Use of combination therapy in the treatment of primary osteoporosis: protocol for a network meta-analysis of randomised trials

INTRODUCTION The existing medications approved for treatment of primary osteoporosis can be divided into antiresorptive drugs and anabolic drugs. According to the mechanisms of action, the combined therapy may produce a synergistic effect on bone mineral density (BMD) compared with monotherapy, and thus improves the efficacy of fracture resistance. This network meta-analysis aims to compare the efficacies of different combined methods for the treatment of primary osteoporosis. METHODS AND ANALYSIS MEDLINE, EMBASE and Cochrane databases will be searched to identify all randomised controlled trials (RCTs) and quasi-RCTs that evaluate the effectiveness of combined therapy versus monotherapy for primary osteoporosis. The primary outcome will be the BMD changes at the lumbar spine and total hip, and the secondary outcome will be the risks of vertebral fracture and non-vertebral fracture. The efficacies of different combined methods will be compared via traditional pairwise meta-analysis, trial sequential analysis and Bayesian network meta-analysis. Risk of bias will be assessed using the Cochrane tool and the quality of evidence will be assessed using the Grading of Recommendations Assessment, Development and Evaluation for network meta-analysis. ETHICS AND DISSEMINATION Ethical approval is not required because this is a protocol for a systematic review without including confidential personal data or data on interventions on patients. Our results will be published in a peer-review journal. TRIAL REGISTRATION NUMBER PROSPERO CRD42016038569.