Combination therapy with parathyroid hormone analogs and antiresorptive agents for osteoporosis: a systematic review and meta-analysis of randomized controlled trials

Combination therapy with parathyroid hormone (PTH) analogs and antiresorptive agents may be more effective than monotherapy for the treatment of osteoporosis. This study aimed to estimate the effectiveness and safety of this combination therapy for osteoporosis. MEDLINE, EMBASE, and Cochrane Library were searched from inception to May 1, 2018, including randomized controlled trials (RCTs) with a duration of at least 6months on adults with osteoporosis treated with combination therapy versus monotherapy. Outcomes included fractures, bone mineral density (BMD) changes, and adverse events. A meta-analysis was performed using a random-effect model, to estimate risk ratios (RRs) for fractures, and mean differences (MDs) for BMD changes. A total of 19 RCTs and 2177 patients were included. Compared with monotherapy, combination therapy had an advantage of 36% (RR, 0.64; 95% confidence interval (CI), 0.42-0.98) regarding fracture risk reduction. It also appears to improve lumbar spine BMD by 4.06% (95%CI=2.60-5.53) and total hip BMD by 1.89% (95%CI=1.25-2.53). No RCT reported an increased risk of serious adverse events. Among patients with osteoporosis, combination therapy was superior to monotherapy regarding improvement of the lumbar spine and total hip BMD, without risk of serious adverse events. Combination therapy also had an advantage over monotherapy on fracture risk reduction. However, owing to the limited sample size, additional larger studies are required to confirm this benefit.