Efficacy and Safety of Postmenopausal Osteoporosis Treatments: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials

Abstract

Although a range of pharmacological interventions is available, it remains uncertain which treatment for osteoporosis is more effective. This network meta-analysis study aimed to compare different drug efficacy and safety in randomized controlled trials (RCTs) for the treatment of postmenopausal osteoporosis. PubMed, EMBASE, MEDLINE, Clinicaltrial.gov, Cochrane library, Google scholar were searched up to 31 October 2020. Randomized placebo-controlled trials that reported measures of bone mineral density (BMD) percentage change and/or numbers of adverse events of postmenopausal osteoporosis patients were included. Network meta-analysis was conducted using frequentist approach. Ninety-four RCTs comprising 15,776 postmenopausal osteoporosis females were included in the network meta-analysis. Compared with placebo, most interventions showed increase in BMD change. According to surfaces under the cumulative ranking curves (SUCRAs), strontium ranelate, fluoride, and hormone replacement therapy were most effective in increasing total hip, lumbar spine, and distal radius BMD, respectively. Parathyroid hormone (PTH) was most effective in preventing new hip fracture. When taking into account all anatomic sites, bisphosphonate (BP), monoclonal antibody (mAb), and fluoride have a balanced efficacy in increasing BMD at all sites. Considering both the effectiveness of increasing BMD and preventing hip fracture, mAb, BP, and PTH are more favorable among all interventions. The treatment effects of different medications on BMD percentage change are anatomic site-dependent. After weighing anti-osteoporosis treatment efficacy against risk of complications, BP and mAb are the more favorable interventions to increase BMD at all sites and reduce the risks of hip fracture and death.

Keywords: bone mineral density; network meta-analysis; osteoporosis; randomized controlled trial; risks of complications.

Figure 1

Flow diagram of this network meta-analysis.

Figure 2

Networks of treatment comparisons for percentage change in bone mineral density (BMD) from baseline at (A) lumbar spine (LS), (B) total hip (TH), and (C) radius (RU) in postmenopausal women with osteoporosis. Abbreviation: BP, bisphosphonate; HRT, hormone replacement therapy; mAb, monoclonal antibody; PTH, parathyroid hormone; SERM, selective estrogen receptor modulator; SrRan, strontium ranelate; Vit D, vitamin D; Vit K, vitamin K.

Figure 2

Networks of treatment comparisons for percentage change in bone mineral density (BMD) from baseline at (A) lumbar spine (LS), (B) total hip (TH), and (C) radius (RU) in postmenopausal women with osteoporosis. Abbreviation: BP, bisphosphonate; HRT, hormone replacement therapy; mAb, monoclonal antibody; PTH, parathyroid hormone; SERM, selective estrogen receptor modulator; SrRan, strontium ranelate; Vit D, vitamin D; Vit K, vitamin K.

Figure 3

Networks of treatment comparisons for the incidence of (A) cancer, (B) cardiovascular disease (CVD), (C) hip fracture, and (D) death in postmenopausal women with osteoporosis. Abbreviation: BP, bisphosphonate; mAb, monoclonal antibody; PTH, parathyroid hormone; SERM, selective estrogen receptor modulator.

Figure 3

Networks of treatment comparisons for the incidence of (A) cancer, (B) cardiovascular disease (CVD), (C) hip fracture, and (D) death in postmenopausal women with osteoporosis. Abbreviation: BP, bisphosphonate; mAb, monoclonal antibody; PTH, parathyroid hormone; SERM, selective estrogen receptor modulator.

Figure 4

Cumulative rankograms: plots of the surface under the cumulative ranking curves (SUCRAs) for the increase in bone mineral density (BMD) at (A) lumbar spine (LS), (B) total hip (TH), and (C) radius (RU) with various treatments in the postmenopausal osteoporosis networks. Ranking indicates the probability to be the best treatment, the second best, and so on, among the different interventions under evaluation. A larger SUCRA score indicates a more effective intervention. Abbreviation: BP, bisphosphonate; HRT, hormone replacement therapy; mAb, monoclonal antibody; PTH, parathyroid hormone; SERM, selective estrogen receptor modulator; SrRan, strontium ranelate; Vit D, vitamin D; Vit K, vitamin K.

Figure 4

Cumulative rankograms: plots of the surface under the cumulative ranking curves (SUCRAs) for the increase in bone mineral density (BMD) at (A) lumbar spine (LS), (B) total hip (TH), and (C) radius (RU) with various treatments in the postmenopausal osteoporosis networks. Ranking indicates the probability to be the best treatment, the second best, and so on, among the different interventions under evaluation. A larger SUCRA score indicates a more effective intervention. Abbreviation: BP, bisphosphonate; HRT, hormone replacement therapy; mAb, monoclonal antibody; PTH, parathyroid hormone; SERM, selective estrogen receptor modulator; SrRan, strontium ranelate; Vit D, vitamin D; Vit K, vitamin K.

Figure 5

Cumulative rankograms: plots of the surface under the cumulative ranking curves (SUCRAs) for the incidence of (A) cancer, (B) cardiovascular disease (CVD), (C) hip fracture, and (D) death with various treatments in the postmenopausal osteoporosis networks. A larger SUCRA score indicates a higher risk for the event to occur with the intervention. Abbreviation: BP: bisphosphonate; mAb: monoclonal antibody; PTH: parathyroid hormone; SERM: selective estrogen receptor modulator.

Figure 6

Clustered ranking plot of the postmenopausal osteoporosis network based on the surface under the cumulative ranking curve (SUCRA) values for (A) the increase of bone mineral density (BMD) percentage simultaneously at the lumbar spine (LS), total hip (TH), and distal radius (RU). Treatments lying in the upper right corner are more effective and acceptable than the other treatments. Clustered ranking plot based on SUCRA values for (B) the increase of BMD percentage at TH versus incidence of new hip fractures. Each color represents a group of treatments that belong to the same cluster. Interventions lying in the upper left corner were more favorable than the other interventions. Here, the red dots indicate the more effective interventions that increase BMD at TH but also reduce incidence of new hip fracture. Abbreviation: BP, bisphosphonate; HRT, hormone replacement therapy; mAb, monoclonal antibody; PTH, parathyroid hormone; SERM, selective estrogen receptor modulator; SrRan, strontium ranelate; Vit D, vitamin D; Vit K, vitamin K.