A systematic review 1 including 30 studies with a total of 8 981 subjects (with breast cancer, multiple myeloma, prostate cancer and various mixed cancer diagnoses) was abstracted in DARE. A meta-analysis of studies lasting at least 6 months (18 studies, n = 2556 to 3894 in different analyses) found that, compared with placebo, bisphosphonates statistically significantly reduced the risk of vertebral fractures (OR 0.69, 95% CI 0.57 to 0.84, P<0.0001), non-vertebral fractures (OR 0.65, 95% CI 0.54 to 0.79, P<0.0001), combined fractures (OR 0.65, 95% CI 0.55 to 0.78, P<0.0001), radiotherapy (OR 0.67, 95% CI 0.57 to 0.79, P<0.0001) and hypercalcaemia (OR 0.54, 95% CI 0.36 to 0.81, P<0.003). There was no effect on spinal cord compression (0.71, 0.47 to 1.08, P = 0.113) or orthopaedic surgery (0.70, 0.46 to 1.05, P = 0.086), although there was a reduction in orthopaedic surgery in studies lasting more than 1 year (OR 0.59, 95% CI 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.
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