Pharmacological prevention of fractures in patients undergoing glucocorticoid therapies: a systematic review and network meta-analysis

Rheumatology (Oxford). 2021 Feb 1;60(2):649-657. doi: 10.1093/rheumatology/keaa228.


Objective: To perform a network meta-analysis (NMA) on the efficacy of antiosteoporotic interventions in the prevention of vertebral and non-vertebral fractures in adult patients taking glucocorticoids (GCs).

Methods: We performed NMAs based on a prospectively developed protocol. A librarian-assisted database search of MEDLINE, EMBASE, Web of Science, Cumulative Index of Nursing and Allied Health Literature (CINAHL), the Cochrane Central Register of Controlled Trials (CENTRAL) and Chinese databases was conducted for randomized controlled trials (RCTs) comparing antiosteoporotic interventions in adult patients taking GCs. Outcomes were vertebral and non-vertebral fracture incidences.

Results: We included 56 RCTs containing 6479 eligible patients in our analysis. We found that alendronate and teriparatide were associated with decreased odds of both vertebral and non-vertebral fractures. Denosumab and risedronate were associated with decreased odds of vertebral fractures, while etidronate, ibandronate and alfacalcidol were associated with decreased odds of non-vertebral fractures. We observed low network heterogeneity as indicated by the I2 statistic, and we did not detect evidence of publication bias. All outcomes were based on a moderate quality of evidence according to GRADE.

Conclusion: Bisphosphonates, teriparatide and denosumab are associated with decreased odds of fracture in patients undergoing GC therapy. Vitamin D metabolites and analogues (e.g. alfacalcidol) may have greater anti-fracture efficacy compared with plain vitamin D.

Systematic review registration: The International Prospective Register of Systematic Reviews (PROSPERO)-CRD42019127073.

Keywords: antiosteoporotic interventions; bone loss; fractures; glucocorticoid-induced osteoporosis; network meta-analysis.

Publication types

  • Systematic Review

MeSH terms

  • Bone Density Conservation Agents / therapeutic use*
  • Glucocorticoids / therapeutic use*
  • Humans
  • Network Meta-Analysis*
  • Osteoporotic Fractures / prevention & control*
  • Vitamin D / therapeutic use*
  • Vitamins / therapeutic use


  • Bone Density Conservation Agents
  • Glucocorticoids
  • Vitamins
  • Vitamin D