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13.04.09 Osteoporosis

Indications for referral
  • Primary prevention
    • Untreated early menopause (<45)
    • Low BMI (<19, anorexia)
    • Untreated hypogonadism in men
    • Aromatase inhibitor treatment
    • Vitamin D deficiency/osteomalacia
    • Primary hyperparathyroidism/Cushing's syndrome
    • Thyrotoxicosis
    • Growth hormone treatment
    • High alcohol intake
    • Liver disease (e.g. PBC)
    • Malabsorption (e.g. celiac)
    • Oral steroids (daily for >3 months)
    • Inflammatory arthropathies
    • Kidney dialysis
    • Transplant assessment
    • Prolonged immobility (>6 months bed ridden)
    • Family history (1st degree relative with osteoporosis)
  • Secondary prevention
    • Follow up scan (usually no sooner than 2-5 years)
    • Height loss/kyphosis (>3 cm)
    • Vertebral fracture
    • Low trauma fracture (e.g. fall from standing position, excluding fingers and toes)
    • Radiological evidence of osteopenia


Parathyroid hormone effects

  • Bone
    • Indirectly stimulates osteoclasts
      • PTH stimulates osteoblasts to increase their expression of RANKL and inhibits their expression of osteoprotegerin (OPG)
        • OPG binds to RANKL and blocks it from interacting with RANK, a receptor for RANKL
      • The binding of RANKL to RANK (facilitated by the decreased amount of OPG) stimulates these osteoclast precursors to fuse, forming new osteoclasts
  • Kidney
    • Enhances active reabsorption of calcium and magnesium from distal tubules and the thick ascending limb
    • Decreases the reabsorption of phosphate, with a net loss in plasma phosphate concentration
      • When the calcium:phosphate ratio increases, more calcium is free in the circulation
  • Intestine
    • Enhances the absorption of calcium in the intestine by increasing the production of activated vitamin D by up-regulating 25-hydroxyvitamin D3 1-alpha-hydroxylase in the kidney
    • 1,25-dihydroxy vitamin D increases the absorption of calcium (as Ca2+ ions) by the intestine via calbindin


FRAX

  • Gives the 10 year probability of a fracture
    • Hip fracture
    • Major osteoporotic fracture (clinical spine, forearm, hip or shoulder fracture)
  • Factors:
    • Current age
    • Gender
    • Prior osteoporotic fracture
      • Morphometric vertebral fracture, prior clinical vertebral fracture or a hip fracture is an especially strong risk factor
    • Femoral neck BMD
    • Low body mass index
    • Oral glucocorticoids for more than 3 months
      • At a dose of prednisolone of 5mg daily or more (or equivalent doses of other glucocorticoids)
    • Current smoking
    • Parental history of hip fracture
    • Alcohol intake (3 or more units a day)
    • Rheumatoid arthritis
    • Secondary osteoporosis
      • e.g. - type I diabetes, untreated long-standing hyperthyroidism, hypogonadism or premature menopause (<45 years), chronic malnutrition, or malabsorption etc.



Denosumab
  • Fully human monoclonal antibody
  • Indications:
    • Osteoporosis, treatment-induced bone loss, bone metastases, rheumatoid arthritis, multiple myeloma, giant cell tumor of bone
  • Designed to inhibit RANKL
  • Contraindicated in patients with hypocalcemia
    • Sufficient calcium and vitamin D levels must be reached before starting on denosumab therapy


Raloxifene

  • Oral selective estrogen receptor modulator (SERM)
  • Has estrogenic actions on bone and anti-estrogenic actions on the uterus and breast
  • Used in the prevention of osteoporosis in postmenopausal women


Calcium ranges

  • Total calcium
    • 2.2-2.6 mmol/L
  • Ionised calcium
    • 1.1-1.4 mmol/L 
    • Biologic effect of calcium is determined by the amount of ionized calcium, rather than the total calcium
    • Ionized calcium does not vary with the albumin level
      • Useful to measure the ionized calcium level when the serum albumin is not within normal ranges, or when a calcium disorder is suspected despite a normal total calcium level
  • Corrected calcium
    • A fall in albumin DECREASES the measured total calcium level
    • Each 1 g/dL decrease of albumin will decrease 0.8 mg/dL in measured serum Ca and thus 0.8 must be added to the measured Calcium to get a corrected Calcium value


Notes

  • Zoledronate is given yearly (5 mg infusion)
  • Flu-like symptoms from bisphosphonates
    • Activate gamma/delta T cells
  • DEXA scan doesn't measure structure, only density
    • Steroids preferentially attack certain trabeculae, potentially weakening bone without reducing density
  • Z score is used for:
    • Very young patients (not yet at peak bone density)
    • Very old patients (to check if their low T score is "normal" or not)
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