Bisphosphonate Prescribing

Bisphosphonates bind to bone and block osteoclasts, so bone loss slows and fracture rates fall by about 40 to 70% for spine fractures and about 20 to 50% for hip fractures. They are used in osteoporosis, glucocorticoid-induced bone loss, Paget disease of bone, hypercalcaemia of malignancy and bone metastases. Effects last for years after stopping because the drug stays in bone.

Oral absorption. Under 1% is absorbed, and any food, drink or calcium cuts absorption further. Correct dosing technique is part of the prescription.

Before starting. Check calcium, 25-hydroxyvitamin D and creatinine clearance, and correct low calcium and vitamin D first. Complete dental work where possible.

Alendronate. First choice in most adults, with the longest evidence.

Risedronate. An alternative with less upper gastrointestinal irritation.

Ibandronate. Monthly oral or three-monthly intravenous use, for spine fractures mainly.

Zoledronic acid. For intolerance of oral drugs, poor adherence, Paget disease, or high risk of fracture.

Pamidronate. Intravenous use in hypercalcaemia, bone metastases and some paediatric conditions.

Contraindications. Oesophageal stricture or achalasia, inability to sit upright for 30 minutes, hypocalcaemia, creatinine clearance under 35 mL/min (alendronate and zoledronic acid) or under 30 mL/min (risedronate and ibandronate), pregnancy, and previous osteonecrosis of the jaw.

Alendronate. 70 mg orally once weekly (or 10 mg once daily). Maximum 70 mg weekly. For Paget disease, 40 mg orally once daily for 6 months.

Risedronate. 35 mg orally once weekly, or 5 mg once daily. For Paget disease, 30 mg once daily for 2 months.

Ibandronate. 150 mg orally once monthly, or 3 mg intravenously over 15 to 30 seconds every 3 months.

Zoledronic acid. 5 mg intravenously in 100 mL over at least 15 minutes, once yearly for osteoporosis, and once only for Paget disease. For hypercalcaemia of malignancy, give 4 mg intravenously over 15 minutes, which may be repeated after 7 days.

Pamidronate. For hypercalcaemia of malignancy, 60 to 90 mg intravenously over 2 to 4 hours, repeated after 7 days if needed.

How to take oral tablets. - Take on waking, with a full glass (200 mL) of plain water. - Stay upright for at least 30 minutes (60 minutes for ibandronate) and do not lie down. - Take no food, drink, calcium, iron or other tablets for at least 30 minutes (60 minutes for ibandronate). - Do not chew or suck tablets.

Infusion preparation. Give 500 mL of fluid before the infusion and confirm creatinine clearance and calcium within 7 days. Confirm vitamin D is replete. Give paracetamol 1 g orally up to 4 times daily for 3 days after the first infusion to reduce the acute phase reaction (fever, myalgia and flu-like symptoms in 1 to 3 days). Use 500 mg to 1 g, with a maximum of 3 g daily, if the patient weighs under 50 kg or has liver disease.

Adverse effects and actions. - Oesophagitis: stop the tablet and use an infusion or another drug. - Hypocalcaemia: give calcium and vitamin D; delay further doses. - Osteonecrosis of the jaw: rare at osteoporosis doses (about 1 in 10,000 to 1 in 100,000), more common in cancer doses; report jaw pain, swelling or loose teeth. - Atypical femoral fracture: rare, with prodromal thigh or groin pain; image both femurs, stop the drug and refer. - Acute kidney injury: avoid in dehydration and with nephrotoxic drugs; check creatinine before each infusion.

Interactions. Calcium, iron, magnesium and antacids block absorption. Non-steroidal anti-inflammatory drugs add to stomach irritation. Aminoglycosides and loop diuretics add to hypocalcaemia risk.

Duration. Review after 5 years of oral treatment or 3 years of zoledronic acid. Continue to 10 years or 6 years if risk stays high, or take a break of 2 to 3 years if risk is low.

Special groups. - Kidney impairment: avoid at creatinine clearance under 35 mL/min; use denosumab with calcium monitoring. - Liver disease: no adjustment; avoid oral bisphosphonates with varices. - Pregnancy: avoid; the drug crosses the placenta and stays in bone. - Breastfeeding: avoid. - Premenopausal women: avoid unless risk is severe. - Older adults: no dose change; use an infusion if unable to sit upright. - Children: specialist use only, with weight-based doses.

Monitoring. Calcium and creatinine before each infusion and after 2 weeks if at risk. Bone density at 2 years and then every 2 to 3 years. Bone turnover marker at 3 to 6 months if adherence is in doubt. Ask about thigh pain and jaw symptoms at each review.

Stopping. Stop for pregnancy, severe hypocalcaemia, oesophageal ulcer, atypical femoral fracture, osteonecrosis of the jaw, or creatinine clearance under 30 mL/min.

After stopping. Bone protection persists for 1 to 3 years. Repeat fracture risk assessment at 2 to 3 years, and restart if a fracture occurs or bone density falls.

Referral and escalation. Refer for fracture on treatment, thigh pain, jaw pain or exposed bone, calcium under 2.0 mmol/L, falling creatinine clearance, or need for treatment in a premenopausal woman or a child.