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Efficacy of osteoporosis pharmacotherapies in preventing fracture among oral glucocorticoid users: a network meta-analysis

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Abstract

Summary

Efficacy of osteoporosis medication is not well-established among patients taking oral glucocorticoids. We assessed the efficacy of approved osteoporosis pharmacotherapies in preventing fracture by combining data from randomized controlled trials. Teriparatide, risedronate, and etidronate were associated with decreased vertebral fracture risk.

Introduction

Several osteoporosis drugs are approved for the prevention and treatment of glucocorticoid (GC)-induced osteoporosis. However, the efficacy of these treatments among oral GC users is still limited. We aimed to examine the comparative efficacy of osteoporosis treatments among oral GC users.

Methods

We updated a systematic review through to March 2015 to identify all double-blinded randomized controlled trials (RCTs) that examined osteoporosis treatment among oral GC users. We used a network meta-analysis with informative priors to derive comparative risk ratios (RRs) and 95 % credible intervals (95 % CrI) for vertebral and non-vertebral fracture and mean differences in lumbar spine (LS) and femoral neck (FN) bone mineral density (BMD). Treatment ranking was estimated using the surface under the cumulative ranking curve (SUCRA) statistic. A meta-regression was completed to assess a subgroup effect between patients with prior GC exposures and GC initiators.

Results

We identified 27 eligible RCTs examining nine active comparators. Etidronate (RR, 0.41; 95%CrI = 0.17–0.90), risedronate (RR = 0.30, 95%CrI = 0.14–0.61), and teriparatide (RR = 0.07, 95%CrI = 0.001–0.48) showed greater efficacy than placebo in preventing vertebral fractures; yet, no treatment effects were statistically significant in reducing non-vertebral fractures. Alendronate, risedronate, and etidronate increased LS BMD while alendronate and raloxifene increased FN BMD. In preventing vertebral fractures, teriparatide was ranked as the best treatment (SUCRA: 77 %), followed by risedronate (77 %) and zoledronic acid (76 %). For non-vertebral fractures, teriparatide also had the highest SUCRA (69 %), followed by risedronate (64 %). No subgroup effect was identified with regards to prior GC exposure.

Conclusions

Despite weak trial evidence available for fracture prevention among GC users, we identified several drugs that are likely to prevent osteoporotic fracture. Teriparatide, risedronate, and etidronate were associated with decreased vertebral fracture risk.

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Abbreviations

BMD:

Bone mineral density

CrI:

Credible interval

GC:

Glucocorticoid

LS:

Lumbar spine

FN:

Femoral neck

MCMC:

Markov Chain Monte Carlo

RCT:

Randomized controlled trial

SUCRA:

Surface Under the Cumulative RAnking curve

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Acknowledgments

MAA is supported by a Canadian Network for Advanced Interdisciplinary Methods for Comparative Effectiveness Research (CAN-AIM) training scholarship and a Leslie Dan Faculty of Pharmacy Dean’s Entrance Scholarship, and was supported by a Drug Safety and Effectiveness Cross-Disciplinary Training scholarship. The funding agencies did not have any role in the design and conduct of the study; analysis or interpretation of the data; or preparation, review, or approval of the manuscript.

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Correspondence to M. A. Amiche.

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Conflicts of interest

JDA reports having participated in clinical trials sponsored by Procter & Gamble, Amgen and by Merck for the prevention and treatment of glucocorticoid-induced osteoporosis. JDA also reports having received consulting fees and research grants from Actavis, Amgen, Eli Lilly, Merck, and Novartis. MAA, JMA, MT, PP, LEL, and SMC state that they have no conflict of interest.

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Amiche, M.A., Albaum, J.M., Tadrous, M. et al. Efficacy of osteoporosis pharmacotherapies in preventing fracture among oral glucocorticoid users: a network meta-analysis. Osteoporos Int 27, 1989–1998 (2016). https://doi.org/10.1007/s00198-015-3476-4

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  • DOI: https://doi.org/10.1007/s00198-015-3476-4

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