Top

18-01-2016 | Osteoporosis | Article

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

Journal: Osteoporosis International

Authors: M. A. Amiche, J. M. Albaum, M. Tadrous, P. Pechlivanoglou, L. E. Lévesque, J. D. Adachi, S. M. Cadarette

Publisher: Springer London

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.

Overman RA, Yeh J-Y, Deal CL (2013) Prevalence of oral glucocorticoid usage in the United States: a general population perspective. Arthritis Care Res 65:294–298CrossRef

Papaioannou A, Morin S, Cheung AM et al (2010) 2010 Clinical practice guidelines for the diagnosis and management of osteoporosis in Canada: summary. Can Med Assoc J 182:1864–1873CrossRef

Freemantle N, Cooper C, Diez-Perez A et al (2013) Results of indirect and mixed treatment comparison of fracture efficacy for osteoporosis treatments: a meta-analysis. Osteoporos Int 24:209–217CrossRefPubMedPubMedCentral

Seibel MJ, Cooper MS, Zhou H (2013) Glucocorticoid-induced osteoporosis: mechanisms, management, and future perspectives. Lancet Diabetes Endocrinol 1:59–70CrossRefPubMed

Grossman JM, Gordon R, Ranganath VK et al (2010) American College of Rheumatology 2010 recommendations for the prevention and treatment of glucocorticoid-induced osteoporosis. Arthritis Care Res 62:1515–1526CrossRef

Van Staa TP, Laan RF, Barton IP et al (2003) Bone density threshold and other predictors of vertebral fracture in patients receiving oral glucocorticoid therapy. Arthritis Rheum 48:3224–3229CrossRefPubMed

Hayashi K, Yamamoto M, Murakawa Y et al (2009) Bone fragility in male glucocorticoid-induced osteoporosis is not defined by bone mineral density. Osteoporos Int 20:1889–1894CrossRefPubMed

de Nijs RNJ, Jacobs JWG, Lems WF et al (2006) Alendronate or alfacalcidol in glucocorticoid-induced osteoporosis. N Engl J Med 355:675–684CrossRefPubMed

Adachi JD, Saag KG, Delmas PD et al (2001) Two-year effects of alendronate on bone mineral density and vertebral fracture in patients receiving glucocorticoids: a randomized, double-blind, placebo-controlled extension trial. Arthritis Rheum 44:202–211CrossRefPubMed

10.

Cohen S, Levy RM, Keller M et al (1999) Risedronate therapy prevents corticosteroid-induced bone loss: a twelve-month, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. Arthritis Rheum 42:2309–2318CrossRefPubMed

11.

Roux C, Oriente P, Laan R et al (1998) Randomized trial of effect of cyclical etidronate in the prevention of corticosteroid-induced bone loss. Ciblos Study Group. J Clin Endocrinol Metab 83:1128–1133CrossRefPubMed

12.

Nawata H, Soen S, Takayanagi R et al (2005) Guidelines on the management and treatment of glucocorticoid-induced osteoporosis of the Japanese Society for Bone and Mineral Research (2004). J Bone Miner Metab 23:105–109CrossRefPubMed

13.

Gluer CC, Marin F, Ringe JD et al (2013) Comparative effects of teriparatide and risedronate in glucocorticoid-induced osteoporosis in men: 18-month results of the EuroGIOPs Trial. J Bone Miner Res 28:1355–1368CrossRefPubMedPubMedCentral

14.

Cummings SR, Martin JS, McClung MR et al (2009) Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med 361:756–765CrossRefPubMed

15.

Kanis JA, Stevenson M, McCloskey EV, Davis S, Lloyd-Jones M (2007) Glucocorticoid-induced osteoporosis: a systematic review and cost-utility analysis. Health Technol Assess 11:1–231CrossRef

16.

Homik J, Cranney A, Shea B, et al. (2000) Bisphosphonates for steroid induced osteoporosis. Cochrane Database Syst Rev CD001347

17.

Cranney A, Welch V, Adachi JD, et al. (2000) Calcitonin for the Treatment and Prevention of Corticosteroid-Induced Osteoporosis. Cochrane Database Syst Rev CD001983

18.

Bucher H, Guyatt G, Griffith L, Walter S (1997) The results of direct and indirect treatment comparisons in meta-analysis of randomized controlled trials. J Clin Epidemiol 50:683–691CrossRefPubMed

19.

Caldwell DM, Ades AE, Higgins JPT (2005) Simultaneous comparison of multiple treatments: combining direct and indirect evidence. BMJ 331:897–900CrossRefPubMedPubMedCentral

20.

Jadad AR, Moore RA, Carroll D et al (1996) Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials 17:1–12CrossRefPubMed

21.

Black D, Cummings S, Karpf D et al (1996) Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures. Fracture Intervention Trial Research Group. Lancet 348:1535–1541CrossRefPubMed

22.

Turner RM, Davey J, Clarke MJ, Thompson SG, Higgins JP (2012) Predicting the extent of heterogeneity in meta-analysis, using empirical data from the Cochrane Database of Systematic Reviews. Int J Epidemiol 41:818–827CrossRefPubMedPubMedCentral

23.

Dias S, Sutton AJ, Ades AE, Welton NJ (2013) Evidence synthesis for decision making 2: a generalized linear modeling framework for pairwise and network meta-analysis of randomized controlled trials. Med Decis Making 33:607–617CrossRefPubMedPubMedCentral

24.

Salanti G, Ades AE, Ioannidis JPA (2011) Graphical methods and numerical summaries for presenting results from multiple-treatment meta-analysis: an overview and tutorial. J Clin Epidemiol 64:163–171CrossRefPubMed

25.

Berger VW, Alperson SY (2009) A general framework for the evaluation of clinical trial quality. Rev Recent Clin Trials 4:79–88CrossRefPubMedPubMedCentral

26.

Homik JE, Cranney A, Shea B et al (1999) A metaanalysis on the use of bisphosphonates in corticosteroid induced osteoporosis. J Rheumatol 26:1148–1157PubMed

27.

Saag KG, Zanchetta JR, Devogelaer JP et al (2009) Effects of teriparatide versus alendronate for treating glucocorticoid-induced osteoporosis: thirty-six-month results of a randomized, double-blind, controlled trial. Arthritis Rheum 60:3346–3355CrossRefPubMed

28.

Ma YL, Zeng QQ, Chiang AY et al (2014) Effects of teriparatide on cortical histomorphometric variables in postmenopausal women with or without prior alendronate treatment. Bone 59:139–147CrossRefPubMed

29.

Abelson A, Ringe JD, Gold DT, Lange JL, Thomas T (2010) Longitudinal change in clinical fracture incidence after initiation of bisphosphonates. Osteoporos Int 21:1021–1029CrossRefPubMedPubMedCentral

30.

Rosen C, Khosla S (2010) Placebo-controlled trials in osteoporosis—proceeding with caution. N Engl J Med 363:1365–1367CrossRefPubMedPubMedCentral