should begin as soon as elevated alkaline phosphatase is diagnosed or positive findings in ultrasonography or bone scans are shown In addition disphosphonates could have long-term effects on prevention when the treatment is finished
Posttraumatic wide exposure and surgical resection
indications severe loss of motion and decreased function
technique wide exposure required to identify all neurovascular
structures that may be involved timing of resection (controversial)
marked decrease in bone scan activity AND normalization of ALP
6 months following general trauma 1 year following SCI 15 years following TBI
some data suggests equivalent results when comparing early versus late resection
postop follow with 5 day course of indomethacin early gentle joint mobilization
The surgery is necessary in patients with symptomatic HO and unsuccessful medical treatment such as
Loss of range of motion and ankylosis with associated functional disability such as sitting difficulties
Complications of immobility such as pressure ulcers
Facilitate rehabilitation and recovery of muscular atrophy secondary to prolonged immobilisation
Difficulties of appropriate hygiene because access to the perineum or bladder care is needed
Severe pain refractory to analgesia Vascular andor nerve compression
Advantages to early excision of heterotopic ossification (vs waiting for maturation) include decreased soft tissue contracture better definition between heterotopic and native bone and decreased waiting time for the patient When the soft tissue envelope is benign one may proceed with operative release While waiting for normalization of alkaline phosphatase levels inactivity on bone scan or radiographic maturity may decrease risk of recurrent heterotopic ossification delaying operative release for these reasons has not been shown to improve results of final elbow range of motion after contracture release
Gartland recommended surgery after six months following traumatic heterotopic ossification one year following spinal cord injury and 18 months after head injury
In the past waiting until maturity in order to minimize the rate of recurrence after the surgical treatment was recommended Nevertheless recent studies do not confirm a higher rate of recurrence when the HO is excised in an earlier phase In addition a long delay before surgery leads to ankylosis a high degree of osteoporosis and more extensive intra-articular injuries These findings are associated with bad functional results and potential complications
Should you wait till lesion maturation
Prevention byHandle tissue carefully Avoid excess bleeding Achieve good hemostasis Beware of lesions that span internervous tissue planes
but if it happens resection of a large enough amount of bone to allow improvement of the range of motion and trying to preserve the joint
Our aim must be
A reactive process that is characterized by a well-circumscribed proliferation of fibroblasts cartilage and bone within muscle
A form of heterotopic ossification that is the result direct trauma intramuscular hematoma
most common location is the diaphysis of long bones Must differentiate from tumors Fibrodysplasia ossificans progressiva (FOP) is a rare subtype of heterotopic ossification
involves mutation of the ACVR1 gene (activin A type I receptor gene a BMP type-1 receptor)
Epidemiology demographics
most common in young active males (15 to 35 years old) body locations
quadriceps brachialis and gluteal muscles Genetics
almost always a posttraumatic condition Prognosis
usually self limiting mass usually begins to decrease in size after 1 yea
Myositis ossificans
PresentationbullSymptoms
bull pain tenderness swelling and decreased range of motion that usually presents within days of the injury
bull pain and size of the mass decrease with timebull mass increases in size over several months(usually 3 to 6 cm)
bull after the mass stops growing it becomes firmbullPhysical exam
bull palpable soft tissue massbull restricted range of motion
ImagingbullRadiographs
bull peripheral bone formation with central lucent areabull may appear as dotted veil pattern
bullMRI with gadolinium bull rim enhancement is seen within the first 3 weeks
bullCT scan bull lesion has an eggshell appearance
bullCharacteristic histology shows zonal pattern bull periphery of lesion
bull mature trabeculae of lamellar and woven bonebull calcification seen on xray
bull center of the lesion bull irregular mass of immature fibroblastsbull cartilage component may be presentbull (no calcification seen on xray) bull no cellular atypia seen
Treatment
bullNonoperative bull rest range of motion exercises and activity modification
bull passive stretching is contraindicated (makes it worse)bull physical therapy
bull utilized to maintain range of motionbull radiographic monitoring
bull obtained to confirm maturation of the lesionbullOperative
bull surgical excision bull indicated only if it remains a problem after it maturesbull do not operate in acute phase wait at least six months
bull excision of the lesion within 6 to 12 months predisposes to local recurrence
A 26-year-old man presents with generalized back and joint stiffness and difficulty opening his mouth His elder sister has similar complaints Since childhood he has had 3 surgeries for excision of recurrent bony prominences around his knees He walks with a stooped over posture seen in Figure A Radiographs of his feet knee hip and spine are seen in Figures B-E respectively
fibrodysplasia ossificans progressiva
Stone Man Disease) which involves a mutation of the ACVR1
There are 2 hallmark characteristics progressive heterotopic ossification (muscles fascia tendons ligaments and joint capsules) and congenital malformation of the great toe (hallux valgus malformed first metatarsal and monophalangism) BMP4 which contributes to the formation of the skeleton in the normal embryo is implicated in this disease
Complications
bullHematoma and intraoperative bleedingbullInfection
bull higher rate of infection following joint arthroplasty if HO is present
bullFractures of osteoporotic bone bull osteopenic from disusebull during surgery or physiotherapy
bullRecurrence bull recurrence rate correlates with neurological injury
bull greater recurrence if severe neurological compromisebullAVN
bull if extensive dissection or stripping is required
HTO AND ISS
When ISS is below 25 the mortality risk is minimal and above 25 it is an almost linear increase
When ISS is 50 the mortality is 50 When above 70 it is close to 100 If an injury is assigned an AIS of 6 (unsurvivable injury) the ISS score is
automatically assigned to 75 Highest ISS score obtainable is 75 For trauma patients of vehicular accidents the scoring system is important
for assessing the effectiveness of medical care in reducing morbidity and mortality
Advantages virtually the only anatomical scoring system in use correlates linearly with
mortality morbidity hospital stay other measures of severity
Weaknesses Any error in AIS scoring increases the ISS error Many different injury patterns can yield the same ISS score Injuries to different body regions are not weighted Not a useful triage tool as a full description of patient injuries is not known
prior to full investigation amp operation
risk factors periosteal stripping off anterior femur male gender obesity post traumatic deformity Anterior and anterolateral approach Cementless
Neurogenic HO around the hip due to SCI occurs more often in the medial region than in the lateral region with ossified tissues extending from the pubic symphysis to the anteromedial femoral shaft posterior to the femoral neurovascular structures Ossification is also seen anteriorly involving the iliopsoas and femoral neurovascular structures laterally within gluteus minimus and posteriorly extending from the ilium to the posterior femur encasing the sciatic nerve
HTO AROUND hip and knee
The Brooker Classification of Heterotopic Ossification around the hip joint Class I has islands of bone within the soft tissues Class II has bone spurs from the pelvis or proximal end of the femur leaving at least 1 cm between opposing surfaces Class III has bone spurs from the pelvis andor proximal end of the femur reducing the space between opposing bone surfaces to less than 1 cm Class IV shows apparent bone ankylosis of the hip
Region I - Heterotopic ossifications are strictly below the tip of the greater trochanter
Region II - Heterotopic ossifications are below and above the tip of the greater trochanter
Region III - Heterotopic ossifications are strictly above the tip of the greater trochanter
Grade A - Single or multiple heterotopic ossifications are less than 10 mm in maximal extent without contact with the pelvis or the femur
Grade B - Heterotopic ossifications are greater than 10 mm without contact with the pelvis but with possible contact with the femur there is no bridging from the femur to the proximal part of the greater trochanter and no evidence of ankylosis
Grade C - Ankylosis by means of firm bridging from the femur to the pelvis is present
Shmidt classification
excision may be performed The results of this procedure are varied Patients may find that their range of movement improves but pain relief is likely to be limited
A patient with heterotopic ossification following total hip arthroplasty is thought to have a 90-100 chance of developing it on the contralateral hip if this hip also undergoes total arthroplasty
it would be prudent to minimize the risk of heterotopic ossification developing after arthroplasty by performing surgery whereby the following are ensured
Exposure is meticulous Retraction is performed carefully and soft tissue
is handled carefully Irrigation is adequate Devitalized tissue is excised Hemostasis is adequate Postoperative drains (when used) are not
retained for longer than necessary Perioperative antibiotic prophylaxis is used Postoperative anticoagulation (when used for
deep vein thrombosis prophylaxis) is carefully controlled
sources of knee stiffness 1-extrinsic severe osteoarthritis of the ipsilateral hip neurologic injury leading to muscle rigidity tight quadriceps or hamstring muscles secondary to muscle injury heterotopic ossification or long-standing juvenile inflammatory conditions limiting knee
range of motion prior to the completion of skeletal growth When extrinsic sources are identified revision total knee arthroplasty is unlikely to be associated with a favorable outcome without correction of the extrinsic problem
2-intrinsic (1) overstuffing of the patellofemoral articulation (2) an
excessively tight flexion andor extension gap (3) a tight posterior cruciate ligament (4) femoral andor tibial malrotation (5) arthrofibrosis and (6) limited bearing excursion in association with a highly conforming mobile-bearing prosthetic design
HTO after TKA
Heterotopic Ossification (HO) following primary Total Knee Replacement (TKR)
Occurs in 3-90 of TKRs 3-grade classification system No correlation between HO and component
alignment or component position
Clinical findings similar to early infection Continuing low-grade fever Warm swollen and erythematous knee Normal blood tests Possibly an association with HLA-A2 and B18 HO patients have worse KSS and function
scores
Patients at HIGH risk for developing HO after TKR (Knee Arthroplasty) (5)
Those with limited postoperative knee flexion
Increased lumbar bone mineral density (BMD) on multivariate analysis (3)
Hypertrophic arthrosis Excessive periosteal trauma Notching of the anterior femur Those who require forced manipulation
after TKA 47 in revision TKR surgery (6) Higher rates in revision TKR cases with
infection (up to 76
DaughertyBell classification of HO of the knee 0 No evidence of HO 1 Bone islands in periarticular soft tissue (no
involvement of femur patella or tibia) or HO within quadriceps expansion measuring lt1 cm
2 Spur formation measuring lt5 cm that involves the femur patella or tibia if more than one bone demonstrates HO separation of HO spurs
measure gt1 cm or HO within quadriceps expansion measuring ge1 cm but lt3 cm
3 Spur formation gt5 cm involving femur patella or tibia if more than one bone demonstrates HO separation of HO spurs measure lt1 cm or HO
within quadriceps expansion measuring ge3 cm 4 Extensive HO of the knee causing ankylosis
class 2 HO begins to involve the major bones of the knee joint with spur formation limited to a size of 5 cm
HO class 2 may be observed in select patients with complete ROM and no reported pain Patients with class 3 HO would likely always benefit from surgical excision
followed by RT prophylaxis Certainly patients in either cohort with a subclass ldquoBrdquo assignment (symptomatic) would
benefit from treatment All patients with class 4 HO require
treatment to alleviate ankylosis
treatment
References Whyte ldquoPagetrsquos Disease of Bonerdquo NEMJ vol 355
2006 Klein and Parvizi ldquoSurgical Manifestations of Pagetrsquos
Diseaserdquo JAAOS vol 14 2006 Orthobullets Campbell Apley Emedicinecom
-Chapter 15 Heterotopic Ossification after Traumatic Brain InjuryBy Jesuacutes Moreta and Joseacute Luis Martiacutenez-de los Mozos DOI 10577257343
Questions
Thank You
lab
Labs elevated serum alkaline phosphatase (gt250IUL)
ALP removes inhibitors of mineralization nonspecific may be elevated with skeletal trauma cannot determine maturity of HO elevated 12wks after surgery is predictor
elevated CRP correlates with inflammatory activity of HO better than ESR normalization of CRP may correlate with maturity of HO
elevated ESR (gt35mmh) 12wks after THA is predictor
elevated CK correlates with involvement of muscle extent of muscle
involvement Histology
mature fatty bone marrow mature trabecular bone
Heterotopic ossification (HO) most commonly occurs at the amputation site if the amputation was performed thru the zone of injury especially if the injury was a blast mechanism
Symptomatic heterotopic ossification of the quadriceps may occur following placement of a large-diameter Steinmann pin for the purpose of temporary skeletal traction
TreatmentThe prevention of heterotopic ossification is focused on three basic principles disrupting the inductive signalling pathways altering the osteoprogenitor cells or modifying the environment
bullphysiotherapy should involve an assisted range of movement exercises with gentle stretch and terminal resistance trainingbullProphylaxis
bull bisphosphonates amp NSAIDS bull indications
bull although no literature supports are commonly usedbull technique
bull indomethacin is most commonly used bull dose is 75mgday for 10days to 6 weeks
bull perioperative radiation bull indications
bull although no literature supports commonly usedbull is thought to be effective by blocking osteoblast differentiation
bull technique bull a single perioperative dose of 700cGy can be given either 4
hours preop or within 72 hours postoperatively bull lt550cGy not effective
Nonsteroidal anti-inflammatory drugs (NSAIDs) These drugs have demonstrated good results in
preventing heterotopic ossification after total hip arthroplasty
A direct effect of NSAIDs on the formation of heterotopic ossification has been described due to the inhibition of the differentiation of mesenchymal cells into oestrogenic cells There is also an indirect effect which refers to the inhibition of bone remodelling by suppression of the prostagland unmediated inflammatory response (specifically PGE-2)
Indomethacin has been considered a useful medication for heterotopic ossification prophylaxis following total hip replacement
prescribed for three to six weeks in a dose of 75mgday within two months of the injury may reduce the incidence of heterotopic ossification by two to three times
Biphosphonates inhibits precipitation of calcium phosphate and blocks the aggregation and mineralisation of hydroxyapatite crystals In primary prevention Banovac et al [56] have suggested that the treatment should begin as soon as elevated alkaline phosphatase is diagnosed or positive findings in ultrasonography or bone scans are shown In addition disphosphonates could have long-term effects on prevention when the treatment is finished
Posttraumatic wide exposure and surgical resection
indications severe loss of motion and decreased function
technique wide exposure required to identify all neurovascular
structures that may be involved timing of resection (controversial)
marked decrease in bone scan activity AND normalization of ALP
6 months following general trauma 1 year following SCI 15 years following TBI
some data suggests equivalent results when comparing early versus late resection
postop follow with 5 day course of indomethacin early gentle joint mobilization
The surgery is necessary in patients with symptomatic HO and unsuccessful medical treatment such as
Loss of range of motion and ankylosis with associated functional disability such as sitting difficulties
Complications of immobility such as pressure ulcers
Facilitate rehabilitation and recovery of muscular atrophy secondary to prolonged immobilisation
Difficulties of appropriate hygiene because access to the perineum or bladder care is needed
Severe pain refractory to analgesia Vascular andor nerve compression
Advantages to early excision of heterotopic ossification (vs waiting for maturation) include decreased soft tissue contracture better definition between heterotopic and native bone and decreased waiting time for the patient When the soft tissue envelope is benign one may proceed with operative release While waiting for normalization of alkaline phosphatase levels inactivity on bone scan or radiographic maturity may decrease risk of recurrent heterotopic ossification delaying operative release for these reasons has not been shown to improve results of final elbow range of motion after contracture release
Gartland recommended surgery after six months following traumatic heterotopic ossification one year following spinal cord injury and 18 months after head injury
In the past waiting until maturity in order to minimize the rate of recurrence after the surgical treatment was recommended Nevertheless recent studies do not confirm a higher rate of recurrence when the HO is excised in an earlier phase In addition a long delay before surgery leads to ankylosis a high degree of osteoporosis and more extensive intra-articular injuries These findings are associated with bad functional results and potential complications
Should you wait till lesion maturation
Prevention byHandle tissue carefully Avoid excess bleeding Achieve good hemostasis Beware of lesions that span internervous tissue planes
but if it happens resection of a large enough amount of bone to allow improvement of the range of motion and trying to preserve the joint
Our aim must be
A reactive process that is characterized by a well-circumscribed proliferation of fibroblasts cartilage and bone within muscle
A form of heterotopic ossification that is the result direct trauma intramuscular hematoma
most common location is the diaphysis of long bones Must differentiate from tumors Fibrodysplasia ossificans progressiva (FOP) is a rare subtype of heterotopic ossification
involves mutation of the ACVR1 gene (activin A type I receptor gene a BMP type-1 receptor)
Epidemiology demographics
most common in young active males (15 to 35 years old) body locations
quadriceps brachialis and gluteal muscles Genetics
almost always a posttraumatic condition Prognosis
usually self limiting mass usually begins to decrease in size after 1 yea
Myositis ossificans
PresentationbullSymptoms
bull pain tenderness swelling and decreased range of motion that usually presents within days of the injury
bull pain and size of the mass decrease with timebull mass increases in size over several months(usually 3 to 6 cm)
bull after the mass stops growing it becomes firmbullPhysical exam
bull palpable soft tissue massbull restricted range of motion
ImagingbullRadiographs
bull peripheral bone formation with central lucent areabull may appear as dotted veil pattern
bullMRI with gadolinium bull rim enhancement is seen within the first 3 weeks
bullCT scan bull lesion has an eggshell appearance
bullCharacteristic histology shows zonal pattern bull periphery of lesion
bull mature trabeculae of lamellar and woven bonebull calcification seen on xray
bull center of the lesion bull irregular mass of immature fibroblastsbull cartilage component may be presentbull (no calcification seen on xray) bull no cellular atypia seen
Treatment
bullNonoperative bull rest range of motion exercises and activity modification
bull passive stretching is contraindicated (makes it worse)bull physical therapy
bull utilized to maintain range of motionbull radiographic monitoring
bull obtained to confirm maturation of the lesionbullOperative
bull surgical excision bull indicated only if it remains a problem after it maturesbull do not operate in acute phase wait at least six months
bull excision of the lesion within 6 to 12 months predisposes to local recurrence
A 26-year-old man presents with generalized back and joint stiffness and difficulty opening his mouth His elder sister has similar complaints Since childhood he has had 3 surgeries for excision of recurrent bony prominences around his knees He walks with a stooped over posture seen in Figure A Radiographs of his feet knee hip and spine are seen in Figures B-E respectively
fibrodysplasia ossificans progressiva
Stone Man Disease) which involves a mutation of the ACVR1
There are 2 hallmark characteristics progressive heterotopic ossification (muscles fascia tendons ligaments and joint capsules) and congenital malformation of the great toe (hallux valgus malformed first metatarsal and monophalangism) BMP4 which contributes to the formation of the skeleton in the normal embryo is implicated in this disease
Complications
bullHematoma and intraoperative bleedingbullInfection
bull higher rate of infection following joint arthroplasty if HO is present
bullFractures of osteoporotic bone bull osteopenic from disusebull during surgery or physiotherapy
bullRecurrence bull recurrence rate correlates with neurological injury
bull greater recurrence if severe neurological compromisebullAVN
bull if extensive dissection or stripping is required
HTO AND ISS
When ISS is below 25 the mortality risk is minimal and above 25 it is an almost linear increase
When ISS is 50 the mortality is 50 When above 70 it is close to 100 If an injury is assigned an AIS of 6 (unsurvivable injury) the ISS score is
automatically assigned to 75 Highest ISS score obtainable is 75 For trauma patients of vehicular accidents the scoring system is important
for assessing the effectiveness of medical care in reducing morbidity and mortality
Advantages virtually the only anatomical scoring system in use correlates linearly with
mortality morbidity hospital stay other measures of severity
Weaknesses Any error in AIS scoring increases the ISS error Many different injury patterns can yield the same ISS score Injuries to different body regions are not weighted Not a useful triage tool as a full description of patient injuries is not known
prior to full investigation amp operation
risk factors periosteal stripping off anterior femur male gender obesity post traumatic deformity Anterior and anterolateral approach Cementless
Neurogenic HO around the hip due to SCI occurs more often in the medial region than in the lateral region with ossified tissues extending from the pubic symphysis to the anteromedial femoral shaft posterior to the femoral neurovascular structures Ossification is also seen anteriorly involving the iliopsoas and femoral neurovascular structures laterally within gluteus minimus and posteriorly extending from the ilium to the posterior femur encasing the sciatic nerve
HTO AROUND hip and knee
The Brooker Classification of Heterotopic Ossification around the hip joint Class I has islands of bone within the soft tissues Class II has bone spurs from the pelvis or proximal end of the femur leaving at least 1 cm between opposing surfaces Class III has bone spurs from the pelvis andor proximal end of the femur reducing the space between opposing bone surfaces to less than 1 cm Class IV shows apparent bone ankylosis of the hip
Region I - Heterotopic ossifications are strictly below the tip of the greater trochanter
Region II - Heterotopic ossifications are below and above the tip of the greater trochanter
Region III - Heterotopic ossifications are strictly above the tip of the greater trochanter
Grade A - Single or multiple heterotopic ossifications are less than 10 mm in maximal extent without contact with the pelvis or the femur
Grade B - Heterotopic ossifications are greater than 10 mm without contact with the pelvis but with possible contact with the femur there is no bridging from the femur to the proximal part of the greater trochanter and no evidence of ankylosis
Grade C - Ankylosis by means of firm bridging from the femur to the pelvis is present
Shmidt classification
excision may be performed The results of this procedure are varied Patients may find that their range of movement improves but pain relief is likely to be limited
A patient with heterotopic ossification following total hip arthroplasty is thought to have a 90-100 chance of developing it on the contralateral hip if this hip also undergoes total arthroplasty
it would be prudent to minimize the risk of heterotopic ossification developing after arthroplasty by performing surgery whereby the following are ensured
Exposure is meticulous Retraction is performed carefully and soft tissue
is handled carefully Irrigation is adequate Devitalized tissue is excised Hemostasis is adequate Postoperative drains (when used) are not
retained for longer than necessary Perioperative antibiotic prophylaxis is used Postoperative anticoagulation (when used for
deep vein thrombosis prophylaxis) is carefully controlled
sources of knee stiffness 1-extrinsic severe osteoarthritis of the ipsilateral hip neurologic injury leading to muscle rigidity tight quadriceps or hamstring muscles secondary to muscle injury heterotopic ossification or long-standing juvenile inflammatory conditions limiting knee
range of motion prior to the completion of skeletal growth When extrinsic sources are identified revision total knee arthroplasty is unlikely to be associated with a favorable outcome without correction of the extrinsic problem
2-intrinsic (1) overstuffing of the patellofemoral articulation (2) an
excessively tight flexion andor extension gap (3) a tight posterior cruciate ligament (4) femoral andor tibial malrotation (5) arthrofibrosis and (6) limited bearing excursion in association with a highly conforming mobile-bearing prosthetic design
HTO after TKA
Heterotopic Ossification (HO) following primary Total Knee Replacement (TKR)
Occurs in 3-90 of TKRs 3-grade classification system No correlation between HO and component
alignment or component position
Clinical findings similar to early infection Continuing low-grade fever Warm swollen and erythematous knee Normal blood tests Possibly an association with HLA-A2 and B18 HO patients have worse KSS and function
scores
Patients at HIGH risk for developing HO after TKR (Knee Arthroplasty) (5)
Those with limited postoperative knee flexion
Increased lumbar bone mineral density (BMD) on multivariate analysis (3)
Hypertrophic arthrosis Excessive periosteal trauma Notching of the anterior femur Those who require forced manipulation
after TKA 47 in revision TKR surgery (6) Higher rates in revision TKR cases with
infection (up to 76
DaughertyBell classification of HO of the knee 0 No evidence of HO 1 Bone islands in periarticular soft tissue (no
involvement of femur patella or tibia) or HO within quadriceps expansion measuring lt1 cm
2 Spur formation measuring lt5 cm that involves the femur patella or tibia if more than one bone demonstrates HO separation of HO spurs
measure gt1 cm or HO within quadriceps expansion measuring ge1 cm but lt3 cm
3 Spur formation gt5 cm involving femur patella or tibia if more than one bone demonstrates HO separation of HO spurs measure lt1 cm or HO
within quadriceps expansion measuring ge3 cm 4 Extensive HO of the knee causing ankylosis
class 2 HO begins to involve the major bones of the knee joint with spur formation limited to a size of 5 cm
HO class 2 may be observed in select patients with complete ROM and no reported pain Patients with class 3 HO would likely always benefit from surgical excision
followed by RT prophylaxis Certainly patients in either cohort with a subclass ldquoBrdquo assignment (symptomatic) would
benefit from treatment All patients with class 4 HO require
treatment to alleviate ankylosis
treatment
References Whyte ldquoPagetrsquos Disease of Bonerdquo NEMJ vol 355
2006 Klein and Parvizi ldquoSurgical Manifestations of Pagetrsquos
Diseaserdquo JAAOS vol 14 2006 Orthobullets Campbell Apley Emedicinecom
-Chapter 15 Heterotopic Ossification after Traumatic Brain InjuryBy Jesuacutes Moreta and Joseacute Luis Martiacutenez-de los Mozos DOI 10577257343
Questions
Thank You
Labs elevated serum alkaline phosphatase (gt250IUL)
ALP removes inhibitors of mineralization nonspecific may be elevated with skeletal trauma cannot determine maturity of HO elevated 12wks after surgery is predictor
elevated CRP correlates with inflammatory activity of HO better than ESR normalization of CRP may correlate with maturity of HO
elevated ESR (gt35mmh) 12wks after THA is predictor
elevated CK correlates with involvement of muscle extent of muscle
involvement Histology
mature fatty bone marrow mature trabecular bone
Heterotopic ossification (HO) most commonly occurs at the amputation site if the amputation was performed thru the zone of injury especially if the injury was a blast mechanism
Symptomatic heterotopic ossification of the quadriceps may occur following placement of a large-diameter Steinmann pin for the purpose of temporary skeletal traction
TreatmentThe prevention of heterotopic ossification is focused on three basic principles disrupting the inductive signalling pathways altering the osteoprogenitor cells or modifying the environment
bullphysiotherapy should involve an assisted range of movement exercises with gentle stretch and terminal resistance trainingbullProphylaxis
bull bisphosphonates amp NSAIDS bull indications
bull although no literature supports are commonly usedbull technique
bull indomethacin is most commonly used bull dose is 75mgday for 10days to 6 weeks
bull perioperative radiation bull indications
bull although no literature supports commonly usedbull is thought to be effective by blocking osteoblast differentiation
bull technique bull a single perioperative dose of 700cGy can be given either 4
hours preop or within 72 hours postoperatively bull lt550cGy not effective
Nonsteroidal anti-inflammatory drugs (NSAIDs) These drugs have demonstrated good results in
preventing heterotopic ossification after total hip arthroplasty
A direct effect of NSAIDs on the formation of heterotopic ossification has been described due to the inhibition of the differentiation of mesenchymal cells into oestrogenic cells There is also an indirect effect which refers to the inhibition of bone remodelling by suppression of the prostagland unmediated inflammatory response (specifically PGE-2)
Indomethacin has been considered a useful medication for heterotopic ossification prophylaxis following total hip replacement
prescribed for three to six weeks in a dose of 75mgday within two months of the injury may reduce the incidence of heterotopic ossification by two to three times
Biphosphonates inhibits precipitation of calcium phosphate and blocks the aggregation and mineralisation of hydroxyapatite crystals In primary prevention Banovac et al [56] have suggested that the treatment should begin as soon as elevated alkaline phosphatase is diagnosed or positive findings in ultrasonography or bone scans are shown In addition disphosphonates could have long-term effects on prevention when the treatment is finished
Posttraumatic wide exposure and surgical resection
indications severe loss of motion and decreased function
technique wide exposure required to identify all neurovascular
structures that may be involved timing of resection (controversial)
marked decrease in bone scan activity AND normalization of ALP
6 months following general trauma 1 year following SCI 15 years following TBI
some data suggests equivalent results when comparing early versus late resection
postop follow with 5 day course of indomethacin early gentle joint mobilization
The surgery is necessary in patients with symptomatic HO and unsuccessful medical treatment such as
Loss of range of motion and ankylosis with associated functional disability such as sitting difficulties
Complications of immobility such as pressure ulcers
Facilitate rehabilitation and recovery of muscular atrophy secondary to prolonged immobilisation
Difficulties of appropriate hygiene because access to the perineum or bladder care is needed
Severe pain refractory to analgesia Vascular andor nerve compression
Advantages to early excision of heterotopic ossification (vs waiting for maturation) include decreased soft tissue contracture better definition between heterotopic and native bone and decreased waiting time for the patient When the soft tissue envelope is benign one may proceed with operative release While waiting for normalization of alkaline phosphatase levels inactivity on bone scan or radiographic maturity may decrease risk of recurrent heterotopic ossification delaying operative release for these reasons has not been shown to improve results of final elbow range of motion after contracture release
Gartland recommended surgery after six months following traumatic heterotopic ossification one year following spinal cord injury and 18 months after head injury
In the past waiting until maturity in order to minimize the rate of recurrence after the surgical treatment was recommended Nevertheless recent studies do not confirm a higher rate of recurrence when the HO is excised in an earlier phase In addition a long delay before surgery leads to ankylosis a high degree of osteoporosis and more extensive intra-articular injuries These findings are associated with bad functional results and potential complications
Should you wait till lesion maturation
Prevention byHandle tissue carefully Avoid excess bleeding Achieve good hemostasis Beware of lesions that span internervous tissue planes
but if it happens resection of a large enough amount of bone to allow improvement of the range of motion and trying to preserve the joint
Our aim must be
A reactive process that is characterized by a well-circumscribed proliferation of fibroblasts cartilage and bone within muscle
A form of heterotopic ossification that is the result direct trauma intramuscular hematoma
most common location is the diaphysis of long bones Must differentiate from tumors Fibrodysplasia ossificans progressiva (FOP) is a rare subtype of heterotopic ossification
involves mutation of the ACVR1 gene (activin A type I receptor gene a BMP type-1 receptor)
Epidemiology demographics
most common in young active males (15 to 35 years old) body locations
quadriceps brachialis and gluteal muscles Genetics
almost always a posttraumatic condition Prognosis
usually self limiting mass usually begins to decrease in size after 1 yea
Myositis ossificans
PresentationbullSymptoms
bull pain tenderness swelling and decreased range of motion that usually presents within days of the injury
bull pain and size of the mass decrease with timebull mass increases in size over several months(usually 3 to 6 cm)
bull after the mass stops growing it becomes firmbullPhysical exam
bull palpable soft tissue massbull restricted range of motion
ImagingbullRadiographs
bull peripheral bone formation with central lucent areabull may appear as dotted veil pattern
bullMRI with gadolinium bull rim enhancement is seen within the first 3 weeks
bullCT scan bull lesion has an eggshell appearance
bullCharacteristic histology shows zonal pattern bull periphery of lesion
bull mature trabeculae of lamellar and woven bonebull calcification seen on xray
bull center of the lesion bull irregular mass of immature fibroblastsbull cartilage component may be presentbull (no calcification seen on xray) bull no cellular atypia seen
Treatment
bullNonoperative bull rest range of motion exercises and activity modification
bull passive stretching is contraindicated (makes it worse)bull physical therapy
bull utilized to maintain range of motionbull radiographic monitoring
bull obtained to confirm maturation of the lesionbullOperative
bull surgical excision bull indicated only if it remains a problem after it maturesbull do not operate in acute phase wait at least six months
bull excision of the lesion within 6 to 12 months predisposes to local recurrence
A 26-year-old man presents with generalized back and joint stiffness and difficulty opening his mouth His elder sister has similar complaints Since childhood he has had 3 surgeries for excision of recurrent bony prominences around his knees He walks with a stooped over posture seen in Figure A Radiographs of his feet knee hip and spine are seen in Figures B-E respectively
fibrodysplasia ossificans progressiva
Stone Man Disease) which involves a mutation of the ACVR1
There are 2 hallmark characteristics progressive heterotopic ossification (muscles fascia tendons ligaments and joint capsules) and congenital malformation of the great toe (hallux valgus malformed first metatarsal and monophalangism) BMP4 which contributes to the formation of the skeleton in the normal embryo is implicated in this disease
Complications
bullHematoma and intraoperative bleedingbullInfection
bull higher rate of infection following joint arthroplasty if HO is present
bullFractures of osteoporotic bone bull osteopenic from disusebull during surgery or physiotherapy
bullRecurrence bull recurrence rate correlates with neurological injury
bull greater recurrence if severe neurological compromisebullAVN
bull if extensive dissection or stripping is required
HTO AND ISS
When ISS is below 25 the mortality risk is minimal and above 25 it is an almost linear increase
When ISS is 50 the mortality is 50 When above 70 it is close to 100 If an injury is assigned an AIS of 6 (unsurvivable injury) the ISS score is
automatically assigned to 75 Highest ISS score obtainable is 75 For trauma patients of vehicular accidents the scoring system is important
for assessing the effectiveness of medical care in reducing morbidity and mortality
Advantages virtually the only anatomical scoring system in use correlates linearly with
mortality morbidity hospital stay other measures of severity
Weaknesses Any error in AIS scoring increases the ISS error Many different injury patterns can yield the same ISS score Injuries to different body regions are not weighted Not a useful triage tool as a full description of patient injuries is not known
prior to full investigation amp operation
risk factors periosteal stripping off anterior femur male gender obesity post traumatic deformity Anterior and anterolateral approach Cementless
Neurogenic HO around the hip due to SCI occurs more often in the medial region than in the lateral region with ossified tissues extending from the pubic symphysis to the anteromedial femoral shaft posterior to the femoral neurovascular structures Ossification is also seen anteriorly involving the iliopsoas and femoral neurovascular structures laterally within gluteus minimus and posteriorly extending from the ilium to the posterior femur encasing the sciatic nerve
HTO AROUND hip and knee
The Brooker Classification of Heterotopic Ossification around the hip joint Class I has islands of bone within the soft tissues Class II has bone spurs from the pelvis or proximal end of the femur leaving at least 1 cm between opposing surfaces Class III has bone spurs from the pelvis andor proximal end of the femur reducing the space between opposing bone surfaces to less than 1 cm Class IV shows apparent bone ankylosis of the hip
Region I - Heterotopic ossifications are strictly below the tip of the greater trochanter
Region II - Heterotopic ossifications are below and above the tip of the greater trochanter
Region III - Heterotopic ossifications are strictly above the tip of the greater trochanter
Grade A - Single or multiple heterotopic ossifications are less than 10 mm in maximal extent without contact with the pelvis or the femur
Grade B - Heterotopic ossifications are greater than 10 mm without contact with the pelvis but with possible contact with the femur there is no bridging from the femur to the proximal part of the greater trochanter and no evidence of ankylosis
Grade C - Ankylosis by means of firm bridging from the femur to the pelvis is present
Shmidt classification
excision may be performed The results of this procedure are varied Patients may find that their range of movement improves but pain relief is likely to be limited
A patient with heterotopic ossification following total hip arthroplasty is thought to have a 90-100 chance of developing it on the contralateral hip if this hip also undergoes total arthroplasty
it would be prudent to minimize the risk of heterotopic ossification developing after arthroplasty by performing surgery whereby the following are ensured
Exposure is meticulous Retraction is performed carefully and soft tissue
is handled carefully Irrigation is adequate Devitalized tissue is excised Hemostasis is adequate Postoperative drains (when used) are not
retained for longer than necessary Perioperative antibiotic prophylaxis is used Postoperative anticoagulation (when used for
deep vein thrombosis prophylaxis) is carefully controlled
sources of knee stiffness 1-extrinsic severe osteoarthritis of the ipsilateral hip neurologic injury leading to muscle rigidity tight quadriceps or hamstring muscles secondary to muscle injury heterotopic ossification or long-standing juvenile inflammatory conditions limiting knee
range of motion prior to the completion of skeletal growth When extrinsic sources are identified revision total knee arthroplasty is unlikely to be associated with a favorable outcome without correction of the extrinsic problem
2-intrinsic (1) overstuffing of the patellofemoral articulation (2) an
excessively tight flexion andor extension gap (3) a tight posterior cruciate ligament (4) femoral andor tibial malrotation (5) arthrofibrosis and (6) limited bearing excursion in association with a highly conforming mobile-bearing prosthetic design
HTO after TKA
Heterotopic Ossification (HO) following primary Total Knee Replacement (TKR)
Occurs in 3-90 of TKRs 3-grade classification system No correlation between HO and component
alignment or component position
Clinical findings similar to early infection Continuing low-grade fever Warm swollen and erythematous knee Normal blood tests Possibly an association with HLA-A2 and B18 HO patients have worse KSS and function
scores
Patients at HIGH risk for developing HO after TKR (Knee Arthroplasty) (5)
Those with limited postoperative knee flexion
Increased lumbar bone mineral density (BMD) on multivariate analysis (3)
Hypertrophic arthrosis Excessive periosteal trauma Notching of the anterior femur Those who require forced manipulation
after TKA 47 in revision TKR surgery (6) Higher rates in revision TKR cases with
infection (up to 76
DaughertyBell classification of HO of the knee 0 No evidence of HO 1 Bone islands in periarticular soft tissue (no
involvement of femur patella or tibia) or HO within quadriceps expansion measuring lt1 cm
2 Spur formation measuring lt5 cm that involves the femur patella or tibia if more than one bone demonstrates HO separation of HO spurs
measure gt1 cm or HO within quadriceps expansion measuring ge1 cm but lt3 cm
3 Spur formation gt5 cm involving femur patella or tibia if more than one bone demonstrates HO separation of HO spurs measure lt1 cm or HO
within quadriceps expansion measuring ge3 cm 4 Extensive HO of the knee causing ankylosis
class 2 HO begins to involve the major bones of the knee joint with spur formation limited to a size of 5 cm
HO class 2 may be observed in select patients with complete ROM and no reported pain Patients with class 3 HO would likely always benefit from surgical excision
followed by RT prophylaxis Certainly patients in either cohort with a subclass ldquoBrdquo assignment (symptomatic) would
benefit from treatment All patients with class 4 HO require
treatment to alleviate ankylosis
treatment
References Whyte ldquoPagetrsquos Disease of Bonerdquo NEMJ vol 355
2006 Klein and Parvizi ldquoSurgical Manifestations of Pagetrsquos
Diseaserdquo JAAOS vol 14 2006 Orthobullets Campbell Apley Emedicinecom
-Chapter 15 Heterotopic Ossification after Traumatic Brain InjuryBy Jesuacutes Moreta and Joseacute Luis Martiacutenez-de los Mozos DOI 10577257343
Questions
Thank You
Heterotopic ossification (HO) most commonly occurs at the amputation site if the amputation was performed thru the zone of injury especially if the injury was a blast mechanism
Symptomatic heterotopic ossification of the quadriceps may occur following placement of a large-diameter Steinmann pin for the purpose of temporary skeletal traction
TreatmentThe prevention of heterotopic ossification is focused on three basic principles disrupting the inductive signalling pathways altering the osteoprogenitor cells or modifying the environment
bullphysiotherapy should involve an assisted range of movement exercises with gentle stretch and terminal resistance trainingbullProphylaxis
bull bisphosphonates amp NSAIDS bull indications
bull although no literature supports are commonly usedbull technique
bull indomethacin is most commonly used bull dose is 75mgday for 10days to 6 weeks
bull perioperative radiation bull indications
bull although no literature supports commonly usedbull is thought to be effective by blocking osteoblast differentiation
bull technique bull a single perioperative dose of 700cGy can be given either 4
hours preop or within 72 hours postoperatively bull lt550cGy not effective
Nonsteroidal anti-inflammatory drugs (NSAIDs) These drugs have demonstrated good results in
preventing heterotopic ossification after total hip arthroplasty
A direct effect of NSAIDs on the formation of heterotopic ossification has been described due to the inhibition of the differentiation of mesenchymal cells into oestrogenic cells There is also an indirect effect which refers to the inhibition of bone remodelling by suppression of the prostagland unmediated inflammatory response (specifically PGE-2)
Indomethacin has been considered a useful medication for heterotopic ossification prophylaxis following total hip replacement
prescribed for three to six weeks in a dose of 75mgday within two months of the injury may reduce the incidence of heterotopic ossification by two to three times
Biphosphonates inhibits precipitation of calcium phosphate and blocks the aggregation and mineralisation of hydroxyapatite crystals In primary prevention Banovac et al [56] have suggested that the treatment should begin as soon as elevated alkaline phosphatase is diagnosed or positive findings in ultrasonography or bone scans are shown In addition disphosphonates could have long-term effects on prevention when the treatment is finished
Posttraumatic wide exposure and surgical resection
indications severe loss of motion and decreased function
technique wide exposure required to identify all neurovascular
structures that may be involved timing of resection (controversial)
marked decrease in bone scan activity AND normalization of ALP
6 months following general trauma 1 year following SCI 15 years following TBI
some data suggests equivalent results when comparing early versus late resection
postop follow with 5 day course of indomethacin early gentle joint mobilization
The surgery is necessary in patients with symptomatic HO and unsuccessful medical treatment such as
Loss of range of motion and ankylosis with associated functional disability such as sitting difficulties
Complications of immobility such as pressure ulcers
Facilitate rehabilitation and recovery of muscular atrophy secondary to prolonged immobilisation
Difficulties of appropriate hygiene because access to the perineum or bladder care is needed
Severe pain refractory to analgesia Vascular andor nerve compression
Advantages to early excision of heterotopic ossification (vs waiting for maturation) include decreased soft tissue contracture better definition between heterotopic and native bone and decreased waiting time for the patient When the soft tissue envelope is benign one may proceed with operative release While waiting for normalization of alkaline phosphatase levels inactivity on bone scan or radiographic maturity may decrease risk of recurrent heterotopic ossification delaying operative release for these reasons has not been shown to improve results of final elbow range of motion after contracture release
Gartland recommended surgery after six months following traumatic heterotopic ossification one year following spinal cord injury and 18 months after head injury
In the past waiting until maturity in order to minimize the rate of recurrence after the surgical treatment was recommended Nevertheless recent studies do not confirm a higher rate of recurrence when the HO is excised in an earlier phase In addition a long delay before surgery leads to ankylosis a high degree of osteoporosis and more extensive intra-articular injuries These findings are associated with bad functional results and potential complications
Should you wait till lesion maturation
Prevention byHandle tissue carefully Avoid excess bleeding Achieve good hemostasis Beware of lesions that span internervous tissue planes
but if it happens resection of a large enough amount of bone to allow improvement of the range of motion and trying to preserve the joint
Our aim must be
A reactive process that is characterized by a well-circumscribed proliferation of fibroblasts cartilage and bone within muscle
A form of heterotopic ossification that is the result direct trauma intramuscular hematoma
most common location is the diaphysis of long bones Must differentiate from tumors Fibrodysplasia ossificans progressiva (FOP) is a rare subtype of heterotopic ossification
involves mutation of the ACVR1 gene (activin A type I receptor gene a BMP type-1 receptor)
Epidemiology demographics
most common in young active males (15 to 35 years old) body locations
quadriceps brachialis and gluteal muscles Genetics
almost always a posttraumatic condition Prognosis
usually self limiting mass usually begins to decrease in size after 1 yea
Myositis ossificans
PresentationbullSymptoms
bull pain tenderness swelling and decreased range of motion that usually presents within days of the injury
bull pain and size of the mass decrease with timebull mass increases in size over several months(usually 3 to 6 cm)
bull after the mass stops growing it becomes firmbullPhysical exam
bull palpable soft tissue massbull restricted range of motion
ImagingbullRadiographs
bull peripheral bone formation with central lucent areabull may appear as dotted veil pattern
bullMRI with gadolinium bull rim enhancement is seen within the first 3 weeks
bullCT scan bull lesion has an eggshell appearance
bullCharacteristic histology shows zonal pattern bull periphery of lesion
bull mature trabeculae of lamellar and woven bonebull calcification seen on xray
bull center of the lesion bull irregular mass of immature fibroblastsbull cartilage component may be presentbull (no calcification seen on xray) bull no cellular atypia seen
Treatment
bullNonoperative bull rest range of motion exercises and activity modification
bull passive stretching is contraindicated (makes it worse)bull physical therapy
bull utilized to maintain range of motionbull radiographic monitoring
bull obtained to confirm maturation of the lesionbullOperative
bull surgical excision bull indicated only if it remains a problem after it maturesbull do not operate in acute phase wait at least six months
bull excision of the lesion within 6 to 12 months predisposes to local recurrence
A 26-year-old man presents with generalized back and joint stiffness and difficulty opening his mouth His elder sister has similar complaints Since childhood he has had 3 surgeries for excision of recurrent bony prominences around his knees He walks with a stooped over posture seen in Figure A Radiographs of his feet knee hip and spine are seen in Figures B-E respectively
fibrodysplasia ossificans progressiva
Stone Man Disease) which involves a mutation of the ACVR1
There are 2 hallmark characteristics progressive heterotopic ossification (muscles fascia tendons ligaments and joint capsules) and congenital malformation of the great toe (hallux valgus malformed first metatarsal and monophalangism) BMP4 which contributes to the formation of the skeleton in the normal embryo is implicated in this disease
Complications
bullHematoma and intraoperative bleedingbullInfection
bull higher rate of infection following joint arthroplasty if HO is present
bullFractures of osteoporotic bone bull osteopenic from disusebull during surgery or physiotherapy
bullRecurrence bull recurrence rate correlates with neurological injury
bull greater recurrence if severe neurological compromisebullAVN
bull if extensive dissection or stripping is required
HTO AND ISS
When ISS is below 25 the mortality risk is minimal and above 25 it is an almost linear increase
When ISS is 50 the mortality is 50 When above 70 it is close to 100 If an injury is assigned an AIS of 6 (unsurvivable injury) the ISS score is
automatically assigned to 75 Highest ISS score obtainable is 75 For trauma patients of vehicular accidents the scoring system is important
for assessing the effectiveness of medical care in reducing morbidity and mortality
Advantages virtually the only anatomical scoring system in use correlates linearly with
mortality morbidity hospital stay other measures of severity
Weaknesses Any error in AIS scoring increases the ISS error Many different injury patterns can yield the same ISS score Injuries to different body regions are not weighted Not a useful triage tool as a full description of patient injuries is not known
prior to full investigation amp operation
risk factors periosteal stripping off anterior femur male gender obesity post traumatic deformity Anterior and anterolateral approach Cementless
Neurogenic HO around the hip due to SCI occurs more often in the medial region than in the lateral region with ossified tissues extending from the pubic symphysis to the anteromedial femoral shaft posterior to the femoral neurovascular structures Ossification is also seen anteriorly involving the iliopsoas and femoral neurovascular structures laterally within gluteus minimus and posteriorly extending from the ilium to the posterior femur encasing the sciatic nerve
HTO AROUND hip and knee
The Brooker Classification of Heterotopic Ossification around the hip joint Class I has islands of bone within the soft tissues Class II has bone spurs from the pelvis or proximal end of the femur leaving at least 1 cm between opposing surfaces Class III has bone spurs from the pelvis andor proximal end of the femur reducing the space between opposing bone surfaces to less than 1 cm Class IV shows apparent bone ankylosis of the hip
Region I - Heterotopic ossifications are strictly below the tip of the greater trochanter
Region II - Heterotopic ossifications are below and above the tip of the greater trochanter
Region III - Heterotopic ossifications are strictly above the tip of the greater trochanter
Grade A - Single or multiple heterotopic ossifications are less than 10 mm in maximal extent without contact with the pelvis or the femur
Grade B - Heterotopic ossifications are greater than 10 mm without contact with the pelvis but with possible contact with the femur there is no bridging from the femur to the proximal part of the greater trochanter and no evidence of ankylosis
Grade C - Ankylosis by means of firm bridging from the femur to the pelvis is present
Shmidt classification
excision may be performed The results of this procedure are varied Patients may find that their range of movement improves but pain relief is likely to be limited
A patient with heterotopic ossification following total hip arthroplasty is thought to have a 90-100 chance of developing it on the contralateral hip if this hip also undergoes total arthroplasty
it would be prudent to minimize the risk of heterotopic ossification developing after arthroplasty by performing surgery whereby the following are ensured
Exposure is meticulous Retraction is performed carefully and soft tissue
is handled carefully Irrigation is adequate Devitalized tissue is excised Hemostasis is adequate Postoperative drains (when used) are not
retained for longer than necessary Perioperative antibiotic prophylaxis is used Postoperative anticoagulation (when used for
deep vein thrombosis prophylaxis) is carefully controlled
sources of knee stiffness 1-extrinsic severe osteoarthritis of the ipsilateral hip neurologic injury leading to muscle rigidity tight quadriceps or hamstring muscles secondary to muscle injury heterotopic ossification or long-standing juvenile inflammatory conditions limiting knee
range of motion prior to the completion of skeletal growth When extrinsic sources are identified revision total knee arthroplasty is unlikely to be associated with a favorable outcome without correction of the extrinsic problem
2-intrinsic (1) overstuffing of the patellofemoral articulation (2) an
excessively tight flexion andor extension gap (3) a tight posterior cruciate ligament (4) femoral andor tibial malrotation (5) arthrofibrosis and (6) limited bearing excursion in association with a highly conforming mobile-bearing prosthetic design
HTO after TKA
Heterotopic Ossification (HO) following primary Total Knee Replacement (TKR)
Occurs in 3-90 of TKRs 3-grade classification system No correlation between HO and component
alignment or component position
Clinical findings similar to early infection Continuing low-grade fever Warm swollen and erythematous knee Normal blood tests Possibly an association with HLA-A2 and B18 HO patients have worse KSS and function
scores
Patients at HIGH risk for developing HO after TKR (Knee Arthroplasty) (5)
Those with limited postoperative knee flexion
Increased lumbar bone mineral density (BMD) on multivariate analysis (3)
Hypertrophic arthrosis Excessive periosteal trauma Notching of the anterior femur Those who require forced manipulation
after TKA 47 in revision TKR surgery (6) Higher rates in revision TKR cases with
infection (up to 76
DaughertyBell classification of HO of the knee 0 No evidence of HO 1 Bone islands in periarticular soft tissue (no
involvement of femur patella or tibia) or HO within quadriceps expansion measuring lt1 cm
2 Spur formation measuring lt5 cm that involves the femur patella or tibia if more than one bone demonstrates HO separation of HO spurs
measure gt1 cm or HO within quadriceps expansion measuring ge1 cm but lt3 cm
3 Spur formation gt5 cm involving femur patella or tibia if more than one bone demonstrates HO separation of HO spurs measure lt1 cm or HO
within quadriceps expansion measuring ge3 cm 4 Extensive HO of the knee causing ankylosis
class 2 HO begins to involve the major bones of the knee joint with spur formation limited to a size of 5 cm
HO class 2 may be observed in select patients with complete ROM and no reported pain Patients with class 3 HO would likely always benefit from surgical excision
followed by RT prophylaxis Certainly patients in either cohort with a subclass ldquoBrdquo assignment (symptomatic) would
benefit from treatment All patients with class 4 HO require
treatment to alleviate ankylosis
treatment
References Whyte ldquoPagetrsquos Disease of Bonerdquo NEMJ vol 355
2006 Klein and Parvizi ldquoSurgical Manifestations of Pagetrsquos
Diseaserdquo JAAOS vol 14 2006 Orthobullets Campbell Apley Emedicinecom
-Chapter 15 Heterotopic Ossification after Traumatic Brain InjuryBy Jesuacutes Moreta and Joseacute Luis Martiacutenez-de los Mozos DOI 10577257343
Questions
Thank You
TreatmentThe prevention of heterotopic ossification is focused on three basic principles disrupting the inductive signalling pathways altering the osteoprogenitor cells or modifying the environment
bullphysiotherapy should involve an assisted range of movement exercises with gentle stretch and terminal resistance trainingbullProphylaxis
bull bisphosphonates amp NSAIDS bull indications
bull although no literature supports are commonly usedbull technique
bull indomethacin is most commonly used bull dose is 75mgday for 10days to 6 weeks
bull perioperative radiation bull indications
bull although no literature supports commonly usedbull is thought to be effective by blocking osteoblast differentiation
bull technique bull a single perioperative dose of 700cGy can be given either 4
hours preop or within 72 hours postoperatively bull lt550cGy not effective
Nonsteroidal anti-inflammatory drugs (NSAIDs) These drugs have demonstrated good results in
preventing heterotopic ossification after total hip arthroplasty
A direct effect of NSAIDs on the formation of heterotopic ossification has been described due to the inhibition of the differentiation of mesenchymal cells into oestrogenic cells There is also an indirect effect which refers to the inhibition of bone remodelling by suppression of the prostagland unmediated inflammatory response (specifically PGE-2)
Indomethacin has been considered a useful medication for heterotopic ossification prophylaxis following total hip replacement
prescribed for three to six weeks in a dose of 75mgday within two months of the injury may reduce the incidence of heterotopic ossification by two to three times
Biphosphonates inhibits precipitation of calcium phosphate and blocks the aggregation and mineralisation of hydroxyapatite crystals In primary prevention Banovac et al [56] have suggested that the treatment should begin as soon as elevated alkaline phosphatase is diagnosed or positive findings in ultrasonography or bone scans are shown In addition disphosphonates could have long-term effects on prevention when the treatment is finished
Posttraumatic wide exposure and surgical resection
indications severe loss of motion and decreased function
technique wide exposure required to identify all neurovascular
structures that may be involved timing of resection (controversial)
marked decrease in bone scan activity AND normalization of ALP
6 months following general trauma 1 year following SCI 15 years following TBI
some data suggests equivalent results when comparing early versus late resection
postop follow with 5 day course of indomethacin early gentle joint mobilization
The surgery is necessary in patients with symptomatic HO and unsuccessful medical treatment such as
Loss of range of motion and ankylosis with associated functional disability such as sitting difficulties
Complications of immobility such as pressure ulcers
Facilitate rehabilitation and recovery of muscular atrophy secondary to prolonged immobilisation
Difficulties of appropriate hygiene because access to the perineum or bladder care is needed
Severe pain refractory to analgesia Vascular andor nerve compression
Advantages to early excision of heterotopic ossification (vs waiting for maturation) include decreased soft tissue contracture better definition between heterotopic and native bone and decreased waiting time for the patient When the soft tissue envelope is benign one may proceed with operative release While waiting for normalization of alkaline phosphatase levels inactivity on bone scan or radiographic maturity may decrease risk of recurrent heterotopic ossification delaying operative release for these reasons has not been shown to improve results of final elbow range of motion after contracture release
Gartland recommended surgery after six months following traumatic heterotopic ossification one year following spinal cord injury and 18 months after head injury
In the past waiting until maturity in order to minimize the rate of recurrence after the surgical treatment was recommended Nevertheless recent studies do not confirm a higher rate of recurrence when the HO is excised in an earlier phase In addition a long delay before surgery leads to ankylosis a high degree of osteoporosis and more extensive intra-articular injuries These findings are associated with bad functional results and potential complications
Should you wait till lesion maturation
Prevention byHandle tissue carefully Avoid excess bleeding Achieve good hemostasis Beware of lesions that span internervous tissue planes
but if it happens resection of a large enough amount of bone to allow improvement of the range of motion and trying to preserve the joint
Our aim must be
A reactive process that is characterized by a well-circumscribed proliferation of fibroblasts cartilage and bone within muscle
A form of heterotopic ossification that is the result direct trauma intramuscular hematoma
most common location is the diaphysis of long bones Must differentiate from tumors Fibrodysplasia ossificans progressiva (FOP) is a rare subtype of heterotopic ossification
involves mutation of the ACVR1 gene (activin A type I receptor gene a BMP type-1 receptor)
Epidemiology demographics
most common in young active males (15 to 35 years old) body locations
quadriceps brachialis and gluteal muscles Genetics
almost always a posttraumatic condition Prognosis
usually self limiting mass usually begins to decrease in size after 1 yea
Myositis ossificans
PresentationbullSymptoms
bull pain tenderness swelling and decreased range of motion that usually presents within days of the injury
bull pain and size of the mass decrease with timebull mass increases in size over several months(usually 3 to 6 cm)
bull after the mass stops growing it becomes firmbullPhysical exam
bull palpable soft tissue massbull restricted range of motion
ImagingbullRadiographs
bull peripheral bone formation with central lucent areabull may appear as dotted veil pattern
bullMRI with gadolinium bull rim enhancement is seen within the first 3 weeks
bullCT scan bull lesion has an eggshell appearance
bullCharacteristic histology shows zonal pattern bull periphery of lesion
bull mature trabeculae of lamellar and woven bonebull calcification seen on xray
bull center of the lesion bull irregular mass of immature fibroblastsbull cartilage component may be presentbull (no calcification seen on xray) bull no cellular atypia seen
Treatment
bullNonoperative bull rest range of motion exercises and activity modification
bull passive stretching is contraindicated (makes it worse)bull physical therapy
bull utilized to maintain range of motionbull radiographic monitoring
bull obtained to confirm maturation of the lesionbullOperative
bull surgical excision bull indicated only if it remains a problem after it maturesbull do not operate in acute phase wait at least six months
bull excision of the lesion within 6 to 12 months predisposes to local recurrence
A 26-year-old man presents with generalized back and joint stiffness and difficulty opening his mouth His elder sister has similar complaints Since childhood he has had 3 surgeries for excision of recurrent bony prominences around his knees He walks with a stooped over posture seen in Figure A Radiographs of his feet knee hip and spine are seen in Figures B-E respectively
fibrodysplasia ossificans progressiva
Stone Man Disease) which involves a mutation of the ACVR1
There are 2 hallmark characteristics progressive heterotopic ossification (muscles fascia tendons ligaments and joint capsules) and congenital malformation of the great toe (hallux valgus malformed first metatarsal and monophalangism) BMP4 which contributes to the formation of the skeleton in the normal embryo is implicated in this disease
Complications
bullHematoma and intraoperative bleedingbullInfection
bull higher rate of infection following joint arthroplasty if HO is present
bullFractures of osteoporotic bone bull osteopenic from disusebull during surgery or physiotherapy
bullRecurrence bull recurrence rate correlates with neurological injury
bull greater recurrence if severe neurological compromisebullAVN
bull if extensive dissection or stripping is required
HTO AND ISS
When ISS is below 25 the mortality risk is minimal and above 25 it is an almost linear increase
When ISS is 50 the mortality is 50 When above 70 it is close to 100 If an injury is assigned an AIS of 6 (unsurvivable injury) the ISS score is
automatically assigned to 75 Highest ISS score obtainable is 75 For trauma patients of vehicular accidents the scoring system is important
for assessing the effectiveness of medical care in reducing morbidity and mortality
Advantages virtually the only anatomical scoring system in use correlates linearly with
mortality morbidity hospital stay other measures of severity
Weaknesses Any error in AIS scoring increases the ISS error Many different injury patterns can yield the same ISS score Injuries to different body regions are not weighted Not a useful triage tool as a full description of patient injuries is not known
prior to full investigation amp operation
risk factors periosteal stripping off anterior femur male gender obesity post traumatic deformity Anterior and anterolateral approach Cementless
Neurogenic HO around the hip due to SCI occurs more often in the medial region than in the lateral region with ossified tissues extending from the pubic symphysis to the anteromedial femoral shaft posterior to the femoral neurovascular structures Ossification is also seen anteriorly involving the iliopsoas and femoral neurovascular structures laterally within gluteus minimus and posteriorly extending from the ilium to the posterior femur encasing the sciatic nerve
HTO AROUND hip and knee
The Brooker Classification of Heterotopic Ossification around the hip joint Class I has islands of bone within the soft tissues Class II has bone spurs from the pelvis or proximal end of the femur leaving at least 1 cm between opposing surfaces Class III has bone spurs from the pelvis andor proximal end of the femur reducing the space between opposing bone surfaces to less than 1 cm Class IV shows apparent bone ankylosis of the hip
Region I - Heterotopic ossifications are strictly below the tip of the greater trochanter
Region II - Heterotopic ossifications are below and above the tip of the greater trochanter
Region III - Heterotopic ossifications are strictly above the tip of the greater trochanter
Grade A - Single or multiple heterotopic ossifications are less than 10 mm in maximal extent without contact with the pelvis or the femur
Grade B - Heterotopic ossifications are greater than 10 mm without contact with the pelvis but with possible contact with the femur there is no bridging from the femur to the proximal part of the greater trochanter and no evidence of ankylosis
Grade C - Ankylosis by means of firm bridging from the femur to the pelvis is present
Shmidt classification
excision may be performed The results of this procedure are varied Patients may find that their range of movement improves but pain relief is likely to be limited
A patient with heterotopic ossification following total hip arthroplasty is thought to have a 90-100 chance of developing it on the contralateral hip if this hip also undergoes total arthroplasty
it would be prudent to minimize the risk of heterotopic ossification developing after arthroplasty by performing surgery whereby the following are ensured
Exposure is meticulous Retraction is performed carefully and soft tissue
is handled carefully Irrigation is adequate Devitalized tissue is excised Hemostasis is adequate Postoperative drains (when used) are not
retained for longer than necessary Perioperative antibiotic prophylaxis is used Postoperative anticoagulation (when used for
deep vein thrombosis prophylaxis) is carefully controlled
sources of knee stiffness 1-extrinsic severe osteoarthritis of the ipsilateral hip neurologic injury leading to muscle rigidity tight quadriceps or hamstring muscles secondary to muscle injury heterotopic ossification or long-standing juvenile inflammatory conditions limiting knee
range of motion prior to the completion of skeletal growth When extrinsic sources are identified revision total knee arthroplasty is unlikely to be associated with a favorable outcome without correction of the extrinsic problem
2-intrinsic (1) overstuffing of the patellofemoral articulation (2) an
excessively tight flexion andor extension gap (3) a tight posterior cruciate ligament (4) femoral andor tibial malrotation (5) arthrofibrosis and (6) limited bearing excursion in association with a highly conforming mobile-bearing prosthetic design
HTO after TKA
Heterotopic Ossification (HO) following primary Total Knee Replacement (TKR)
Occurs in 3-90 of TKRs 3-grade classification system No correlation between HO and component
alignment or component position
Clinical findings similar to early infection Continuing low-grade fever Warm swollen and erythematous knee Normal blood tests Possibly an association with HLA-A2 and B18 HO patients have worse KSS and function
scores
Patients at HIGH risk for developing HO after TKR (Knee Arthroplasty) (5)
Those with limited postoperative knee flexion
Increased lumbar bone mineral density (BMD) on multivariate analysis (3)
Hypertrophic arthrosis Excessive periosteal trauma Notching of the anterior femur Those who require forced manipulation
after TKA 47 in revision TKR surgery (6) Higher rates in revision TKR cases with
infection (up to 76
DaughertyBell classification of HO of the knee 0 No evidence of HO 1 Bone islands in periarticular soft tissue (no
involvement of femur patella or tibia) or HO within quadriceps expansion measuring lt1 cm
2 Spur formation measuring lt5 cm that involves the femur patella or tibia if more than one bone demonstrates HO separation of HO spurs
measure gt1 cm or HO within quadriceps expansion measuring ge1 cm but lt3 cm
3 Spur formation gt5 cm involving femur patella or tibia if more than one bone demonstrates HO separation of HO spurs measure lt1 cm or HO
within quadriceps expansion measuring ge3 cm 4 Extensive HO of the knee causing ankylosis
class 2 HO begins to involve the major bones of the knee joint with spur formation limited to a size of 5 cm
HO class 2 may be observed in select patients with complete ROM and no reported pain Patients with class 3 HO would likely always benefit from surgical excision
followed by RT prophylaxis Certainly patients in either cohort with a subclass ldquoBrdquo assignment (symptomatic) would
benefit from treatment All patients with class 4 HO require
treatment to alleviate ankylosis
treatment
References Whyte ldquoPagetrsquos Disease of Bonerdquo NEMJ vol 355
2006 Klein and Parvizi ldquoSurgical Manifestations of Pagetrsquos
Diseaserdquo JAAOS vol 14 2006 Orthobullets Campbell Apley Emedicinecom
-Chapter 15 Heterotopic Ossification after Traumatic Brain InjuryBy Jesuacutes Moreta and Joseacute Luis Martiacutenez-de los Mozos DOI 10577257343
Questions
Thank You
Nonsteroidal anti-inflammatory drugs (NSAIDs) These drugs have demonstrated good results in
preventing heterotopic ossification after total hip arthroplasty
A direct effect of NSAIDs on the formation of heterotopic ossification has been described due to the inhibition of the differentiation of mesenchymal cells into oestrogenic cells There is also an indirect effect which refers to the inhibition of bone remodelling by suppression of the prostagland unmediated inflammatory response (specifically PGE-2)
Indomethacin has been considered a useful medication for heterotopic ossification prophylaxis following total hip replacement
prescribed for three to six weeks in a dose of 75mgday within two months of the injury may reduce the incidence of heterotopic ossification by two to three times
Biphosphonates inhibits precipitation of calcium phosphate and blocks the aggregation and mineralisation of hydroxyapatite crystals In primary prevention Banovac et al [56] have suggested that the treatment should begin as soon as elevated alkaline phosphatase is diagnosed or positive findings in ultrasonography or bone scans are shown In addition disphosphonates could have long-term effects on prevention when the treatment is finished
Posttraumatic wide exposure and surgical resection
indications severe loss of motion and decreased function
technique wide exposure required to identify all neurovascular
structures that may be involved timing of resection (controversial)
marked decrease in bone scan activity AND normalization of ALP
6 months following general trauma 1 year following SCI 15 years following TBI
some data suggests equivalent results when comparing early versus late resection
postop follow with 5 day course of indomethacin early gentle joint mobilization
The surgery is necessary in patients with symptomatic HO and unsuccessful medical treatment such as
Loss of range of motion and ankylosis with associated functional disability such as sitting difficulties
Complications of immobility such as pressure ulcers
Facilitate rehabilitation and recovery of muscular atrophy secondary to prolonged immobilisation
Difficulties of appropriate hygiene because access to the perineum or bladder care is needed
Severe pain refractory to analgesia Vascular andor nerve compression
Advantages to early excision of heterotopic ossification (vs waiting for maturation) include decreased soft tissue contracture better definition between heterotopic and native bone and decreased waiting time for the patient When the soft tissue envelope is benign one may proceed with operative release While waiting for normalization of alkaline phosphatase levels inactivity on bone scan or radiographic maturity may decrease risk of recurrent heterotopic ossification delaying operative release for these reasons has not been shown to improve results of final elbow range of motion after contracture release
Gartland recommended surgery after six months following traumatic heterotopic ossification one year following spinal cord injury and 18 months after head injury
In the past waiting until maturity in order to minimize the rate of recurrence after the surgical treatment was recommended Nevertheless recent studies do not confirm a higher rate of recurrence when the HO is excised in an earlier phase In addition a long delay before surgery leads to ankylosis a high degree of osteoporosis and more extensive intra-articular injuries These findings are associated with bad functional results and potential complications
Should you wait till lesion maturation
Prevention byHandle tissue carefully Avoid excess bleeding Achieve good hemostasis Beware of lesions that span internervous tissue planes
but if it happens resection of a large enough amount of bone to allow improvement of the range of motion and trying to preserve the joint
Our aim must be
A reactive process that is characterized by a well-circumscribed proliferation of fibroblasts cartilage and bone within muscle
A form of heterotopic ossification that is the result direct trauma intramuscular hematoma
most common location is the diaphysis of long bones Must differentiate from tumors Fibrodysplasia ossificans progressiva (FOP) is a rare subtype of heterotopic ossification
involves mutation of the ACVR1 gene (activin A type I receptor gene a BMP type-1 receptor)
Epidemiology demographics
most common in young active males (15 to 35 years old) body locations
quadriceps brachialis and gluteal muscles Genetics
almost always a posttraumatic condition Prognosis
usually self limiting mass usually begins to decrease in size after 1 yea
Myositis ossificans
PresentationbullSymptoms
bull pain tenderness swelling and decreased range of motion that usually presents within days of the injury
bull pain and size of the mass decrease with timebull mass increases in size over several months(usually 3 to 6 cm)
bull after the mass stops growing it becomes firmbullPhysical exam
bull palpable soft tissue massbull restricted range of motion
ImagingbullRadiographs
bull peripheral bone formation with central lucent areabull may appear as dotted veil pattern
bullMRI with gadolinium bull rim enhancement is seen within the first 3 weeks
bullCT scan bull lesion has an eggshell appearance
bullCharacteristic histology shows zonal pattern bull periphery of lesion
bull mature trabeculae of lamellar and woven bonebull calcification seen on xray
bull center of the lesion bull irregular mass of immature fibroblastsbull cartilage component may be presentbull (no calcification seen on xray) bull no cellular atypia seen
Treatment
bullNonoperative bull rest range of motion exercises and activity modification
bull passive stretching is contraindicated (makes it worse)bull physical therapy
bull utilized to maintain range of motionbull radiographic monitoring
bull obtained to confirm maturation of the lesionbullOperative
bull surgical excision bull indicated only if it remains a problem after it maturesbull do not operate in acute phase wait at least six months
bull excision of the lesion within 6 to 12 months predisposes to local recurrence
A 26-year-old man presents with generalized back and joint stiffness and difficulty opening his mouth His elder sister has similar complaints Since childhood he has had 3 surgeries for excision of recurrent bony prominences around his knees He walks with a stooped over posture seen in Figure A Radiographs of his feet knee hip and spine are seen in Figures B-E respectively
fibrodysplasia ossificans progressiva
Stone Man Disease) which involves a mutation of the ACVR1
There are 2 hallmark characteristics progressive heterotopic ossification (muscles fascia tendons ligaments and joint capsules) and congenital malformation of the great toe (hallux valgus malformed first metatarsal and monophalangism) BMP4 which contributes to the formation of the skeleton in the normal embryo is implicated in this disease
Complications
bullHematoma and intraoperative bleedingbullInfection
bull higher rate of infection following joint arthroplasty if HO is present
bullFractures of osteoporotic bone bull osteopenic from disusebull during surgery or physiotherapy
bullRecurrence bull recurrence rate correlates with neurological injury
bull greater recurrence if severe neurological compromisebullAVN
bull if extensive dissection or stripping is required
HTO AND ISS
When ISS is below 25 the mortality risk is minimal and above 25 it is an almost linear increase
When ISS is 50 the mortality is 50 When above 70 it is close to 100 If an injury is assigned an AIS of 6 (unsurvivable injury) the ISS score is
automatically assigned to 75 Highest ISS score obtainable is 75 For trauma patients of vehicular accidents the scoring system is important
for assessing the effectiveness of medical care in reducing morbidity and mortality
Advantages virtually the only anatomical scoring system in use correlates linearly with
mortality morbidity hospital stay other measures of severity
Weaknesses Any error in AIS scoring increases the ISS error Many different injury patterns can yield the same ISS score Injuries to different body regions are not weighted Not a useful triage tool as a full description of patient injuries is not known
prior to full investigation amp operation
risk factors periosteal stripping off anterior femur male gender obesity post traumatic deformity Anterior and anterolateral approach Cementless
Neurogenic HO around the hip due to SCI occurs more often in the medial region than in the lateral region with ossified tissues extending from the pubic symphysis to the anteromedial femoral shaft posterior to the femoral neurovascular structures Ossification is also seen anteriorly involving the iliopsoas and femoral neurovascular structures laterally within gluteus minimus and posteriorly extending from the ilium to the posterior femur encasing the sciatic nerve
HTO AROUND hip and knee
The Brooker Classification of Heterotopic Ossification around the hip joint Class I has islands of bone within the soft tissues Class II has bone spurs from the pelvis or proximal end of the femur leaving at least 1 cm between opposing surfaces Class III has bone spurs from the pelvis andor proximal end of the femur reducing the space between opposing bone surfaces to less than 1 cm Class IV shows apparent bone ankylosis of the hip
Region I - Heterotopic ossifications are strictly below the tip of the greater trochanter
Region II - Heterotopic ossifications are below and above the tip of the greater trochanter
Region III - Heterotopic ossifications are strictly above the tip of the greater trochanter
Grade A - Single or multiple heterotopic ossifications are less than 10 mm in maximal extent without contact with the pelvis or the femur
Grade B - Heterotopic ossifications are greater than 10 mm without contact with the pelvis but with possible contact with the femur there is no bridging from the femur to the proximal part of the greater trochanter and no evidence of ankylosis
Grade C - Ankylosis by means of firm bridging from the femur to the pelvis is present
Shmidt classification
excision may be performed The results of this procedure are varied Patients may find that their range of movement improves but pain relief is likely to be limited
A patient with heterotopic ossification following total hip arthroplasty is thought to have a 90-100 chance of developing it on the contralateral hip if this hip also undergoes total arthroplasty
it would be prudent to minimize the risk of heterotopic ossification developing after arthroplasty by performing surgery whereby the following are ensured
Exposure is meticulous Retraction is performed carefully and soft tissue
is handled carefully Irrigation is adequate Devitalized tissue is excised Hemostasis is adequate Postoperative drains (when used) are not
retained for longer than necessary Perioperative antibiotic prophylaxis is used Postoperative anticoagulation (when used for
deep vein thrombosis prophylaxis) is carefully controlled
sources of knee stiffness 1-extrinsic severe osteoarthritis of the ipsilateral hip neurologic injury leading to muscle rigidity tight quadriceps or hamstring muscles secondary to muscle injury heterotopic ossification or long-standing juvenile inflammatory conditions limiting knee
range of motion prior to the completion of skeletal growth When extrinsic sources are identified revision total knee arthroplasty is unlikely to be associated with a favorable outcome without correction of the extrinsic problem
2-intrinsic (1) overstuffing of the patellofemoral articulation (2) an
excessively tight flexion andor extension gap (3) a tight posterior cruciate ligament (4) femoral andor tibial malrotation (5) arthrofibrosis and (6) limited bearing excursion in association with a highly conforming mobile-bearing prosthetic design
HTO after TKA
Heterotopic Ossification (HO) following primary Total Knee Replacement (TKR)
Occurs in 3-90 of TKRs 3-grade classification system No correlation between HO and component
alignment or component position
Clinical findings similar to early infection Continuing low-grade fever Warm swollen and erythematous knee Normal blood tests Possibly an association with HLA-A2 and B18 HO patients have worse KSS and function
scores
Patients at HIGH risk for developing HO after TKR (Knee Arthroplasty) (5)
Those with limited postoperative knee flexion
Increased lumbar bone mineral density (BMD) on multivariate analysis (3)
Hypertrophic arthrosis Excessive periosteal trauma Notching of the anterior femur Those who require forced manipulation
after TKA 47 in revision TKR surgery (6) Higher rates in revision TKR cases with
infection (up to 76
DaughertyBell classification of HO of the knee 0 No evidence of HO 1 Bone islands in periarticular soft tissue (no
involvement of femur patella or tibia) or HO within quadriceps expansion measuring lt1 cm
2 Spur formation measuring lt5 cm that involves the femur patella or tibia if more than one bone demonstrates HO separation of HO spurs
measure gt1 cm or HO within quadriceps expansion measuring ge1 cm but lt3 cm
3 Spur formation gt5 cm involving femur patella or tibia if more than one bone demonstrates HO separation of HO spurs measure lt1 cm or HO
within quadriceps expansion measuring ge3 cm 4 Extensive HO of the knee causing ankylosis
class 2 HO begins to involve the major bones of the knee joint with spur formation limited to a size of 5 cm
HO class 2 may be observed in select patients with complete ROM and no reported pain Patients with class 3 HO would likely always benefit from surgical excision
followed by RT prophylaxis Certainly patients in either cohort with a subclass ldquoBrdquo assignment (symptomatic) would
benefit from treatment All patients with class 4 HO require
treatment to alleviate ankylosis
treatment
References Whyte ldquoPagetrsquos Disease of Bonerdquo NEMJ vol 355
2006 Klein and Parvizi ldquoSurgical Manifestations of Pagetrsquos
Diseaserdquo JAAOS vol 14 2006 Orthobullets Campbell Apley Emedicinecom
-Chapter 15 Heterotopic Ossification after Traumatic Brain InjuryBy Jesuacutes Moreta and Joseacute Luis Martiacutenez-de los Mozos DOI 10577257343
Questions
Thank You
Biphosphonates inhibits precipitation of calcium phosphate and blocks the aggregation and mineralisation of hydroxyapatite crystals In primary prevention Banovac et al [56] have suggested that the treatment should begin as soon as elevated alkaline phosphatase is diagnosed or positive findings in ultrasonography or bone scans are shown In addition disphosphonates could have long-term effects on prevention when the treatment is finished
Posttraumatic wide exposure and surgical resection
indications severe loss of motion and decreased function
technique wide exposure required to identify all neurovascular
structures that may be involved timing of resection (controversial)
marked decrease in bone scan activity AND normalization of ALP
6 months following general trauma 1 year following SCI 15 years following TBI
some data suggests equivalent results when comparing early versus late resection
postop follow with 5 day course of indomethacin early gentle joint mobilization
The surgery is necessary in patients with symptomatic HO and unsuccessful medical treatment such as
Loss of range of motion and ankylosis with associated functional disability such as sitting difficulties
Complications of immobility such as pressure ulcers
Facilitate rehabilitation and recovery of muscular atrophy secondary to prolonged immobilisation
Difficulties of appropriate hygiene because access to the perineum or bladder care is needed
Severe pain refractory to analgesia Vascular andor nerve compression
Advantages to early excision of heterotopic ossification (vs waiting for maturation) include decreased soft tissue contracture better definition between heterotopic and native bone and decreased waiting time for the patient When the soft tissue envelope is benign one may proceed with operative release While waiting for normalization of alkaline phosphatase levels inactivity on bone scan or radiographic maturity may decrease risk of recurrent heterotopic ossification delaying operative release for these reasons has not been shown to improve results of final elbow range of motion after contracture release
Gartland recommended surgery after six months following traumatic heterotopic ossification one year following spinal cord injury and 18 months after head injury
In the past waiting until maturity in order to minimize the rate of recurrence after the surgical treatment was recommended Nevertheless recent studies do not confirm a higher rate of recurrence when the HO is excised in an earlier phase In addition a long delay before surgery leads to ankylosis a high degree of osteoporosis and more extensive intra-articular injuries These findings are associated with bad functional results and potential complications
Should you wait till lesion maturation
Prevention byHandle tissue carefully Avoid excess bleeding Achieve good hemostasis Beware of lesions that span internervous tissue planes
but if it happens resection of a large enough amount of bone to allow improvement of the range of motion and trying to preserve the joint
Our aim must be
A reactive process that is characterized by a well-circumscribed proliferation of fibroblasts cartilage and bone within muscle
A form of heterotopic ossification that is the result direct trauma intramuscular hematoma
most common location is the diaphysis of long bones Must differentiate from tumors Fibrodysplasia ossificans progressiva (FOP) is a rare subtype of heterotopic ossification
involves mutation of the ACVR1 gene (activin A type I receptor gene a BMP type-1 receptor)
Epidemiology demographics
most common in young active males (15 to 35 years old) body locations
quadriceps brachialis and gluteal muscles Genetics
almost always a posttraumatic condition Prognosis
usually self limiting mass usually begins to decrease in size after 1 yea
Myositis ossificans
PresentationbullSymptoms
bull pain tenderness swelling and decreased range of motion that usually presents within days of the injury
bull pain and size of the mass decrease with timebull mass increases in size over several months(usually 3 to 6 cm)
bull after the mass stops growing it becomes firmbullPhysical exam
bull palpable soft tissue massbull restricted range of motion
ImagingbullRadiographs
bull peripheral bone formation with central lucent areabull may appear as dotted veil pattern
bullMRI with gadolinium bull rim enhancement is seen within the first 3 weeks
bullCT scan bull lesion has an eggshell appearance
bullCharacteristic histology shows zonal pattern bull periphery of lesion
bull mature trabeculae of lamellar and woven bonebull calcification seen on xray
bull center of the lesion bull irregular mass of immature fibroblastsbull cartilage component may be presentbull (no calcification seen on xray) bull no cellular atypia seen
Treatment
bullNonoperative bull rest range of motion exercises and activity modification
bull passive stretching is contraindicated (makes it worse)bull physical therapy
bull utilized to maintain range of motionbull radiographic monitoring
bull obtained to confirm maturation of the lesionbullOperative
bull surgical excision bull indicated only if it remains a problem after it maturesbull do not operate in acute phase wait at least six months
bull excision of the lesion within 6 to 12 months predisposes to local recurrence
A 26-year-old man presents with generalized back and joint stiffness and difficulty opening his mouth His elder sister has similar complaints Since childhood he has had 3 surgeries for excision of recurrent bony prominences around his knees He walks with a stooped over posture seen in Figure A Radiographs of his feet knee hip and spine are seen in Figures B-E respectively
fibrodysplasia ossificans progressiva
Stone Man Disease) which involves a mutation of the ACVR1
There are 2 hallmark characteristics progressive heterotopic ossification (muscles fascia tendons ligaments and joint capsules) and congenital malformation of the great toe (hallux valgus malformed first metatarsal and monophalangism) BMP4 which contributes to the formation of the skeleton in the normal embryo is implicated in this disease
Complications
bullHematoma and intraoperative bleedingbullInfection
bull higher rate of infection following joint arthroplasty if HO is present
bullFractures of osteoporotic bone bull osteopenic from disusebull during surgery or physiotherapy
bullRecurrence bull recurrence rate correlates with neurological injury
bull greater recurrence if severe neurological compromisebullAVN
bull if extensive dissection or stripping is required
HTO AND ISS
When ISS is below 25 the mortality risk is minimal and above 25 it is an almost linear increase
When ISS is 50 the mortality is 50 When above 70 it is close to 100 If an injury is assigned an AIS of 6 (unsurvivable injury) the ISS score is
automatically assigned to 75 Highest ISS score obtainable is 75 For trauma patients of vehicular accidents the scoring system is important
for assessing the effectiveness of medical care in reducing morbidity and mortality
Advantages virtually the only anatomical scoring system in use correlates linearly with
mortality morbidity hospital stay other measures of severity
Weaknesses Any error in AIS scoring increases the ISS error Many different injury patterns can yield the same ISS score Injuries to different body regions are not weighted Not a useful triage tool as a full description of patient injuries is not known
prior to full investigation amp operation
risk factors periosteal stripping off anterior femur male gender obesity post traumatic deformity Anterior and anterolateral approach Cementless
Neurogenic HO around the hip due to SCI occurs more often in the medial region than in the lateral region with ossified tissues extending from the pubic symphysis to the anteromedial femoral shaft posterior to the femoral neurovascular structures Ossification is also seen anteriorly involving the iliopsoas and femoral neurovascular structures laterally within gluteus minimus and posteriorly extending from the ilium to the posterior femur encasing the sciatic nerve
HTO AROUND hip and knee
The Brooker Classification of Heterotopic Ossification around the hip joint Class I has islands of bone within the soft tissues Class II has bone spurs from the pelvis or proximal end of the femur leaving at least 1 cm between opposing surfaces Class III has bone spurs from the pelvis andor proximal end of the femur reducing the space between opposing bone surfaces to less than 1 cm Class IV shows apparent bone ankylosis of the hip
Region I - Heterotopic ossifications are strictly below the tip of the greater trochanter
Region II - Heterotopic ossifications are below and above the tip of the greater trochanter
Region III - Heterotopic ossifications are strictly above the tip of the greater trochanter
Grade A - Single or multiple heterotopic ossifications are less than 10 mm in maximal extent without contact with the pelvis or the femur
Grade B - Heterotopic ossifications are greater than 10 mm without contact with the pelvis but with possible contact with the femur there is no bridging from the femur to the proximal part of the greater trochanter and no evidence of ankylosis
Grade C - Ankylosis by means of firm bridging from the femur to the pelvis is present
Shmidt classification
excision may be performed The results of this procedure are varied Patients may find that their range of movement improves but pain relief is likely to be limited
A patient with heterotopic ossification following total hip arthroplasty is thought to have a 90-100 chance of developing it on the contralateral hip if this hip also undergoes total arthroplasty
it would be prudent to minimize the risk of heterotopic ossification developing after arthroplasty by performing surgery whereby the following are ensured
Exposure is meticulous Retraction is performed carefully and soft tissue
is handled carefully Irrigation is adequate Devitalized tissue is excised Hemostasis is adequate Postoperative drains (when used) are not
retained for longer than necessary Perioperative antibiotic prophylaxis is used Postoperative anticoagulation (when used for
deep vein thrombosis prophylaxis) is carefully controlled
sources of knee stiffness 1-extrinsic severe osteoarthritis of the ipsilateral hip neurologic injury leading to muscle rigidity tight quadriceps or hamstring muscles secondary to muscle injury heterotopic ossification or long-standing juvenile inflammatory conditions limiting knee
range of motion prior to the completion of skeletal growth When extrinsic sources are identified revision total knee arthroplasty is unlikely to be associated with a favorable outcome without correction of the extrinsic problem
2-intrinsic (1) overstuffing of the patellofemoral articulation (2) an
excessively tight flexion andor extension gap (3) a tight posterior cruciate ligament (4) femoral andor tibial malrotation (5) arthrofibrosis and (6) limited bearing excursion in association with a highly conforming mobile-bearing prosthetic design
HTO after TKA
Heterotopic Ossification (HO) following primary Total Knee Replacement (TKR)
Occurs in 3-90 of TKRs 3-grade classification system No correlation between HO and component
alignment or component position
Clinical findings similar to early infection Continuing low-grade fever Warm swollen and erythematous knee Normal blood tests Possibly an association with HLA-A2 and B18 HO patients have worse KSS and function
scores
Patients at HIGH risk for developing HO after TKR (Knee Arthroplasty) (5)
Those with limited postoperative knee flexion
Increased lumbar bone mineral density (BMD) on multivariate analysis (3)
Hypertrophic arthrosis Excessive periosteal trauma Notching of the anterior femur Those who require forced manipulation
after TKA 47 in revision TKR surgery (6) Higher rates in revision TKR cases with
infection (up to 76
DaughertyBell classification of HO of the knee 0 No evidence of HO 1 Bone islands in periarticular soft tissue (no
involvement of femur patella or tibia) or HO within quadriceps expansion measuring lt1 cm
2 Spur formation measuring lt5 cm that involves the femur patella or tibia if more than one bone demonstrates HO separation of HO spurs
measure gt1 cm or HO within quadriceps expansion measuring ge1 cm but lt3 cm
3 Spur formation gt5 cm involving femur patella or tibia if more than one bone demonstrates HO separation of HO spurs measure lt1 cm or HO
within quadriceps expansion measuring ge3 cm 4 Extensive HO of the knee causing ankylosis
class 2 HO begins to involve the major bones of the knee joint with spur formation limited to a size of 5 cm
HO class 2 may be observed in select patients with complete ROM and no reported pain Patients with class 3 HO would likely always benefit from surgical excision
followed by RT prophylaxis Certainly patients in either cohort with a subclass ldquoBrdquo assignment (symptomatic) would
benefit from treatment All patients with class 4 HO require
treatment to alleviate ankylosis
treatment
References Whyte ldquoPagetrsquos Disease of Bonerdquo NEMJ vol 355
2006 Klein and Parvizi ldquoSurgical Manifestations of Pagetrsquos
Diseaserdquo JAAOS vol 14 2006 Orthobullets Campbell Apley Emedicinecom
-Chapter 15 Heterotopic Ossification after Traumatic Brain InjuryBy Jesuacutes Moreta and Joseacute Luis Martiacutenez-de los Mozos DOI 10577257343
Questions
Thank You
Posttraumatic wide exposure and surgical resection
indications severe loss of motion and decreased function
technique wide exposure required to identify all neurovascular
structures that may be involved timing of resection (controversial)
marked decrease in bone scan activity AND normalization of ALP
6 months following general trauma 1 year following SCI 15 years following TBI
some data suggests equivalent results when comparing early versus late resection
postop follow with 5 day course of indomethacin early gentle joint mobilization
The surgery is necessary in patients with symptomatic HO and unsuccessful medical treatment such as
Loss of range of motion and ankylosis with associated functional disability such as sitting difficulties
Complications of immobility such as pressure ulcers
Facilitate rehabilitation and recovery of muscular atrophy secondary to prolonged immobilisation
Difficulties of appropriate hygiene because access to the perineum or bladder care is needed
Severe pain refractory to analgesia Vascular andor nerve compression
Advantages to early excision of heterotopic ossification (vs waiting for maturation) include decreased soft tissue contracture better definition between heterotopic and native bone and decreased waiting time for the patient When the soft tissue envelope is benign one may proceed with operative release While waiting for normalization of alkaline phosphatase levels inactivity on bone scan or radiographic maturity may decrease risk of recurrent heterotopic ossification delaying operative release for these reasons has not been shown to improve results of final elbow range of motion after contracture release
Gartland recommended surgery after six months following traumatic heterotopic ossification one year following spinal cord injury and 18 months after head injury
In the past waiting until maturity in order to minimize the rate of recurrence after the surgical treatment was recommended Nevertheless recent studies do not confirm a higher rate of recurrence when the HO is excised in an earlier phase In addition a long delay before surgery leads to ankylosis a high degree of osteoporosis and more extensive intra-articular injuries These findings are associated with bad functional results and potential complications
Should you wait till lesion maturation
Prevention byHandle tissue carefully Avoid excess bleeding Achieve good hemostasis Beware of lesions that span internervous tissue planes
but if it happens resection of a large enough amount of bone to allow improvement of the range of motion and trying to preserve the joint
Our aim must be
A reactive process that is characterized by a well-circumscribed proliferation of fibroblasts cartilage and bone within muscle
A form of heterotopic ossification that is the result direct trauma intramuscular hematoma
most common location is the diaphysis of long bones Must differentiate from tumors Fibrodysplasia ossificans progressiva (FOP) is a rare subtype of heterotopic ossification
involves mutation of the ACVR1 gene (activin A type I receptor gene a BMP type-1 receptor)
Epidemiology demographics
most common in young active males (15 to 35 years old) body locations
quadriceps brachialis and gluteal muscles Genetics
almost always a posttraumatic condition Prognosis
usually self limiting mass usually begins to decrease in size after 1 yea
Myositis ossificans
PresentationbullSymptoms
bull pain tenderness swelling and decreased range of motion that usually presents within days of the injury
bull pain and size of the mass decrease with timebull mass increases in size over several months(usually 3 to 6 cm)
bull after the mass stops growing it becomes firmbullPhysical exam
bull palpable soft tissue massbull restricted range of motion
ImagingbullRadiographs
bull peripheral bone formation with central lucent areabull may appear as dotted veil pattern
bullMRI with gadolinium bull rim enhancement is seen within the first 3 weeks
bullCT scan bull lesion has an eggshell appearance
bullCharacteristic histology shows zonal pattern bull periphery of lesion
bull mature trabeculae of lamellar and woven bonebull calcification seen on xray
bull center of the lesion bull irregular mass of immature fibroblastsbull cartilage component may be presentbull (no calcification seen on xray) bull no cellular atypia seen
Treatment
bullNonoperative bull rest range of motion exercises and activity modification
bull passive stretching is contraindicated (makes it worse)bull physical therapy
bull utilized to maintain range of motionbull radiographic monitoring
bull obtained to confirm maturation of the lesionbullOperative
bull surgical excision bull indicated only if it remains a problem after it maturesbull do not operate in acute phase wait at least six months
bull excision of the lesion within 6 to 12 months predisposes to local recurrence
A 26-year-old man presents with generalized back and joint stiffness and difficulty opening his mouth His elder sister has similar complaints Since childhood he has had 3 surgeries for excision of recurrent bony prominences around his knees He walks with a stooped over posture seen in Figure A Radiographs of his feet knee hip and spine are seen in Figures B-E respectively
fibrodysplasia ossificans progressiva
Stone Man Disease) which involves a mutation of the ACVR1
There are 2 hallmark characteristics progressive heterotopic ossification (muscles fascia tendons ligaments and joint capsules) and congenital malformation of the great toe (hallux valgus malformed first metatarsal and monophalangism) BMP4 which contributes to the formation of the skeleton in the normal embryo is implicated in this disease
Complications
bullHematoma and intraoperative bleedingbullInfection
bull higher rate of infection following joint arthroplasty if HO is present
bullFractures of osteoporotic bone bull osteopenic from disusebull during surgery or physiotherapy
bullRecurrence bull recurrence rate correlates with neurological injury
bull greater recurrence if severe neurological compromisebullAVN
bull if extensive dissection or stripping is required
HTO AND ISS
When ISS is below 25 the mortality risk is minimal and above 25 it is an almost linear increase
When ISS is 50 the mortality is 50 When above 70 it is close to 100 If an injury is assigned an AIS of 6 (unsurvivable injury) the ISS score is
automatically assigned to 75 Highest ISS score obtainable is 75 For trauma patients of vehicular accidents the scoring system is important
for assessing the effectiveness of medical care in reducing morbidity and mortality
Advantages virtually the only anatomical scoring system in use correlates linearly with
mortality morbidity hospital stay other measures of severity
Weaknesses Any error in AIS scoring increases the ISS error Many different injury patterns can yield the same ISS score Injuries to different body regions are not weighted Not a useful triage tool as a full description of patient injuries is not known
prior to full investigation amp operation
risk factors periosteal stripping off anterior femur male gender obesity post traumatic deformity Anterior and anterolateral approach Cementless
Neurogenic HO around the hip due to SCI occurs more often in the medial region than in the lateral region with ossified tissues extending from the pubic symphysis to the anteromedial femoral shaft posterior to the femoral neurovascular structures Ossification is also seen anteriorly involving the iliopsoas and femoral neurovascular structures laterally within gluteus minimus and posteriorly extending from the ilium to the posterior femur encasing the sciatic nerve
HTO AROUND hip and knee
The Brooker Classification of Heterotopic Ossification around the hip joint Class I has islands of bone within the soft tissues Class II has bone spurs from the pelvis or proximal end of the femur leaving at least 1 cm between opposing surfaces Class III has bone spurs from the pelvis andor proximal end of the femur reducing the space between opposing bone surfaces to less than 1 cm Class IV shows apparent bone ankylosis of the hip
Region I - Heterotopic ossifications are strictly below the tip of the greater trochanter
Region II - Heterotopic ossifications are below and above the tip of the greater trochanter
Region III - Heterotopic ossifications are strictly above the tip of the greater trochanter
Grade A - Single or multiple heterotopic ossifications are less than 10 mm in maximal extent without contact with the pelvis or the femur
Grade B - Heterotopic ossifications are greater than 10 mm without contact with the pelvis but with possible contact with the femur there is no bridging from the femur to the proximal part of the greater trochanter and no evidence of ankylosis
Grade C - Ankylosis by means of firm bridging from the femur to the pelvis is present
Shmidt classification
excision may be performed The results of this procedure are varied Patients may find that their range of movement improves but pain relief is likely to be limited
A patient with heterotopic ossification following total hip arthroplasty is thought to have a 90-100 chance of developing it on the contralateral hip if this hip also undergoes total arthroplasty
it would be prudent to minimize the risk of heterotopic ossification developing after arthroplasty by performing surgery whereby the following are ensured
Exposure is meticulous Retraction is performed carefully and soft tissue
is handled carefully Irrigation is adequate Devitalized tissue is excised Hemostasis is adequate Postoperative drains (when used) are not
retained for longer than necessary Perioperative antibiotic prophylaxis is used Postoperative anticoagulation (when used for
deep vein thrombosis prophylaxis) is carefully controlled
sources of knee stiffness 1-extrinsic severe osteoarthritis of the ipsilateral hip neurologic injury leading to muscle rigidity tight quadriceps or hamstring muscles secondary to muscle injury heterotopic ossification or long-standing juvenile inflammatory conditions limiting knee
range of motion prior to the completion of skeletal growth When extrinsic sources are identified revision total knee arthroplasty is unlikely to be associated with a favorable outcome without correction of the extrinsic problem
2-intrinsic (1) overstuffing of the patellofemoral articulation (2) an
excessively tight flexion andor extension gap (3) a tight posterior cruciate ligament (4) femoral andor tibial malrotation (5) arthrofibrosis and (6) limited bearing excursion in association with a highly conforming mobile-bearing prosthetic design
HTO after TKA
Heterotopic Ossification (HO) following primary Total Knee Replacement (TKR)
Occurs in 3-90 of TKRs 3-grade classification system No correlation between HO and component
alignment or component position
Clinical findings similar to early infection Continuing low-grade fever Warm swollen and erythematous knee Normal blood tests Possibly an association with HLA-A2 and B18 HO patients have worse KSS and function
scores
Patients at HIGH risk for developing HO after TKR (Knee Arthroplasty) (5)
Those with limited postoperative knee flexion
Increased lumbar bone mineral density (BMD) on multivariate analysis (3)
Hypertrophic arthrosis Excessive periosteal trauma Notching of the anterior femur Those who require forced manipulation
after TKA 47 in revision TKR surgery (6) Higher rates in revision TKR cases with
infection (up to 76
DaughertyBell classification of HO of the knee 0 No evidence of HO 1 Bone islands in periarticular soft tissue (no
involvement of femur patella or tibia) or HO within quadriceps expansion measuring lt1 cm
2 Spur formation measuring lt5 cm that involves the femur patella or tibia if more than one bone demonstrates HO separation of HO spurs
measure gt1 cm or HO within quadriceps expansion measuring ge1 cm but lt3 cm
3 Spur formation gt5 cm involving femur patella or tibia if more than one bone demonstrates HO separation of HO spurs measure lt1 cm or HO
within quadriceps expansion measuring ge3 cm 4 Extensive HO of the knee causing ankylosis
class 2 HO begins to involve the major bones of the knee joint with spur formation limited to a size of 5 cm
HO class 2 may be observed in select patients with complete ROM and no reported pain Patients with class 3 HO would likely always benefit from surgical excision
followed by RT prophylaxis Certainly patients in either cohort with a subclass ldquoBrdquo assignment (symptomatic) would
benefit from treatment All patients with class 4 HO require
treatment to alleviate ankylosis
treatment
References Whyte ldquoPagetrsquos Disease of Bonerdquo NEMJ vol 355
2006 Klein and Parvizi ldquoSurgical Manifestations of Pagetrsquos
Diseaserdquo JAAOS vol 14 2006 Orthobullets Campbell Apley Emedicinecom
-Chapter 15 Heterotopic Ossification after Traumatic Brain InjuryBy Jesuacutes Moreta and Joseacute Luis Martiacutenez-de los Mozos DOI 10577257343
Questions
Thank You
The surgery is necessary in patients with symptomatic HO and unsuccessful medical treatment such as
Loss of range of motion and ankylosis with associated functional disability such as sitting difficulties
Complications of immobility such as pressure ulcers
Facilitate rehabilitation and recovery of muscular atrophy secondary to prolonged immobilisation
Difficulties of appropriate hygiene because access to the perineum or bladder care is needed
Severe pain refractory to analgesia Vascular andor nerve compression
Advantages to early excision of heterotopic ossification (vs waiting for maturation) include decreased soft tissue contracture better definition between heterotopic and native bone and decreased waiting time for the patient When the soft tissue envelope is benign one may proceed with operative release While waiting for normalization of alkaline phosphatase levels inactivity on bone scan or radiographic maturity may decrease risk of recurrent heterotopic ossification delaying operative release for these reasons has not been shown to improve results of final elbow range of motion after contracture release
Gartland recommended surgery after six months following traumatic heterotopic ossification one year following spinal cord injury and 18 months after head injury
In the past waiting until maturity in order to minimize the rate of recurrence after the surgical treatment was recommended Nevertheless recent studies do not confirm a higher rate of recurrence when the HO is excised in an earlier phase In addition a long delay before surgery leads to ankylosis a high degree of osteoporosis and more extensive intra-articular injuries These findings are associated with bad functional results and potential complications
Should you wait till lesion maturation
Prevention byHandle tissue carefully Avoid excess bleeding Achieve good hemostasis Beware of lesions that span internervous tissue planes
but if it happens resection of a large enough amount of bone to allow improvement of the range of motion and trying to preserve the joint
Our aim must be
A reactive process that is characterized by a well-circumscribed proliferation of fibroblasts cartilage and bone within muscle
A form of heterotopic ossification that is the result direct trauma intramuscular hematoma
most common location is the diaphysis of long bones Must differentiate from tumors Fibrodysplasia ossificans progressiva (FOP) is a rare subtype of heterotopic ossification
involves mutation of the ACVR1 gene (activin A type I receptor gene a BMP type-1 receptor)
Epidemiology demographics
most common in young active males (15 to 35 years old) body locations
quadriceps brachialis and gluteal muscles Genetics
almost always a posttraumatic condition Prognosis
usually self limiting mass usually begins to decrease in size after 1 yea
Myositis ossificans
PresentationbullSymptoms
bull pain tenderness swelling and decreased range of motion that usually presents within days of the injury
bull pain and size of the mass decrease with timebull mass increases in size over several months(usually 3 to 6 cm)
bull after the mass stops growing it becomes firmbullPhysical exam
bull palpable soft tissue massbull restricted range of motion
ImagingbullRadiographs
bull peripheral bone formation with central lucent areabull may appear as dotted veil pattern
bullMRI with gadolinium bull rim enhancement is seen within the first 3 weeks
bullCT scan bull lesion has an eggshell appearance
bullCharacteristic histology shows zonal pattern bull periphery of lesion
bull mature trabeculae of lamellar and woven bonebull calcification seen on xray
bull center of the lesion bull irregular mass of immature fibroblastsbull cartilage component may be presentbull (no calcification seen on xray) bull no cellular atypia seen
Treatment
bullNonoperative bull rest range of motion exercises and activity modification
bull passive stretching is contraindicated (makes it worse)bull physical therapy
bull utilized to maintain range of motionbull radiographic monitoring
bull obtained to confirm maturation of the lesionbullOperative
bull surgical excision bull indicated only if it remains a problem after it maturesbull do not operate in acute phase wait at least six months
bull excision of the lesion within 6 to 12 months predisposes to local recurrence
A 26-year-old man presents with generalized back and joint stiffness and difficulty opening his mouth His elder sister has similar complaints Since childhood he has had 3 surgeries for excision of recurrent bony prominences around his knees He walks with a stooped over posture seen in Figure A Radiographs of his feet knee hip and spine are seen in Figures B-E respectively
fibrodysplasia ossificans progressiva
Stone Man Disease) which involves a mutation of the ACVR1
There are 2 hallmark characteristics progressive heterotopic ossification (muscles fascia tendons ligaments and joint capsules) and congenital malformation of the great toe (hallux valgus malformed first metatarsal and monophalangism) BMP4 which contributes to the formation of the skeleton in the normal embryo is implicated in this disease
Complications
bullHematoma and intraoperative bleedingbullInfection
bull higher rate of infection following joint arthroplasty if HO is present
bullFractures of osteoporotic bone bull osteopenic from disusebull during surgery or physiotherapy
bullRecurrence bull recurrence rate correlates with neurological injury
bull greater recurrence if severe neurological compromisebullAVN
bull if extensive dissection or stripping is required
HTO AND ISS
When ISS is below 25 the mortality risk is minimal and above 25 it is an almost linear increase
When ISS is 50 the mortality is 50 When above 70 it is close to 100 If an injury is assigned an AIS of 6 (unsurvivable injury) the ISS score is
automatically assigned to 75 Highest ISS score obtainable is 75 For trauma patients of vehicular accidents the scoring system is important
for assessing the effectiveness of medical care in reducing morbidity and mortality
Advantages virtually the only anatomical scoring system in use correlates linearly with
mortality morbidity hospital stay other measures of severity
Weaknesses Any error in AIS scoring increases the ISS error Many different injury patterns can yield the same ISS score Injuries to different body regions are not weighted Not a useful triage tool as a full description of patient injuries is not known
prior to full investigation amp operation
risk factors periosteal stripping off anterior femur male gender obesity post traumatic deformity Anterior and anterolateral approach Cementless
Neurogenic HO around the hip due to SCI occurs more often in the medial region than in the lateral region with ossified tissues extending from the pubic symphysis to the anteromedial femoral shaft posterior to the femoral neurovascular structures Ossification is also seen anteriorly involving the iliopsoas and femoral neurovascular structures laterally within gluteus minimus and posteriorly extending from the ilium to the posterior femur encasing the sciatic nerve
HTO AROUND hip and knee
The Brooker Classification of Heterotopic Ossification around the hip joint Class I has islands of bone within the soft tissues Class II has bone spurs from the pelvis or proximal end of the femur leaving at least 1 cm between opposing surfaces Class III has bone spurs from the pelvis andor proximal end of the femur reducing the space between opposing bone surfaces to less than 1 cm Class IV shows apparent bone ankylosis of the hip
Region I - Heterotopic ossifications are strictly below the tip of the greater trochanter
Region II - Heterotopic ossifications are below and above the tip of the greater trochanter
Region III - Heterotopic ossifications are strictly above the tip of the greater trochanter
Grade A - Single or multiple heterotopic ossifications are less than 10 mm in maximal extent without contact with the pelvis or the femur
Grade B - Heterotopic ossifications are greater than 10 mm without contact with the pelvis but with possible contact with the femur there is no bridging from the femur to the proximal part of the greater trochanter and no evidence of ankylosis
Grade C - Ankylosis by means of firm bridging from the femur to the pelvis is present
Shmidt classification
excision may be performed The results of this procedure are varied Patients may find that their range of movement improves but pain relief is likely to be limited
A patient with heterotopic ossification following total hip arthroplasty is thought to have a 90-100 chance of developing it on the contralateral hip if this hip also undergoes total arthroplasty
it would be prudent to minimize the risk of heterotopic ossification developing after arthroplasty by performing surgery whereby the following are ensured
Exposure is meticulous Retraction is performed carefully and soft tissue
is handled carefully Irrigation is adequate Devitalized tissue is excised Hemostasis is adequate Postoperative drains (when used) are not
retained for longer than necessary Perioperative antibiotic prophylaxis is used Postoperative anticoagulation (when used for
deep vein thrombosis prophylaxis) is carefully controlled
sources of knee stiffness 1-extrinsic severe osteoarthritis of the ipsilateral hip neurologic injury leading to muscle rigidity tight quadriceps or hamstring muscles secondary to muscle injury heterotopic ossification or long-standing juvenile inflammatory conditions limiting knee
range of motion prior to the completion of skeletal growth When extrinsic sources are identified revision total knee arthroplasty is unlikely to be associated with a favorable outcome without correction of the extrinsic problem
2-intrinsic (1) overstuffing of the patellofemoral articulation (2) an
excessively tight flexion andor extension gap (3) a tight posterior cruciate ligament (4) femoral andor tibial malrotation (5) arthrofibrosis and (6) limited bearing excursion in association with a highly conforming mobile-bearing prosthetic design
HTO after TKA
Heterotopic Ossification (HO) following primary Total Knee Replacement (TKR)
Occurs in 3-90 of TKRs 3-grade classification system No correlation between HO and component
alignment or component position
Clinical findings similar to early infection Continuing low-grade fever Warm swollen and erythematous knee Normal blood tests Possibly an association with HLA-A2 and B18 HO patients have worse KSS and function
scores
Patients at HIGH risk for developing HO after TKR (Knee Arthroplasty) (5)
Those with limited postoperative knee flexion
Increased lumbar bone mineral density (BMD) on multivariate analysis (3)
Hypertrophic arthrosis Excessive periosteal trauma Notching of the anterior femur Those who require forced manipulation
after TKA 47 in revision TKR surgery (6) Higher rates in revision TKR cases with
infection (up to 76
DaughertyBell classification of HO of the knee 0 No evidence of HO 1 Bone islands in periarticular soft tissue (no
involvement of femur patella or tibia) or HO within quadriceps expansion measuring lt1 cm
2 Spur formation measuring lt5 cm that involves the femur patella or tibia if more than one bone demonstrates HO separation of HO spurs
measure gt1 cm or HO within quadriceps expansion measuring ge1 cm but lt3 cm
3 Spur formation gt5 cm involving femur patella or tibia if more than one bone demonstrates HO separation of HO spurs measure lt1 cm or HO
within quadriceps expansion measuring ge3 cm 4 Extensive HO of the knee causing ankylosis
class 2 HO begins to involve the major bones of the knee joint with spur formation limited to a size of 5 cm
HO class 2 may be observed in select patients with complete ROM and no reported pain Patients with class 3 HO would likely always benefit from surgical excision
followed by RT prophylaxis Certainly patients in either cohort with a subclass ldquoBrdquo assignment (symptomatic) would
benefit from treatment All patients with class 4 HO require
treatment to alleviate ankylosis
treatment
References Whyte ldquoPagetrsquos Disease of Bonerdquo NEMJ vol 355
2006 Klein and Parvizi ldquoSurgical Manifestations of Pagetrsquos
Diseaserdquo JAAOS vol 14 2006 Orthobullets Campbell Apley Emedicinecom
-Chapter 15 Heterotopic Ossification after Traumatic Brain InjuryBy Jesuacutes Moreta and Joseacute Luis Martiacutenez-de los Mozos DOI 10577257343
Questions
Thank You
Advantages to early excision of heterotopic ossification (vs waiting for maturation) include decreased soft tissue contracture better definition between heterotopic and native bone and decreased waiting time for the patient When the soft tissue envelope is benign one may proceed with operative release While waiting for normalization of alkaline phosphatase levels inactivity on bone scan or radiographic maturity may decrease risk of recurrent heterotopic ossification delaying operative release for these reasons has not been shown to improve results of final elbow range of motion after contracture release
Gartland recommended surgery after six months following traumatic heterotopic ossification one year following spinal cord injury and 18 months after head injury
In the past waiting until maturity in order to minimize the rate of recurrence after the surgical treatment was recommended Nevertheless recent studies do not confirm a higher rate of recurrence when the HO is excised in an earlier phase In addition a long delay before surgery leads to ankylosis a high degree of osteoporosis and more extensive intra-articular injuries These findings are associated with bad functional results and potential complications
Should you wait till lesion maturation
Prevention byHandle tissue carefully Avoid excess bleeding Achieve good hemostasis Beware of lesions that span internervous tissue planes
but if it happens resection of a large enough amount of bone to allow improvement of the range of motion and trying to preserve the joint
Our aim must be
A reactive process that is characterized by a well-circumscribed proliferation of fibroblasts cartilage and bone within muscle
A form of heterotopic ossification that is the result direct trauma intramuscular hematoma
most common location is the diaphysis of long bones Must differentiate from tumors Fibrodysplasia ossificans progressiva (FOP) is a rare subtype of heterotopic ossification
involves mutation of the ACVR1 gene (activin A type I receptor gene a BMP type-1 receptor)
Epidemiology demographics
most common in young active males (15 to 35 years old) body locations
quadriceps brachialis and gluteal muscles Genetics
almost always a posttraumatic condition Prognosis
usually self limiting mass usually begins to decrease in size after 1 yea
Myositis ossificans
PresentationbullSymptoms
bull pain tenderness swelling and decreased range of motion that usually presents within days of the injury
bull pain and size of the mass decrease with timebull mass increases in size over several months(usually 3 to 6 cm)
bull after the mass stops growing it becomes firmbullPhysical exam
bull palpable soft tissue massbull restricted range of motion
ImagingbullRadiographs
bull peripheral bone formation with central lucent areabull may appear as dotted veil pattern
bullMRI with gadolinium bull rim enhancement is seen within the first 3 weeks
bullCT scan bull lesion has an eggshell appearance
bullCharacteristic histology shows zonal pattern bull periphery of lesion
bull mature trabeculae of lamellar and woven bonebull calcification seen on xray
bull center of the lesion bull irregular mass of immature fibroblastsbull cartilage component may be presentbull (no calcification seen on xray) bull no cellular atypia seen
Treatment
bullNonoperative bull rest range of motion exercises and activity modification
bull passive stretching is contraindicated (makes it worse)bull physical therapy
bull utilized to maintain range of motionbull radiographic monitoring
bull obtained to confirm maturation of the lesionbullOperative
bull surgical excision bull indicated only if it remains a problem after it maturesbull do not operate in acute phase wait at least six months
bull excision of the lesion within 6 to 12 months predisposes to local recurrence
A 26-year-old man presents with generalized back and joint stiffness and difficulty opening his mouth His elder sister has similar complaints Since childhood he has had 3 surgeries for excision of recurrent bony prominences around his knees He walks with a stooped over posture seen in Figure A Radiographs of his feet knee hip and spine are seen in Figures B-E respectively
fibrodysplasia ossificans progressiva
Stone Man Disease) which involves a mutation of the ACVR1
There are 2 hallmark characteristics progressive heterotopic ossification (muscles fascia tendons ligaments and joint capsules) and congenital malformation of the great toe (hallux valgus malformed first metatarsal and monophalangism) BMP4 which contributes to the formation of the skeleton in the normal embryo is implicated in this disease
Complications
bullHematoma and intraoperative bleedingbullInfection
bull higher rate of infection following joint arthroplasty if HO is present
bullFractures of osteoporotic bone bull osteopenic from disusebull during surgery or physiotherapy
bullRecurrence bull recurrence rate correlates with neurological injury
bull greater recurrence if severe neurological compromisebullAVN
bull if extensive dissection or stripping is required
HTO AND ISS
When ISS is below 25 the mortality risk is minimal and above 25 it is an almost linear increase
When ISS is 50 the mortality is 50 When above 70 it is close to 100 If an injury is assigned an AIS of 6 (unsurvivable injury) the ISS score is
automatically assigned to 75 Highest ISS score obtainable is 75 For trauma patients of vehicular accidents the scoring system is important
for assessing the effectiveness of medical care in reducing morbidity and mortality
Advantages virtually the only anatomical scoring system in use correlates linearly with
mortality morbidity hospital stay other measures of severity
Weaknesses Any error in AIS scoring increases the ISS error Many different injury patterns can yield the same ISS score Injuries to different body regions are not weighted Not a useful triage tool as a full description of patient injuries is not known
prior to full investigation amp operation
risk factors periosteal stripping off anterior femur male gender obesity post traumatic deformity Anterior and anterolateral approach Cementless
Neurogenic HO around the hip due to SCI occurs more often in the medial region than in the lateral region with ossified tissues extending from the pubic symphysis to the anteromedial femoral shaft posterior to the femoral neurovascular structures Ossification is also seen anteriorly involving the iliopsoas and femoral neurovascular structures laterally within gluteus minimus and posteriorly extending from the ilium to the posterior femur encasing the sciatic nerve
HTO AROUND hip and knee
The Brooker Classification of Heterotopic Ossification around the hip joint Class I has islands of bone within the soft tissues Class II has bone spurs from the pelvis or proximal end of the femur leaving at least 1 cm between opposing surfaces Class III has bone spurs from the pelvis andor proximal end of the femur reducing the space between opposing bone surfaces to less than 1 cm Class IV shows apparent bone ankylosis of the hip
Region I - Heterotopic ossifications are strictly below the tip of the greater trochanter
Region II - Heterotopic ossifications are below and above the tip of the greater trochanter
Region III - Heterotopic ossifications are strictly above the tip of the greater trochanter
Grade A - Single or multiple heterotopic ossifications are less than 10 mm in maximal extent without contact with the pelvis or the femur
Grade B - Heterotopic ossifications are greater than 10 mm without contact with the pelvis but with possible contact with the femur there is no bridging from the femur to the proximal part of the greater trochanter and no evidence of ankylosis
Grade C - Ankylosis by means of firm bridging from the femur to the pelvis is present
Shmidt classification
excision may be performed The results of this procedure are varied Patients may find that their range of movement improves but pain relief is likely to be limited
A patient with heterotopic ossification following total hip arthroplasty is thought to have a 90-100 chance of developing it on the contralateral hip if this hip also undergoes total arthroplasty
it would be prudent to minimize the risk of heterotopic ossification developing after arthroplasty by performing surgery whereby the following are ensured
Exposure is meticulous Retraction is performed carefully and soft tissue
is handled carefully Irrigation is adequate Devitalized tissue is excised Hemostasis is adequate Postoperative drains (when used) are not
retained for longer than necessary Perioperative antibiotic prophylaxis is used Postoperative anticoagulation (when used for
deep vein thrombosis prophylaxis) is carefully controlled
sources of knee stiffness 1-extrinsic severe osteoarthritis of the ipsilateral hip neurologic injury leading to muscle rigidity tight quadriceps or hamstring muscles secondary to muscle injury heterotopic ossification or long-standing juvenile inflammatory conditions limiting knee
range of motion prior to the completion of skeletal growth When extrinsic sources are identified revision total knee arthroplasty is unlikely to be associated with a favorable outcome without correction of the extrinsic problem
2-intrinsic (1) overstuffing of the patellofemoral articulation (2) an
excessively tight flexion andor extension gap (3) a tight posterior cruciate ligament (4) femoral andor tibial malrotation (5) arthrofibrosis and (6) limited bearing excursion in association with a highly conforming mobile-bearing prosthetic design
HTO after TKA
Heterotopic Ossification (HO) following primary Total Knee Replacement (TKR)
Occurs in 3-90 of TKRs 3-grade classification system No correlation between HO and component
alignment or component position
Clinical findings similar to early infection Continuing low-grade fever Warm swollen and erythematous knee Normal blood tests Possibly an association with HLA-A2 and B18 HO patients have worse KSS and function
scores
Patients at HIGH risk for developing HO after TKR (Knee Arthroplasty) (5)
Those with limited postoperative knee flexion
Increased lumbar bone mineral density (BMD) on multivariate analysis (3)
Hypertrophic arthrosis Excessive periosteal trauma Notching of the anterior femur Those who require forced manipulation
after TKA 47 in revision TKR surgery (6) Higher rates in revision TKR cases with
infection (up to 76
DaughertyBell classification of HO of the knee 0 No evidence of HO 1 Bone islands in periarticular soft tissue (no
involvement of femur patella or tibia) or HO within quadriceps expansion measuring lt1 cm
2 Spur formation measuring lt5 cm that involves the femur patella or tibia if more than one bone demonstrates HO separation of HO spurs
measure gt1 cm or HO within quadriceps expansion measuring ge1 cm but lt3 cm
3 Spur formation gt5 cm involving femur patella or tibia if more than one bone demonstrates HO separation of HO spurs measure lt1 cm or HO
within quadriceps expansion measuring ge3 cm 4 Extensive HO of the knee causing ankylosis
class 2 HO begins to involve the major bones of the knee joint with spur formation limited to a size of 5 cm
HO class 2 may be observed in select patients with complete ROM and no reported pain Patients with class 3 HO would likely always benefit from surgical excision
followed by RT prophylaxis Certainly patients in either cohort with a subclass ldquoBrdquo assignment (symptomatic) would
benefit from treatment All patients with class 4 HO require
treatment to alleviate ankylosis
treatment
References Whyte ldquoPagetrsquos Disease of Bonerdquo NEMJ vol 355
2006 Klein and Parvizi ldquoSurgical Manifestations of Pagetrsquos
Diseaserdquo JAAOS vol 14 2006 Orthobullets Campbell Apley Emedicinecom
-Chapter 15 Heterotopic Ossification after Traumatic Brain InjuryBy Jesuacutes Moreta and Joseacute Luis Martiacutenez-de los Mozos DOI 10577257343
Questions
Thank You
Gartland recommended surgery after six months following traumatic heterotopic ossification one year following spinal cord injury and 18 months after head injury
In the past waiting until maturity in order to minimize the rate of recurrence after the surgical treatment was recommended Nevertheless recent studies do not confirm a higher rate of recurrence when the HO is excised in an earlier phase In addition a long delay before surgery leads to ankylosis a high degree of osteoporosis and more extensive intra-articular injuries These findings are associated with bad functional results and potential complications
Should you wait till lesion maturation
Prevention byHandle tissue carefully Avoid excess bleeding Achieve good hemostasis Beware of lesions that span internervous tissue planes
but if it happens resection of a large enough amount of bone to allow improvement of the range of motion and trying to preserve the joint
Our aim must be
A reactive process that is characterized by a well-circumscribed proliferation of fibroblasts cartilage and bone within muscle
A form of heterotopic ossification that is the result direct trauma intramuscular hematoma
most common location is the diaphysis of long bones Must differentiate from tumors Fibrodysplasia ossificans progressiva (FOP) is a rare subtype of heterotopic ossification
involves mutation of the ACVR1 gene (activin A type I receptor gene a BMP type-1 receptor)
Epidemiology demographics
most common in young active males (15 to 35 years old) body locations
quadriceps brachialis and gluteal muscles Genetics
almost always a posttraumatic condition Prognosis
usually self limiting mass usually begins to decrease in size after 1 yea
Myositis ossificans
PresentationbullSymptoms
bull pain tenderness swelling and decreased range of motion that usually presents within days of the injury
bull pain and size of the mass decrease with timebull mass increases in size over several months(usually 3 to 6 cm)
bull after the mass stops growing it becomes firmbullPhysical exam
bull palpable soft tissue massbull restricted range of motion
ImagingbullRadiographs
bull peripheral bone formation with central lucent areabull may appear as dotted veil pattern
bullMRI with gadolinium bull rim enhancement is seen within the first 3 weeks
bullCT scan bull lesion has an eggshell appearance
bullCharacteristic histology shows zonal pattern bull periphery of lesion
bull mature trabeculae of lamellar and woven bonebull calcification seen on xray
bull center of the lesion bull irregular mass of immature fibroblastsbull cartilage component may be presentbull (no calcification seen on xray) bull no cellular atypia seen
Treatment
bullNonoperative bull rest range of motion exercises and activity modification
bull passive stretching is contraindicated (makes it worse)bull physical therapy
bull utilized to maintain range of motionbull radiographic monitoring
bull obtained to confirm maturation of the lesionbullOperative
bull surgical excision bull indicated only if it remains a problem after it maturesbull do not operate in acute phase wait at least six months
bull excision of the lesion within 6 to 12 months predisposes to local recurrence
A 26-year-old man presents with generalized back and joint stiffness and difficulty opening his mouth His elder sister has similar complaints Since childhood he has had 3 surgeries for excision of recurrent bony prominences around his knees He walks with a stooped over posture seen in Figure A Radiographs of his feet knee hip and spine are seen in Figures B-E respectively
fibrodysplasia ossificans progressiva
Stone Man Disease) which involves a mutation of the ACVR1
There are 2 hallmark characteristics progressive heterotopic ossification (muscles fascia tendons ligaments and joint capsules) and congenital malformation of the great toe (hallux valgus malformed first metatarsal and monophalangism) BMP4 which contributes to the formation of the skeleton in the normal embryo is implicated in this disease
Complications
bullHematoma and intraoperative bleedingbullInfection
bull higher rate of infection following joint arthroplasty if HO is present
bullFractures of osteoporotic bone bull osteopenic from disusebull during surgery or physiotherapy
bullRecurrence bull recurrence rate correlates with neurological injury
bull greater recurrence if severe neurological compromisebullAVN
bull if extensive dissection or stripping is required
HTO AND ISS
When ISS is below 25 the mortality risk is minimal and above 25 it is an almost linear increase
When ISS is 50 the mortality is 50 When above 70 it is close to 100 If an injury is assigned an AIS of 6 (unsurvivable injury) the ISS score is
automatically assigned to 75 Highest ISS score obtainable is 75 For trauma patients of vehicular accidents the scoring system is important
for assessing the effectiveness of medical care in reducing morbidity and mortality
Advantages virtually the only anatomical scoring system in use correlates linearly with
mortality morbidity hospital stay other measures of severity
Weaknesses Any error in AIS scoring increases the ISS error Many different injury patterns can yield the same ISS score Injuries to different body regions are not weighted Not a useful triage tool as a full description of patient injuries is not known
prior to full investigation amp operation
risk factors periosteal stripping off anterior femur male gender obesity post traumatic deformity Anterior and anterolateral approach Cementless
Neurogenic HO around the hip due to SCI occurs more often in the medial region than in the lateral region with ossified tissues extending from the pubic symphysis to the anteromedial femoral shaft posterior to the femoral neurovascular structures Ossification is also seen anteriorly involving the iliopsoas and femoral neurovascular structures laterally within gluteus minimus and posteriorly extending from the ilium to the posterior femur encasing the sciatic nerve
HTO AROUND hip and knee
The Brooker Classification of Heterotopic Ossification around the hip joint Class I has islands of bone within the soft tissues Class II has bone spurs from the pelvis or proximal end of the femur leaving at least 1 cm between opposing surfaces Class III has bone spurs from the pelvis andor proximal end of the femur reducing the space between opposing bone surfaces to less than 1 cm Class IV shows apparent bone ankylosis of the hip
Region I - Heterotopic ossifications are strictly below the tip of the greater trochanter
Region II - Heterotopic ossifications are below and above the tip of the greater trochanter
Region III - Heterotopic ossifications are strictly above the tip of the greater trochanter
Grade A - Single or multiple heterotopic ossifications are less than 10 mm in maximal extent without contact with the pelvis or the femur
Grade B - Heterotopic ossifications are greater than 10 mm without contact with the pelvis but with possible contact with the femur there is no bridging from the femur to the proximal part of the greater trochanter and no evidence of ankylosis
Grade C - Ankylosis by means of firm bridging from the femur to the pelvis is present
Shmidt classification
excision may be performed The results of this procedure are varied Patients may find that their range of movement improves but pain relief is likely to be limited
A patient with heterotopic ossification following total hip arthroplasty is thought to have a 90-100 chance of developing it on the contralateral hip if this hip also undergoes total arthroplasty
it would be prudent to minimize the risk of heterotopic ossification developing after arthroplasty by performing surgery whereby the following are ensured
Exposure is meticulous Retraction is performed carefully and soft tissue
is handled carefully Irrigation is adequate Devitalized tissue is excised Hemostasis is adequate Postoperative drains (when used) are not
retained for longer than necessary Perioperative antibiotic prophylaxis is used Postoperative anticoagulation (when used for
deep vein thrombosis prophylaxis) is carefully controlled
sources of knee stiffness 1-extrinsic severe osteoarthritis of the ipsilateral hip neurologic injury leading to muscle rigidity tight quadriceps or hamstring muscles secondary to muscle injury heterotopic ossification or long-standing juvenile inflammatory conditions limiting knee
range of motion prior to the completion of skeletal growth When extrinsic sources are identified revision total knee arthroplasty is unlikely to be associated with a favorable outcome without correction of the extrinsic problem
2-intrinsic (1) overstuffing of the patellofemoral articulation (2) an
excessively tight flexion andor extension gap (3) a tight posterior cruciate ligament (4) femoral andor tibial malrotation (5) arthrofibrosis and (6) limited bearing excursion in association with a highly conforming mobile-bearing prosthetic design
HTO after TKA
Heterotopic Ossification (HO) following primary Total Knee Replacement (TKR)
Occurs in 3-90 of TKRs 3-grade classification system No correlation between HO and component
alignment or component position
Clinical findings similar to early infection Continuing low-grade fever Warm swollen and erythematous knee Normal blood tests Possibly an association with HLA-A2 and B18 HO patients have worse KSS and function
scores
Patients at HIGH risk for developing HO after TKR (Knee Arthroplasty) (5)
Those with limited postoperative knee flexion
Increased lumbar bone mineral density (BMD) on multivariate analysis (3)
Hypertrophic arthrosis Excessive periosteal trauma Notching of the anterior femur Those who require forced manipulation
after TKA 47 in revision TKR surgery (6) Higher rates in revision TKR cases with
infection (up to 76
DaughertyBell classification of HO of the knee 0 No evidence of HO 1 Bone islands in periarticular soft tissue (no
involvement of femur patella or tibia) or HO within quadriceps expansion measuring lt1 cm
2 Spur formation measuring lt5 cm that involves the femur patella or tibia if more than one bone demonstrates HO separation of HO spurs
measure gt1 cm or HO within quadriceps expansion measuring ge1 cm but lt3 cm
3 Spur formation gt5 cm involving femur patella or tibia if more than one bone demonstrates HO separation of HO spurs measure lt1 cm or HO
within quadriceps expansion measuring ge3 cm 4 Extensive HO of the knee causing ankylosis
class 2 HO begins to involve the major bones of the knee joint with spur formation limited to a size of 5 cm
HO class 2 may be observed in select patients with complete ROM and no reported pain Patients with class 3 HO would likely always benefit from surgical excision
followed by RT prophylaxis Certainly patients in either cohort with a subclass ldquoBrdquo assignment (symptomatic) would
benefit from treatment All patients with class 4 HO require
treatment to alleviate ankylosis
treatment
References Whyte ldquoPagetrsquos Disease of Bonerdquo NEMJ vol 355
2006 Klein and Parvizi ldquoSurgical Manifestations of Pagetrsquos
Diseaserdquo JAAOS vol 14 2006 Orthobullets Campbell Apley Emedicinecom
-Chapter 15 Heterotopic Ossification after Traumatic Brain InjuryBy Jesuacutes Moreta and Joseacute Luis Martiacutenez-de los Mozos DOI 10577257343
Questions
Thank You
Prevention byHandle tissue carefully Avoid excess bleeding Achieve good hemostasis Beware of lesions that span internervous tissue planes
but if it happens resection of a large enough amount of bone to allow improvement of the range of motion and trying to preserve the joint
Our aim must be
A reactive process that is characterized by a well-circumscribed proliferation of fibroblasts cartilage and bone within muscle
A form of heterotopic ossification that is the result direct trauma intramuscular hematoma
most common location is the diaphysis of long bones Must differentiate from tumors Fibrodysplasia ossificans progressiva (FOP) is a rare subtype of heterotopic ossification
involves mutation of the ACVR1 gene (activin A type I receptor gene a BMP type-1 receptor)
Epidemiology demographics
most common in young active males (15 to 35 years old) body locations
quadriceps brachialis and gluteal muscles Genetics
almost always a posttraumatic condition Prognosis
usually self limiting mass usually begins to decrease in size after 1 yea
Myositis ossificans
PresentationbullSymptoms
bull pain tenderness swelling and decreased range of motion that usually presents within days of the injury
bull pain and size of the mass decrease with timebull mass increases in size over several months(usually 3 to 6 cm)
bull after the mass stops growing it becomes firmbullPhysical exam
bull palpable soft tissue massbull restricted range of motion
ImagingbullRadiographs
bull peripheral bone formation with central lucent areabull may appear as dotted veil pattern
bullMRI with gadolinium bull rim enhancement is seen within the first 3 weeks
bullCT scan bull lesion has an eggshell appearance
bullCharacteristic histology shows zonal pattern bull periphery of lesion
bull mature trabeculae of lamellar and woven bonebull calcification seen on xray
bull center of the lesion bull irregular mass of immature fibroblastsbull cartilage component may be presentbull (no calcification seen on xray) bull no cellular atypia seen
Treatment
bullNonoperative bull rest range of motion exercises and activity modification
bull passive stretching is contraindicated (makes it worse)bull physical therapy
bull utilized to maintain range of motionbull radiographic monitoring
bull obtained to confirm maturation of the lesionbullOperative
bull surgical excision bull indicated only if it remains a problem after it maturesbull do not operate in acute phase wait at least six months
bull excision of the lesion within 6 to 12 months predisposes to local recurrence
A 26-year-old man presents with generalized back and joint stiffness and difficulty opening his mouth His elder sister has similar complaints Since childhood he has had 3 surgeries for excision of recurrent bony prominences around his knees He walks with a stooped over posture seen in Figure A Radiographs of his feet knee hip and spine are seen in Figures B-E respectively
fibrodysplasia ossificans progressiva
Stone Man Disease) which involves a mutation of the ACVR1
There are 2 hallmark characteristics progressive heterotopic ossification (muscles fascia tendons ligaments and joint capsules) and congenital malformation of the great toe (hallux valgus malformed first metatarsal and monophalangism) BMP4 which contributes to the formation of the skeleton in the normal embryo is implicated in this disease
Complications
bullHematoma and intraoperative bleedingbullInfection
bull higher rate of infection following joint arthroplasty if HO is present
bullFractures of osteoporotic bone bull osteopenic from disusebull during surgery or physiotherapy
bullRecurrence bull recurrence rate correlates with neurological injury
bull greater recurrence if severe neurological compromisebullAVN
bull if extensive dissection or stripping is required
HTO AND ISS
When ISS is below 25 the mortality risk is minimal and above 25 it is an almost linear increase
When ISS is 50 the mortality is 50 When above 70 it is close to 100 If an injury is assigned an AIS of 6 (unsurvivable injury) the ISS score is
automatically assigned to 75 Highest ISS score obtainable is 75 For trauma patients of vehicular accidents the scoring system is important
for assessing the effectiveness of medical care in reducing morbidity and mortality
Advantages virtually the only anatomical scoring system in use correlates linearly with
mortality morbidity hospital stay other measures of severity
Weaknesses Any error in AIS scoring increases the ISS error Many different injury patterns can yield the same ISS score Injuries to different body regions are not weighted Not a useful triage tool as a full description of patient injuries is not known
prior to full investigation amp operation
risk factors periosteal stripping off anterior femur male gender obesity post traumatic deformity Anterior and anterolateral approach Cementless
Neurogenic HO around the hip due to SCI occurs more often in the medial region than in the lateral region with ossified tissues extending from the pubic symphysis to the anteromedial femoral shaft posterior to the femoral neurovascular structures Ossification is also seen anteriorly involving the iliopsoas and femoral neurovascular structures laterally within gluteus minimus and posteriorly extending from the ilium to the posterior femur encasing the sciatic nerve
HTO AROUND hip and knee
The Brooker Classification of Heterotopic Ossification around the hip joint Class I has islands of bone within the soft tissues Class II has bone spurs from the pelvis or proximal end of the femur leaving at least 1 cm between opposing surfaces Class III has bone spurs from the pelvis andor proximal end of the femur reducing the space between opposing bone surfaces to less than 1 cm Class IV shows apparent bone ankylosis of the hip
Region I - Heterotopic ossifications are strictly below the tip of the greater trochanter
Region II - Heterotopic ossifications are below and above the tip of the greater trochanter
Region III - Heterotopic ossifications are strictly above the tip of the greater trochanter
Grade A - Single or multiple heterotopic ossifications are less than 10 mm in maximal extent without contact with the pelvis or the femur
Grade B - Heterotopic ossifications are greater than 10 mm without contact with the pelvis but with possible contact with the femur there is no bridging from the femur to the proximal part of the greater trochanter and no evidence of ankylosis
Grade C - Ankylosis by means of firm bridging from the femur to the pelvis is present
Shmidt classification
excision may be performed The results of this procedure are varied Patients may find that their range of movement improves but pain relief is likely to be limited
A patient with heterotopic ossification following total hip arthroplasty is thought to have a 90-100 chance of developing it on the contralateral hip if this hip also undergoes total arthroplasty
it would be prudent to minimize the risk of heterotopic ossification developing after arthroplasty by performing surgery whereby the following are ensured
Exposure is meticulous Retraction is performed carefully and soft tissue
is handled carefully Irrigation is adequate Devitalized tissue is excised Hemostasis is adequate Postoperative drains (when used) are not
retained for longer than necessary Perioperative antibiotic prophylaxis is used Postoperative anticoagulation (when used for
deep vein thrombosis prophylaxis) is carefully controlled
sources of knee stiffness 1-extrinsic severe osteoarthritis of the ipsilateral hip neurologic injury leading to muscle rigidity tight quadriceps or hamstring muscles secondary to muscle injury heterotopic ossification or long-standing juvenile inflammatory conditions limiting knee
range of motion prior to the completion of skeletal growth When extrinsic sources are identified revision total knee arthroplasty is unlikely to be associated with a favorable outcome without correction of the extrinsic problem
2-intrinsic (1) overstuffing of the patellofemoral articulation (2) an
excessively tight flexion andor extension gap (3) a tight posterior cruciate ligament (4) femoral andor tibial malrotation (5) arthrofibrosis and (6) limited bearing excursion in association with a highly conforming mobile-bearing prosthetic design
HTO after TKA
Heterotopic Ossification (HO) following primary Total Knee Replacement (TKR)
Occurs in 3-90 of TKRs 3-grade classification system No correlation between HO and component
alignment or component position
Clinical findings similar to early infection Continuing low-grade fever Warm swollen and erythematous knee Normal blood tests Possibly an association with HLA-A2 and B18 HO patients have worse KSS and function
scores
Patients at HIGH risk for developing HO after TKR (Knee Arthroplasty) (5)
Those with limited postoperative knee flexion
Increased lumbar bone mineral density (BMD) on multivariate analysis (3)
Hypertrophic arthrosis Excessive periosteal trauma Notching of the anterior femur Those who require forced manipulation
after TKA 47 in revision TKR surgery (6) Higher rates in revision TKR cases with
infection (up to 76
DaughertyBell classification of HO of the knee 0 No evidence of HO 1 Bone islands in periarticular soft tissue (no
involvement of femur patella or tibia) or HO within quadriceps expansion measuring lt1 cm
2 Spur formation measuring lt5 cm that involves the femur patella or tibia if more than one bone demonstrates HO separation of HO spurs
measure gt1 cm or HO within quadriceps expansion measuring ge1 cm but lt3 cm
3 Spur formation gt5 cm involving femur patella or tibia if more than one bone demonstrates HO separation of HO spurs measure lt1 cm or HO
within quadriceps expansion measuring ge3 cm 4 Extensive HO of the knee causing ankylosis
class 2 HO begins to involve the major bones of the knee joint with spur formation limited to a size of 5 cm
HO class 2 may be observed in select patients with complete ROM and no reported pain Patients with class 3 HO would likely always benefit from surgical excision
followed by RT prophylaxis Certainly patients in either cohort with a subclass ldquoBrdquo assignment (symptomatic) would
benefit from treatment All patients with class 4 HO require
treatment to alleviate ankylosis
treatment
References Whyte ldquoPagetrsquos Disease of Bonerdquo NEMJ vol 355
2006 Klein and Parvizi ldquoSurgical Manifestations of Pagetrsquos
Diseaserdquo JAAOS vol 14 2006 Orthobullets Campbell Apley Emedicinecom
-Chapter 15 Heterotopic Ossification after Traumatic Brain InjuryBy Jesuacutes Moreta and Joseacute Luis Martiacutenez-de los Mozos DOI 10577257343
Questions
Thank You
A reactive process that is characterized by a well-circumscribed proliferation of fibroblasts cartilage and bone within muscle
A form of heterotopic ossification that is the result direct trauma intramuscular hematoma
most common location is the diaphysis of long bones Must differentiate from tumors Fibrodysplasia ossificans progressiva (FOP) is a rare subtype of heterotopic ossification
involves mutation of the ACVR1 gene (activin A type I receptor gene a BMP type-1 receptor)
Epidemiology demographics
most common in young active males (15 to 35 years old) body locations
quadriceps brachialis and gluteal muscles Genetics
almost always a posttraumatic condition Prognosis
usually self limiting mass usually begins to decrease in size after 1 yea
Myositis ossificans
PresentationbullSymptoms
bull pain tenderness swelling and decreased range of motion that usually presents within days of the injury
bull pain and size of the mass decrease with timebull mass increases in size over several months(usually 3 to 6 cm)
bull after the mass stops growing it becomes firmbullPhysical exam
bull palpable soft tissue massbull restricted range of motion
ImagingbullRadiographs
bull peripheral bone formation with central lucent areabull may appear as dotted veil pattern
bullMRI with gadolinium bull rim enhancement is seen within the first 3 weeks
bullCT scan bull lesion has an eggshell appearance
bullCharacteristic histology shows zonal pattern bull periphery of lesion
bull mature trabeculae of lamellar and woven bonebull calcification seen on xray
bull center of the lesion bull irregular mass of immature fibroblastsbull cartilage component may be presentbull (no calcification seen on xray) bull no cellular atypia seen
Treatment
bullNonoperative bull rest range of motion exercises and activity modification
bull passive stretching is contraindicated (makes it worse)bull physical therapy
bull utilized to maintain range of motionbull radiographic monitoring
bull obtained to confirm maturation of the lesionbullOperative
bull surgical excision bull indicated only if it remains a problem after it maturesbull do not operate in acute phase wait at least six months
bull excision of the lesion within 6 to 12 months predisposes to local recurrence
A 26-year-old man presents with generalized back and joint stiffness and difficulty opening his mouth His elder sister has similar complaints Since childhood he has had 3 surgeries for excision of recurrent bony prominences around his knees He walks with a stooped over posture seen in Figure A Radiographs of his feet knee hip and spine are seen in Figures B-E respectively
fibrodysplasia ossificans progressiva
Stone Man Disease) which involves a mutation of the ACVR1
There are 2 hallmark characteristics progressive heterotopic ossification (muscles fascia tendons ligaments and joint capsules) and congenital malformation of the great toe (hallux valgus malformed first metatarsal and monophalangism) BMP4 which contributes to the formation of the skeleton in the normal embryo is implicated in this disease
Complications
bullHematoma and intraoperative bleedingbullInfection
bull higher rate of infection following joint arthroplasty if HO is present
bullFractures of osteoporotic bone bull osteopenic from disusebull during surgery or physiotherapy
bullRecurrence bull recurrence rate correlates with neurological injury
bull greater recurrence if severe neurological compromisebullAVN
bull if extensive dissection or stripping is required
HTO AND ISS
When ISS is below 25 the mortality risk is minimal and above 25 it is an almost linear increase
When ISS is 50 the mortality is 50 When above 70 it is close to 100 If an injury is assigned an AIS of 6 (unsurvivable injury) the ISS score is
automatically assigned to 75 Highest ISS score obtainable is 75 For trauma patients of vehicular accidents the scoring system is important
for assessing the effectiveness of medical care in reducing morbidity and mortality
Advantages virtually the only anatomical scoring system in use correlates linearly with
mortality morbidity hospital stay other measures of severity
Weaknesses Any error in AIS scoring increases the ISS error Many different injury patterns can yield the same ISS score Injuries to different body regions are not weighted Not a useful triage tool as a full description of patient injuries is not known
prior to full investigation amp operation
risk factors periosteal stripping off anterior femur male gender obesity post traumatic deformity Anterior and anterolateral approach Cementless
Neurogenic HO around the hip due to SCI occurs more often in the medial region than in the lateral region with ossified tissues extending from the pubic symphysis to the anteromedial femoral shaft posterior to the femoral neurovascular structures Ossification is also seen anteriorly involving the iliopsoas and femoral neurovascular structures laterally within gluteus minimus and posteriorly extending from the ilium to the posterior femur encasing the sciatic nerve
HTO AROUND hip and knee
The Brooker Classification of Heterotopic Ossification around the hip joint Class I has islands of bone within the soft tissues Class II has bone spurs from the pelvis or proximal end of the femur leaving at least 1 cm between opposing surfaces Class III has bone spurs from the pelvis andor proximal end of the femur reducing the space between opposing bone surfaces to less than 1 cm Class IV shows apparent bone ankylosis of the hip
Region I - Heterotopic ossifications are strictly below the tip of the greater trochanter
Region II - Heterotopic ossifications are below and above the tip of the greater trochanter
Region III - Heterotopic ossifications are strictly above the tip of the greater trochanter
Grade A - Single or multiple heterotopic ossifications are less than 10 mm in maximal extent without contact with the pelvis or the femur
Grade B - Heterotopic ossifications are greater than 10 mm without contact with the pelvis but with possible contact with the femur there is no bridging from the femur to the proximal part of the greater trochanter and no evidence of ankylosis
Grade C - Ankylosis by means of firm bridging from the femur to the pelvis is present
Shmidt classification
excision may be performed The results of this procedure are varied Patients may find that their range of movement improves but pain relief is likely to be limited
A patient with heterotopic ossification following total hip arthroplasty is thought to have a 90-100 chance of developing it on the contralateral hip if this hip also undergoes total arthroplasty
it would be prudent to minimize the risk of heterotopic ossification developing after arthroplasty by performing surgery whereby the following are ensured
Exposure is meticulous Retraction is performed carefully and soft tissue
is handled carefully Irrigation is adequate Devitalized tissue is excised Hemostasis is adequate Postoperative drains (when used) are not
retained for longer than necessary Perioperative antibiotic prophylaxis is used Postoperative anticoagulation (when used for
deep vein thrombosis prophylaxis) is carefully controlled
sources of knee stiffness 1-extrinsic severe osteoarthritis of the ipsilateral hip neurologic injury leading to muscle rigidity tight quadriceps or hamstring muscles secondary to muscle injury heterotopic ossification or long-standing juvenile inflammatory conditions limiting knee
range of motion prior to the completion of skeletal growth When extrinsic sources are identified revision total knee arthroplasty is unlikely to be associated with a favorable outcome without correction of the extrinsic problem
2-intrinsic (1) overstuffing of the patellofemoral articulation (2) an
excessively tight flexion andor extension gap (3) a tight posterior cruciate ligament (4) femoral andor tibial malrotation (5) arthrofibrosis and (6) limited bearing excursion in association with a highly conforming mobile-bearing prosthetic design
HTO after TKA
Heterotopic Ossification (HO) following primary Total Knee Replacement (TKR)
Occurs in 3-90 of TKRs 3-grade classification system No correlation between HO and component
alignment or component position
Clinical findings similar to early infection Continuing low-grade fever Warm swollen and erythematous knee Normal blood tests Possibly an association with HLA-A2 and B18 HO patients have worse KSS and function
scores
Patients at HIGH risk for developing HO after TKR (Knee Arthroplasty) (5)
Those with limited postoperative knee flexion
Increased lumbar bone mineral density (BMD) on multivariate analysis (3)
Hypertrophic arthrosis Excessive periosteal trauma Notching of the anterior femur Those who require forced manipulation
after TKA 47 in revision TKR surgery (6) Higher rates in revision TKR cases with
infection (up to 76
DaughertyBell classification of HO of the knee 0 No evidence of HO 1 Bone islands in periarticular soft tissue (no
involvement of femur patella or tibia) or HO within quadriceps expansion measuring lt1 cm
2 Spur formation measuring lt5 cm that involves the femur patella or tibia if more than one bone demonstrates HO separation of HO spurs
measure gt1 cm or HO within quadriceps expansion measuring ge1 cm but lt3 cm
3 Spur formation gt5 cm involving femur patella or tibia if more than one bone demonstrates HO separation of HO spurs measure lt1 cm or HO
within quadriceps expansion measuring ge3 cm 4 Extensive HO of the knee causing ankylosis
class 2 HO begins to involve the major bones of the knee joint with spur formation limited to a size of 5 cm
HO class 2 may be observed in select patients with complete ROM and no reported pain Patients with class 3 HO would likely always benefit from surgical excision
followed by RT prophylaxis Certainly patients in either cohort with a subclass ldquoBrdquo assignment (symptomatic) would
benefit from treatment All patients with class 4 HO require
treatment to alleviate ankylosis
treatment
References Whyte ldquoPagetrsquos Disease of Bonerdquo NEMJ vol 355
2006 Klein and Parvizi ldquoSurgical Manifestations of Pagetrsquos
Diseaserdquo JAAOS vol 14 2006 Orthobullets Campbell Apley Emedicinecom
-Chapter 15 Heterotopic Ossification after Traumatic Brain InjuryBy Jesuacutes Moreta and Joseacute Luis Martiacutenez-de los Mozos DOI 10577257343
Questions
Thank You
PresentationbullSymptoms
bull pain tenderness swelling and decreased range of motion that usually presents within days of the injury
bull pain and size of the mass decrease with timebull mass increases in size over several months(usually 3 to 6 cm)
bull after the mass stops growing it becomes firmbullPhysical exam
bull palpable soft tissue massbull restricted range of motion
ImagingbullRadiographs
bull peripheral bone formation with central lucent areabull may appear as dotted veil pattern
bullMRI with gadolinium bull rim enhancement is seen within the first 3 weeks
bullCT scan bull lesion has an eggshell appearance
bullCharacteristic histology shows zonal pattern bull periphery of lesion
bull mature trabeculae of lamellar and woven bonebull calcification seen on xray
bull center of the lesion bull irregular mass of immature fibroblastsbull cartilage component may be presentbull (no calcification seen on xray) bull no cellular atypia seen
Treatment
bullNonoperative bull rest range of motion exercises and activity modification
bull passive stretching is contraindicated (makes it worse)bull physical therapy
bull utilized to maintain range of motionbull radiographic monitoring
bull obtained to confirm maturation of the lesionbullOperative
bull surgical excision bull indicated only if it remains a problem after it maturesbull do not operate in acute phase wait at least six months
bull excision of the lesion within 6 to 12 months predisposes to local recurrence
A 26-year-old man presents with generalized back and joint stiffness and difficulty opening his mouth His elder sister has similar complaints Since childhood he has had 3 surgeries for excision of recurrent bony prominences around his knees He walks with a stooped over posture seen in Figure A Radiographs of his feet knee hip and spine are seen in Figures B-E respectively
fibrodysplasia ossificans progressiva
Stone Man Disease) which involves a mutation of the ACVR1
There are 2 hallmark characteristics progressive heterotopic ossification (muscles fascia tendons ligaments and joint capsules) and congenital malformation of the great toe (hallux valgus malformed first metatarsal and monophalangism) BMP4 which contributes to the formation of the skeleton in the normal embryo is implicated in this disease
Complications
bullHematoma and intraoperative bleedingbullInfection
bull higher rate of infection following joint arthroplasty if HO is present
bullFractures of osteoporotic bone bull osteopenic from disusebull during surgery or physiotherapy
bullRecurrence bull recurrence rate correlates with neurological injury
bull greater recurrence if severe neurological compromisebullAVN
bull if extensive dissection or stripping is required
HTO AND ISS
When ISS is below 25 the mortality risk is minimal and above 25 it is an almost linear increase
When ISS is 50 the mortality is 50 When above 70 it is close to 100 If an injury is assigned an AIS of 6 (unsurvivable injury) the ISS score is
automatically assigned to 75 Highest ISS score obtainable is 75 For trauma patients of vehicular accidents the scoring system is important
for assessing the effectiveness of medical care in reducing morbidity and mortality
Advantages virtually the only anatomical scoring system in use correlates linearly with
mortality morbidity hospital stay other measures of severity
Weaknesses Any error in AIS scoring increases the ISS error Many different injury patterns can yield the same ISS score Injuries to different body regions are not weighted Not a useful triage tool as a full description of patient injuries is not known
prior to full investigation amp operation
risk factors periosteal stripping off anterior femur male gender obesity post traumatic deformity Anterior and anterolateral approach Cementless
Neurogenic HO around the hip due to SCI occurs more often in the medial region than in the lateral region with ossified tissues extending from the pubic symphysis to the anteromedial femoral shaft posterior to the femoral neurovascular structures Ossification is also seen anteriorly involving the iliopsoas and femoral neurovascular structures laterally within gluteus minimus and posteriorly extending from the ilium to the posterior femur encasing the sciatic nerve
HTO AROUND hip and knee
The Brooker Classification of Heterotopic Ossification around the hip joint Class I has islands of bone within the soft tissues Class II has bone spurs from the pelvis or proximal end of the femur leaving at least 1 cm between opposing surfaces Class III has bone spurs from the pelvis andor proximal end of the femur reducing the space between opposing bone surfaces to less than 1 cm Class IV shows apparent bone ankylosis of the hip
Region I - Heterotopic ossifications are strictly below the tip of the greater trochanter
Region II - Heterotopic ossifications are below and above the tip of the greater trochanter
Region III - Heterotopic ossifications are strictly above the tip of the greater trochanter
Grade A - Single or multiple heterotopic ossifications are less than 10 mm in maximal extent without contact with the pelvis or the femur
Grade B - Heterotopic ossifications are greater than 10 mm without contact with the pelvis but with possible contact with the femur there is no bridging from the femur to the proximal part of the greater trochanter and no evidence of ankylosis
Grade C - Ankylosis by means of firm bridging from the femur to the pelvis is present
Shmidt classification
excision may be performed The results of this procedure are varied Patients may find that their range of movement improves but pain relief is likely to be limited
A patient with heterotopic ossification following total hip arthroplasty is thought to have a 90-100 chance of developing it on the contralateral hip if this hip also undergoes total arthroplasty
it would be prudent to minimize the risk of heterotopic ossification developing after arthroplasty by performing surgery whereby the following are ensured
Exposure is meticulous Retraction is performed carefully and soft tissue
is handled carefully Irrigation is adequate Devitalized tissue is excised Hemostasis is adequate Postoperative drains (when used) are not
retained for longer than necessary Perioperative antibiotic prophylaxis is used Postoperative anticoagulation (when used for
deep vein thrombosis prophylaxis) is carefully controlled
sources of knee stiffness 1-extrinsic severe osteoarthritis of the ipsilateral hip neurologic injury leading to muscle rigidity tight quadriceps or hamstring muscles secondary to muscle injury heterotopic ossification or long-standing juvenile inflammatory conditions limiting knee
range of motion prior to the completion of skeletal growth When extrinsic sources are identified revision total knee arthroplasty is unlikely to be associated with a favorable outcome without correction of the extrinsic problem
2-intrinsic (1) overstuffing of the patellofemoral articulation (2) an
excessively tight flexion andor extension gap (3) a tight posterior cruciate ligament (4) femoral andor tibial malrotation (5) arthrofibrosis and (6) limited bearing excursion in association with a highly conforming mobile-bearing prosthetic design
HTO after TKA
Heterotopic Ossification (HO) following primary Total Knee Replacement (TKR)
Occurs in 3-90 of TKRs 3-grade classification system No correlation between HO and component
alignment or component position
Clinical findings similar to early infection Continuing low-grade fever Warm swollen and erythematous knee Normal blood tests Possibly an association with HLA-A2 and B18 HO patients have worse KSS and function
scores
Patients at HIGH risk for developing HO after TKR (Knee Arthroplasty) (5)
Those with limited postoperative knee flexion
Increased lumbar bone mineral density (BMD) on multivariate analysis (3)
Hypertrophic arthrosis Excessive periosteal trauma Notching of the anterior femur Those who require forced manipulation
after TKA 47 in revision TKR surgery (6) Higher rates in revision TKR cases with
infection (up to 76
DaughertyBell classification of HO of the knee 0 No evidence of HO 1 Bone islands in periarticular soft tissue (no
involvement of femur patella or tibia) or HO within quadriceps expansion measuring lt1 cm
2 Spur formation measuring lt5 cm that involves the femur patella or tibia if more than one bone demonstrates HO separation of HO spurs
measure gt1 cm or HO within quadriceps expansion measuring ge1 cm but lt3 cm
3 Spur formation gt5 cm involving femur patella or tibia if more than one bone demonstrates HO separation of HO spurs measure lt1 cm or HO
within quadriceps expansion measuring ge3 cm 4 Extensive HO of the knee causing ankylosis
class 2 HO begins to involve the major bones of the knee joint with spur formation limited to a size of 5 cm
HO class 2 may be observed in select patients with complete ROM and no reported pain Patients with class 3 HO would likely always benefit from surgical excision
followed by RT prophylaxis Certainly patients in either cohort with a subclass ldquoBrdquo assignment (symptomatic) would
benefit from treatment All patients with class 4 HO require
treatment to alleviate ankylosis
treatment
References Whyte ldquoPagetrsquos Disease of Bonerdquo NEMJ vol 355
2006 Klein and Parvizi ldquoSurgical Manifestations of Pagetrsquos
Diseaserdquo JAAOS vol 14 2006 Orthobullets Campbell Apley Emedicinecom
-Chapter 15 Heterotopic Ossification after Traumatic Brain InjuryBy Jesuacutes Moreta and Joseacute Luis Martiacutenez-de los Mozos DOI 10577257343
Questions
Thank You
bullCharacteristic histology shows zonal pattern bull periphery of lesion
bull mature trabeculae of lamellar and woven bonebull calcification seen on xray
bull center of the lesion bull irregular mass of immature fibroblastsbull cartilage component may be presentbull (no calcification seen on xray) bull no cellular atypia seen
Treatment
bullNonoperative bull rest range of motion exercises and activity modification
bull passive stretching is contraindicated (makes it worse)bull physical therapy
bull utilized to maintain range of motionbull radiographic monitoring
bull obtained to confirm maturation of the lesionbullOperative
bull surgical excision bull indicated only if it remains a problem after it maturesbull do not operate in acute phase wait at least six months
bull excision of the lesion within 6 to 12 months predisposes to local recurrence
A 26-year-old man presents with generalized back and joint stiffness and difficulty opening his mouth His elder sister has similar complaints Since childhood he has had 3 surgeries for excision of recurrent bony prominences around his knees He walks with a stooped over posture seen in Figure A Radiographs of his feet knee hip and spine are seen in Figures B-E respectively
fibrodysplasia ossificans progressiva
Stone Man Disease) which involves a mutation of the ACVR1
There are 2 hallmark characteristics progressive heterotopic ossification (muscles fascia tendons ligaments and joint capsules) and congenital malformation of the great toe (hallux valgus malformed first metatarsal and monophalangism) BMP4 which contributes to the formation of the skeleton in the normal embryo is implicated in this disease
Complications
bullHematoma and intraoperative bleedingbullInfection
bull higher rate of infection following joint arthroplasty if HO is present
bullFractures of osteoporotic bone bull osteopenic from disusebull during surgery or physiotherapy
bullRecurrence bull recurrence rate correlates with neurological injury
bull greater recurrence if severe neurological compromisebullAVN
bull if extensive dissection or stripping is required
HTO AND ISS
When ISS is below 25 the mortality risk is minimal and above 25 it is an almost linear increase
When ISS is 50 the mortality is 50 When above 70 it is close to 100 If an injury is assigned an AIS of 6 (unsurvivable injury) the ISS score is
automatically assigned to 75 Highest ISS score obtainable is 75 For trauma patients of vehicular accidents the scoring system is important
for assessing the effectiveness of medical care in reducing morbidity and mortality
Advantages virtually the only anatomical scoring system in use correlates linearly with
mortality morbidity hospital stay other measures of severity
Weaknesses Any error in AIS scoring increases the ISS error Many different injury patterns can yield the same ISS score Injuries to different body regions are not weighted Not a useful triage tool as a full description of patient injuries is not known
prior to full investigation amp operation
risk factors periosteal stripping off anterior femur male gender obesity post traumatic deformity Anterior and anterolateral approach Cementless
Neurogenic HO around the hip due to SCI occurs more often in the medial region than in the lateral region with ossified tissues extending from the pubic symphysis to the anteromedial femoral shaft posterior to the femoral neurovascular structures Ossification is also seen anteriorly involving the iliopsoas and femoral neurovascular structures laterally within gluteus minimus and posteriorly extending from the ilium to the posterior femur encasing the sciatic nerve
HTO AROUND hip and knee
The Brooker Classification of Heterotopic Ossification around the hip joint Class I has islands of bone within the soft tissues Class II has bone spurs from the pelvis or proximal end of the femur leaving at least 1 cm between opposing surfaces Class III has bone spurs from the pelvis andor proximal end of the femur reducing the space between opposing bone surfaces to less than 1 cm Class IV shows apparent bone ankylosis of the hip
Region I - Heterotopic ossifications are strictly below the tip of the greater trochanter
Region II - Heterotopic ossifications are below and above the tip of the greater trochanter
Region III - Heterotopic ossifications are strictly above the tip of the greater trochanter
Grade A - Single or multiple heterotopic ossifications are less than 10 mm in maximal extent without contact with the pelvis or the femur
Grade B - Heterotopic ossifications are greater than 10 mm without contact with the pelvis but with possible contact with the femur there is no bridging from the femur to the proximal part of the greater trochanter and no evidence of ankylosis
Grade C - Ankylosis by means of firm bridging from the femur to the pelvis is present
Shmidt classification
excision may be performed The results of this procedure are varied Patients may find that their range of movement improves but pain relief is likely to be limited
A patient with heterotopic ossification following total hip arthroplasty is thought to have a 90-100 chance of developing it on the contralateral hip if this hip also undergoes total arthroplasty
it would be prudent to minimize the risk of heterotopic ossification developing after arthroplasty by performing surgery whereby the following are ensured
Exposure is meticulous Retraction is performed carefully and soft tissue
is handled carefully Irrigation is adequate Devitalized tissue is excised Hemostasis is adequate Postoperative drains (when used) are not
retained for longer than necessary Perioperative antibiotic prophylaxis is used Postoperative anticoagulation (when used for
deep vein thrombosis prophylaxis) is carefully controlled
sources of knee stiffness 1-extrinsic severe osteoarthritis of the ipsilateral hip neurologic injury leading to muscle rigidity tight quadriceps or hamstring muscles secondary to muscle injury heterotopic ossification or long-standing juvenile inflammatory conditions limiting knee
range of motion prior to the completion of skeletal growth When extrinsic sources are identified revision total knee arthroplasty is unlikely to be associated with a favorable outcome without correction of the extrinsic problem
2-intrinsic (1) overstuffing of the patellofemoral articulation (2) an
excessively tight flexion andor extension gap (3) a tight posterior cruciate ligament (4) femoral andor tibial malrotation (5) arthrofibrosis and (6) limited bearing excursion in association with a highly conforming mobile-bearing prosthetic design
HTO after TKA
Heterotopic Ossification (HO) following primary Total Knee Replacement (TKR)
Occurs in 3-90 of TKRs 3-grade classification system No correlation between HO and component
alignment or component position
Clinical findings similar to early infection Continuing low-grade fever Warm swollen and erythematous knee Normal blood tests Possibly an association with HLA-A2 and B18 HO patients have worse KSS and function
scores
Patients at HIGH risk for developing HO after TKR (Knee Arthroplasty) (5)
Those with limited postoperative knee flexion
Increased lumbar bone mineral density (BMD) on multivariate analysis (3)
Hypertrophic arthrosis Excessive periosteal trauma Notching of the anterior femur Those who require forced manipulation
after TKA 47 in revision TKR surgery (6) Higher rates in revision TKR cases with
infection (up to 76
DaughertyBell classification of HO of the knee 0 No evidence of HO 1 Bone islands in periarticular soft tissue (no
involvement of femur patella or tibia) or HO within quadriceps expansion measuring lt1 cm
2 Spur formation measuring lt5 cm that involves the femur patella or tibia if more than one bone demonstrates HO separation of HO spurs
measure gt1 cm or HO within quadriceps expansion measuring ge1 cm but lt3 cm
3 Spur formation gt5 cm involving femur patella or tibia if more than one bone demonstrates HO separation of HO spurs measure lt1 cm or HO
within quadriceps expansion measuring ge3 cm 4 Extensive HO of the knee causing ankylosis
class 2 HO begins to involve the major bones of the knee joint with spur formation limited to a size of 5 cm
HO class 2 may be observed in select patients with complete ROM and no reported pain Patients with class 3 HO would likely always benefit from surgical excision
followed by RT prophylaxis Certainly patients in either cohort with a subclass ldquoBrdquo assignment (symptomatic) would
benefit from treatment All patients with class 4 HO require
treatment to alleviate ankylosis
treatment
References Whyte ldquoPagetrsquos Disease of Bonerdquo NEMJ vol 355
2006 Klein and Parvizi ldquoSurgical Manifestations of Pagetrsquos
Diseaserdquo JAAOS vol 14 2006 Orthobullets Campbell Apley Emedicinecom
-Chapter 15 Heterotopic Ossification after Traumatic Brain InjuryBy Jesuacutes Moreta and Joseacute Luis Martiacutenez-de los Mozos DOI 10577257343
Questions
Thank You
A 26-year-old man presents with generalized back and joint stiffness and difficulty opening his mouth His elder sister has similar complaints Since childhood he has had 3 surgeries for excision of recurrent bony prominences around his knees He walks with a stooped over posture seen in Figure A Radiographs of his feet knee hip and spine are seen in Figures B-E respectively
fibrodysplasia ossificans progressiva
Stone Man Disease) which involves a mutation of the ACVR1
There are 2 hallmark characteristics progressive heterotopic ossification (muscles fascia tendons ligaments and joint capsules) and congenital malformation of the great toe (hallux valgus malformed first metatarsal and monophalangism) BMP4 which contributes to the formation of the skeleton in the normal embryo is implicated in this disease
Complications
bullHematoma and intraoperative bleedingbullInfection
bull higher rate of infection following joint arthroplasty if HO is present
bullFractures of osteoporotic bone bull osteopenic from disusebull during surgery or physiotherapy
bullRecurrence bull recurrence rate correlates with neurological injury
bull greater recurrence if severe neurological compromisebullAVN
bull if extensive dissection or stripping is required
HTO AND ISS
When ISS is below 25 the mortality risk is minimal and above 25 it is an almost linear increase
When ISS is 50 the mortality is 50 When above 70 it is close to 100 If an injury is assigned an AIS of 6 (unsurvivable injury) the ISS score is
automatically assigned to 75 Highest ISS score obtainable is 75 For trauma patients of vehicular accidents the scoring system is important
for assessing the effectiveness of medical care in reducing morbidity and mortality
Advantages virtually the only anatomical scoring system in use correlates linearly with
mortality morbidity hospital stay other measures of severity
Weaknesses Any error in AIS scoring increases the ISS error Many different injury patterns can yield the same ISS score Injuries to different body regions are not weighted Not a useful triage tool as a full description of patient injuries is not known
prior to full investigation amp operation
risk factors periosteal stripping off anterior femur male gender obesity post traumatic deformity Anterior and anterolateral approach Cementless
Neurogenic HO around the hip due to SCI occurs more often in the medial region than in the lateral region with ossified tissues extending from the pubic symphysis to the anteromedial femoral shaft posterior to the femoral neurovascular structures Ossification is also seen anteriorly involving the iliopsoas and femoral neurovascular structures laterally within gluteus minimus and posteriorly extending from the ilium to the posterior femur encasing the sciatic nerve
HTO AROUND hip and knee
The Brooker Classification of Heterotopic Ossification around the hip joint Class I has islands of bone within the soft tissues Class II has bone spurs from the pelvis or proximal end of the femur leaving at least 1 cm between opposing surfaces Class III has bone spurs from the pelvis andor proximal end of the femur reducing the space between opposing bone surfaces to less than 1 cm Class IV shows apparent bone ankylosis of the hip
Region I - Heterotopic ossifications are strictly below the tip of the greater trochanter
Region II - Heterotopic ossifications are below and above the tip of the greater trochanter
Region III - Heterotopic ossifications are strictly above the tip of the greater trochanter
Grade A - Single or multiple heterotopic ossifications are less than 10 mm in maximal extent without contact with the pelvis or the femur
Grade B - Heterotopic ossifications are greater than 10 mm without contact with the pelvis but with possible contact with the femur there is no bridging from the femur to the proximal part of the greater trochanter and no evidence of ankylosis
Grade C - Ankylosis by means of firm bridging from the femur to the pelvis is present
Shmidt classification
excision may be performed The results of this procedure are varied Patients may find that their range of movement improves but pain relief is likely to be limited
A patient with heterotopic ossification following total hip arthroplasty is thought to have a 90-100 chance of developing it on the contralateral hip if this hip also undergoes total arthroplasty
it would be prudent to minimize the risk of heterotopic ossification developing after arthroplasty by performing surgery whereby the following are ensured
Exposure is meticulous Retraction is performed carefully and soft tissue
is handled carefully Irrigation is adequate Devitalized tissue is excised Hemostasis is adequate Postoperative drains (when used) are not
retained for longer than necessary Perioperative antibiotic prophylaxis is used Postoperative anticoagulation (when used for
deep vein thrombosis prophylaxis) is carefully controlled
sources of knee stiffness 1-extrinsic severe osteoarthritis of the ipsilateral hip neurologic injury leading to muscle rigidity tight quadriceps or hamstring muscles secondary to muscle injury heterotopic ossification or long-standing juvenile inflammatory conditions limiting knee
range of motion prior to the completion of skeletal growth When extrinsic sources are identified revision total knee arthroplasty is unlikely to be associated with a favorable outcome without correction of the extrinsic problem
2-intrinsic (1) overstuffing of the patellofemoral articulation (2) an
excessively tight flexion andor extension gap (3) a tight posterior cruciate ligament (4) femoral andor tibial malrotation (5) arthrofibrosis and (6) limited bearing excursion in association with a highly conforming mobile-bearing prosthetic design
HTO after TKA
Heterotopic Ossification (HO) following primary Total Knee Replacement (TKR)
Occurs in 3-90 of TKRs 3-grade classification system No correlation between HO and component
alignment or component position
Clinical findings similar to early infection Continuing low-grade fever Warm swollen and erythematous knee Normal blood tests Possibly an association with HLA-A2 and B18 HO patients have worse KSS and function
scores
Patients at HIGH risk for developing HO after TKR (Knee Arthroplasty) (5)
Those with limited postoperative knee flexion
Increased lumbar bone mineral density (BMD) on multivariate analysis (3)
Hypertrophic arthrosis Excessive periosteal trauma Notching of the anterior femur Those who require forced manipulation
after TKA 47 in revision TKR surgery (6) Higher rates in revision TKR cases with
infection (up to 76
DaughertyBell classification of HO of the knee 0 No evidence of HO 1 Bone islands in periarticular soft tissue (no
involvement of femur patella or tibia) or HO within quadriceps expansion measuring lt1 cm
2 Spur formation measuring lt5 cm that involves the femur patella or tibia if more than one bone demonstrates HO separation of HO spurs
measure gt1 cm or HO within quadriceps expansion measuring ge1 cm but lt3 cm
3 Spur formation gt5 cm involving femur patella or tibia if more than one bone demonstrates HO separation of HO spurs measure lt1 cm or HO
within quadriceps expansion measuring ge3 cm 4 Extensive HO of the knee causing ankylosis
class 2 HO begins to involve the major bones of the knee joint with spur formation limited to a size of 5 cm
HO class 2 may be observed in select patients with complete ROM and no reported pain Patients with class 3 HO would likely always benefit from surgical excision
followed by RT prophylaxis Certainly patients in either cohort with a subclass ldquoBrdquo assignment (symptomatic) would
benefit from treatment All patients with class 4 HO require
treatment to alleviate ankylosis
treatment
References Whyte ldquoPagetrsquos Disease of Bonerdquo NEMJ vol 355
2006 Klein and Parvizi ldquoSurgical Manifestations of Pagetrsquos
Diseaserdquo JAAOS vol 14 2006 Orthobullets Campbell Apley Emedicinecom
-Chapter 15 Heterotopic Ossification after Traumatic Brain InjuryBy Jesuacutes Moreta and Joseacute Luis Martiacutenez-de los Mozos DOI 10577257343
Questions
Thank You
Stone Man Disease) which involves a mutation of the ACVR1
There are 2 hallmark characteristics progressive heterotopic ossification (muscles fascia tendons ligaments and joint capsules) and congenital malformation of the great toe (hallux valgus malformed first metatarsal and monophalangism) BMP4 which contributes to the formation of the skeleton in the normal embryo is implicated in this disease
Complications
bullHematoma and intraoperative bleedingbullInfection
bull higher rate of infection following joint arthroplasty if HO is present
bullFractures of osteoporotic bone bull osteopenic from disusebull during surgery or physiotherapy
bullRecurrence bull recurrence rate correlates with neurological injury
bull greater recurrence if severe neurological compromisebullAVN
bull if extensive dissection or stripping is required
HTO AND ISS
When ISS is below 25 the mortality risk is minimal and above 25 it is an almost linear increase
When ISS is 50 the mortality is 50 When above 70 it is close to 100 If an injury is assigned an AIS of 6 (unsurvivable injury) the ISS score is
automatically assigned to 75 Highest ISS score obtainable is 75 For trauma patients of vehicular accidents the scoring system is important
for assessing the effectiveness of medical care in reducing morbidity and mortality
Advantages virtually the only anatomical scoring system in use correlates linearly with
mortality morbidity hospital stay other measures of severity
Weaknesses Any error in AIS scoring increases the ISS error Many different injury patterns can yield the same ISS score Injuries to different body regions are not weighted Not a useful triage tool as a full description of patient injuries is not known
prior to full investigation amp operation
risk factors periosteal stripping off anterior femur male gender obesity post traumatic deformity Anterior and anterolateral approach Cementless
Neurogenic HO around the hip due to SCI occurs more often in the medial region than in the lateral region with ossified tissues extending from the pubic symphysis to the anteromedial femoral shaft posterior to the femoral neurovascular structures Ossification is also seen anteriorly involving the iliopsoas and femoral neurovascular structures laterally within gluteus minimus and posteriorly extending from the ilium to the posterior femur encasing the sciatic nerve
HTO AROUND hip and knee
The Brooker Classification of Heterotopic Ossification around the hip joint Class I has islands of bone within the soft tissues Class II has bone spurs from the pelvis or proximal end of the femur leaving at least 1 cm between opposing surfaces Class III has bone spurs from the pelvis andor proximal end of the femur reducing the space between opposing bone surfaces to less than 1 cm Class IV shows apparent bone ankylosis of the hip
Region I - Heterotopic ossifications are strictly below the tip of the greater trochanter
Region II - Heterotopic ossifications are below and above the tip of the greater trochanter
Region III - Heterotopic ossifications are strictly above the tip of the greater trochanter
Grade A - Single or multiple heterotopic ossifications are less than 10 mm in maximal extent without contact with the pelvis or the femur
Grade B - Heterotopic ossifications are greater than 10 mm without contact with the pelvis but with possible contact with the femur there is no bridging from the femur to the proximal part of the greater trochanter and no evidence of ankylosis
Grade C - Ankylosis by means of firm bridging from the femur to the pelvis is present
Shmidt classification
excision may be performed The results of this procedure are varied Patients may find that their range of movement improves but pain relief is likely to be limited
A patient with heterotopic ossification following total hip arthroplasty is thought to have a 90-100 chance of developing it on the contralateral hip if this hip also undergoes total arthroplasty
it would be prudent to minimize the risk of heterotopic ossification developing after arthroplasty by performing surgery whereby the following are ensured
Exposure is meticulous Retraction is performed carefully and soft tissue
is handled carefully Irrigation is adequate Devitalized tissue is excised Hemostasis is adequate Postoperative drains (when used) are not
retained for longer than necessary Perioperative antibiotic prophylaxis is used Postoperative anticoagulation (when used for
deep vein thrombosis prophylaxis) is carefully controlled
sources of knee stiffness 1-extrinsic severe osteoarthritis of the ipsilateral hip neurologic injury leading to muscle rigidity tight quadriceps or hamstring muscles secondary to muscle injury heterotopic ossification or long-standing juvenile inflammatory conditions limiting knee
range of motion prior to the completion of skeletal growth When extrinsic sources are identified revision total knee arthroplasty is unlikely to be associated with a favorable outcome without correction of the extrinsic problem
2-intrinsic (1) overstuffing of the patellofemoral articulation (2) an
excessively tight flexion andor extension gap (3) a tight posterior cruciate ligament (4) femoral andor tibial malrotation (5) arthrofibrosis and (6) limited bearing excursion in association with a highly conforming mobile-bearing prosthetic design
HTO after TKA
Heterotopic Ossification (HO) following primary Total Knee Replacement (TKR)
Occurs in 3-90 of TKRs 3-grade classification system No correlation between HO and component
alignment or component position
Clinical findings similar to early infection Continuing low-grade fever Warm swollen and erythematous knee Normal blood tests Possibly an association with HLA-A2 and B18 HO patients have worse KSS and function
scores
Patients at HIGH risk for developing HO after TKR (Knee Arthroplasty) (5)
Those with limited postoperative knee flexion
Increased lumbar bone mineral density (BMD) on multivariate analysis (3)
Hypertrophic arthrosis Excessive periosteal trauma Notching of the anterior femur Those who require forced manipulation
after TKA 47 in revision TKR surgery (6) Higher rates in revision TKR cases with
infection (up to 76
DaughertyBell classification of HO of the knee 0 No evidence of HO 1 Bone islands in periarticular soft tissue (no
involvement of femur patella or tibia) or HO within quadriceps expansion measuring lt1 cm
2 Spur formation measuring lt5 cm that involves the femur patella or tibia if more than one bone demonstrates HO separation of HO spurs
measure gt1 cm or HO within quadriceps expansion measuring ge1 cm but lt3 cm
3 Spur formation gt5 cm involving femur patella or tibia if more than one bone demonstrates HO separation of HO spurs measure lt1 cm or HO
within quadriceps expansion measuring ge3 cm 4 Extensive HO of the knee causing ankylosis
class 2 HO begins to involve the major bones of the knee joint with spur formation limited to a size of 5 cm
HO class 2 may be observed in select patients with complete ROM and no reported pain Patients with class 3 HO would likely always benefit from surgical excision
followed by RT prophylaxis Certainly patients in either cohort with a subclass ldquoBrdquo assignment (symptomatic) would
benefit from treatment All patients with class 4 HO require
treatment to alleviate ankylosis
treatment
References Whyte ldquoPagetrsquos Disease of Bonerdquo NEMJ vol 355
2006 Klein and Parvizi ldquoSurgical Manifestations of Pagetrsquos
Diseaserdquo JAAOS vol 14 2006 Orthobullets Campbell Apley Emedicinecom
-Chapter 15 Heterotopic Ossification after Traumatic Brain InjuryBy Jesuacutes Moreta and Joseacute Luis Martiacutenez-de los Mozos DOI 10577257343
Questions
Thank You
There are 2 hallmark characteristics progressive heterotopic ossification (muscles fascia tendons ligaments and joint capsules) and congenital malformation of the great toe (hallux valgus malformed first metatarsal and monophalangism) BMP4 which contributes to the formation of the skeleton in the normal embryo is implicated in this disease
Complications
bullHematoma and intraoperative bleedingbullInfection
bull higher rate of infection following joint arthroplasty if HO is present
bullFractures of osteoporotic bone bull osteopenic from disusebull during surgery or physiotherapy
bullRecurrence bull recurrence rate correlates with neurological injury
bull greater recurrence if severe neurological compromisebullAVN
bull if extensive dissection or stripping is required
HTO AND ISS
When ISS is below 25 the mortality risk is minimal and above 25 it is an almost linear increase
When ISS is 50 the mortality is 50 When above 70 it is close to 100 If an injury is assigned an AIS of 6 (unsurvivable injury) the ISS score is
automatically assigned to 75 Highest ISS score obtainable is 75 For trauma patients of vehicular accidents the scoring system is important
for assessing the effectiveness of medical care in reducing morbidity and mortality
Advantages virtually the only anatomical scoring system in use correlates linearly with
mortality morbidity hospital stay other measures of severity
Weaknesses Any error in AIS scoring increases the ISS error Many different injury patterns can yield the same ISS score Injuries to different body regions are not weighted Not a useful triage tool as a full description of patient injuries is not known
prior to full investigation amp operation
risk factors periosteal stripping off anterior femur male gender obesity post traumatic deformity Anterior and anterolateral approach Cementless
Neurogenic HO around the hip due to SCI occurs more often in the medial region than in the lateral region with ossified tissues extending from the pubic symphysis to the anteromedial femoral shaft posterior to the femoral neurovascular structures Ossification is also seen anteriorly involving the iliopsoas and femoral neurovascular structures laterally within gluteus minimus and posteriorly extending from the ilium to the posterior femur encasing the sciatic nerve
HTO AROUND hip and knee
The Brooker Classification of Heterotopic Ossification around the hip joint Class I has islands of bone within the soft tissues Class II has bone spurs from the pelvis or proximal end of the femur leaving at least 1 cm between opposing surfaces Class III has bone spurs from the pelvis andor proximal end of the femur reducing the space between opposing bone surfaces to less than 1 cm Class IV shows apparent bone ankylosis of the hip
Region I - Heterotopic ossifications are strictly below the tip of the greater trochanter
Region II - Heterotopic ossifications are below and above the tip of the greater trochanter
Region III - Heterotopic ossifications are strictly above the tip of the greater trochanter
Grade A - Single or multiple heterotopic ossifications are less than 10 mm in maximal extent without contact with the pelvis or the femur
Grade B - Heterotopic ossifications are greater than 10 mm without contact with the pelvis but with possible contact with the femur there is no bridging from the femur to the proximal part of the greater trochanter and no evidence of ankylosis
Grade C - Ankylosis by means of firm bridging from the femur to the pelvis is present
Shmidt classification
excision may be performed The results of this procedure are varied Patients may find that their range of movement improves but pain relief is likely to be limited
A patient with heterotopic ossification following total hip arthroplasty is thought to have a 90-100 chance of developing it on the contralateral hip if this hip also undergoes total arthroplasty
it would be prudent to minimize the risk of heterotopic ossification developing after arthroplasty by performing surgery whereby the following are ensured
Exposure is meticulous Retraction is performed carefully and soft tissue
is handled carefully Irrigation is adequate Devitalized tissue is excised Hemostasis is adequate Postoperative drains (when used) are not
retained for longer than necessary Perioperative antibiotic prophylaxis is used Postoperative anticoagulation (when used for
deep vein thrombosis prophylaxis) is carefully controlled
sources of knee stiffness 1-extrinsic severe osteoarthritis of the ipsilateral hip neurologic injury leading to muscle rigidity tight quadriceps or hamstring muscles secondary to muscle injury heterotopic ossification or long-standing juvenile inflammatory conditions limiting knee
range of motion prior to the completion of skeletal growth When extrinsic sources are identified revision total knee arthroplasty is unlikely to be associated with a favorable outcome without correction of the extrinsic problem
2-intrinsic (1) overstuffing of the patellofemoral articulation (2) an
excessively tight flexion andor extension gap (3) a tight posterior cruciate ligament (4) femoral andor tibial malrotation (5) arthrofibrosis and (6) limited bearing excursion in association with a highly conforming mobile-bearing prosthetic design
HTO after TKA
Heterotopic Ossification (HO) following primary Total Knee Replacement (TKR)
Occurs in 3-90 of TKRs 3-grade classification system No correlation between HO and component
alignment or component position
Clinical findings similar to early infection Continuing low-grade fever Warm swollen and erythematous knee Normal blood tests Possibly an association with HLA-A2 and B18 HO patients have worse KSS and function
scores
Patients at HIGH risk for developing HO after TKR (Knee Arthroplasty) (5)
Those with limited postoperative knee flexion
Increased lumbar bone mineral density (BMD) on multivariate analysis (3)
Hypertrophic arthrosis Excessive periosteal trauma Notching of the anterior femur Those who require forced manipulation
after TKA 47 in revision TKR surgery (6) Higher rates in revision TKR cases with
infection (up to 76
DaughertyBell classification of HO of the knee 0 No evidence of HO 1 Bone islands in periarticular soft tissue (no
involvement of femur patella or tibia) or HO within quadriceps expansion measuring lt1 cm
2 Spur formation measuring lt5 cm that involves the femur patella or tibia if more than one bone demonstrates HO separation of HO spurs
measure gt1 cm or HO within quadriceps expansion measuring ge1 cm but lt3 cm
3 Spur formation gt5 cm involving femur patella or tibia if more than one bone demonstrates HO separation of HO spurs measure lt1 cm or HO
within quadriceps expansion measuring ge3 cm 4 Extensive HO of the knee causing ankylosis
class 2 HO begins to involve the major bones of the knee joint with spur formation limited to a size of 5 cm
HO class 2 may be observed in select patients with complete ROM and no reported pain Patients with class 3 HO would likely always benefit from surgical excision
followed by RT prophylaxis Certainly patients in either cohort with a subclass ldquoBrdquo assignment (symptomatic) would
benefit from treatment All patients with class 4 HO require
treatment to alleviate ankylosis
treatment
References Whyte ldquoPagetrsquos Disease of Bonerdquo NEMJ vol 355
2006 Klein and Parvizi ldquoSurgical Manifestations of Pagetrsquos
Diseaserdquo JAAOS vol 14 2006 Orthobullets Campbell Apley Emedicinecom
-Chapter 15 Heterotopic Ossification after Traumatic Brain InjuryBy Jesuacutes Moreta and Joseacute Luis Martiacutenez-de los Mozos DOI 10577257343
Questions
Thank You
Complications
bullHematoma and intraoperative bleedingbullInfection
bull higher rate of infection following joint arthroplasty if HO is present
bullFractures of osteoporotic bone bull osteopenic from disusebull during surgery or physiotherapy
bullRecurrence bull recurrence rate correlates with neurological injury
bull greater recurrence if severe neurological compromisebullAVN
bull if extensive dissection or stripping is required
HTO AND ISS
When ISS is below 25 the mortality risk is minimal and above 25 it is an almost linear increase
When ISS is 50 the mortality is 50 When above 70 it is close to 100 If an injury is assigned an AIS of 6 (unsurvivable injury) the ISS score is
automatically assigned to 75 Highest ISS score obtainable is 75 For trauma patients of vehicular accidents the scoring system is important
for assessing the effectiveness of medical care in reducing morbidity and mortality
Advantages virtually the only anatomical scoring system in use correlates linearly with
mortality morbidity hospital stay other measures of severity
Weaknesses Any error in AIS scoring increases the ISS error Many different injury patterns can yield the same ISS score Injuries to different body regions are not weighted Not a useful triage tool as a full description of patient injuries is not known
prior to full investigation amp operation
risk factors periosteal stripping off anterior femur male gender obesity post traumatic deformity Anterior and anterolateral approach Cementless
Neurogenic HO around the hip due to SCI occurs more often in the medial region than in the lateral region with ossified tissues extending from the pubic symphysis to the anteromedial femoral shaft posterior to the femoral neurovascular structures Ossification is also seen anteriorly involving the iliopsoas and femoral neurovascular structures laterally within gluteus minimus and posteriorly extending from the ilium to the posterior femur encasing the sciatic nerve
HTO AROUND hip and knee
The Brooker Classification of Heterotopic Ossification around the hip joint Class I has islands of bone within the soft tissues Class II has bone spurs from the pelvis or proximal end of the femur leaving at least 1 cm between opposing surfaces Class III has bone spurs from the pelvis andor proximal end of the femur reducing the space between opposing bone surfaces to less than 1 cm Class IV shows apparent bone ankylosis of the hip
Region I - Heterotopic ossifications are strictly below the tip of the greater trochanter
Region II - Heterotopic ossifications are below and above the tip of the greater trochanter
Region III - Heterotopic ossifications are strictly above the tip of the greater trochanter
Grade A - Single or multiple heterotopic ossifications are less than 10 mm in maximal extent without contact with the pelvis or the femur
Grade B - Heterotopic ossifications are greater than 10 mm without contact with the pelvis but with possible contact with the femur there is no bridging from the femur to the proximal part of the greater trochanter and no evidence of ankylosis
Grade C - Ankylosis by means of firm bridging from the femur to the pelvis is present
Shmidt classification
excision may be performed The results of this procedure are varied Patients may find that their range of movement improves but pain relief is likely to be limited
A patient with heterotopic ossification following total hip arthroplasty is thought to have a 90-100 chance of developing it on the contralateral hip if this hip also undergoes total arthroplasty
it would be prudent to minimize the risk of heterotopic ossification developing after arthroplasty by performing surgery whereby the following are ensured
Exposure is meticulous Retraction is performed carefully and soft tissue
is handled carefully Irrigation is adequate Devitalized tissue is excised Hemostasis is adequate Postoperative drains (when used) are not
retained for longer than necessary Perioperative antibiotic prophylaxis is used Postoperative anticoagulation (when used for
deep vein thrombosis prophylaxis) is carefully controlled
sources of knee stiffness 1-extrinsic severe osteoarthritis of the ipsilateral hip neurologic injury leading to muscle rigidity tight quadriceps or hamstring muscles secondary to muscle injury heterotopic ossification or long-standing juvenile inflammatory conditions limiting knee
range of motion prior to the completion of skeletal growth When extrinsic sources are identified revision total knee arthroplasty is unlikely to be associated with a favorable outcome without correction of the extrinsic problem
2-intrinsic (1) overstuffing of the patellofemoral articulation (2) an
excessively tight flexion andor extension gap (3) a tight posterior cruciate ligament (4) femoral andor tibial malrotation (5) arthrofibrosis and (6) limited bearing excursion in association with a highly conforming mobile-bearing prosthetic design
HTO after TKA
Heterotopic Ossification (HO) following primary Total Knee Replacement (TKR)
Occurs in 3-90 of TKRs 3-grade classification system No correlation between HO and component
alignment or component position
Clinical findings similar to early infection Continuing low-grade fever Warm swollen and erythematous knee Normal blood tests Possibly an association with HLA-A2 and B18 HO patients have worse KSS and function
scores
Patients at HIGH risk for developing HO after TKR (Knee Arthroplasty) (5)
Those with limited postoperative knee flexion
Increased lumbar bone mineral density (BMD) on multivariate analysis (3)
Hypertrophic arthrosis Excessive periosteal trauma Notching of the anterior femur Those who require forced manipulation
after TKA 47 in revision TKR surgery (6) Higher rates in revision TKR cases with
infection (up to 76
DaughertyBell classification of HO of the knee 0 No evidence of HO 1 Bone islands in periarticular soft tissue (no
involvement of femur patella or tibia) or HO within quadriceps expansion measuring lt1 cm
2 Spur formation measuring lt5 cm that involves the femur patella or tibia if more than one bone demonstrates HO separation of HO spurs
measure gt1 cm or HO within quadriceps expansion measuring ge1 cm but lt3 cm
3 Spur formation gt5 cm involving femur patella or tibia if more than one bone demonstrates HO separation of HO spurs measure lt1 cm or HO
within quadriceps expansion measuring ge3 cm 4 Extensive HO of the knee causing ankylosis
class 2 HO begins to involve the major bones of the knee joint with spur formation limited to a size of 5 cm
HO class 2 may be observed in select patients with complete ROM and no reported pain Patients with class 3 HO would likely always benefit from surgical excision
followed by RT prophylaxis Certainly patients in either cohort with a subclass ldquoBrdquo assignment (symptomatic) would
benefit from treatment All patients with class 4 HO require
treatment to alleviate ankylosis
treatment
References Whyte ldquoPagetrsquos Disease of Bonerdquo NEMJ vol 355
2006 Klein and Parvizi ldquoSurgical Manifestations of Pagetrsquos
Diseaserdquo JAAOS vol 14 2006 Orthobullets Campbell Apley Emedicinecom
-Chapter 15 Heterotopic Ossification after Traumatic Brain InjuryBy Jesuacutes Moreta and Joseacute Luis Martiacutenez-de los Mozos DOI 10577257343
Questions
Thank You
HTO AND ISS
When ISS is below 25 the mortality risk is minimal and above 25 it is an almost linear increase
When ISS is 50 the mortality is 50 When above 70 it is close to 100 If an injury is assigned an AIS of 6 (unsurvivable injury) the ISS score is
automatically assigned to 75 Highest ISS score obtainable is 75 For trauma patients of vehicular accidents the scoring system is important
for assessing the effectiveness of medical care in reducing morbidity and mortality
Advantages virtually the only anatomical scoring system in use correlates linearly with
mortality morbidity hospital stay other measures of severity
Weaknesses Any error in AIS scoring increases the ISS error Many different injury patterns can yield the same ISS score Injuries to different body regions are not weighted Not a useful triage tool as a full description of patient injuries is not known
prior to full investigation amp operation
risk factors periosteal stripping off anterior femur male gender obesity post traumatic deformity Anterior and anterolateral approach Cementless
Neurogenic HO around the hip due to SCI occurs more often in the medial region than in the lateral region with ossified tissues extending from the pubic symphysis to the anteromedial femoral shaft posterior to the femoral neurovascular structures Ossification is also seen anteriorly involving the iliopsoas and femoral neurovascular structures laterally within gluteus minimus and posteriorly extending from the ilium to the posterior femur encasing the sciatic nerve
HTO AROUND hip and knee
The Brooker Classification of Heterotopic Ossification around the hip joint Class I has islands of bone within the soft tissues Class II has bone spurs from the pelvis or proximal end of the femur leaving at least 1 cm between opposing surfaces Class III has bone spurs from the pelvis andor proximal end of the femur reducing the space between opposing bone surfaces to less than 1 cm Class IV shows apparent bone ankylosis of the hip
Region I - Heterotopic ossifications are strictly below the tip of the greater trochanter
Region II - Heterotopic ossifications are below and above the tip of the greater trochanter
Region III - Heterotopic ossifications are strictly above the tip of the greater trochanter
Grade A - Single or multiple heterotopic ossifications are less than 10 mm in maximal extent without contact with the pelvis or the femur
Grade B - Heterotopic ossifications are greater than 10 mm without contact with the pelvis but with possible contact with the femur there is no bridging from the femur to the proximal part of the greater trochanter and no evidence of ankylosis
Grade C - Ankylosis by means of firm bridging from the femur to the pelvis is present
Shmidt classification
excision may be performed The results of this procedure are varied Patients may find that their range of movement improves but pain relief is likely to be limited
A patient with heterotopic ossification following total hip arthroplasty is thought to have a 90-100 chance of developing it on the contralateral hip if this hip also undergoes total arthroplasty
it would be prudent to minimize the risk of heterotopic ossification developing after arthroplasty by performing surgery whereby the following are ensured
Exposure is meticulous Retraction is performed carefully and soft tissue
is handled carefully Irrigation is adequate Devitalized tissue is excised Hemostasis is adequate Postoperative drains (when used) are not
retained for longer than necessary Perioperative antibiotic prophylaxis is used Postoperative anticoagulation (when used for
deep vein thrombosis prophylaxis) is carefully controlled
sources of knee stiffness 1-extrinsic severe osteoarthritis of the ipsilateral hip neurologic injury leading to muscle rigidity tight quadriceps or hamstring muscles secondary to muscle injury heterotopic ossification or long-standing juvenile inflammatory conditions limiting knee
range of motion prior to the completion of skeletal growth When extrinsic sources are identified revision total knee arthroplasty is unlikely to be associated with a favorable outcome without correction of the extrinsic problem
2-intrinsic (1) overstuffing of the patellofemoral articulation (2) an
excessively tight flexion andor extension gap (3) a tight posterior cruciate ligament (4) femoral andor tibial malrotation (5) arthrofibrosis and (6) limited bearing excursion in association with a highly conforming mobile-bearing prosthetic design
HTO after TKA
Heterotopic Ossification (HO) following primary Total Knee Replacement (TKR)
Occurs in 3-90 of TKRs 3-grade classification system No correlation between HO and component
alignment or component position
Clinical findings similar to early infection Continuing low-grade fever Warm swollen and erythematous knee Normal blood tests Possibly an association with HLA-A2 and B18 HO patients have worse KSS and function
scores
Patients at HIGH risk for developing HO after TKR (Knee Arthroplasty) (5)
Those with limited postoperative knee flexion
Increased lumbar bone mineral density (BMD) on multivariate analysis (3)
Hypertrophic arthrosis Excessive periosteal trauma Notching of the anterior femur Those who require forced manipulation
after TKA 47 in revision TKR surgery (6) Higher rates in revision TKR cases with
infection (up to 76
DaughertyBell classification of HO of the knee 0 No evidence of HO 1 Bone islands in periarticular soft tissue (no
involvement of femur patella or tibia) or HO within quadriceps expansion measuring lt1 cm
2 Spur formation measuring lt5 cm that involves the femur patella or tibia if more than one bone demonstrates HO separation of HO spurs
measure gt1 cm or HO within quadriceps expansion measuring ge1 cm but lt3 cm
3 Spur formation gt5 cm involving femur patella or tibia if more than one bone demonstrates HO separation of HO spurs measure lt1 cm or HO
within quadriceps expansion measuring ge3 cm 4 Extensive HO of the knee causing ankylosis
class 2 HO begins to involve the major bones of the knee joint with spur formation limited to a size of 5 cm
HO class 2 may be observed in select patients with complete ROM and no reported pain Patients with class 3 HO would likely always benefit from surgical excision
followed by RT prophylaxis Certainly patients in either cohort with a subclass ldquoBrdquo assignment (symptomatic) would
benefit from treatment All patients with class 4 HO require
treatment to alleviate ankylosis
treatment
References Whyte ldquoPagetrsquos Disease of Bonerdquo NEMJ vol 355
2006 Klein and Parvizi ldquoSurgical Manifestations of Pagetrsquos
Diseaserdquo JAAOS vol 14 2006 Orthobullets Campbell Apley Emedicinecom
-Chapter 15 Heterotopic Ossification after Traumatic Brain InjuryBy Jesuacutes Moreta and Joseacute Luis Martiacutenez-de los Mozos DOI 10577257343
Questions
Thank You
When ISS is below 25 the mortality risk is minimal and above 25 it is an almost linear increase
When ISS is 50 the mortality is 50 When above 70 it is close to 100 If an injury is assigned an AIS of 6 (unsurvivable injury) the ISS score is
automatically assigned to 75 Highest ISS score obtainable is 75 For trauma patients of vehicular accidents the scoring system is important
for assessing the effectiveness of medical care in reducing morbidity and mortality
Advantages virtually the only anatomical scoring system in use correlates linearly with
mortality morbidity hospital stay other measures of severity
Weaknesses Any error in AIS scoring increases the ISS error Many different injury patterns can yield the same ISS score Injuries to different body regions are not weighted Not a useful triage tool as a full description of patient injuries is not known
prior to full investigation amp operation
risk factors periosteal stripping off anterior femur male gender obesity post traumatic deformity Anterior and anterolateral approach Cementless
Neurogenic HO around the hip due to SCI occurs more often in the medial region than in the lateral region with ossified tissues extending from the pubic symphysis to the anteromedial femoral shaft posterior to the femoral neurovascular structures Ossification is also seen anteriorly involving the iliopsoas and femoral neurovascular structures laterally within gluteus minimus and posteriorly extending from the ilium to the posterior femur encasing the sciatic nerve
HTO AROUND hip and knee
The Brooker Classification of Heterotopic Ossification around the hip joint Class I has islands of bone within the soft tissues Class II has bone spurs from the pelvis or proximal end of the femur leaving at least 1 cm between opposing surfaces Class III has bone spurs from the pelvis andor proximal end of the femur reducing the space between opposing bone surfaces to less than 1 cm Class IV shows apparent bone ankylosis of the hip
Region I - Heterotopic ossifications are strictly below the tip of the greater trochanter
Region II - Heterotopic ossifications are below and above the tip of the greater trochanter
Region III - Heterotopic ossifications are strictly above the tip of the greater trochanter
Grade A - Single or multiple heterotopic ossifications are less than 10 mm in maximal extent without contact with the pelvis or the femur
Grade B - Heterotopic ossifications are greater than 10 mm without contact with the pelvis but with possible contact with the femur there is no bridging from the femur to the proximal part of the greater trochanter and no evidence of ankylosis
Grade C - Ankylosis by means of firm bridging from the femur to the pelvis is present
Shmidt classification
excision may be performed The results of this procedure are varied Patients may find that their range of movement improves but pain relief is likely to be limited
A patient with heterotopic ossification following total hip arthroplasty is thought to have a 90-100 chance of developing it on the contralateral hip if this hip also undergoes total arthroplasty
it would be prudent to minimize the risk of heterotopic ossification developing after arthroplasty by performing surgery whereby the following are ensured
Exposure is meticulous Retraction is performed carefully and soft tissue
is handled carefully Irrigation is adequate Devitalized tissue is excised Hemostasis is adequate Postoperative drains (when used) are not
retained for longer than necessary Perioperative antibiotic prophylaxis is used Postoperative anticoagulation (when used for
deep vein thrombosis prophylaxis) is carefully controlled
sources of knee stiffness 1-extrinsic severe osteoarthritis of the ipsilateral hip neurologic injury leading to muscle rigidity tight quadriceps or hamstring muscles secondary to muscle injury heterotopic ossification or long-standing juvenile inflammatory conditions limiting knee
range of motion prior to the completion of skeletal growth When extrinsic sources are identified revision total knee arthroplasty is unlikely to be associated with a favorable outcome without correction of the extrinsic problem
2-intrinsic (1) overstuffing of the patellofemoral articulation (2) an
excessively tight flexion andor extension gap (3) a tight posterior cruciate ligament (4) femoral andor tibial malrotation (5) arthrofibrosis and (6) limited bearing excursion in association with a highly conforming mobile-bearing prosthetic design
HTO after TKA
Heterotopic Ossification (HO) following primary Total Knee Replacement (TKR)
Occurs in 3-90 of TKRs 3-grade classification system No correlation between HO and component
alignment or component position
Clinical findings similar to early infection Continuing low-grade fever Warm swollen and erythematous knee Normal blood tests Possibly an association with HLA-A2 and B18 HO patients have worse KSS and function
scores
Patients at HIGH risk for developing HO after TKR (Knee Arthroplasty) (5)
Those with limited postoperative knee flexion
Increased lumbar bone mineral density (BMD) on multivariate analysis (3)
Hypertrophic arthrosis Excessive periosteal trauma Notching of the anterior femur Those who require forced manipulation
after TKA 47 in revision TKR surgery (6) Higher rates in revision TKR cases with
infection (up to 76
DaughertyBell classification of HO of the knee 0 No evidence of HO 1 Bone islands in periarticular soft tissue (no
involvement of femur patella or tibia) or HO within quadriceps expansion measuring lt1 cm
2 Spur formation measuring lt5 cm that involves the femur patella or tibia if more than one bone demonstrates HO separation of HO spurs
measure gt1 cm or HO within quadriceps expansion measuring ge1 cm but lt3 cm
3 Spur formation gt5 cm involving femur patella or tibia if more than one bone demonstrates HO separation of HO spurs measure lt1 cm or HO
within quadriceps expansion measuring ge3 cm 4 Extensive HO of the knee causing ankylosis
class 2 HO begins to involve the major bones of the knee joint with spur formation limited to a size of 5 cm
HO class 2 may be observed in select patients with complete ROM and no reported pain Patients with class 3 HO would likely always benefit from surgical excision
followed by RT prophylaxis Certainly patients in either cohort with a subclass ldquoBrdquo assignment (symptomatic) would
benefit from treatment All patients with class 4 HO require
treatment to alleviate ankylosis
treatment
References Whyte ldquoPagetrsquos Disease of Bonerdquo NEMJ vol 355
2006 Klein and Parvizi ldquoSurgical Manifestations of Pagetrsquos
Diseaserdquo JAAOS vol 14 2006 Orthobullets Campbell Apley Emedicinecom
-Chapter 15 Heterotopic Ossification after Traumatic Brain InjuryBy Jesuacutes Moreta and Joseacute Luis Martiacutenez-de los Mozos DOI 10577257343
Questions
Thank You
risk factors periosteal stripping off anterior femur male gender obesity post traumatic deformity Anterior and anterolateral approach Cementless
Neurogenic HO around the hip due to SCI occurs more often in the medial region than in the lateral region with ossified tissues extending from the pubic symphysis to the anteromedial femoral shaft posterior to the femoral neurovascular structures Ossification is also seen anteriorly involving the iliopsoas and femoral neurovascular structures laterally within gluteus minimus and posteriorly extending from the ilium to the posterior femur encasing the sciatic nerve
HTO AROUND hip and knee
The Brooker Classification of Heterotopic Ossification around the hip joint Class I has islands of bone within the soft tissues Class II has bone spurs from the pelvis or proximal end of the femur leaving at least 1 cm between opposing surfaces Class III has bone spurs from the pelvis andor proximal end of the femur reducing the space between opposing bone surfaces to less than 1 cm Class IV shows apparent bone ankylosis of the hip
Region I - Heterotopic ossifications are strictly below the tip of the greater trochanter
Region II - Heterotopic ossifications are below and above the tip of the greater trochanter
Region III - Heterotopic ossifications are strictly above the tip of the greater trochanter
Grade A - Single or multiple heterotopic ossifications are less than 10 mm in maximal extent without contact with the pelvis or the femur
Grade B - Heterotopic ossifications are greater than 10 mm without contact with the pelvis but with possible contact with the femur there is no bridging from the femur to the proximal part of the greater trochanter and no evidence of ankylosis
Grade C - Ankylosis by means of firm bridging from the femur to the pelvis is present
Shmidt classification
excision may be performed The results of this procedure are varied Patients may find that their range of movement improves but pain relief is likely to be limited
A patient with heterotopic ossification following total hip arthroplasty is thought to have a 90-100 chance of developing it on the contralateral hip if this hip also undergoes total arthroplasty
it would be prudent to minimize the risk of heterotopic ossification developing after arthroplasty by performing surgery whereby the following are ensured
Exposure is meticulous Retraction is performed carefully and soft tissue
is handled carefully Irrigation is adequate Devitalized tissue is excised Hemostasis is adequate Postoperative drains (when used) are not
retained for longer than necessary Perioperative antibiotic prophylaxis is used Postoperative anticoagulation (when used for
deep vein thrombosis prophylaxis) is carefully controlled
sources of knee stiffness 1-extrinsic severe osteoarthritis of the ipsilateral hip neurologic injury leading to muscle rigidity tight quadriceps or hamstring muscles secondary to muscle injury heterotopic ossification or long-standing juvenile inflammatory conditions limiting knee
range of motion prior to the completion of skeletal growth When extrinsic sources are identified revision total knee arthroplasty is unlikely to be associated with a favorable outcome without correction of the extrinsic problem
2-intrinsic (1) overstuffing of the patellofemoral articulation (2) an
excessively tight flexion andor extension gap (3) a tight posterior cruciate ligament (4) femoral andor tibial malrotation (5) arthrofibrosis and (6) limited bearing excursion in association with a highly conforming mobile-bearing prosthetic design
HTO after TKA
Heterotopic Ossification (HO) following primary Total Knee Replacement (TKR)
Occurs in 3-90 of TKRs 3-grade classification system No correlation between HO and component
alignment or component position
Clinical findings similar to early infection Continuing low-grade fever Warm swollen and erythematous knee Normal blood tests Possibly an association with HLA-A2 and B18 HO patients have worse KSS and function
scores
Patients at HIGH risk for developing HO after TKR (Knee Arthroplasty) (5)
Those with limited postoperative knee flexion
Increased lumbar bone mineral density (BMD) on multivariate analysis (3)
Hypertrophic arthrosis Excessive periosteal trauma Notching of the anterior femur Those who require forced manipulation
after TKA 47 in revision TKR surgery (6) Higher rates in revision TKR cases with
infection (up to 76
DaughertyBell classification of HO of the knee 0 No evidence of HO 1 Bone islands in periarticular soft tissue (no
involvement of femur patella or tibia) or HO within quadriceps expansion measuring lt1 cm
2 Spur formation measuring lt5 cm that involves the femur patella or tibia if more than one bone demonstrates HO separation of HO spurs
measure gt1 cm or HO within quadriceps expansion measuring ge1 cm but lt3 cm
3 Spur formation gt5 cm involving femur patella or tibia if more than one bone demonstrates HO separation of HO spurs measure lt1 cm or HO
within quadriceps expansion measuring ge3 cm 4 Extensive HO of the knee causing ankylosis
class 2 HO begins to involve the major bones of the knee joint with spur formation limited to a size of 5 cm
HO class 2 may be observed in select patients with complete ROM and no reported pain Patients with class 3 HO would likely always benefit from surgical excision
followed by RT prophylaxis Certainly patients in either cohort with a subclass ldquoBrdquo assignment (symptomatic) would
benefit from treatment All patients with class 4 HO require
treatment to alleviate ankylosis
treatment
References Whyte ldquoPagetrsquos Disease of Bonerdquo NEMJ vol 355
2006 Klein and Parvizi ldquoSurgical Manifestations of Pagetrsquos
Diseaserdquo JAAOS vol 14 2006 Orthobullets Campbell Apley Emedicinecom
-Chapter 15 Heterotopic Ossification after Traumatic Brain InjuryBy Jesuacutes Moreta and Joseacute Luis Martiacutenez-de los Mozos DOI 10577257343
Questions
Thank You
The Brooker Classification of Heterotopic Ossification around the hip joint Class I has islands of bone within the soft tissues Class II has bone spurs from the pelvis or proximal end of the femur leaving at least 1 cm between opposing surfaces Class III has bone spurs from the pelvis andor proximal end of the femur reducing the space between opposing bone surfaces to less than 1 cm Class IV shows apparent bone ankylosis of the hip
Region I - Heterotopic ossifications are strictly below the tip of the greater trochanter
Region II - Heterotopic ossifications are below and above the tip of the greater trochanter
Region III - Heterotopic ossifications are strictly above the tip of the greater trochanter
Grade A - Single or multiple heterotopic ossifications are less than 10 mm in maximal extent without contact with the pelvis or the femur
Grade B - Heterotopic ossifications are greater than 10 mm without contact with the pelvis but with possible contact with the femur there is no bridging from the femur to the proximal part of the greater trochanter and no evidence of ankylosis
Grade C - Ankylosis by means of firm bridging from the femur to the pelvis is present
Shmidt classification
excision may be performed The results of this procedure are varied Patients may find that their range of movement improves but pain relief is likely to be limited
A patient with heterotopic ossification following total hip arthroplasty is thought to have a 90-100 chance of developing it on the contralateral hip if this hip also undergoes total arthroplasty
it would be prudent to minimize the risk of heterotopic ossification developing after arthroplasty by performing surgery whereby the following are ensured
Exposure is meticulous Retraction is performed carefully and soft tissue
is handled carefully Irrigation is adequate Devitalized tissue is excised Hemostasis is adequate Postoperative drains (when used) are not
retained for longer than necessary Perioperative antibiotic prophylaxis is used Postoperative anticoagulation (when used for
deep vein thrombosis prophylaxis) is carefully controlled
sources of knee stiffness 1-extrinsic severe osteoarthritis of the ipsilateral hip neurologic injury leading to muscle rigidity tight quadriceps or hamstring muscles secondary to muscle injury heterotopic ossification or long-standing juvenile inflammatory conditions limiting knee
range of motion prior to the completion of skeletal growth When extrinsic sources are identified revision total knee arthroplasty is unlikely to be associated with a favorable outcome without correction of the extrinsic problem
2-intrinsic (1) overstuffing of the patellofemoral articulation (2) an
excessively tight flexion andor extension gap (3) a tight posterior cruciate ligament (4) femoral andor tibial malrotation (5) arthrofibrosis and (6) limited bearing excursion in association with a highly conforming mobile-bearing prosthetic design
HTO after TKA
Heterotopic Ossification (HO) following primary Total Knee Replacement (TKR)
Occurs in 3-90 of TKRs 3-grade classification system No correlation between HO and component
alignment or component position
Clinical findings similar to early infection Continuing low-grade fever Warm swollen and erythematous knee Normal blood tests Possibly an association with HLA-A2 and B18 HO patients have worse KSS and function
scores
Patients at HIGH risk for developing HO after TKR (Knee Arthroplasty) (5)
Those with limited postoperative knee flexion
Increased lumbar bone mineral density (BMD) on multivariate analysis (3)
Hypertrophic arthrosis Excessive periosteal trauma Notching of the anterior femur Those who require forced manipulation
after TKA 47 in revision TKR surgery (6) Higher rates in revision TKR cases with
infection (up to 76
DaughertyBell classification of HO of the knee 0 No evidence of HO 1 Bone islands in periarticular soft tissue (no
involvement of femur patella or tibia) or HO within quadriceps expansion measuring lt1 cm
2 Spur formation measuring lt5 cm that involves the femur patella or tibia if more than one bone demonstrates HO separation of HO spurs
measure gt1 cm or HO within quadriceps expansion measuring ge1 cm but lt3 cm
3 Spur formation gt5 cm involving femur patella or tibia if more than one bone demonstrates HO separation of HO spurs measure lt1 cm or HO
within quadriceps expansion measuring ge3 cm 4 Extensive HO of the knee causing ankylosis
class 2 HO begins to involve the major bones of the knee joint with spur formation limited to a size of 5 cm
HO class 2 may be observed in select patients with complete ROM and no reported pain Patients with class 3 HO would likely always benefit from surgical excision
followed by RT prophylaxis Certainly patients in either cohort with a subclass ldquoBrdquo assignment (symptomatic) would
benefit from treatment All patients with class 4 HO require
treatment to alleviate ankylosis
treatment
References Whyte ldquoPagetrsquos Disease of Bonerdquo NEMJ vol 355
2006 Klein and Parvizi ldquoSurgical Manifestations of Pagetrsquos
Diseaserdquo JAAOS vol 14 2006 Orthobullets Campbell Apley Emedicinecom
-Chapter 15 Heterotopic Ossification after Traumatic Brain InjuryBy Jesuacutes Moreta and Joseacute Luis Martiacutenez-de los Mozos DOI 10577257343
Questions
Thank You
Region I - Heterotopic ossifications are strictly below the tip of the greater trochanter
Region II - Heterotopic ossifications are below and above the tip of the greater trochanter
Region III - Heterotopic ossifications are strictly above the tip of the greater trochanter
Grade A - Single or multiple heterotopic ossifications are less than 10 mm in maximal extent without contact with the pelvis or the femur
Grade B - Heterotopic ossifications are greater than 10 mm without contact with the pelvis but with possible contact with the femur there is no bridging from the femur to the proximal part of the greater trochanter and no evidence of ankylosis
Grade C - Ankylosis by means of firm bridging from the femur to the pelvis is present
Shmidt classification
excision may be performed The results of this procedure are varied Patients may find that their range of movement improves but pain relief is likely to be limited
A patient with heterotopic ossification following total hip arthroplasty is thought to have a 90-100 chance of developing it on the contralateral hip if this hip also undergoes total arthroplasty
it would be prudent to minimize the risk of heterotopic ossification developing after arthroplasty by performing surgery whereby the following are ensured
Exposure is meticulous Retraction is performed carefully and soft tissue
is handled carefully Irrigation is adequate Devitalized tissue is excised Hemostasis is adequate Postoperative drains (when used) are not
retained for longer than necessary Perioperative antibiotic prophylaxis is used Postoperative anticoagulation (when used for
deep vein thrombosis prophylaxis) is carefully controlled
sources of knee stiffness 1-extrinsic severe osteoarthritis of the ipsilateral hip neurologic injury leading to muscle rigidity tight quadriceps or hamstring muscles secondary to muscle injury heterotopic ossification or long-standing juvenile inflammatory conditions limiting knee
range of motion prior to the completion of skeletal growth When extrinsic sources are identified revision total knee arthroplasty is unlikely to be associated with a favorable outcome without correction of the extrinsic problem
2-intrinsic (1) overstuffing of the patellofemoral articulation (2) an
excessively tight flexion andor extension gap (3) a tight posterior cruciate ligament (4) femoral andor tibial malrotation (5) arthrofibrosis and (6) limited bearing excursion in association with a highly conforming mobile-bearing prosthetic design
HTO after TKA
Heterotopic Ossification (HO) following primary Total Knee Replacement (TKR)
Occurs in 3-90 of TKRs 3-grade classification system No correlation between HO and component
alignment or component position
Clinical findings similar to early infection Continuing low-grade fever Warm swollen and erythematous knee Normal blood tests Possibly an association with HLA-A2 and B18 HO patients have worse KSS and function
scores
Patients at HIGH risk for developing HO after TKR (Knee Arthroplasty) (5)
Those with limited postoperative knee flexion
Increased lumbar bone mineral density (BMD) on multivariate analysis (3)
Hypertrophic arthrosis Excessive periosteal trauma Notching of the anterior femur Those who require forced manipulation
after TKA 47 in revision TKR surgery (6) Higher rates in revision TKR cases with
infection (up to 76
DaughertyBell classification of HO of the knee 0 No evidence of HO 1 Bone islands in periarticular soft tissue (no
involvement of femur patella or tibia) or HO within quadriceps expansion measuring lt1 cm
2 Spur formation measuring lt5 cm that involves the femur patella or tibia if more than one bone demonstrates HO separation of HO spurs
measure gt1 cm or HO within quadriceps expansion measuring ge1 cm but lt3 cm
3 Spur formation gt5 cm involving femur patella or tibia if more than one bone demonstrates HO separation of HO spurs measure lt1 cm or HO
within quadriceps expansion measuring ge3 cm 4 Extensive HO of the knee causing ankylosis
class 2 HO begins to involve the major bones of the knee joint with spur formation limited to a size of 5 cm
HO class 2 may be observed in select patients with complete ROM and no reported pain Patients with class 3 HO would likely always benefit from surgical excision
followed by RT prophylaxis Certainly patients in either cohort with a subclass ldquoBrdquo assignment (symptomatic) would
benefit from treatment All patients with class 4 HO require
treatment to alleviate ankylosis
treatment
References Whyte ldquoPagetrsquos Disease of Bonerdquo NEMJ vol 355
2006 Klein and Parvizi ldquoSurgical Manifestations of Pagetrsquos
Diseaserdquo JAAOS vol 14 2006 Orthobullets Campbell Apley Emedicinecom
-Chapter 15 Heterotopic Ossification after Traumatic Brain InjuryBy Jesuacutes Moreta and Joseacute Luis Martiacutenez-de los Mozos DOI 10577257343
Questions
Thank You
excision may be performed The results of this procedure are varied Patients may find that their range of movement improves but pain relief is likely to be limited
A patient with heterotopic ossification following total hip arthroplasty is thought to have a 90-100 chance of developing it on the contralateral hip if this hip also undergoes total arthroplasty
it would be prudent to minimize the risk of heterotopic ossification developing after arthroplasty by performing surgery whereby the following are ensured
Exposure is meticulous Retraction is performed carefully and soft tissue
is handled carefully Irrigation is adequate Devitalized tissue is excised Hemostasis is adequate Postoperative drains (when used) are not
retained for longer than necessary Perioperative antibiotic prophylaxis is used Postoperative anticoagulation (when used for
deep vein thrombosis prophylaxis) is carefully controlled
sources of knee stiffness 1-extrinsic severe osteoarthritis of the ipsilateral hip neurologic injury leading to muscle rigidity tight quadriceps or hamstring muscles secondary to muscle injury heterotopic ossification or long-standing juvenile inflammatory conditions limiting knee
range of motion prior to the completion of skeletal growth When extrinsic sources are identified revision total knee arthroplasty is unlikely to be associated with a favorable outcome without correction of the extrinsic problem
2-intrinsic (1) overstuffing of the patellofemoral articulation (2) an
excessively tight flexion andor extension gap (3) a tight posterior cruciate ligament (4) femoral andor tibial malrotation (5) arthrofibrosis and (6) limited bearing excursion in association with a highly conforming mobile-bearing prosthetic design
HTO after TKA
Heterotopic Ossification (HO) following primary Total Knee Replacement (TKR)
Occurs in 3-90 of TKRs 3-grade classification system No correlation between HO and component
alignment or component position
Clinical findings similar to early infection Continuing low-grade fever Warm swollen and erythematous knee Normal blood tests Possibly an association with HLA-A2 and B18 HO patients have worse KSS and function
scores
Patients at HIGH risk for developing HO after TKR (Knee Arthroplasty) (5)
Those with limited postoperative knee flexion
Increased lumbar bone mineral density (BMD) on multivariate analysis (3)
Hypertrophic arthrosis Excessive periosteal trauma Notching of the anterior femur Those who require forced manipulation
after TKA 47 in revision TKR surgery (6) Higher rates in revision TKR cases with
infection (up to 76
DaughertyBell classification of HO of the knee 0 No evidence of HO 1 Bone islands in periarticular soft tissue (no
involvement of femur patella or tibia) or HO within quadriceps expansion measuring lt1 cm
2 Spur formation measuring lt5 cm that involves the femur patella or tibia if more than one bone demonstrates HO separation of HO spurs
measure gt1 cm or HO within quadriceps expansion measuring ge1 cm but lt3 cm
3 Spur formation gt5 cm involving femur patella or tibia if more than one bone demonstrates HO separation of HO spurs measure lt1 cm or HO
within quadriceps expansion measuring ge3 cm 4 Extensive HO of the knee causing ankylosis
class 2 HO begins to involve the major bones of the knee joint with spur formation limited to a size of 5 cm
HO class 2 may be observed in select patients with complete ROM and no reported pain Patients with class 3 HO would likely always benefit from surgical excision
followed by RT prophylaxis Certainly patients in either cohort with a subclass ldquoBrdquo assignment (symptomatic) would
benefit from treatment All patients with class 4 HO require
treatment to alleviate ankylosis
treatment
References Whyte ldquoPagetrsquos Disease of Bonerdquo NEMJ vol 355
2006 Klein and Parvizi ldquoSurgical Manifestations of Pagetrsquos
Diseaserdquo JAAOS vol 14 2006 Orthobullets Campbell Apley Emedicinecom
-Chapter 15 Heterotopic Ossification after Traumatic Brain InjuryBy Jesuacutes Moreta and Joseacute Luis Martiacutenez-de los Mozos DOI 10577257343
Questions
Thank You
it would be prudent to minimize the risk of heterotopic ossification developing after arthroplasty by performing surgery whereby the following are ensured
Exposure is meticulous Retraction is performed carefully and soft tissue
is handled carefully Irrigation is adequate Devitalized tissue is excised Hemostasis is adequate Postoperative drains (when used) are not
retained for longer than necessary Perioperative antibiotic prophylaxis is used Postoperative anticoagulation (when used for
deep vein thrombosis prophylaxis) is carefully controlled
sources of knee stiffness 1-extrinsic severe osteoarthritis of the ipsilateral hip neurologic injury leading to muscle rigidity tight quadriceps or hamstring muscles secondary to muscle injury heterotopic ossification or long-standing juvenile inflammatory conditions limiting knee
range of motion prior to the completion of skeletal growth When extrinsic sources are identified revision total knee arthroplasty is unlikely to be associated with a favorable outcome without correction of the extrinsic problem
2-intrinsic (1) overstuffing of the patellofemoral articulation (2) an
excessively tight flexion andor extension gap (3) a tight posterior cruciate ligament (4) femoral andor tibial malrotation (5) arthrofibrosis and (6) limited bearing excursion in association with a highly conforming mobile-bearing prosthetic design
HTO after TKA
Heterotopic Ossification (HO) following primary Total Knee Replacement (TKR)
Occurs in 3-90 of TKRs 3-grade classification system No correlation between HO and component
alignment or component position
Clinical findings similar to early infection Continuing low-grade fever Warm swollen and erythematous knee Normal blood tests Possibly an association with HLA-A2 and B18 HO patients have worse KSS and function
scores
Patients at HIGH risk for developing HO after TKR (Knee Arthroplasty) (5)
Those with limited postoperative knee flexion
Increased lumbar bone mineral density (BMD) on multivariate analysis (3)
Hypertrophic arthrosis Excessive periosteal trauma Notching of the anterior femur Those who require forced manipulation
after TKA 47 in revision TKR surgery (6) Higher rates in revision TKR cases with
infection (up to 76
DaughertyBell classification of HO of the knee 0 No evidence of HO 1 Bone islands in periarticular soft tissue (no
involvement of femur patella or tibia) or HO within quadriceps expansion measuring lt1 cm
2 Spur formation measuring lt5 cm that involves the femur patella or tibia if more than one bone demonstrates HO separation of HO spurs
measure gt1 cm or HO within quadriceps expansion measuring ge1 cm but lt3 cm
3 Spur formation gt5 cm involving femur patella or tibia if more than one bone demonstrates HO separation of HO spurs measure lt1 cm or HO
within quadriceps expansion measuring ge3 cm 4 Extensive HO of the knee causing ankylosis
class 2 HO begins to involve the major bones of the knee joint with spur formation limited to a size of 5 cm
HO class 2 may be observed in select patients with complete ROM and no reported pain Patients with class 3 HO would likely always benefit from surgical excision
followed by RT prophylaxis Certainly patients in either cohort with a subclass ldquoBrdquo assignment (symptomatic) would
benefit from treatment All patients with class 4 HO require
treatment to alleviate ankylosis
treatment
References Whyte ldquoPagetrsquos Disease of Bonerdquo NEMJ vol 355
2006 Klein and Parvizi ldquoSurgical Manifestations of Pagetrsquos
Diseaserdquo JAAOS vol 14 2006 Orthobullets Campbell Apley Emedicinecom
-Chapter 15 Heterotopic Ossification after Traumatic Brain InjuryBy Jesuacutes Moreta and Joseacute Luis Martiacutenez-de los Mozos DOI 10577257343
Questions
Thank You
sources of knee stiffness 1-extrinsic severe osteoarthritis of the ipsilateral hip neurologic injury leading to muscle rigidity tight quadriceps or hamstring muscles secondary to muscle injury heterotopic ossification or long-standing juvenile inflammatory conditions limiting knee
range of motion prior to the completion of skeletal growth When extrinsic sources are identified revision total knee arthroplasty is unlikely to be associated with a favorable outcome without correction of the extrinsic problem
2-intrinsic (1) overstuffing of the patellofemoral articulation (2) an
excessively tight flexion andor extension gap (3) a tight posterior cruciate ligament (4) femoral andor tibial malrotation (5) arthrofibrosis and (6) limited bearing excursion in association with a highly conforming mobile-bearing prosthetic design
HTO after TKA
Heterotopic Ossification (HO) following primary Total Knee Replacement (TKR)
Occurs in 3-90 of TKRs 3-grade classification system No correlation between HO and component
alignment or component position
Clinical findings similar to early infection Continuing low-grade fever Warm swollen and erythematous knee Normal blood tests Possibly an association with HLA-A2 and B18 HO patients have worse KSS and function
scores
Patients at HIGH risk for developing HO after TKR (Knee Arthroplasty) (5)
Those with limited postoperative knee flexion
Increased lumbar bone mineral density (BMD) on multivariate analysis (3)
Hypertrophic arthrosis Excessive periosteal trauma Notching of the anterior femur Those who require forced manipulation
after TKA 47 in revision TKR surgery (6) Higher rates in revision TKR cases with
infection (up to 76
DaughertyBell classification of HO of the knee 0 No evidence of HO 1 Bone islands in periarticular soft tissue (no
involvement of femur patella or tibia) or HO within quadriceps expansion measuring lt1 cm
2 Spur formation measuring lt5 cm that involves the femur patella or tibia if more than one bone demonstrates HO separation of HO spurs
measure gt1 cm or HO within quadriceps expansion measuring ge1 cm but lt3 cm
3 Spur formation gt5 cm involving femur patella or tibia if more than one bone demonstrates HO separation of HO spurs measure lt1 cm or HO
within quadriceps expansion measuring ge3 cm 4 Extensive HO of the knee causing ankylosis
class 2 HO begins to involve the major bones of the knee joint with spur formation limited to a size of 5 cm
HO class 2 may be observed in select patients with complete ROM and no reported pain Patients with class 3 HO would likely always benefit from surgical excision
followed by RT prophylaxis Certainly patients in either cohort with a subclass ldquoBrdquo assignment (symptomatic) would
benefit from treatment All patients with class 4 HO require
treatment to alleviate ankylosis
treatment
References Whyte ldquoPagetrsquos Disease of Bonerdquo NEMJ vol 355
2006 Klein and Parvizi ldquoSurgical Manifestations of Pagetrsquos
Diseaserdquo JAAOS vol 14 2006 Orthobullets Campbell Apley Emedicinecom
-Chapter 15 Heterotopic Ossification after Traumatic Brain InjuryBy Jesuacutes Moreta and Joseacute Luis Martiacutenez-de los Mozos DOI 10577257343
Questions
Thank You
Heterotopic Ossification (HO) following primary Total Knee Replacement (TKR)
Occurs in 3-90 of TKRs 3-grade classification system No correlation between HO and component
alignment or component position
Clinical findings similar to early infection Continuing low-grade fever Warm swollen and erythematous knee Normal blood tests Possibly an association with HLA-A2 and B18 HO patients have worse KSS and function
scores
Patients at HIGH risk for developing HO after TKR (Knee Arthroplasty) (5)
Those with limited postoperative knee flexion
Increased lumbar bone mineral density (BMD) on multivariate analysis (3)
Hypertrophic arthrosis Excessive periosteal trauma Notching of the anterior femur Those who require forced manipulation
after TKA 47 in revision TKR surgery (6) Higher rates in revision TKR cases with
infection (up to 76
DaughertyBell classification of HO of the knee 0 No evidence of HO 1 Bone islands in periarticular soft tissue (no
involvement of femur patella or tibia) or HO within quadriceps expansion measuring lt1 cm
2 Spur formation measuring lt5 cm that involves the femur patella or tibia if more than one bone demonstrates HO separation of HO spurs
measure gt1 cm or HO within quadriceps expansion measuring ge1 cm but lt3 cm
3 Spur formation gt5 cm involving femur patella or tibia if more than one bone demonstrates HO separation of HO spurs measure lt1 cm or HO
within quadriceps expansion measuring ge3 cm 4 Extensive HO of the knee causing ankylosis
class 2 HO begins to involve the major bones of the knee joint with spur formation limited to a size of 5 cm
HO class 2 may be observed in select patients with complete ROM and no reported pain Patients with class 3 HO would likely always benefit from surgical excision
followed by RT prophylaxis Certainly patients in either cohort with a subclass ldquoBrdquo assignment (symptomatic) would
benefit from treatment All patients with class 4 HO require
treatment to alleviate ankylosis
treatment
References Whyte ldquoPagetrsquos Disease of Bonerdquo NEMJ vol 355
2006 Klein and Parvizi ldquoSurgical Manifestations of Pagetrsquos
Diseaserdquo JAAOS vol 14 2006 Orthobullets Campbell Apley Emedicinecom
-Chapter 15 Heterotopic Ossification after Traumatic Brain InjuryBy Jesuacutes Moreta and Joseacute Luis Martiacutenez-de los Mozos DOI 10577257343
Questions
Thank You
Patients at HIGH risk for developing HO after TKR (Knee Arthroplasty) (5)
Those with limited postoperative knee flexion
Increased lumbar bone mineral density (BMD) on multivariate analysis (3)
Hypertrophic arthrosis Excessive periosteal trauma Notching of the anterior femur Those who require forced manipulation
after TKA 47 in revision TKR surgery (6) Higher rates in revision TKR cases with
infection (up to 76
DaughertyBell classification of HO of the knee 0 No evidence of HO 1 Bone islands in periarticular soft tissue (no
involvement of femur patella or tibia) or HO within quadriceps expansion measuring lt1 cm
2 Spur formation measuring lt5 cm that involves the femur patella or tibia if more than one bone demonstrates HO separation of HO spurs
measure gt1 cm or HO within quadriceps expansion measuring ge1 cm but lt3 cm
3 Spur formation gt5 cm involving femur patella or tibia if more than one bone demonstrates HO separation of HO spurs measure lt1 cm or HO
within quadriceps expansion measuring ge3 cm 4 Extensive HO of the knee causing ankylosis
class 2 HO begins to involve the major bones of the knee joint with spur formation limited to a size of 5 cm
HO class 2 may be observed in select patients with complete ROM and no reported pain Patients with class 3 HO would likely always benefit from surgical excision
followed by RT prophylaxis Certainly patients in either cohort with a subclass ldquoBrdquo assignment (symptomatic) would
benefit from treatment All patients with class 4 HO require
treatment to alleviate ankylosis
treatment
References Whyte ldquoPagetrsquos Disease of Bonerdquo NEMJ vol 355
2006 Klein and Parvizi ldquoSurgical Manifestations of Pagetrsquos
Diseaserdquo JAAOS vol 14 2006 Orthobullets Campbell Apley Emedicinecom
-Chapter 15 Heterotopic Ossification after Traumatic Brain InjuryBy Jesuacutes Moreta and Joseacute Luis Martiacutenez-de los Mozos DOI 10577257343
Questions
Thank You
DaughertyBell classification of HO of the knee 0 No evidence of HO 1 Bone islands in periarticular soft tissue (no
involvement of femur patella or tibia) or HO within quadriceps expansion measuring lt1 cm
2 Spur formation measuring lt5 cm that involves the femur patella or tibia if more than one bone demonstrates HO separation of HO spurs
measure gt1 cm or HO within quadriceps expansion measuring ge1 cm but lt3 cm
3 Spur formation gt5 cm involving femur patella or tibia if more than one bone demonstrates HO separation of HO spurs measure lt1 cm or HO
within quadriceps expansion measuring ge3 cm 4 Extensive HO of the knee causing ankylosis
class 2 HO begins to involve the major bones of the knee joint with spur formation limited to a size of 5 cm
HO class 2 may be observed in select patients with complete ROM and no reported pain Patients with class 3 HO would likely always benefit from surgical excision
followed by RT prophylaxis Certainly patients in either cohort with a subclass ldquoBrdquo assignment (symptomatic) would
benefit from treatment All patients with class 4 HO require
treatment to alleviate ankylosis
treatment
References Whyte ldquoPagetrsquos Disease of Bonerdquo NEMJ vol 355
2006 Klein and Parvizi ldquoSurgical Manifestations of Pagetrsquos
Diseaserdquo JAAOS vol 14 2006 Orthobullets Campbell Apley Emedicinecom
-Chapter 15 Heterotopic Ossification after Traumatic Brain InjuryBy Jesuacutes Moreta and Joseacute Luis Martiacutenez-de los Mozos DOI 10577257343
Questions
Thank You
class 2 HO begins to involve the major bones of the knee joint with spur formation limited to a size of 5 cm
HO class 2 may be observed in select patients with complete ROM and no reported pain Patients with class 3 HO would likely always benefit from surgical excision
followed by RT prophylaxis Certainly patients in either cohort with a subclass ldquoBrdquo assignment (symptomatic) would
benefit from treatment All patients with class 4 HO require
treatment to alleviate ankylosis
treatment
References Whyte ldquoPagetrsquos Disease of Bonerdquo NEMJ vol 355
2006 Klein and Parvizi ldquoSurgical Manifestations of Pagetrsquos
Diseaserdquo JAAOS vol 14 2006 Orthobullets Campbell Apley Emedicinecom
-Chapter 15 Heterotopic Ossification after Traumatic Brain InjuryBy Jesuacutes Moreta and Joseacute Luis Martiacutenez-de los Mozos DOI 10577257343
Questions
Thank You
References Whyte ldquoPagetrsquos Disease of Bonerdquo NEMJ vol 355
2006 Klein and Parvizi ldquoSurgical Manifestations of Pagetrsquos
Diseaserdquo JAAOS vol 14 2006 Orthobullets Campbell Apley Emedicinecom
-Chapter 15 Heterotopic Ossification after Traumatic Brain InjuryBy Jesuacutes Moreta and Joseacute Luis Martiacutenez-de los Mozos DOI 10577257343
Questions
Thank You
Questions
Thank You
