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

Abstract Objective To review the evidence for the use ofbisphosphonates to reduce skeletal morbidity incancer patients with bone metastases. Data sources Electronic databases, scanning referencelists, and consultation with experts andpharmaceutical companies. Foreign language paperswere included. Study selection Included trials were randomisedcontrolled trials of patients with malignant diseaseand bone metastases who were treated with oral orintravenous bisphosphonate compared with anotherbisphosphonate, placebo, or standard care. All trialsmeasured at least one outcome of skeletal morbidity. Results 95 articles were identified; 30 studies fulfilledinclusion criteria. In studies that lasted ≥6 months,compared with placebo bisphosphonates significantlyreduced 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; combined0.65, 0.55 to 0.78, P<0.0001), radiotherapy (0.67, 0.57to 0.79, P<0.0001), and hypercalcaemia (0.54, 0.36 to0.81, 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 inorthopaedic surgery was significant in studies thatlasted over a year (0.59, 0.39 to 0.88, P=0.009). Use ofbisphosphonates significantly increased time to firstskeletal related event but did not increase survival.Subanalyses showed that most evidence supports useof intravenous aminobisphosphonates.