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)