The effect of sequential therapy for postmenopausal women with osteoporosis A PRISMA-compliant meta-analysis of randomized controlled trials

Background: Osteoporosis, more likely to occur in postmenopausal women, is a chronic condition that usually requires a long-term treatment strategy, but the use of either antiresorptive or anabolic drugs should be limited to 18 to 24 months. Discontinuing antiosteoporosis drugs may result in rapidly declining bone mineral density (BMD). Therefore, many patients are treated with the sequential use of 2 or more drugs. However, whether switching treatment from anabolic to antiresorptive drugs or the reverse could maintain or further increase BMD; and whether the sequential therapy could outperform the monotherapy under the same treatment duration still remains unclear. Nowadays, no firm conclusions were drawn. Methods: We searched Medline, Embase, and Cochrane Library from January 1, 1974 until February 1, 2016 to identify all randomized controlled trials for evaluating the effectiveness of sequential therapy of antiresorptive and anabolic drugs in postmenopausal osteoporosis women with the BMD changes of lumbar spine, femoral neck, and total hip as the outcomes. We evaluated the methodological quality and abstracted relevant data according to the Cochrane Handbook. Results: Eight trials involving 1509 patients were included. The pooled data showed that after switching treatment, the alternative drugs maintained the BMD and significantly increased the percentage change in BMD at the lumbar spine (MD, 3.59; 95% CI, 2.26-4.93), femoral neck (MD, 1.44; 95% CI, 0.60-2.27), and total hip (MD, 1.24; 95% CI, -0.12 to 2.60), although change in BMD was not significantly increased at the total hip. The sequential therapy significantly increased BMD from baseline at the lumbar spine (SMD, 0.59; 95% CI, 0.26-0.91), femoral neck (SMD, 0.22; 95% CI, 0.06-0.37), and total hip (SMD, 0.28; 95% CI, 0.01-0.56). Conclusions: After switching treatment, sequential therapy further increased BMD. The sequential therapy showed a more significant improvement in BMD compared with any anti-resorptive drug given for the same treatment duration and was as effective as anabolic drugs. Thus, sequential therapy may be recommended as an effective treatment for osteoporotic women. However, more randomized controlled trials are still needed to determine the best sequence and the most appropriate drugs of sequential therapy.