Osteoporosis Medicine Selection

Osteoporosis medicine selection is matching a patient with a high fracture risk to the drug most likely to prevent fractures with the fewest harms. Treat after a fragility fracture of the hip or spine, a bone density T-score of minus 2.5 or lower, or a high fracture risk score. Treat after a fracture without delay, because the risk of a second fracture is highest in the first 2 years.

Before any drug. Exclude secondary causes: low vitamin D, hyperparathyroidism, hypogonadism, thyroid excess, myeloma, coeliac disease, kidney disease, HIV (including tenofovir), and long-term steroids. Check calcium, phosphate, alkaline phosphatase, creatinine and 25-hydroxyvitamin D.

Foundation therapy for all. Calcium intake of 1000 to 1200 mg daily from diet and supplements, vitamin D3 (colecalciferol) 800 to 2000 units daily, adequate protein, weight-bearing exercise, stopping smoking, and reducing alcohol. Falls prevention matters as much as the drug.

First line. Oral alendronate or risedronate in postmenopausal women and in men, because they are effective, cheap and widely available.

When oral drugs fail or are unsuitable. Zoledronic acid by yearly infusion for swallowing problems, reflux, poor adherence or intolerance. Denosumab 60 mg subcutaneously every 6 months for a creatinine clearance under 35 mL/min or when bisphosphonates are not tolerated.

Very high risk. Recent vertebral fractures, multiple fractures, a fracture on treatment, or a T-score under minus 3.0 with a fracture. Use an anabolic agent first, then an antiresorptive: - Teriparatide 20 micrograms subcutaneously once daily for up to 24 months. - Romosozumab 210 mg subcutaneously once monthly for 12 months, avoided if there has been a myocardial infarction or stroke in the past year.

Other options. - Raloxifene 60 mg orally daily protects the spine only and raises thrombosis risk, so it is used in younger postmenopausal women at low thrombosis risk. - Menopausal hormone therapy is used for women under 60 years or within 10 years of menopause with menopausal symptoms, and in premature ovarian insufficiency until the age of 50 to 51 years. - Testosterone replacement in men with proven hypogonadism, together with an antiresorptive.

Supply. Zoledronic acid, denosumab and anabolic agents are limited and costly in many East African centres. Confirm supply before starting denosumab, because it cannot be interrupted.

Replete vitamin D first. If 25-hydroxyvitamin D is under 30 nmol/L, give colecalciferol 50,000 units orally once weekly for 6 weeks, then 800 to 2000 units daily. Correct hypocalcaemia before any antiresorptive.

Calcium. If dietary intake is under 700 mg daily, give calcium carbonate or calcium citrate to supply 500 to 600 mg of elemental calcium daily, taken apart from levothyroxine and iron by 4 hours.

Bisphosphonates. Alendronate 70 mg orally once weekly, risedronate 35 mg orally once weekly, or zoledronic acid 5 mg intravenously once yearly. Avoid at creatinine clearance under 35 mL/min for alendronate and zoledronic acid, and under 30 mL/min for risedronate.

Denosumab. 60 mg subcutaneously every 6 months, with calcium and vitamin D. Give doses on time, and when stopping move to a bisphosphonate within 6 months of the last dose, since rapid bone loss and multiple vertebral fractures follow a missed dose. In advanced kidney disease check calcium within 14 days of each dose.

Glucocorticoid-induced osteoporosis. Treat adults on prednisolone 7.5 mg daily or more (or equivalent) for 3 months or longer, with a bisphosphonate and calcium with vitamin D; use teriparatide if the risk is very high.

Men. Alendronate, risedronate, zoledronic acid or denosumab, and teriparatide when risk is very high.

Duration and sequence. Review after 5 years of oral treatment or 3 years of zoledronic acid. Continue to 10 years of oral or 6 years of intravenous treatment if the hip T-score is minus 2.5 or lower, there was a hip or vertebral fracture, or a fracture occurred on treatment. If risk is low, plan a break of 2 to 3 years, with review.

Special groups.

• Kidney impairment: avoid bisphosphonates at creatinine clearance under 35 mL/min; use denosumab with calcium monitoring.
• Liver disease: no routine adjustment; avoid oral bisphosphonates if oesophageal varices are present.
• Pregnancy: avoid all osteoporosis drugs; calcium and vitamin D only.
• Breastfeeding: avoid bisphosphonates, denosumab and teriparatide.
• Premenopausal women: avoid bisphosphonates unless the risk is severe, because the drug stays in bone for years and may reach a future foetus.
• Older adults: add vitamin D and falls prevention; accept frailty when choosing between oral and intravenous drugs.
• Children: specialist care only.

Monitoring. Check calcium, creatinine and vitamin D at baseline. Measure bone density at 2 years and then every 2 to 3 years while treated. A bone turnover marker (CTX) at 3 to 6 months should fall by at least 25%, and shows adherence. Review new fractures, height loss and dental health.

Dental health. Complete dental work before starting treatment where possible, and report any jaw pain, swelling or loose teeth.

Stopping. Stop for pregnancy, severe hypocalcaemia, atypical femoral fracture or osteonecrosis of the jaw.

Referral and escalation. Refer to a bone specialist for a fracture on treatment, T-score under minus 3.5, very high risk, creatinine clearance under 30 mL/min, hypercalcaemia, young adults with osteoporosis, or suspected secondary causes.