Fracture risk reduction and safety by osteoporosis treatment compared with placebo or active comparator in postmenopausal women: systematic review, network meta-analysis, and meta-regression analysis of randomised clinical trials.

To review the comparative effectiveness of osteoporosis treatments, including the bone anabolic agents, abaloparatide and romosozumab, on reducing the risk of fractures in postmenopausal women, and to characterise the effect of antiosteoporosis drug treatments on the risk of fractures according to baseline risk factors. Systematic review, network meta-analysis, and meta-regression analysis of randomised clinical trials. Medline, Embase, and Cochrane Library to identify randomised controlled trials published between 1 January 1996 and 24 November 2021 that examined the effect of bisphosphonates, denosumab, selective oestrogen receptor modulators, parathyroid hormone receptor agonists, and romosozumab compared with placebo or active comparator. Randomised controlled trials that included non-Asian postmenopausal women with no restriction on age, when interventions looked at bone quality in a broad perspective. The primary outcome was clinical fractures. Secondary outcomes were vertebral, non-vertebral, hip, and major osteoporotic fractures, all cause mortality, adverse events, and serious cardiovascular adverse events. The results were based on 69 trials (>80 000 patients). For clinical fractures, synthesis of the results showed a protective effect of bisphosphonates, parathyroid hormone receptor agonists, and romosozumab compared with placebo. Compared with parathyroid hormone receptor agonists, bisphosphonates were less effective in reducing clinical fractures (odds ratio 1.49, 95% confidence interval 1.12 to 2.00). Compared with parathyroid hormone receptor agonists and romosozumab, denosumab was less effective in reducing clinical fractures (odds ratio 1.85, 1.18 to 2.92 for denosumab v parathyroid hormone receptor agonists and 1.56, 1.02 to 2.39 for denosumab v romosozumab). An effect of all treatments on vertebral fractures compared with placebo was found. In the active treatment comparisons, denosumab, parathyroid hormone receptor agonists, and romosozumab were more effective than oral bisphosphonates in preventing vertebral fractures. The effect of all treatments was unaffected by baseline risk indicators, except for antiresorptive treatments that showed a greater reduction of clinical fractures compared with placebo with increasing mean age (number of studies=17; β=0.98, 95% confidence interval 0.96 to 0.99). No harm outcomes were seen. The certainty in the effect estimates was moderate to low for all individual outcomes, mainly because of limitations in reporting, nominally indicating a serious risk of bias and imprecision. The evidence indicated a benefit of a range of treatments for osteoporosis in postmenopausal women for clinical and vertebral fractures. Bone anabolic treatments were more effective than bisphosphonates in the prevention of clinical and vertebral fractures, irrespective of baseline risk indicators. Hence this analysis provided no clinical evidence for restricting the use of anabolic treatment to patients with a very high risk of fractures. PROSPERO CRD42019128391.

Händel MN ，Cardoso I ，von Bülow C ，Rohde JF ，Ussing A ，Nielsen SM ，Christensen R ，Body JJ ，Brandi ML ，Diez-Perez A ，Hadji P ，Javaid MK ，Lems WF ，Nogues X ，Roux C ，Minisola S ，Kurth A ，Thomas T ，Prieto-Alhambra D ，Ferrari SL ，Langdahl B ，Abrahamsen B ... -  《BMJ-British Medical Journal》

Denosumab, raloxifene, romosozumab and teriparatide to prevent osteoporotic fragility fractures: a systematic review and economic evaluation.

Davis S ，Simpson E ，Hamilton J ，James MM ，Rawdin A ，Wong R ，Goka E ，Gittoes N ，Selby P ... -  《-》

Effectiveness and Safety of Treatments to Prevent Fractures in People With Low Bone Mass or Primary Osteoporosis: A Living Systematic Review and Network Meta-analysis for the American College of Physicians.

Ayers C ，Kansagara D ，Lazur B ，Fu R ，Kwon A ，Harrod C ... -  《-》

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 ... -  《-》

Efficacy of Pharmacological Therapies for the Prevention of Fractures in Postmenopausal Women: A Network Meta-Analysis.

Osteoporosis and osteopenia are associated with increased fracture incidence in postmenopausal women. We aimed to determine the comparative effectiveness of various available pharmacological therapies. We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, ISI Web of Science, and Scopus for randomized controlled trials that enrolled postmenopausal women with primary osteoporosis and evaluated the risk of hip, vertebral, or nonvertebral fractures. A network meta-analysis was conducted using the multivariate random effects method. We included 107 trials (193,987 postmenopausal women; mean age, 66 years; 55% white; median follow-up, 28 months). A significant reduction in hip fractures was observed with romosozumab, alendronate, zoledronate, risedronate, denosumab, estrogen with progesterone, and calcium in combination with vitamin D. A significant reduction in nonvertebral fractures was observed with abaloparatide, romosozumab, denosumab, teriparatide, alendronate, risedronate, zoledronate, lasofoxifene, tibolone, estrogen with progesterone, and vitamin D. A significant reduction in vertebral fractures was observed with abaloparatide, teriparatide, parathyroid hormone 1-84, romosozumab, strontium ranelate, denosumab, zoledronate, risedronate, alendronate, ibandronate, raloxifene, bazedoxifene, lasofoxifene, estrogen with progesterone, tibolone, and calcitonin. Teriparatide, abaloparatide, denosumab, and romosozumab were associated with the highest relative risk reductions, whereas ibandronate and selective estrogen receptor modulators had lower efficacy. The evidence for the treatment of fractures with vitamin D and calcium remains limited despite numerous large trials. This network meta-analysis provides comparative effective estimates for the various available treatments to reduce the risk of fragility fractures in postmenopausal women.

Barrionuevo P ，Kapoor E ，Asi N ，Alahdab F ，Mohammed K ，Benkhadra K ，Almasri J ，Farah W ，Sarigianni M ，Muthusamy K ，Al Nofal A ，Haydour Q ，Wang Z ，Murad MH ... -  《-》