2. Metabolic bone disease Flashcards
Types of metabolic bone diseases
- Osteoporosis
- Osteomalacia & Rickets
- Hyperparathyroidism
- Paget’s disease
- Osteopetrosis
Definition of osteoporosis
Systemic skeletal disease characterised by low bone mass & microarchitectural deterioration of bone tissue with consequent increase in bone fragility & susceptibility of fracture
WHO Quantitative Criteria
- Bone density study using dual energy X-ray absorptiometry
i. Osteoporosis: bone mass > 2.5 SD below young normal mean
ii. Osteopenia: 2.5 SD > bone mass > 1 SD below young normal mean
Causes of osteoporosis
Primary causes:
- Old age (senile osteoporosis)
- Decreased replicative ability of osteoprogenitor
- Decreased synthetic ability of osteoblasts
- Decreased biologic activity of matrix-bound growth factors
- Reduced physical activity (as mechanical forces are needed to induce bone remodeling) - Menopause
- Decreased serum estrogen levels
- Increased RANK & RANKL expression which increases osteoclast generation & activity
Secondary causes:
- Endocrine causes
- Cushing syndrome
- Hyperparathyroidism
- Hyperthyroidism
- Hypogonadism
- Type I diabetes mellitus - Gastrointestinal causes (malnutrition)
- Vitamin C & D deficiency
- Liver insufficiency - Drugs
- Corticosteroids
- Chemotherapy - Immobilization
- Bone diseases
- Multiple myeloma
- Osteogenesis imperfecta
Sites affected in osteoporosis
- Spongy bone of vertebral bone
- Affected first (high surface area for osteoclast action)
- Causes loss of vertebral height in elderly, leading to
dowager’s hump - Cortex in hip & wrist
- Thinning of cortex (subperiosteal & endosteal resorption with widening of haversian systems)
Morphology of osteoporosis
Histologically:
- Thin trabeculae disconnected from one another
- Normal mineralization
Management of Osteoporosis
- Prevention:
- Maximize peak bone mass attained during early adulthood by ensuring adequate calcium intake during adolescence
- Regular exercise to promote bone remodelling - Treatment:
- Hormone replacement therapy
- Bisphosphonates (binds to bone to inhibit osteoclast)
- Vitamin D + calcium supplementation
Definition of Osteomalacia & Rickets
Defect in matrix mineralization often due to Vitamin D deficiency; rickets is the clinical manifestation seen in children whereas osteomalacia is its adult counterpart
Causes of Osteomalacia & Rickets
- Vitamin D deficiency
- Dietary insufficiency, malabsorption
- Reduced skin synthesis due to insufficient exposure to sunlight - Abnormal Vitamin D metabolism
- Increased degradation (drugs)
- Chronic liver disease (diminished 25-hydroxylation)
- Renal failure (diminished 1-hydroxylation) - Causes with normal Vitamin D levels
- End organ resistance (type 2 Vitamin D resistant
rickets)
- Hypophosphatemia (renal tubular disorders such as
in Fanconi syndrome) - Abnormal bone mineralization
- Low bone alkaline phosphatase (hypophosphatasia)
- Chemical drugs (aluminium toxicity)
Morphology of Osteomalacia & Rickets
- Excessive osteoid forming thickened seams (due to delay in mineralization of bone matrix)
- Deficient calcification front (lack of effective endochondral ossification)
- Irregular thickening of the hypertrophic zone of the
epiphyseal growth plate in rickets (due to failure to mineralize, which prevents osteoclastic resorption of the cartilage)
- Loss of normally orderly columns of cells
- Marked increase in axial height
- Disorderly proliferation of cells with only a small amount of intervening matrix
Clinical Features of Osteomalacia & Rickets
- Presentation:
- Rickets: bowing of legs, lumbar lordosis - Xray findings:
- ‘Looser zone’ or pseudofracture (a thin tranverse band of rarefaction; also seen in Paget’s disease)
- Incomplete stress fractures which heal with callus lacking in calcium
Definition of hyperparathyroidism
Overactivity of the parathyroid glands leading to increased osteoclastic activity which results in bone disease
Causes of Hyperparathyroidism
- Primary Hyperparathyroidism
- Parathyroid adenomas
- Parathyroid hyperplasia (seen in MEN I & IIa) - Secondary Hyperparathyroidism
- Physiological response to hypocalcemia in various conditions (chronic renal failure, deficient calcium intake, Vitamin D deficiency) - Tertiary Hyperparathyroidism
- Autonomous hyperplastic nodule in long standing secondary hyperparathyroidism
Morphology of hyperparathyroidism
Histologically:
- Increased number of osteoclasts
- Dissecting osteitis (osteoclasts boring through the centre of bony trabeculae) due to increased osteoclastic resorption
- Bone loss & replacement by immature woven bone & fibrous tissue
- Brown tumour (mass formed due to extensive accumulation of osteoclastic giant cells with hemorrhage & fibrous tissue; can mimic giant cell tumours)
Clinical features of hyperparathyroidism
Location: affects entire skeleton, cortical bone more so than medullary bone
Presentation:
1. Presents in young to middle-aged adults
2. Only 25% have bone disease:
- Typically presents as bone pain
- Recklinghausen disease (aka osteitis fibrosa
cystica; a combined picture of increased bone cell activity, peritrabecular fibrosis & cystic brown tumour formation) rarely seen nowadays due to early detection
3. Recurring kidney stones, peptic ulcer, nausea,
vomiting, weakness & headaches
Lab findings: Marked hypercalcemia & hypophosphatemia
Xray findings:
- Expansile lytic lesions with occasional intralesional trabeculations
- Surrounding periosteum produces reactive bone & margins of the tumour may be well-defined or indistinct
Definition of Paget’s disease
Bone disease characterized by excessive turnover of bone resulting in disorganization of its architecture; not to be confused with Paget’s disease of the breast