Indications: Treatment of Paget's disease of bone, Treatment of postmenopausal osteoporosis and osteoporosis in men (including corticosteroid-induced osteoporosis).

Cautions: correct disturbances of calcium metabolism (e.g. vitamin D deficiency, hypocalcaemia) before starting; monitor serum electrolytes, calcium, phosphate and magnesium; cardiac disease (avoid fluid overload); consider dental check-up before initiating bisphosphonate (risk of osteonecrosis of the jaw, see Bisphosphonates: Osteonecrosis of the Jaw).

Contra-indications: women of child-bearing potential.

Hepatic impairment: caution in severe hepatic impairment—limited information available.

Renal impairment: avoid if serum creatinine above 400 micromol/litre in tumour-induced hypercalcaemia; in advanced malignancies involving bone, if eGFR 50–60 ml/minute/1.73 m2 reduce dose to 3.5 mg every 3–4 weeks, if eGFR 40–50 ml/minute/1.73 m2 reduce dose to 3.3 mg every 3–4 weeks, if eGFR 30–40 ml/minute/1.73 m2 reduce dose to 3 mg every 3–4 weeks, avoid if eGFR less than 30 ml/minute/1.73 m2 (or if serum creatinine greater than 265 micromol/litre); if renal function deteriorates in patients with bone metastases, withhold dose until serum creatinine returns to within 10% of baseline value; avoid in Paget's disease, treatment of postmenopausal osteoporosis and osteoporosis in men if eGFR less than 35 ml/minute/1.73 m2; see also cautions above.

Pregnancy: avoid—toxicity in animal studies

Breast-feeding: avoid—no information available

Side Effects: hypophosphataemia, anaemia, influenza- like symptoms including bone pain, myalgia, arthralgia, fever and rigors; gastro-intestinal disturbances; atrial fibrillation; headache, dizziness, conjunctivitis, renal impairment (rarely acute renal failure); less commonly anorexia, taste disturbance, dry mouth, stomatitis, chest pain, hypertension, hypotension, dyspnea, cough, paraesthesia, tremor, anxiety, lethargy, sleep disturbance, blurred vision, weight gain, pruritus, rash, sweating, muscle cramps, haematuria, proteinuria, urinary frequency, hypersensitivity reactions (including angioedema), asthenia, peripheral oedema, thrombocytopenia, leucopenia, hypomagnesaemia, hypokalaemia, also injection-site reactions; rarely bradycardia, confusion, hyperkalaemia, hypernatraemia, pancytopenia, osteonecrosis of the jaw, atypical femoral fractures.very rarely uveitis and episcleritis.

Dose: reduction of bone damage in advanced malignancies involving bone, by intravenous infusion, 4 mg over at least 15 minutes every 3–4 weeks; child not recommended.

Note: Calcium 500 mg daily and vitamin D 400 units daily should also be taken, Hypercalcaemia of malignancy, by intravenous infusion, 4 mg as a single dose over at least 15 minutes; child not recommended.