Should bisphosphonates be part of the standard therapy of patients with multiple myeloma or bone metastases from other cancers? An evidence-based review

To review objectively the evidence for the use of bisphosphonates for the reduction of skeletal events or the management of pain due to multiple myeloma or bone metastases from other types of cancer. MEDLINE was searched from 1976 onwards using the MeSH terms "exp diphosphonates/," "exp bone neoplasms/," "exp multiple myeloma/," and "bone metastases" as text words. Bibliographies of reports on these topics and major medical and scientific journals were searched. Experts in the field were approached. The question was defined and the evidence stratified in a hierarchical manner according to classification of study design. There were sufficient studies to enable the use of randomized trials only to address the questions. Effectiveness was defined and the evidence reviewed in a systematic manner. Eighteen randomized trials were identified. No meta-analyses are available. There is level I evidence (defined as an appropriately conducted randomized clinical trial with a statistically significant result) for the use of bisphosphonates to reduce both skeletal events and pain in multiple myeloma and in breast cancer patients with metastatic bone disease. There is also level I evidence for their use as part of a pain management program for bone metastases from carcinoma of the breast, lung, and prostate, and for symptomatic myeloma. The bisphosphonates appear to be well tolerated.