Metabolic Bone disease:

Things I didn’t understand as a Medical student/ FY1/ SHO/ SPR

James Bateman

Arthritis Research UK Educational Research Fellow

Aims and Objectives

• Aims– Understand the definition and spectrum of

metabolic bone diseases

• Objectives– demonstrate understanding of epidemiology,

aetiology, clinical features and management of osteoporosis, osteomalacia, Paget’s disease and renal osteodystrophy

Case 1

• 72 year old lady • Acute onset severe thoracic pain• Keeping her awake at night• Radiates around ribs• No history of trauma• PMH – COPD• DH - Inhalers

• What other questions would you ask?

Case 1 - contd

• On examination – – Frail lady– Apyrexial– Thoracic kyphosis– Tender over spinous processes T7/8– No neurological deficit

– differential diagnosis?

Diff. Diagnosis of Back Pain

• Simple mechanical eg ligamentous strain• Degenerative disease with/without neural, cord

or canal compromise• Metabolic – osteoporosis, Pagets • Inflammatory – Ankylosing spondylitis• Infective – bacterial and TB• Neoplastic• Others, (trauma,congenital)• Visceral

Case 1

• Investigations

• HB 12.9, WCC 9.0, Plts 245

• Na 139, K 4.4, U 7.3, Cr 96

• Alk Phos 297, ALT 32, Bil 13, Ca 2.41

• CRP 8

Osteoporosis

Reduction in bone mass leading to increase risk of fracture

Ratio of mineralised bone: “matrix is normal”

Imbalance of bone remodelling

• Risk factors for osteoporosis?

• Measurement and definition of OP?

T scores

• Typical OP # ?

OP fractures

250,000 # / yr in UK

• Treatment for OP ?

Osteoporosis

• Lifestyle factors– Falls prevention– Hip protectors

• Ca and Vit D

• Bisphosphonates

• Strontium

• SERMs

• Teriparatide- PTH

Preventing steroid induced osteoporosis

• All: lifestyle advise, calcium and vit D

• Age <65 DEXA- if T score -1.0 or less then alendronate

• Age >65 alendronate

NICE guidance

• http://guidance.nice.org.uk/TA87/?c=91524

• www.sheffield.ac.uk/FRAX/tool

Case 2

• 33 year old Asian lady• Presents with 3 /12 history of generalised

bony pain• PMH – depression• DH – sertraline

• O/E – generalised bony tenderness• Joints – normal ROM, no inflammation

Investigations

• Hb 12.9 (11.5-16.5) Calcium 2.18 (2.2-2.6)

• WCC 4.7 (4.9-11.0) Phosphate 0.79 (0.85-1.45)

• Plt 253 (150-400) Albumin 39 (35-50)• ESR 12 Alk Phos 172 (25-96)• Clotting Normal Total protein 72 (60-80)• Urea 4.2 (3.0-6.5) LFTs normal• Creat 85 (35-120)

• Diagnosis?

Osteomalacia

• Rickets of adulthood• Deficiency OR resistance to Vit D OR Phosphate

handling problem• Defective mineralization of bone• Proximal myopathy, Bony pain, malaise

– Deformities much less common than with rickets

• AP raised, Ca and Vit D low or normal• PO4 low or normal

What I didn’t understand as a medical student…

• Bone remodelling is a continuous process with uptake and laying down of new matrix (osteoid) and its mineralisation (Ca&PO4)

• In osteomalacia: the osteoid is normal (the matrix laid down by the osteoblasts)

• Normally calcium and phosphate are then ladi down some 15 dyas later, and converted to hydroxyapatite)

What I didn’t understand as a medical student…

• You need enough phosphate to mineralise bone:

• PTH stops you the renal re-absorbtion of phosphate

• So that’s why osteomalacia happens with vitamin D deficiency

Causes?

Causes of osteomalacia/rickets

• Reduced availability of Vit D

– Diet: oily fish, eggs, breakfast cereals

– Elderly individuals with minimal sun exposure

– Dark skin, skin covering when outside

– Kidney failure

– malabsorption

• malabsorption– Coeliac– Intestinal bypass– Gastrectomy– Chronic pancreatitis– Pbc

• Epilepsy: phenytoin, phenobarbitones

• Defective metabolism of Vitamin D– Chronic renal failure, Vit D dependent rickets,– Liver failure, anticonvulsants

• Receptor Defects

• Altered phosphate homeostasis– Malabsorption, RTA, hypophosphatasia (rare,

low levels of alk phos)

Loosers zones

Treatment

• Vitamin D –usually oral- HIGH DOSE

• Calcium supplements

Case 3

• 62 year old lady referred with generalised muscular pain

• PMH – hypertension• DH – bendrofluazide• Examination – largely unremarkable• Routine bloods all normal except Calcium of

2.95• She has come back to clinic for results• What would you do now?

Symptoms of hypercalcaemia

• Stones,

• Bones,

• Moans,

• Psychic Groans

An approach to hypercalcaemia

• Stones, Renal colic

• Bones, Joint, bone, muscle pain, Muscle weakness

• Moans, Constipation Abdominal pains

• Psychic Groans Depression, confusion, altered mental state, Fatigue, lethargy

• Dehydration, polyuria

Causes of Hypercalcaemia?

Causes of Hypercalcaemia

• Malignancy

• Hyperparathyroidism – primary or tertiary

• Increased intake

• Myeloma

• Sarcoid

• Adrenal failure

Treatment of acute hypercalcaemia?

Treatment of acute hypercalcaemia

• Hydration, IV if Ca very high

• Bisphosphonates

• Treat cause

Hyperparathyroidism

• Primary hyperparathyroidism:– Often an incidental finding

– May be part of MEN I, MEN II

• Secondary hyperparathyroidism– Compensates for chronic low Ca eg. Renal failure or malabsorption

– [Ca2+] and [PO42-] normal PTH high

• Tertiary hyperparathyroidism– Hyperplasia in longstanding secondary disease

Multiple endocrine neoplasia

• Aut dom

• MEN 1 parathyroid tumours, ant pituitary, pancreas

• MEN 2A thyroid tumour, phaeochromocytomas, parathyroid hyperplasia

• MEN 2B thyroid tumours and phaeos

Hypoparathyroidism

Causes

• Destruction of gland- surgical (thyroidectomy- may be transient)

• Autoimmune- polyglandular autoimmune glandular syndrome

• Irradiation or infiltration (cancer, wilsons)

• Abnormal gland development

Case 4

This 73 year old lady was referred from her GP to ENT with deafness.

They asked her to see the rheumatologist

Why?

Paget’s Disease

• Disease of bone remodeling

• Accelerated bone resorption and formation

• Disorganised mosaic pattern bone with increased vascularity and fibrosis

• Cause unknown

– paramyxovirus, canine distemper

– Genetics- susceptibility loci

• More common in caucasian

• M:F ratio 3:2 10% in over 70’s

Paget’s Disease: clinical manifestations

• Bone pain

• Joint pain

• Deformity

• Spontaneous fractures

Pagets Disease: complications

• Fractures

• Deafness

• Nerve entrapment

• Spinal stenosis

• Cardiac failure

• Osteogenic sarcoma

• Hypercalcaemia (only if immobilized)

Paget’s Disease: investigations

• Raised serum alk phos

• (Urinary hydroxyproline, pyridinoline cross-links)

• Radiology:

Normal

• Radiology

– cortical thickening

– osteolytic, osteosclerotic and mixed lesions

– osteoporosis circumscripta

– bone scan

Paget’s Treatment

• Bisphosphonates– calcitonin

• Indicated if – Complications– Pain– Deformity– AP 2-3X Upper limit– Skull disease

Questions?