AP: Metabolic Bone Disease

Question 1

Causes of hypercalcemia.

Answer 1

• Primary hyperparathyroidism.
• Malignancy.
• Sarcoidosis.
• Vit D intoxication.
• Milk alkali syndrome.
• Familial conditions.
• Drugs.
• Other endocrine disorders.
• Immobilisation.
• Renal disease.

Question 2

Describe osteoporosis

Answer 2

completely normal bone in terms of structure and cellularity, just less of it.

Question 3

What are the normal constituents of bones?

Answer 3

• Cells: osteocytes, -blasts, -clasts
• Mineral: calcium hydroxyapatite crystals
• Organic matrix: collagen (type1), glycosaminoglycans

Question 4

What is osteoid?

Answer 4

The non-mineralised matrix synthesised by osteoblasts

Question 5

What does mineralisation require?

Answer 5

• Adequate calcium, phosphate

- Normal cellular function

Question 6

What are the primary regulators of calcium and phosphate?

Answer 6

• Parathyroid hormone

- Vitamin D

Question 7

What are the two principal functions of bone remodelling?

Answer 7

1. Allows repair of microscopic areas of damage within bone to maintain skeletal strength
2. Allows release of calcium to maintain serum calcium levels

Question 8

Where does trabecular bone loss tend to occur?

Answer 8

Women: spine, distal radius, hips

Men: spine and hips

Question 9

What factors influence osteoporosis development?

Answer 9

• Peak bone mass
• Rate of bone loss
• Imbalance resorption and formation
• Calcium metabolism
• Hormonal status

Question 10

What are the 3 different types of osteoporosis?

Answer 10

Type 1 - post menopausal (trabecular, forearm, spinal fractures)

Type 2 - age related (cortical and trabecular, hip fracture)

Secondary - caused by some other endocrine disease (e.g. Cushing’s, hyperparathyroidism), drugs, malabsorption and rheumatological diseases

Question 11

How does osteoporosis present clinically?

Answer 11

Typically asymptomatic: presents with complications:

• pain
• microfractures
• deformity
• fractures

Question 12

How do you diagnose osteoporosis?

Answer 12

Densitometry: bone mineral density by dual x-ray absorptiometry (DEXA)

** X-ray can see fractures, cortical thinning, & reduced density but has low sensitivity.

Question 13

How are DEXA scans scored, and what are the WHO classifications?

Where are the scans taken?

Answer 13

T-score = number of standard deviations above/below the density of a young person (peak bone mass) of the same race as the patient.

Normal = T score > -1
Osteopenia = T score -1 to -2.5
Osteoporosis = T score < -2.5
Severe osteoporosis = T score

Question 14

What is osteomalacia?

Answer 14

Defective mineralisation of organic matrix; relative excess of osteoid.

Deficiency of both quality & quantity of bone. Loss of stiffness of bone and increased susceptibility to compressive forces.

Question 15

What is osteomalacia in children?

Answer 15

Rickett’s

Question 16

What are some causes of osteomalacia/ricketts?

Answer 16

• Dietary deficiencies (Vit D, Ca, P)
• Lack Vit D (no sun exposure, malabsorption, chronic renal or hepatic disease)
• Vit D resistance (phosphate wasting)
• Hypophosphatemia (renal tubular disorders, antacids)
• Drugs (heavy metals)
• Neoplasia (oncogenic osteomalacia)

Question 17

What are clinical presentations of osteomalacia?

Answer 17

May be asymptomatic: soft (deforms), fragile bone (fractures), bone pain, proximal muscle weakness (hypocalcemia)

Generalised osteopenia (reduced skeletal mass)

Question 18

What is a hallmark of Ricketts?

Answer 18

Abnormal, thickened epiphyses: often terrible deformities
If untreated causes reduced long bone growth
Patients show weakness & hypotonia

Question 19

Are we likely to see lots of Osteomalacia in Australia?

Answer 19

Tends to occur more in impoverished countries, mores in low SES contexts.

Most of developed world has adequate sunlight and/or fortified foods

Question 20

What is hyperparathyroidism and what are its consequences?

Answer 20

Excess of parathyroid hormone secrete by parathyroid

Excess activation of osteoclasts - chomp bone up

Question 21

What are the causes of primary hyperparathyroidism?

Answer 21

Parathyroid adenoma (80%)
Parathyroid hyperplasia (15-20%). Mostly sporadic, genetic conditions = small proportion of these. 

In both cases, pump out parathyroid hormone for no reason (autonomously)

Question 22

What are the causes of secondary hyperparathyroidism?

Answer 22

• Chronic hypocalcaemia (perpetually low Calcium levels e.g. in chronic renal failure)
• lack of negative feedback
  » Hypersecretion of PTH

Bone effects usually less severe than primary

Question 23

What are clinical manifestation of hyperparathyroidism?

Answer 23

• Dissecting/tunnelling bone resorption
• Diffuse osteopenia

Tunneling resorption: fibrosis and osteoclastic activity from the inside of the trabeculae
Dissecting resorption: Haversian systems expanded w irregular scalloping of walls

Question 24

What is Paget’s disease of bone?

Answer 24

Poorly understood idiopathic disorder where bone decides to remodel itself for some reason

Question 25

What are the 3 stages of Paget’s?

Answer 25

1) osteolytic
2) mixed (lytic and blastic)
3) osteoblastic/sclerotic phases

Results in thick, soft, porous bone, prone to compression and deformity

Question 26

What are the common sites and symptoms of Paget’s?

Answer 26

• Skull: enlargement, cranial nerve compression
• Thoraco-lumbar spine: pain, neurological, cord compression
• Pelvis sacrum: pain, arthritis
• Femur, tibia: pain, deformity, path fracture

Question 27

What is renal osteodystrophy?

Answer 27

Range of bone abnormalities seen in chronic renal disease and haemodialysis (basically combo of everything else in lecture)

Question 28

Explain the pathophysiology of renal osteodystrophy

Answer 28

renal failure = hypocalcaemia

Low serum calcium —> hyperparathyroidism = osteoclastic activity = Reduced skeletal mass

Renal failure —> vitamin D problem

Question 29

What are 3 types of localised osteoporosis?

Answer 29

Not caused by systemic metabolism issues like general osteoporosis, localised to area of neuro/vascular/mechanical issue.

1. disuse, immobilised (ie plaster cast)
2. vasomotor injury (complex regional pain syndrome = loss of density in one limb/area)
3. Transient regional (similar to disuse but not immobilised)

Question 30

Laboratory & microscopic signs of osteomalacia

Answer 30

Vary according to the underlying cause of the disease process

• low to normal serum calcium
• low phosphate
• high alkaline phosphatase

Microscopic = increased osteoid (unmineralised matrix) on surfaces of bone trabeculae.