Importance of Time Point-Specific Indirect Treatment Comparisons of Osteoporosis Treatments: A Systematic Literature Review and Network Meta-Analyses.

The efficacy comparison of osteoporosis treatments can be hindered by the absence of head-to-head trials; instead, network meta-analyses (NMAs) have been used to determine comparative effectiveness. This study was the first to investigate the impact of time point-specific NMAs of osteoporosis treatments on variability in treatments' onset of action caused by their different mechanisms of actions and trial designs. A systematic literature review was conducted to identify randomized controlled trials (RCTs) of treatments for postmenopausal women with osteoporosis, including romosozumab (ROMO), teriparatide (TPTD), abaloparatide (ABL), alendronate (ALN), risedronate (RIS), ibandronate (IB), zoledronic acid/zoledronate (ZOL), denosumab (DEN), and raloxifene (RLX), on at least 1 fracture or bone mineral density (BMD) outcome. Of 100 RCTs identified in 5 databases, 27 RCTs were included for NMAs of new vertebral, nonvertebral, and hip fracture outcomes at 12, 24, and 36 months, and 47 RCTs were included for NMAs of BMD outcomes at lumbar spine, total hip, and femoral neck to compare the relative efficacy of osteoporosis treatments. Quality of included studies was assessed using the Cochrane Risk of Bias tool. For vertebral fractures, TPTD (83.63%), ABL (69.11%), and ROMO/ALN (78.70%) had the highest probability to be the most effective treatment at 12, 24, and 36 months, respectively. ROMO/ALN had the highest probability (54.4%, 64.69%, and 90.29%, respectively) to be the most effective treatment for nonvertebral fractures at 12, 24, and 36 months. For hip fractures, ROMO/ALN (46.31%), ABL (61.1%), and DEN (55.21%) had the highest probability to be the most effective treatment at 12, 24, and 36 months, respectively. ROMO had the highest probability (76.06%, 44.19%, and 51.78%, respectively) to be the most effective treatment for BMD outcomes at lumbar spine, total hip, and femoral neck. The importance of indirectly comparing available osteoporosis treatments using time point-specific NMAs was confirmed because indirect comparison results differed substantially across time points.

Willems D ，Javaid MK ，Pinedo-Villanueva R ，Libanati C ，Yehoshua A ，Charokopou M ... -  《-》

Clinical effectiveness of denosumab, raloxifene, romosozumab, and teriparatide for the prevention of osteoporotic fragility fractures: A systematic review and network meta-analysis.

To determine the clinical effectiveness of denosumab (DEN), raloxifene (RLX), romosozumab (ROMO) and teriparatide (TPTD), within their licensed (or anticipated licensed) indications, for the treatment of osteoporosis. A systematic review was conducted. Nine electronic databases and trial registries were searched up to the end of July 2018. Studies were eligible for inclusion if they were randomised controlled trials (RCT) in a population at risk of osteoporotic fracture, comparing these four non-bisphosphonates DEN, RLX, ROMO, or TPTD with each other, a non-active treatment, or the bisphosphonates alendronate (ALN), risedronate (RIS), ibandronate (IBN) and zoledronic acid (ZOL). Quality of included studies was assessed using the Cochrane Risk of Bias tool. Network meta-analyses (NMA) were used to determine the relative effectiveness of treatments. The systematic review identified 7898 citations. Forty-six RCTs of non-bisphosphonates met the inclusion criteria for the review and provided data for analyses. Additionally 49 RCTs of bisphosphonates were used in the NMAs. Forty-six RCTs were included in the NMA of vertebral fracture data, 23 RCTs for hip fractures and 73 RCTs in the NMA of femoral neck bone mineral density (FN BMD). For vertebral fractures, all four non-bisphosphonates showed statistically significant benefit relative to placebo: TPTD HR 0.23 (95% credible internal (CrI) 0.16, 0.32); ROMO followed by ALN 0.25 (95% CrI 0.15, 0.43); DEN HR 0.30 (95% CrI 0.21, 0.43); RLX HR 0.61 (95% CrI 0.44, 0.80). The four non-bisphosphonates interventions studied also showed statistically significant benefit relative to placebo for FN BMD, and for hip fractures TPTD, ROMO followed by ALN, and DEN showed statistically significant benefit relative to placebo. The four non-bisphosphonate interventions studied were all statistically significantly clinically effective for reducing vertebral fractures when compared to placebo, and were beneficial for change in FN BMD compared to placebo. All reduced hip fractures, and this was statistically significant for TPTD, ROMO followed by ALN, and DEN.

Simpson EL ，Martyn-St James M ，Hamilton J ，Wong R ，Gittoes N ，Selby P ，Davis S ... -  《-》

Comparative efficacy of bone anabolic therapies in women with postmenopausal osteoporosis: A systematic review and network meta-analysis of randomized controlled trials.

To systematically evaluate the effects of bone anabolic therapies (BATs) - specifically, drug therapy with teriparatide, abaloparatide or romosozumab - on fractures, bone mineral density (BMD), and bone metabolites in postmenopausal osteoporosis. Six computerized engines were searched through to November 2018. We selected randomized controlled trials (RCTs) evaluating the effect of BATs on postmenopausal osteoporosis and with at least 6 months of follow-up. Controls were placebo, no treatment, or bisphosphonates. Primary outcomes were vertebral and non-vertebral fractures. Secondary outcomes were: BMD determined by dual energy X-ray absorptiometry at total hip, lumbar spine, and femoral neck; N-terminal propeptide of type I procollagen (PINP); C-terminal telopeptide of type I collagen (CTX); and severe adverse events (SAE). We followed the PRISMA guidelines for reporting, and used version 2 of the Cochrane risk-of-bias tool. Frequentist network meta-analyses were performed per outcome. Effects for dichotomous and continuous outcomes were expressed as relative risks and mean differences and their 95% confidence intervals. We used p-scores to rank best treatments per outcome. Sixteen RCTs (n = 18,940) were evaluated. Mean ages ranged between 61 and 74 years, and follow-up times between 6 and 30 months. Four RCTs (n = 971) excluded patients with previous fractures. In contrast to placebo/no treatment, all BATs significantly reduced the risk of vertebral fractures, but no intervention significantly reduced the risk of non-vertebral fractures; abaloparatide ranked better than other interventions for both fracture types (p-scores: 0.95, and 0.89, respectively). All BATs significantly increased BMD at all locations in comparison with placebo/no treatment; romosozumab consistently ranked better than other interventions at all BMD locations (p-scores >0.86). Teriparatide ranked better than other interventions for increasing PINP. No differences in SAE were observed among treatments. Abaloparatide, romosozumab, and teriparatide are the best treatments, respectively, to reduce vertebral/non-vertebral fractures, increase BMD, and increase bone formation.

Hernandez AV ，Pérez-López FR ，Piscoya A ，Pasupuleti V ，Roman YM ，Thota P ，Herrera A ... -  《-》

CLINICAL EVALUATION OF COST EFFICACY OF DRUGS FOR TREATMENT OF OSTEOPOROSIS: A META-ANALYSIS.

Albert SG ，Reddy S 《Endocrine Practice》

Summary of AHRQ's comparative effectiveness review of treatment to prevent fractures in men and women with low bone density or osteoporosis: update of the 2007 report.

Levis S ，Theodore G 《-》