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Osteoporosis

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  • 1. Osteoporosis
  • 2. Osteoporosis - Hx
    • Symptoms: pain (bone, toe), proximal muscle weakness (these can happen in osteomalacia, characterised by defective bone mineralisation in adults – due to Vit D deficiency, must exclude malabsorption).
    • Fractures: wrist, hip, humerus and ribs, and vertebral compression fractures (esp. T12) – with minimal stress (risk increases from age 55).
    • Risk factors: menstrual history, age of onset of menopause, symptoms of thyroid excess or thyroid hormone replacement (thyroxine), symptoms or a history of anaemia (coeliac disease).
    • Previous investigation: X-ray
    • Drug history: alcohol, heparin, steroids, thyroxine-overreplacement, anticonvulsants (by affecting Vit D metabolism), and cyclosporin.
    • Life style: a low-fat diet (limits calcium intake), inadequate sun exposure (NH resident), renal disease, phenytoin use (all risk factors for osteomalacia), exercise (preserves bone mass), smoking (decreases bone mass).
    • Complications: falls, fractures (PE/nosocomial infection)
    • Social impact: immobility, pain, fear of falling.
  • 3. Osteoporosis – physical examination
    • Bone tenderness and proximal muscle weakness (osteomalacia), thoracic kyphosis, bowing of the legs (rickets)
    • Thyroid disease/Cushing’s syndrome
    • Weight and general nutritional status
  • 4. Osteoporosis - investigations
    • Blood tests: calcium, AP results
      • FBE, ESR (?myeloproliferative disease)
      • EUC, LFTs (exclude renal, hepatic disease)
      • TSH (rule out thyrotoxicosis)
      • Men: testosterone level
      • if severe osteoporosis ( serum EPG to rule out multiple myeloma )
      • Osteoporosis – normal calcium, normal AP
      • Osteomalacia – increased AP, also check 25-OH vitamin D levels (if risk of osteomalacia)
      • Vitamin D deficiency – low 25-OH vitamin D levels
        • Vitamin D malabsorption
        • Chronic liver disease
        • Lack of sun exposure (NH resident)
      • DDx for elevated AP:
        • Osteomalacia
        • Paget’s disease
        • Metastatic malignancy to bone
  • 5. Osteoporosis - investigations
    • Skeletal x-rays:
      • Spine: loss of trabecular bone in the vertebral body, accentuatoin of the vertebral endplates, more prominent vertebral trabeculae with the loss of horizontal trabeculae. Collapse, anterior wedging and the codfish deformity.
      • Osteomalacia –
        • decrease in bone density, coarsening of trabecular and blurring of the margins.
        • Looser’s zones (pseudo fractures) in the long bone shafts, ribbon-like zones of rarefaction
        • Triangular pelvis and biconcave collapsed vertebrae.
        • If there is secondary hyperparathyroidism present with osteomalacia, then bone cysts, erosion of the distal ends of the clavicles and subperiosteal resorption in the phalanges may be seen.
  • 6. Osteoporosis - investigations
    • Bone densitometry – dual-energy X-ray absorptiometry (DEXA) – T score
      • Lumbar spine
      • Proximal femur
        • Osteopenia – 1-2.5 SD below peak bone mass
        • Osteoporosis - <2.5 SD below peak bone mass
      • What is T score – the number of standard deviations by which the measured bone density falls below the average for a young normal person of the same sex.
  • 7. Osteoporosis - investigations
    • In difficult cases: an iliac crest bone biopsy with double tetracycline labelling can help distinguish osteoporosis from osteomalacia.
    • If secondary causes are suspected – search for the cause
  • 8. Osteoporosis - treatment
    • Goal – prevention, correct secondary causes, prevent complications
      • Life style – stop smoking, avoid excess alcohol consumption, fall prevention (consider hip protector), prescribe regular weight-bearing exercise.
      • Calcium – absorption decreases with age, age >65 (have 1200-1500 mg of calcium daily is advisable)
      • Vitamin D supplementation –
        • Moderate to severe vitamin D deficiency (serum 25-OH D < 25 nmol/L)
          • High dose Vit D of 3000-5000 IU/day for 6-12 weeks
          • Then 1000 IU/day from then on
        • Elderly women in NH who have inadequate intake should receive supplementation of Vit D 800IU/day and calcium 1200 mg/day (reduce non-vertebral fracture risk).
  • 9. Osteoporosis - treatment
    • Bisphosphonates (risedronate and alendronate):
      • Benefits:
        • Increase bone mineral density in postmenopausal women with osteoporosis and
        • Reduce the risk of fracture for postmenopausal women with osteoporosis by 50%.
      • If cannot tolerate oral agents:
        • Infusion once every 3 months or
        • Once a year (zolendronic acid)
        • S/E:
          • Oesophageal ulceration (presents with odynophagia, 1-2 months after starting the treatment)
          • Osteonecrosis of the jaw – more likely with IV formulations with dental infections.
          • Indications:
            • >70 y.o. with a T score of < -3
            • A fracture after minimal trauma
  • 10. Osteoporosis – treatment (PBS criteria for long-term steroid treatment )
    • Treatment as the sole PBS-subsidised anti-resorptive agent for corticosteroid-induced osteoporosis in a patient currently on long-term ( at least 3 months ), high-dose (at least 7.5 mg per day prednisolone or equivalent) corticosteroid therapy with a Bone Mineral Density (BMD) T-score of -1.5 or less. The duration and dose of corticosteroid therapy together with the date, site (femoral neck or lumbar spine) and score of the qualifying BMD measurement must be documented in the patient's medical records when treatment is initiated.
  • 11. Osteoporosis – treatment (PBS criteria for osteoporosis without fracture)
    • Treatment as the sole PBS-subsidised anti-resorptive agent for osteoporosis in a patient aged 70 years of age or older with a Bone Mineral Density (BMD) T-score of -3.0 or less. The date, site (femoral neck or lumbar spine) and score of the qualifying BMD measurement must be documented in the patient's medical records when treatment is initiated.
  • 12. Osteoporosis – treatment (PBS criteria - osteoporosis in patients with fracture due to minimal trauma )
    • The fracture must have been demonstrated radiologically and the year of plain x-ray or CT-scan or MRI scan must be documented in the patient's medical records when treatment is initiated. A vertebral fracture is defined as a 20% or greater reduction in height of the anterior or mid portion of a vertebral body relative to the posterior height of that body, or, a 20% or greater reduction in any of these heights compared to the vertebral body above or below the affected vertebral body.
    • Anti-resorptive agents in established osteoporosis include alendronate sodium, risedronate sodium, denosumab, disodium etidronate, raloxifene hydrochloride, strontium ranelate and zoledronic acid.
  • 13. Osteoporosis – treatment (alternative)
    • Strontium ranelate – for people who cannot tolerate bisphosphonate.
    • Effective in vertebral and rib fractures but the effect is not established in hip fracture yet.
    • It should be taken at bed time at least 2 hours after eating.
  • 14. Osteoporosis – treatment
    • Oestrogen – HRT
      • Prevent loss of cortical and trabecular bone in postmenopausal women.
      • Most effect if started earlier in menopause as bone loss is most rapid then.
      • S/E of Oestrogen
        • Increases the risk of endometrial cancer, so combination with progesterone is important unless pt had hysterectomy
        • Increases breast cancer
        • Increases DVT/PE risks
        • Increases CVS risks (hence the use in post-menopausal women has declined)
  • 15. Osteoporosis – treatment
    • Selective oestrogen receptor modulators:
      • Raloxifene (closely related to tamoxifen)
        • Reduces the risk of spine fractures
        • Increases the risk of DVT
        • Lowers the risk of breast cancer
        • Not associated with an increase in endometrial cancer.
      • Tamoxifen (a mixed oestrogen receptor antagonist and agonist that prevents bone loss)
        • Increases the risk of endometrial cancer
  • 16. Osteoporosis – treatment
    • Parathyroid hormone peptide – very effective for osteoporosis but very expensive.
    • Calcitonin (s/c or intranasal):
      • Inconsistent results
      • Any effect is smaller than with other therapies
      • S/E: nausea, flushing, and inflammation.
  • 17. Osteoporosis – treatment
    • Men with osteoporosis:
      • Check testosterone level: if low then androgen replacement (unless history of prostatic carcinoma)
      • If secondary hypogonadism, human chorionic gonadotrophine or pulsatile gonadotrophin-releasing hormone may be worthwhile.
      • Bisphosphonates and teriparatide (PTH) are efficacious in men
      • The role of raloxifene is not clear.
  • 18. Osteoporosis – treatment
    • Steroid-induced osteoporosis:
      • Measures to prevent bone loss are important from the time steroids are begun, particularly in postmenopausal women or when high doses are needed.
      • Co-administration of bisphosphonates is of value here.
      • Calcium and 25-OH vitamin D in combination have also been shown to be effective.
      • These drugs have been shown to reduce fracture risk for patients on steroids.
  • 19. Osteoporosis – treatment (surgical)
    • Assessment of anaesthetic risk
    • Pain management
    • Prevent prolonged bed rest if possible.
    • Injection of bone cement into the vertebral body (vertebroplasty) is a new treatment that may relieve pain and possibly has other benefits.