Efficacy and Safety of First- and Second-Line Drugs to Prevent Glucocorticoid-Induced Fractures

Context: The evidence about benefits and harms of drugs for glucocorticoid (GC)-induced osteoporosis (GIOP) is limited, and the comparative efficacy and safety of first-line and second-line agents to prevent GC-induced (GI) fractures remains unclear. Objective: To assess the comparative clinical efficacy, safety, and tolerability of first-line and second-line agents in preventing GI fractures. Data Sources: We searched 3 different databases through March 5, 2019. Study Selection: We included randomized controlled trials enrolling patients receiving long-term GCs and compared a first-line and second-line agent with one another and with placebo. Data Extraction: Two reviewers independently extracted study and participant characteristics and outcome data. Data Synthesis: We performed multivariate random-effects network meta-analyses including base, 3 subgroups, and 12 sensitivity analyses. We included 22 papers from 19 unique trials involving 4328 patients receiving GCs. Teriparatide (risk ratio [RR] 0.11, 95% confidence interval [CI] 0.03-0.47), denosumab (RR 0.21, 95% CI 0.09-0.49), and risedronate (RR 0.33, 95% CI 0.19-0.58) reduced the risk of GI vertebral fractures, and the former 2 were the most efficacious according to violin plots including the surface under the cumulative ranking curve values calculated by base and sensitivity analyses. Oral alendronate (RR 0.33, 95% CI 0.12-0.93) reduced this risk in patients receiving GCs with at least 7.5 mg/day, while intravenous ibandronate (RR 0.25, 95% CI 0.06-0.99) was efficacious for the primary prevention of GIOP. Six drugs were similar in terms of the 5 other outcomes. Conclusions: In terms of clinical efficacy and safety, second-line teriparatide and denosumab pose a challenge to first-line oral bisphosphonates for prevention of GI fractures.