BMJ  2003;327:469 (30 August), doi:10.1136/bmj.327.7413.469

Paper

Systematic review of role of bisphosphonates on skeletal morbidity in metastatic cancer

¹ Department of Palliative Medicine, Royal Marsden Hospital, London SW3 6JJ, ² Department of Palliative Care and Policy, Kings College, London SE5 9RS, ³ Systematic Reviews Training Unit, Institute of Child Health, London WC1N 1EH, ⁴ Department of Medicine, Royal Marsden Hospital, London

Objective To review the evidence for the use of bisphosphonates to reduce skeletal morbidity in cancer patients with bone metastases.

Data sources Electronic databases, scanning reference lists, and consultation with experts and pharmaceutical companies. Foreign language papers were included.

Study selection Included trials were randomised controlled trials of patients with malignant disease and bone metastases who were treated with oral or intravenous bisphosphonate compared with another bisphosphonate, placebo, or standard care. All trials measured at least one outcome of skeletal morbidity.

Results 95 articles were identified; 30 studies fulfilled inclusion criteria. In studies that lasted 6 months, compared with placebo bisphosphonates significantly reduced the odds ratio for fractures (vertebral 0.69, 95% confidence interval 0.57 to 0.84, P < 0.0001; non-vertebral 0.65, 0.54 to 0.79, P < 0.0001; combined 0.65, 0.55 to 0.78, P < 0.0001), radiotherapy (0.67, 0.57 to 0.79, P < 0.0001), and hypercalcaemia (0.54, 0.36 to 0.81, P = 0.003) but not for orthopaedic surgery (0.70, 0.46 to 1.05, P = 0.086) or spinal cord compression (0.71, 0.47 to 1.08, P = 0.113). The reduction in orthopaedic surgery was significant in studies that lasted over a year (0.59, 0.39 to 0.88, P = 0.009). Use of bisphosphonates significantly increased time to first skeletal related event but did not increase survival. Subanalyses showed that most evidence supports use of intravenous aminobisphosphonates.

Conclusions In people with metastatic bone disease bisphosphonates significantly decrease skeletal morbidity, except for spinal cord compression and increased time to first skeletal related event. Treatment should start when bone metastases are diagnosed and continue until it is no longer clinically relevant.

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