Ri Long Jin. Osteoporosis Osteoporosis Prevalence Affects 200 million women worldwide 1/3 of women...

Ri Long Jin

Osteoporosis

Osteoporosis Prevalence Affects 200 million women worldwide

1/3 of women aged 60 to 70 2/3 of women aged 80 or older

Approximately 30% of women over the age of 50 have one or more vertebral fractures

Approximately one in five men over the age of 50 will have an osteoporosis-related fracture in their remaining lifetime

IOF, 2005 (www.osteofound.org)

Osteoporosis

Loss of bone massIncrease bone fragilityIncrease risk of fractures

Osteoporosis, or porous bone, is a devastating disease that robs its victims of bone mass.

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Normal Bone Osteoporotic Bone

Osteoporosis

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Wrist Fractures:200,000+

Hip Fractures:300,000+

Vertebral Fractures:700,000+

Other Fractures:300,000+

Source: National Osteoporosis Foundation, 2000

1.5 Million Fractures Annually1.5 Million Fractures Annually

Normal Spine

Osteoporotic Spine

Source: National Osteoporosis Foundation, 2000

BoneBoneMineralisedMineralised

BoneBone

Osteoid

Osteoid

Osteoid

Osteoid

Osteoblasts

Osteoblasts

OsteoclastsOsteoclasts

Courtesy of Michael AmlingCourtesy of Michael Amling

Unbalanced Remodeling: Unbalanced Remodeling: Bone LossBone Loss

Unbalanced Remodeling: Unbalanced Remodeling: Bone LossBone Loss

ResorptionResorption

ReversalReversal

FormationFormation

QuiescenceQuiescence

Insufficientformation - aging

Insufficientformation - aging

ExcessResorption - menopause - hyperPTH

ExcessResorption - menopause - hyperPTH

Bone Loss Bone Loss

I. Primary osteoporosis Idiopathic osteoporosis Type I osteoporosis – postmenopausal ; affecting

trabeculae; compression Fx of spine Type II osteoporosis – senile ; affecting both cortex &

trabeculae; hip Fx, Colles’ Fx

II. Secondary osteoporosis 1.Endocrine disease Hypogonadism; Cushing syndrome Cretinsm; Hyperparathyroidism Diabetes Calcium deficiency

3. Marrow disorders Multiple myeloma

4. Collagen disease Osteogenesis imperfecta; Ehlers-Danlos syndrome Marfan syndrome

2.GI disease Gastrectomy Malabsorption syndrome Chronic obstructive jaundice Severe nutritional deficiency

5. Others COPDLack of exerciseChronic alcoholism RA Smoking

Postmenopausal osteoporosis (type I) Caused by lack of estrogen Causes PTH to overstimulate osteoclasts Excessive loss of trabecular bone

Age-associated osteoporosis (type II) Bone loss due to increased bone turnover Malabsorption Mineral and vitamin deficiency

Secondary osteoporosis

(ex, steroid, heparin, hyperthyroidism,

hyperparathyroidism, Cushing’s syndrome, etc)

Type I Type II Type I Type II

Age(yr)Age(yr)

Sex ratio(F:M)Sex ratio(F:M)

Type of bone lossType of bone loss

Rate of bone lossRate of bone loss

Bone markerBone marker

Fracture sitesFracture sites

Parathyroid functionParathyroid function

Calcium absorptionCalcium absorption

Metabolism of 25OH-D Metabolism of 25OH-D to 1,25(OH)2Dto 1,25(OH)2D

Main causesMain causes

Age(yr)Age(yr)

Sex ratio(F:M)Sex ratio(F:M)

Type of bone lossType of bone loss

Rate of bone lossRate of bone loss

Bone markerBone marker

Fracture sitesFracture sites

Parathyroid functionParathyroid function

Calcium absorptionCalcium absorption

Metabolism of 25OH-D Metabolism of 25OH-D to 1,25(OH)2Dto 1,25(OH)2D

Main causesMain causes

51 - 70

6 : 1

Mainly trabecular

Accelerated

Increased

Vertebrae & distal radius

Decreased

Decreased

Secondary decrease

Related to menopause

51 - 70

6 : 1

Mainly trabecular

Accelerated

Increased

Vertebrae & distal radius

Decreased

Decreased

Secondary decrease

Related to menopause

> 70> 70

2 : 12 : 1

Trabecular & corticalTrabecular & cortical

Not acceleratedNot accelerated

Not increasedNot increased

Vertebrae & hipVertebrae & hip

IncreasedIncreased

Markedly decreasedMarkedly decreased

Primary decreasePrimary decrease

Related to agingRelated to aging

> 70> 70

2 : 12 : 1

Trabecular & corticalTrabecular & cortical

Not acceleratedNot accelerated

Not increasedNot increased

Vertebrae & hipVertebrae & hip

IncreasedIncreased

Markedly decreasedMarkedly decreased

Primary decreasePrimary decrease

Related to agingRelated to aging

Persistent, unexplained back pain

Shorter than you used to be Spinal deformities

Recurrent fractures Fracture from minimal trauma

Experiencing chronic medical problems

1) Genetic or constitutional factors

a. white or Asia ethnicity b. maternal history of fractures c. small body frame d. long hip axis length e. premature menopause (<45 years) f. late menarche

1) Genetic or constitutional factors

a. white or Asia ethnicity b. maternal history of fractures c. small body frame d. long hip axis length e. premature menopause (<45 years) f. late menarche

European Osteoporosis FoundationEuropean Osteoporosis FoundationEuropean Osteoporosis FoundationEuropean Osteoporosis Foundation

Factors contributing to osteoporosis II

Factors contributing to osteoporosis II

2) Lifestyle and nutritional factors

a. nulliparity

b. prolonged secondary amenorrhea

c. smoking

d. excessive alcohol intake

e. inactivity

f. prolonged immobilization

g. prolonged parenteral nutrition

h. low body weight

2) Lifestyle and nutritional factors

a. nulliparity

b. prolonged secondary amenorrhea

c. smoking

d. excessive alcohol intake

e. inactivity

f. prolonged immobilization

g. prolonged parenteral nutrition

h. low body weight

European Osteoporosis FoundationEuropean Osteoporosis FoundationEuropean Osteoporosis FoundationEuropean Osteoporosis Foundation

“Women married to a smoker

have a 91% greater

risk of heart disease”

TOBACCO USE CAN TOBACCO USE CAN MAKE YOU IMPOTENTMAKE YOU IMPOTENT

Cigarettes may cause sexual impotence due to decreased blood flow to the penis. This can prevent you from having an erection.

Health Canada

WARNINGWARNING

a. anorexia nervosa

b. malabsorption due to gastrointestinal and hepatobiliary disease

c. primary hyperparathyroidism d. thyrotoxicosis

e. primary hypogonadism f. prolactinoma

g. hypercortisolism (Cushing's disease or syndrome)

h. Osteogenesis imperfecta i. rheumatoid arthritis

j. chronic obstructive pulmonary disease k. post transplantation

l. chronic neurological disorders m. chronic renal failure

n. mastocytosis o. type I diabetes

a. anorexia nervosa

b. malabsorption due to gastrointestinal and hepatobiliary disease

c. primary hyperparathyroidism d. thyrotoxicosis

e. primary hypogonadism f. prolactinoma

g. hypercortisolism (Cushing's disease or syndrome)

h. Osteogenesis imperfecta i. rheumatoid arthritis

j. chronic obstructive pulmonary disease k. post transplantation

l. chronic neurological disorders m. chronic renal failure

n. mastocytosis o. type I diabetes

3) medical disorders 3) medical disorders

Factors contributing to osteoporosis IIIFactors contributing to osteoporosis III

European Osteoporosis FoundationEuropean Osteoporosis FoundationEuropean Osteoporosis FoundationEuropean Osteoporosis Foundation

4) Drugs

a. chronic corticosteroid therapy

b. excessive thyroid therapy

c. anticoagulants

d. chemotherapy

e. gonadotropin releasing hormone agonist or

antagonist

f. chronic phosphate-binding antacid use

g. anticonvulsant

4) Drugs

a. chronic corticosteroid therapy

b. excessive thyroid therapy

c. anticoagulants

d. chemotherapy

e. gonadotropin releasing hormone agonist or

antagonist

f. chronic phosphate-binding antacid use

g. anticonvulsant

Factors contributing to osteoporosis IVFactors contributing to osteoporosis IV

European Osteoporosis FoundationEuropean Osteoporosis FoundationEuropean Osteoporosis FoundationEuropean Osteoporosis Foundation

BMD test Biochemical markers - Blood - urine

BMD test Biochemical markers - Blood - urine

X-ray finding:

1.Mineral loss 30-40%2. Generalized decreased density of bone 3. Spine –manifested in early stage Loss trabeculae (transverse >longitudinal), thining of cortex, codfish spine; Wedging of vertebra caused by compression Fx > round back or kyphotic deformity4. Widening of medullary canal – loss of both cortical & trabecular bones 5. Bone densitometries a. Singh’s index b. Photon absorptiometry c. Dual energy X-ray absorptiometry DEXA d. Quantitative computed tomography, QCT

low energy and high energy X-ray

lumbar spine A-P & Lat., femoral

neck, whole body, ulnar & radius

good precision and accuracy

low dose X-ray (1/50 of chest X-

ray)

Most popular

low energy and high energy X-ray

lumbar spine A-P & Lat., femoral

neck, whole body, ulnar & radius

good precision and accuracy

low dose X-ray (1/50 of chest X-

ray)

Most popular

Normal : T-score > -1.0Osteopenia : -2.5 < T-score < -1.0 Osteoporosis : T-score < -2.5Servere osteoporosis : T-score < -2.5 with presence of one or more fractures (established osteoporosis)

Normal : T-score > -1.0Osteopenia : -2.5 < T-score < -1.0 Osteoporosis : T-score < -2.5Servere osteoporosis : T-score < -2.5 with presence of one or more fractures (established osteoporosis)

WHO criteria of osteoporosisWHO criteria of osteoporosis

T-score ; adult peak bone density 와 비교한 score

Bone resorption

Pyridinoline & Deoxypyridinoline

Type I collagen telopeptide N-terminal C-terminal

Hydroxyproline

Tartrate resistant acid phosphatase

Galactosyl hydroxylysine

Bone resorption

Pyridinoline & Deoxypyridinoline

Type I collagen telopeptide N-terminal C-terminal

Hydroxyproline

Tartrate resistant acid phosphatase

Galactosyl hydroxylysine

Bone formationBone formation

Osteocalcin (bone gla protein)Osteocalcin (bone gla protein)

Bone-specific alkaline Bone-specific alkaline

phosphatasephosphatase

Procollagen type I propeptidesProcollagen type I propeptides C-terminal (PICP)C-terminal (PICP) N-terminal (PINP)N-terminal (PINP)

Bone formationBone formation

Osteocalcin (bone gla protein)Osteocalcin (bone gla protein)

Bone-specific alkaline Bone-specific alkaline

phosphatasephosphatase

Procollagen type I propeptidesProcollagen type I propeptides C-terminal (PICP)C-terminal (PICP) N-terminal (PINP)N-terminal (PINP)

Anyone with a fragility fracture All women age 65 and older Postmenopausal younger than 65

with risk factors Men over 50 with risk factors

Treatment of Osteoporosis

1. Treament for primary factor or disease & regular exercise

2. medication: - Enough dose of calcium + activated

Vitamin D (1(OH)D3 or 1.25(OH)2D3)

- Estrogen threapy for type I osteoporosis - Synthectic calcitonin3. Fracture : Avoid longterm bed rest Early ambulation after firm internal fixation

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Bisphosphonates Fosamax Actonel Didronel Estrogen Replacement Therapy Medications made from natural hormones SERMs Raloxifene (Evista)

Calcitonin Sodium Flouride

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Vitamin D metabolites

Parathyroid hormone

New bisphosphonates

New SERMs

Weight-Bearing Exercise

Inflammation of a joint usually accompanied by pain swelling and changes in structure

Etiology Degenerative Joint Disease

Osteoarthritis, Rheumatoid Metabolic disturbances

Gout Infection

Gonococcus, TB, Pneumonia

1. Classification:

major socio-ecomomic problem

I. Rheumatoid Arthritis (RA)

II. Degenerative arthritis ․Primary osteoarthritis ․Secondary osteoarthritis

III. Others :

Hemophilic Arthritis

Gouty Arthritis

Neuropathic or Charcot Joint

Chondrocalcinosis &Pseudogout

PainStiffnessRednessSwellingKnee effusions Crepitus

Chronic, Systemic Autoimmune Disease Inflammation of the connective tissue, Inflammation of the joint

Prevalence 0.5-1% 30-50 yrs F>M

unkonwn Infectious : hemolytic and nonhemolytic

types streptococci Endocrine: this is suggested by response

to adrenocortical steroids. Autoimmune: frequently exhibit various

allergic manifestations. = Eosinophilia is frequent.

Metabolic:

Diffuse proliferative synovitis Villous processes hypertrophy -> necrotic

&extruded into the joint .• Fibrinoid necrosis around with fibroblasts • ->fibrous tissue • Synovium making->pannus- cover the

articular surface with fibrous connective tissue• Vascular granulation tissue ->growing from

medullary->distruction articular cartilage

Joint symptoms Pain, swelling, stiffness (↑in morning) Deformity and muscle atrophy Limited ROM

Other Symptoms Fatigue Anorexia Low-grade fever Inflammatory changes of heart and

lungs

3. Dx of RA: ACR classification criteria for RA

Morning stiffness at least 1 hour Swelling of 3 or more joint Swelling of hand joints (P.I.P M.C.P. or Wrist) Symmetric joint swelling Erosion or decalcification on radiograph of hand Rheumatoid nodule Presence of serum rheumatoid factor

1987 USA RA Association:

4 of more of sever criteria

History and physical exam Labs

Rheumatoid factors (RF) ESR (Erythrocyte Sedimentation Rate) Synovial fluid exam

X-rays Symmetric periarticular osteoporosis Narrowing joint space Bony trabeculation bridge, obliterate the

joint space: ankylosis

ESRî Slight Leukocytosis, ±eosinophlilia (immune reaction) usually normocytic,hypochromic anemia refractory to iron. Alpha2 fraction of gamma globulin(RF, IgM gamma globulin

against Fc portion of IgG) îSerum albumin Serum (because of the presence of abnormal macroglobulins called

rheumatoid factors) will agglutinate or flocculate suspended particles such as hemolytic streptococci, sheep erythrocytes, latex, and with bentonite sensitized with human gama globulin

Latex fixation test on serum; unknown serum +gamma globulin-latex suspension

Inhibition test : rheumatoid serum of known high agglutinating activity + unknown euglobulin +standard gamma glubulin-latex suspension

4. RA 的病因和预后

① Pathogenesis of RA.

unknown

Genetic predisposition

Chromic antoimmune responces

② Indications of poor prognosis in RA.

reduced functional states

early radigraphic changes

multiple involved joints

older age at onset

high titiers of rhematoid factor

prolonged elevation of ESR

lower educational level

genetics

NO CURE

Goals of Treatment Relieve pain Reduce inflammation Stop or slow joint damage and deformity Improve well-being and ability to function

5. RA medical treatment

․NSAID ․DMARD ․Steroid ․others

6. RA operative treatment ․Synovectomy ․Arthrodesis ․Arthroplasty

Metabolic disorder

Inflammation 2° deposits of uric acid crystals in joint

Body produces too much uric acid Or

Body excretes too little uric acid

Uric acid is a waste product formed from the breakdown of purines

High levels of purines are found in organ meats (liver, brains, kidney), anchovies, herring, mackerel. Alcohol and some drugs may affect

purine excretion.

Uric acid levels elevated to 9-10 range (normals ~ 3 – 6)

No symptoms

Client may not progress to symptomatic disease

Sudden onset, acute pain, redness, swelling

Usually hits the big toe, may affect another joint

Fever, chills Elevated WBC, sed rate “Attack” lasts hours to weeks 60% have recurrent attack in 1 yr

Hyperuricemia untreated

Tophi (urate crystals deposits) develop in cartilage, synovial membranes, tendons, soft tissues

Pain, ulceration, nerve damage

Uric acid crystals—>kidney stones

Symptom: hyperuricemia ( >7mg%). Several yrs

① acute : 1st metatarsophalangeal joint , sudden onset

* Intercritical Period: weeks -years

recurr factor: meat, high purine diet, drug, fatigue, trauma, surgery

② chronic: continuous slight pain, degenerative arthritis, fibrous ankylosing

Dx: ① family history ② Repeated attacks with intervals of freedom from pain ③ Renal disturbance as urate calculus ④ Hyperuricemia ⑤ Satisfactory response to adequate doses of colchicine ⑥ Sodium biurate crystals ( rod type, blunt ended, strong

negative birefringence under polarized microscope, uricase digested) at joint aspirate ensure.

* tophi : subcutaneous tissue -> urate salt deposit -> ear site -> chalky white material.

Pain Indocin NSAIDS, Narcotics Steroids (po/intra-articular)

Interrupt urate crystal formation Colchicine: Does NOT alter uric acid

levels Inhibit tubular reabsorption of uric

acid Probenecid (Benemid)

Reduce the production of uric acid Allopurinol (Zyloprim)

Dietary Management Drink 3-4 quarts of fluids daily Avoid alcohol Sometimes no diet is prescribed

Low purine diet Meats, seafood, yeast, beans, peas,

lentils, oatmeal, spinach, asparagus, cauliflower, mushrooms