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)