AP: Metabolic Bone Disease Flashcards
Causes of hypercalcemia.
- Primary hyperparathyroidism.
- Malignancy.
- Sarcoidosis.
- Vit D intoxication.
- Milk alkali syndrome.
- Familial conditions.
- Drugs.
- Other endocrine disorders.
- Immobilisation.
- Renal disease.
Describe osteoporosis
completely normal bone in terms of structure and cellularity, just less of it.
What are the normal constituents of bones?
- Cells: osteocytes, -blasts, -clasts
- Mineral: calcium hydroxyapatite crystals
- Organic matrix: collagen (type1), glycosaminoglycans
What is osteoid?
The non-mineralised matrix synthesised by osteoblasts
What does mineralisation require?
- Adequate calcium, phosphate
- Normal cellular function
What are the primary regulators of calcium and phosphate?
- Parathyroid hormone
- Vitamin D
What are the two principal functions of bone remodelling?
- Allows repair of microscopic areas of damage within bone to maintain skeletal strength
- Allows release of calcium to maintain serum calcium levels
Where does trabecular bone loss tend to occur?
Women: spine, distal radius, hips
Men: spine and hips
What factors influence osteoporosis development?
- Peak bone mass
- Rate of bone loss
- Imbalance resorption and formation
- Calcium metabolism
- Hormonal status
What are the 3 different types of osteoporosis?
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
How does osteoporosis present clinically?
Typically asymptomatic: presents with complications:
- pain
- microfractures
- deformity
- fractures
How do you diagnose osteoporosis?
Densitometry: bone mineral density by dual x-ray absorptiometry (DEXA)
** X-ray can see fractures, cortical thinning, & reduced density but has low sensitivity.
How are DEXA scans scored, and what are the WHO classifications?
Where are the scans taken?
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
What is osteomalacia?
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.
What is osteomalacia in children?
Rickett’s
What are some causes of osteomalacia/ricketts?
- 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)
What are clinical presentations of osteomalacia?
May be asymptomatic: soft (deforms), fragile bone (fractures), bone pain, proximal muscle weakness (hypocalcemia)
Generalised osteopenia (reduced skeletal mass)
What is a hallmark of Ricketts?
Abnormal, thickened epiphyses: often terrible deformities
If untreated causes reduced long bone growth
Patients show weakness & hypotonia
Are we likely to see lots of Osteomalacia in Australia?
Tends to occur more in impoverished countries, mores in low SES contexts.
Most of developed world has adequate sunlight and/or fortified foods
What is hyperparathyroidism and what are its consequences?
Excess of parathyroid hormone secrete by parathyroid
Excess activation of osteoclasts - chomp bone up
What are the causes of primary hyperparathyroidism?
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)
What are the causes of secondary hyperparathyroidism?
- 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
What are clinical manifestation of hyperparathyroidism?
- 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
What is Paget’s disease of bone?
Poorly understood idiopathic disorder where bone decides to remodel itself for some reason
What are the 3 stages of Paget’s?
1) osteolytic
2) mixed (lytic and blastic)
3) osteoblastic/sclerotic phases
Results in thick, soft, porous bone, prone to compression and deformity
What are the common sites and symptoms of Paget’s?
- Skull: enlargement, cranial nerve compression
- Thoraco-lumbar spine: pain, neurological, cord compression
- Pelvis sacrum: pain, arthritis
- Femur, tibia: pain, deformity, path fracture
What is renal osteodystrophy?
Range of bone abnormalities seen in chronic renal disease and haemodialysis (basically combo of everything else in lecture)
Explain the pathophysiology of renal osteodystrophy
renal failure = hypocalcaemia
Low serum calcium —> hyperparathyroidism = osteoclastic activity = Reduced skeletal mass
Renal failure —> vitamin D problem
What are 3 types of localised osteoporosis?
Not caused by systemic metabolism issues like general osteoporosis, localised to area of neuro/vascular/mechanical issue.
- disuse, immobilised (ie plaster cast)
- vasomotor injury (complex regional pain syndrome = loss of density in one limb/area)
- Transient regional (similar to disuse but not immobilised)
Laboratory & microscopic signs of osteomalacia
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.
