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Am Fam Physician. 2004;69(5):1277-1281

Bone metastasis causes significant complications in cancer patients, such as pathologic fractures, nerve root compression, hypercalcemia, pain, and bone marrow infiltration. Bisphosphonates reduce bone resorption and may directly disrupt the metabolism and adhesive abilities of tumor cells. Ross and colleagues studied the effect of bisphosphonate therapy on bone metastasis.

They reviewed randomized controlled trials of bisphosphonate therapy in malignant disease, excluding hematologic conditions but including multiple myeloma. Eligible studies were identified from electronic databases, references of articles, and information from experts and pharmaceutical companies. All studies were assessed for quality of allocation concealment and blinding.

Of the 30 studies identified, 18 met eligibility and quality criteria for the review. Treatment with bisphosphonates significantly reduced the occurrence of vertebral fractures, nonvertebral fractures, and all fractures (odds ratios, 0.69, 0.65, and 0.65, respectively) in studies of 2,587 to 3,376 patients. Bisphosphonate therapy also significantly reduced the occurrence of hypercalcemia (odds ratio, 0.54) and use of radiotherapy (odds ratio, 0.67) in studies involving 3,140 and 3,894 patients, respectively. The use of orthopedic surgery and occurrence of spinal cord compression were not significantly changed by bisphosphonate therapy. Overall, the risk of a skeletal event was 65 percent lower in patients taking bisphosphonates. In eight studies, the time to first significant skeletal event was significantly increased in patients taking bisphosphonates. In all studies, bisphosphonates were well tolerated, but no study reported any improvement in overall survival in patients taking this therapy.

The authors conclude that bisphosphonates significantly reduce morbidity from skeletal metastasis in patients with cancer but do not improve survival. In their analysis, therapy would have to be given for at least six months before the benefit is apparent. Further research is needed to clarify differences between bisphosphonate drugs and determine optimal treatment regimens.

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