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METABOLIC BONE DISEASE (OSTEOMALACIA (CAUSES (Vitamin d deficiency: (poor…

- - - - alcohol >4 units daily
      - rheumatoid arthritis
      - parental history
      - bmi <19
      - prolonged immobility
      - untreated menopause.
    - - Hyperthyroidism, hyperparathyroidism, hypercalciuria.
      - Alcohol and tobacco use ↑.
      - Steroid use of >5mg/d of prednisolone.
      - Thin (bmi <18.5).
      - Testosterone ↓ (eg antiandrogen ca prostate ℞).
      - Early menopause.
      - Renal or liver failure.
      - Erosive/inflammatory bone disease (eg myeloma or rheumatoid arthritis).
      - Dietary ↓Ca2+/malabsorption; diabetes mellitus type 1.
  - - - Each decrease of 1 sd in bmd ≈ 2.6-fold ↑ in risk of hip fracture.
      - INDICATIONS
        
        Prior to giving long-term prednisolone (eg ≳3 months at >5mg/d). Steroids cause osteoporosis by promoting osteoclast bone resorption, ↓muscle mass, and ↓Ca2+ absorption from the gut.
        
        dexa is not needed pre-treatment for women over 75yrs if previous low-trauma fracture, or ≥ 2 present of rheumatoid arthritis, alcohol excess, or positive family history.
        
        if previous low-trauma fracture,
        
        The benefits of universal screening for osteoporosis remain unproven, but some authorities recommend this for men and women over 70—and earlier if risk factors are present
        
        Men or women with osteopenia if low-trauma, non-vertebral fracture.
        
        or for women ≥ 65yrs with one or more risk factors for osteoporosis, or younger if two or more.
        
        Bone and bone-remodelling disorders (eg parathyroid disorders, myeloma, hiv, esp. if on protease inhibitors).
      - The ‘t-score’ is the number of standard deviations (sd, p[link]) the bone mineral density (bmd) is from the youthful average
        
        −2.5 or worse Osteoporosis. Offer lifestyle advice and treatment. Repeat dexa in 2yrs.
        
        −1 to −2.5 Osteopenia. Risk of later osteoporotic fracture. Offer lifestyle advice.
        
        0 to −1 bmd is in the top 84%: no evidence of osteoporosis.
        
        t-score >0 bmd is better than the reference.
      - better to scan the hip than the lumbar spine
  - - - Balance exercises such as tai chi reduce risk of falls.
      - Calcium and vitamin d-rich diet (use supplements if diet is insufficient—see ‘Pharmacological measures’ later in this topic).
      - Weight-bearing exercise may increase bone mineral density
      - Home-based fall-prevention programme, with visual assessment and a home visit. nb: hip-protectors are unreliable for preventing fractures
      - Quit smoking and reduce alcohol consumption.
    - - Calcium and vitamin d:
        
        rarely used alone for prophylaxis, as questionable efficacy and some evidence of a small ↑cv risk.
        
        Offer if evidence of deficiency, eg calcium 1g/d + vit d 800u/d. Target serum 25-hydroxy-vitamin d level ≥75nmol/L.
      - Strontium ranelate:
        
        due to an increased risk of cardiac problems it should only be used in those with severe intolerance of other agents and without cardiovascular disease.
      - Hormone replacement therapy (hrt)
        
        can prevent (not treat) osteoporosis in post-menopausal women.
        
        Relative risk of breast cancer is 1.4 if used >10yrs; ↑ cv risk.
      - Bisphosphonates:
        
        Use also for prevention in long-term steroid use.
        
        If intolerant, try etidronate or risedronate.
        
        alendronic acid is 1st line (10mg/d or 70mg/wk; not if egfr <35).
        
        Tell patient to swallow pills with plenty of water while remaining upright for >30min and wait 30min before eating or other drugs.
        
        (se: photosensitivity; gi upset; oesophageal ulcers—stop if dysphagia or abdo pain; rarely, jaw osteonecrosis).
      - Raloxifene
        
        is a selective oestrogen receptor modulator (serm) that acts similarly to hrt, but with ↓ breast cancer risk.
      - Teriparatide (recombinant pth)
        
        is useful in those who suffer further fractures despite treatment with other agents. There is a potential ↑ risk of renal malignancy.
      - Calcitonin
        
        may reduce pain after a vertebral fracture.
      - Testosterone
        
        may help in hypogonadal men by promoting trabecular connectivity.
      - Denosumab
        
        monoclonal Ab to rank ligand, given sc twice yearly ↓ reabsorption.
- - - - Once walking:
        
        bow-legged
        
        deformities of the metaphyseal-epiphyseal junction (eg the rachitic rosary)
        
        knock-kneed
      - apathy in infants.
      - hypotonia.
      - Children with rickets are ill
      - Growth retardation
    - - proximal myopathy (waddling gait)
        
        due to ↓PO43− and vitamin d deficiency per se.
      - fractures (esp. femoral neck)
      - Bone pain and tenderness
  - - - A number of mainly inherited conditions in which the osteomalacia responds to high doses of vitamin d
    - - Due to reduced hydroxylation of vitamin d to 25-hydroxy-cholecalciferol and malabsorption of vitamin d, eg in cirrhosis
    - - Anticonvulsants may induce liver enzymes, leading to an increased breakdown of 25-hydroxy-vitamin d.
    - - (Oncogenic hypophosphataemia.) Mediated by raised tumour production of phosphatonin fibroblast growth factor 23 (fgf-23) which causes hyperphosphaturia. ↓serum PO43− often causes myalgia and weakness
    - - Renal failure leads to 1,25-dihydroxy-cholecalciferol deficiency [1,25(oh)2-vitamin d deficiency].
    - - poor diet
      - lack of sunlight
      - Due to malabsorption
  - - - Bone biopsy shows incomplete mineralization.
      - Muscle biopsy (if proximal myopathy) is normal
    - - In osteomalacia, there is a loss of cortical bone
      - apparent partial fractures without displacement may be seen especially on the lateral border of the scapula, inferior femoral neck, and medial femoral shaft (Looser’s zones)
      - Cupped, ragged metaphyseal surfaces are seen in rickets
    - - Mildly ↓Ca2+ (but may be severe)
      - ↓PO43−
      - ↑alp
      - pth high
      - ↓25(oh)-vitamin d, except in vitamin d resistance
      - In renal failure, ↓1,25(oh)2-vitamin d
  - - - type II has end-organ resistance to 1,25-dihydroxy-vitamin d3, due to a point mutation in the receptor.
      - Type I has low renal 1α‎-hydroxy-lase activity,
      - Both are treated with large doses of calcitriol.
    - - Rickets develops in early childhood and is associated with poor growth
      - Plasma PO43− is low, alp is high, and there is phosphaturia.
      - Dominantly inherited—due to a defect in renal phosphate handling (due to mutations in the pex or phex genes which encode an endopeptidase).
      - Treatment is with high doses of oral phosphate, and calcitriol
- - - - pathological fractures
      - osteoarthritis
      - ↑Ca2+
      - nerve compression due to bone overgrowth (eg deafness, root compression)
      - high-output ccf (if >40% of skeleton involved)
      - osteosarcoma (<1% of those affected for >10yrs—suspect if sudden onset or worsening of bone pain)
  - - - Patchy cortical thickening with sclerosis, osteolysis, and deformity (eg osteoporosis circumscripta of the skull)
      - Affinity for axial skeleton, long bones, and skull.
      - Localized enlargement of bone
      - Bone scan may reveal ‘hot spots’.
    - - alp markedly raised
      - Ca2+ and PO43− normal