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

Maturitas. 2019 Nov:129:12-22. doi: 10.1016/j.maturitas.2019.08.003. Epub 2019 Aug 10.

Abstract

Objective: 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.

Methods: 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.

Results: 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.

Conclusions: Abaloparatide, romosozumab, and teriparatide are the best treatments, respectively, to reduce vertebral/non-vertebral fractures, increase BMD, and increase bone formation.

Keywords: Abaloparatide; Anabolic therapy; Bone; Fractures; Postmenopausal osteoporosis; Romosozumab; Teriparatide.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Monoclonal / therapeutic use*
  • Bone Density / drug effects
  • Bone Density Conservation Agents / pharmacology
  • Bone Density Conservation Agents / therapeutic use*
  • Collagen Type I / blood
  • Female
  • Humans
  • Network Meta-Analysis
  • Osteoporosis, Postmenopausal / blood
  • Osteoporosis, Postmenopausal / drug therapy*
  • Osteoporotic Fractures / prevention & control*
  • Parathyroid Hormone-Related Protein / pharmacology
  • Parathyroid Hormone-Related Protein / therapeutic use*
  • Peptide Fragments / blood
  • Peptides / blood
  • Procollagen / blood
  • Randomized Controlled Trials as Topic
  • Teriparatide / pharmacology
  • Teriparatide / therapeutic use*

Substances

  • Antibodies, Monoclonal
  • Bone Density Conservation Agents
  • Collagen Type I
  • Parathyroid Hormone-Related Protein
  • Peptide Fragments
  • Peptides
  • Procollagen
  • collagen type I trimeric cross-linked peptide
  • procollagen Type I N-terminal peptide
  • Teriparatide
  • romosozumab
  • abaloparatide