Metabolic Bone Disease

1
Metabolic Bone Disease
2
Metabolic Bone Disease

• Hypercalcaemia
• Hyperparathyroid bone disease
• Hypocalcaemia
• Osteomalacia
• Pagets Disease

3
Actions of PTH

• Increase Ca2, decrease PO42-
• In bone
• osteoclastic reabsorption releases Ca2 and PO42-
  
• In kidney
• increased PO42- excretion
• increased Ca2 reabsorption
• increased hydroxylation of vitamin D

4
Actions of vitamin D

• Kidney
• decreased Ca2 excretion
• Bone
• increased bone mineralisation
• Small bowel
• increased Ca2 and PO42- absorption

5
(No Transcript)
6
Case 1
7
Case 1

• 63 year old woman
• abdo pains, nocturia, kidney stones
• generally unwell
• Hb 12.9 (11.5-16.5) Calcium 3.05 (2.2-2.6)
• WCC 4.7 (4.9-11.0) Phosphate 0.82 (0.85-1.45)
• Plt 253 (150-400) Albumin 39 (35-50)
• ESR 12 Alk Phos 96 (25-96)
• Clotting Normal Total protein 72 (60-80)
• Urea 10.2 (3.0-6.5) LFTs normal
• Creat 142 (35-120)

8
results

• Bone scan Normal
• PTH 5.6 pmol/L (1.16.5)
• Xrays, other scans.

9
Metabolic Bone Disease

• Hypercalcaemia
• Hyperparathyroid bone disease
• Hypocalcaemia
• Osteomalacia
• Pagets Disease

10
Hyperparathyroidism
Xrays sub-periosteal resorption pepper pot
skull rugger jersey spine cystic brown tumours
11
Hyperparathyroidism
Xrays sub-periosteal resorption pepper pot
skull rugger jersey spine cystic brown tumours
12
Hyperparathyroidism
Xrays sub-periosteal resorption pepper pot
skull rugger jersey spine cystic brown tumours
13
Hyperparathyroidism
Xrays sub-periosteal resorption pepper pot
skull rugger jersey spine cystic brown tumours
14
Hyperparathyroidism
Xrays sub-periosteal resorption pepper pot
skull rugger jersey spine cystic brown tumours
15
Hyperparathyroidism

• Ca2 high
• PO42- low
• PTH high
• Prevalence 1 in 1000 (ish)

16
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

17
Primary hyperparathyroidism

• PTH raised inappropriately relative to Ca2
• may be within normal range
• Pathology
• Single adenoma 85
• hyperplasia 14
• due to carcinoma lt1
• Xrays can be helpful if chronic
• bone scan negative unless severe

18
Primary hyperparathyroidism

• Management
• moderate Ca2 (lt2.9mmol/l) watch
• high Ca2, renal failure, symptomatic
  parathyroidectomy by experienced surgeon
• Sestamibi scan can be used to localise

19
Hyperparathyroidism
Sestamibi scan
20
Case 2
21
Case 2
58 year old male admitted to AE following a
fall Xray pathologic fracture of the humerus,
lytic lesion. Orthopaedics requested urgent
bone scan bloods History of general malaise
weight loss Recurrent infections bout of
shingles Hb 8.9 (13.0-18.0) Calcium 3.24
(2.2-2.6) WCC 9.7 (4.9-11.0) Phosphate 0.89
(0.85-1.45) Plt 388 (150-400) Albumin 30
(35-50) ESR 112 Alk Phos 89 (25-96) Clotting
Normal Total protein 92 (60-80) Urea 11.5
(3.0-6.5) LFTs normal Creat 245 (35-120)
22
investigations

• Immunoglobulins
• IgA 0.3g/l (0.5-4.0)
• IgG 16.9g/l (5.0-15)
• IgM 0.4g/l (0.6-2.8)
• Monoclonal band on electophoresis
• bence jones protein positive Kappa chains

23
(No Transcript)
24
(No Transcript)
25
(No Transcript)
26

• Xray appearance
• holes in bone without sclerotic reaction
• no reaction of the host bone to the lesions
• Bone scan may be negative

27
Myeloma

• Management
• Immediate care
• treat hypercalcaemia
• renal input
• haematology input

28
Metabolic Bone Disease

• Hypercalcaemia
• Hyperparathyroid bone disease
• Hypocalcaemia
• Osteomalacia
• Pagets Disease

29
Hypercalcaemia

• Hyperparathyroidism
• Malignancy
• Myeloma
• Increased Calcium or vitamin D intake
• Others
• sarcoid
• adrenal failure

30
Hypercalcaemia

• Malaise
• Muscle weakness
• Confusion
• Lethargy
• Kidney stones
• Constipation

31
Hypercalcaemia

• Re-hydrate
• consider i.v. bisphosphonate
• Treat cause
• ?steroids

32
Case 3
33
Case 3

• 65 male with Ca prostate, ? Metastatic
• Hb 13.9 (13.0-18.0) Calcium 2.3 (2.2-2.6)
• WCC 9.7 (4.9-11.0) Phosphate 0.89 (0.85-1.45)
• Plt 222 (150-400) Albumin 39 (35-50)
• ESR 1 Alk Phos 985 (25-96)
• Clotting Normal Total protein 71 (60-80)
• Urea 4.5 (3.0-6.5) LFTs normal
• Creat 112 (35-120)

34
Normal Patient
35
Metastatic Ca Prostate Patient
36
Metabolic Bone Disease

• Hypercalcaemia
• Hyperparathyroid bone disease
• Hypocalcaemia
• Osteomalacia
• Pagets Disease

37
Pagets Disease

• Disease of bone remodelling
• osteoclast mediated bone resorption followed by
  new bone formation
• Disorganised mosaic pattern bone with increased
  vascularity and fibrosis
• Cause unknown ?virus
• paramyxovirus, canine distemper
• More common in caucasian
• MF ratio 32 10 in over 70s

38
Pagets Disease clinical manifestations

• Bone pain
• Joint pain
• Deformity
• Spontaneous fractures
• Alk Phos high
• Ca2 normal unless immobilised

39
Pagets Disease complications

• Fractures
• Deafness
• Nerve entrapment
• Spinal stenosis
• Cardiac failure
• Osteogenic sarcoma
• Hypercalcaemia

40
Pagets Disease investigations

• Raised serum alk phos
• Urinary hydroxyproline, pyridinoline cross-links
• Radiology
• cortical thickening
• osteolytic, osteosclerotic and mixed lesions
• osteoporosis circumscripta
• bone scan

41
Normal
42
(No Transcript)
43
(No Transcript)
44
(No Transcript)
45
Pagets Disease
46
Pagets Disease
47
Osteoporosis circumscripta
48
Blade of grass lytic front
49
Pagets Disease treatment

• Bisphosphonates
• Disodium etidronate
• risedronate
• Pamidronate (iv)
• Calcitonin

50
Pagets Indications for Therapy

• bone pain
• osteolytic lesion in wt bearing bone
• neurological complications
• mal-union of fractures
• immobilisation hypercalcaemia
• pre- or post-surgery

51
Case 4
52
Case 4

• 63 woman post-op parathyroidectomy
• acutely unwell, paresthesiae
• muscular irritability
• Hb 12.9 (11.5-16.5) Calcium 2.2 (2.2-2.6)
• WCC 4.7 (4.9-11.0) Phosphate 0.84 (0.85-1.45)
• Plt 253 (150-400) Albumin 39 (35-50)
• ESR 12 Alk Phos 96 (25-96)
• Clotting Normal Total protein 72 (60-80)
• Urea 6.5 (3.0-6.5) LFTs normal
• Creat 132 (35-120)

53
Signs of hypocalcaemia

• Chvosteks sign
• tap facial nerve twitching of facial muscles
• Trousseaus sign
• Inflate arm cuff gt diastolic BP 3
  minutes carpopedal spasm
• Flexion at Wrist
• Flexion at MCP joints
• Flexion of thumb against palm
• Extension of PIP joints and DIP joints
• Adduction of fingers (forms a cone)

54
Metabolic Bone Disease

• Hypercalcaemia
• Hyperparathyroid bone disease
• Hypocalcaemia
• Osteomalacia
• Pagets Disease

55
Hypocalcaemia causes

• Post-surgical!
• Hypoparathyroidism
• Hypovitaminosis D (osteomalacia)
• Renal failure
• Others eg. Rhabdomyolysis, sepsis

56
Hypocalcaemia clinical features

• Neuromuscular excitability
• Tetani
• Seizures
• Muscle weakness
• Confusion
• Paresthesiae
• Prolonged Q-T syndrome

57
Treatment

• In this case
• Restore calcium levels with immediate infusion of
  calcium gluconate in saline

58
Case 5
59
Case 5

• 23 woman
• flitting arthritis 3/52
• tender red rash, generally unwell
• Hb 11.0 (11.5-16.5) Calcium 2.76 (2.2-2.6)
• WCC 15.2 (4.9-11.0) Phosphate 0.84 (0.85-1.45)
• Plt 390 (150-400) Albumin 39 (35-50)
• ESR 43 Alk Phos 72 (25-96)
• Clotting Normal Total protein 72 (60-80)
• Urea 6.0 (3.0-6.5) LFTs normal
• Creat 87 (35-120) ANA,ENA -ve
• RhF 140 Xrays soft tissue swelling

60
(No Transcript)
61
CXR
62
CXR
63
Skin lesions
64
Hands
65
Sarcoid clinical features

• Hypercalcemia (13)
• intestinal Ca2 absorption due to production of
  vit D metabolite by lung macrophages
• BHL 90
• neurosarcoid
• Uveitis
• lymphadenopathy
• cardiac involvement
• biopsy non-caseating granulomata
• elevated ACE (unhelpful 60)

66
Sarcoid treatment

• Steroids, immune supressants
• NSAIDs (arthritis)
• Many resolve spontaneously

67
Case 6
68
Case 6

• 32yr asian woman
• All over bony pain, weakness, vegetarian
• 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)

69
Metabolic Bone Disease

• Hypercalcaemia
• Hyperparathyroid bone disease
• Hypocalcaemia
• Osteomalacia
• Pagets Disease

70
Osteomalacia

• Equivalent to Rickets in children
• Pathology
• Inadequate mineralisation of bone
• less mineralisation per unit volume of bone
• Ca2 low PO42- low
• Alk Phos high PTH high

71
Osteomalacia causes

• Vit D deficiency
• low intake plus inadequate sunlight exposure
• malabsorption
• Abnormal vit D metabolism
• Liver disease
• Renal disease
• Drugs (anticonvulsants)
• Hypophosphatasia
• Low intake
• Genetic

72
Vitamin D Deficiency risk factors

• Infancy
• Elderly individuals with minimal sun exposure
• Dark skin
• Skin covering when outside
• Fat malabsorption syndromes
• Kidney failure
• Genetic disease
• Epilepsy (phenytoin, phenobarbitones)

73
Osteomalacia clinical manifestations

• malaise
• Bone pain
• Proximal muscle weakness
• Alk phos high
• Ca2 low or normal
• PO42- low or normal
• Looser zones in X-rays

74
Rickets
75
Normal
Osteomalacia
76
Normal Osteoporosis
77
frogleg view loosers zone
AP view loosers zone
78
Osteomalacia Bone scan
79
Osteomalacia treatment

• Treatment of Vitamin D deficiency is replacement!
• Oral vitamin D replacement
• High dose available, injections not required
• Adults require 400IU/day
• Elderly 800IU/day ( prevention)

80
The End