A total of 18 RCTs were included in the review; nine were non blinded and nine double-blind. It was not possible to calculate the number of participants in the included studies. The mean quality score was 2.89: two studies scored 1; four studies scored 2; eight studies scored 3; two studies scored 4; and two studies scored 5. The included studies were too small to detect the presence or absence of publication bias.
Compared with placebo, all three bisphosphonates yielded a significant reduction in skeletal-related events for cancer patients with metastatic bone disease: zoledronate (RR 0.70, 95% CI 0.61 to 0.81; four studies, n=1,211); pamidronate (RR 0.81, 95% CI 0.73 to 0.91; five studies, n=2,251); and clodronate (RR 0.87, 95% CI 0.75 to 1.00; four studies, n=681). Heterogeneity was absent for all comparisons except for pamidronate. Compared with placebo, a significant reduction in pathologic fractures was observed for clodronate (RR 0.76, 95% CI 0.64 to 0.90; six studies, n=1,096) and zoledronate (RR 0.60, 95% CI 0.47 to 0.76; three studies, n=1,165), but not for pamidronate; heterogeneity was absent for all comparisons. In the sensitivity analysis the results for all skeletal-related events for zoledronate and pamidronate were sensitive to the study quality and those for clodronate were not.
Radiation to bone or bone surgery:
Compared with placebo, a significant reduction was observed for pamidronate (RR 0.72, 95% CI 0.62 to 0.84; six studies, n=2,127) and zoledronate (RR 0.67, 95% CI 0.46 to 0.97; three studies, n=1,165); heterogeneity was present for these comparisons.
Compared with placebo, a significant reduction was observed for zoledronate (RR 0.27, 95% CI 0.10 to 0.72; two studies, n=743), pamidronate (RR 0.60, 95% CI 0.41 to 0.86; six studies, n=2,127) and for clodronate (RR 0.73, 95% CI 0.56 to 0.97; five studies, n=1,079); heterogeneity was absent for all comparisons.
None of the bisphosphonates significantly improved overall mortality compared with placebo.