StephenJ. Gallacher

COMPARISON OF THREE INTRAVENOUS BISPHOSPHONATES IN CANCER-ASSOCIATED HYPERCALCAEMIA

Three intravenous bisphosphonates were compared in the treatment of cancer-associated hypercalcaemia. 48 patients were randomly allocated to one of three treatment groups (each with 16 subjects)--30 mg pamidronate or 600 mg clodronate, both as single intravenous infusions; or etidronate as three infusions of 7.5 mg/kg per day for three consecutive days. Patients were rehydrated with normal saline before bisphosphonate treatment. All three bisphosphonates lowered serum calcium by inhibiting bone resorption; pamidronate was the most potent in this respect. By comparison with the other groups, more patients in the pamidronate group became normocalcaemic, and the effect on serum calcium was apparent sooner and lasted longer.

Mineralisation defects with pamidronate therapy for Paget's disease

Bone biopsy samples were taken from 20 patients with Pagets disease before and after intravenous pamidronate therapy. In 10 patients given 180 or 360 mg during 6 or 9 weeks, bone turnover decreased as measured biochemically and histologically, but osteomalacia developed in 1 patient and mineralisation defects in 3. 10 other patients received 45 mg every 3 months for 1 year. Bone turnover decreased biochemically but not histologically, and osteoid thickness increased, suggesting impaired mineralisation. Despite overall efficacy, pamidronate has a narrow therapeutic range between resorption inhibition and mineralisation defects. Short courses given to achieve biochemical remission should be administered with caution.