- •Bone anabolic therapies (BATs) include teriparatide, abaloparatide and romosozumab.
- •All bone anabolic therapies significantly increase bone mineral density at all locations.
- •All bone anabolic therapies reduce the risk of vertebral fractures.
- •No intervention significantly reduces the risk of non-vertebral fractures.
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.
Abbreviations:95%CIs (95% confidence interval), AP (alkaline phosphatase), BAT (bone anabolic therapy), BMD (bone mineral density), BMI (body mass index), CTX (C-terminal telopeptide of type I collagen), DEXA (dual energy X-ray absorptiometry), HRT (hormone replacement therapy), IU (international unit), MD (mean difference), NMA (network meta-analysis), NTX (crosslinked N-telopeptide of type I collagen), PINP (N-terminal propeptide of type I procollagen), PRISMA (Preferred Reporting Items of Systematic Reviews and Meta-analyses), PTH (parathyroid hormone), RCT (randomized controlled trial), RR (risk ratio), SAE (severe adverse event), SC (subcutaneous), SERM (Selective estrogen receptor modulator)
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Published online: August 10, 2019
Accepted: August 6, 2019
Received in revised form: August 5, 2019
Received: June 5, 2019
© 2019 Elsevier B.V. All rights reserved.