Osteoporosis Pharmacotherapy

Osteoporosis pharmacotherapy reduces fracture risk by slowing bone resorption (antiresorptives) or stimulating bone formation (anabolic agents). It is started on the basis of absolute fracture risk, not bone density alone, and always rests on adequate calcium, vitamin D, protein, weight-bearing activity and treatment of secondary causes.

Mechanism. Bisphosphonates and denosumab suppress osteoclast activity. Raloxifene is a selective oestrogen receptor modulator that reduces resorption. Teriparatide and abaloparatide stimulate osteoblasts when given intermittently. Romosozumab inhibits sclerostin, increasing formation and reducing resorption.

Classification. Antiresorptive: bisphosphonates, denosumab, raloxifene, menopausal hormone therapy, calcitonin (little used). Anabolic: teriparatide, abaloparatide. Dual action: romosozumab. Strontium ranelate has been withdrawn or restricted in most regions.

Differences. Bisphosphonates reduce vertebral, non-vertebral and hip fractures (alendronate, risedronate, zoledronic acid) and are the first choice, being cheap and widely available. Denosumab suits renal impairment and oral intolerance but must not be stopped without follow-on therapy. Anabolic agents give the largest early vertebral fracture reduction. Raloxifene reduces vertebral fractures and breast cancer but not hip fractures, and raises venous thromboembolism risk.

• Who to treat: any hip or vertebral fragility fracture; a bone density T-score of minus 2.5 or lower with risk factors; a high absolute fracture risk by a validated tool; and prolonged glucocorticoid exposure (prednisolone 7.5 mg daily or more for 3 months or longer) in patients over 40 or with fractures.
• Very high risk (recent vertebral fracture, multiple fractures, T-score under minus 3.0): start an anabolic agent first, then an antiresorptive to keep the gain.
• Baseline for all: total calcium intake of 1000 to 1200 mg daily (diet first, supplement the gap) and vitamin D 800 to 1000 IU (20 to 25 micrograms) daily, with correction of vitamin D deficiency before an antiresorptive.
• Duration: oral bisphosphonate 5 years, intravenous 3 years, then reassess; continue to 10 and 6 years in high-risk patients.
• Men: same drugs, with testosterone for hypogonadism.
• Secondary causes to exclude: hyperparathyroidism, hypogonadism, thyrotoxicosis, coeliac disease, myeloma, chronic kidney disease, HIV and tenofovir, glucocorticoids, anticonvulsants and heparin.

Special groups. Pregnancy and breastfeeding: avoid all, apart from calcium and vitamin D. Premenopausal women: treat the cause, with specialist advice. Older adults: falls prevention and hip protection. Kidney impairment: avoid bisphosphonates at eGFR under 35 mL/min; denosumab is an alternative with calcium monitoring. Liver impairment: caution with raloxifene. Regional: dietary calcium is low in many East African diets, vitamin D deficiency is common despite sun (covering clothing, darker skin), and HIV and antiretroviral exposure lower bone density.

Adverse effects. Oesophagitis (oral bisphosphonates), acute phase reaction (intravenous), hypocalcaemia, osteonecrosis of the jaw and atypical femoral fracture (rare), rebound vertebral fractures after stopping denosumab, hot flushes and thromboembolism (raloxifene), and cardiovascular events (romosozumab).

Contraindications. Hypocalcaemia and pregnancy for all; romosozumab after myocardial infarction or stroke within 1 year.

Interactions. Calcium, iron and antacids reduce oral bisphosphonate absorption. Aminoglycosides add hypocalcaemia.

Monitoring. Calcium, creatinine and vitamin D at baseline; bone density at 1 to 2 years then every 2 years; adherence at each visit; dental review and thigh pain screening.

Referral and escalation. New fracture on treatment, very high risk, secondary causes, renal impairment, or a planned drug holiday.