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Erschienen in: Osteoporosis International 4/2019

08.01.2019 | Review Article

A systematic review and meta-analysis of the effect of bisphosphonate drug holidays on bone mineral density and osteoporotic fracture risk

verfasst von: S. Nayak, S. L. Greenspan

Erschienen in: Osteoporosis International | Ausgabe 4/2019

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Abstract

Summary

We performed a systematic review on the effect of drug holidays (discontinuation) on bone mineral density (BMD) and fracture risk. Bisphosphonate discontinuation may be considered for women who do not have low hip BMD after 3–5 years of initial treatment, while women who have low hip BMD may benefit from treatment continuation.

Introduction

We performed a systematic review and meta-analysis on the effect of drug holidays (discontinuation) on BMD and fracture risk.

Methods

We searched PubMed, Embase, and Cochrane Library databases to locate controlled clinical trials and cohort studies evaluating the effect of drug holidays/discontinuation versus osteoporosis treatment continuation. We performed random-effects meta-analyses of hazard ratios of hip and any clinical osteoporotic fracture for individuals who discontinued bisphosphonates compared to persistent users.

Results

Thirteen records reporting results from eight different studies met inclusion criteria. The FLEX study found a reduced clinical vertebral fracture risk with 10 years of alendronate therapy compared to 5 (RR 0.45, 95% CI 0.24–0.85), and the HORIZON extension studies found a reduced risk of morphometric vertebral fracture with 6 years of zoledronic acid therapy compared to 3 (OR = 0.51, 95% CI 0.26–0.95); subgroup analyses showed that women with low hip BMD T-scores after the initial treatment period benefitted from continued treatment in terms of reduced vertebral fracture risk. Meta-analysis of adjusted hazard ratios of hip and any clinical osteoporotic fracture for women who discontinued bisphosphonates revealed no significant differences in the risk of hip fracture (summary estimate of HR 1.09, 95% CI 0.87–1.37) or any clinical fracture (summary estimate of HR 1.13, 95% CI 0.75–1.70) compared to persistent users.

Conclusions

Bisphosphonate discontinuation may be considered for women who do not have low hip BMD after 3 to 5 years of initial treatment, while women who have low hip BMD may benefit from treatment continuation.
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Literatur
1.
Zurück zum Zitat Wright NC, Looker AC, Saag KG, Curtis JR, Delzell ES, Randall S, Dawson-Hughes B (2014) The recent prevalence of osteoporosis and low bone mass in the United States based on bone mineral density at the femoral neck or lumbar spine. J Bone Miner Res 29:2520–2526CrossRefPubMed Wright NC, Looker AC, Saag KG, Curtis JR, Delzell ES, Randall S, Dawson-Hughes B (2014) The recent prevalence of osteoporosis and low bone mass in the United States based on bone mineral density at the femoral neck or lumbar spine. J Bone Miner Res 29:2520–2526CrossRefPubMed
2.
Zurück zum Zitat U.S. Department of Health and Human Services. Bone health and osteoporosis: a report of the surgeon general. Rockville, MD: U.S. Department of Health and Human Services, Office of the Surgeon General, 2004 U.S. Department of Health and Human Services. Bone health and osteoporosis: a report of the surgeon general. Rockville, MD: U.S. Department of Health and Human Services, Office of the Surgeon General, 2004
3.
Zurück zum Zitat Osteoporosis prevention, diagnosis, and therapy. NIH Consens Statement 2000;17(1):1–45 Osteoporosis prevention, diagnosis, and therapy. NIH Consens Statement 2000;17(1):1–45
4.
Zurück zum Zitat Lin JT, Lane JM (2004) Osteoporosis: a review. Clin Orthop Relat Res 425:126–134CrossRef Lin JT, Lane JM (2004) Osteoporosis: a review. Clin Orthop Relat Res 425:126–134CrossRef
5.
Zurück zum Zitat Nguyen ND, Ahlborg HG, Center JR, Eisman JA, Nguyen TV (2007) Residual lifetime risk of fractures in women and men. J Bone Miner Res 22:781–788CrossRefPubMed Nguyen ND, Ahlborg HG, Center JR, Eisman JA, Nguyen TV (2007) Residual lifetime risk of fractures in women and men. J Bone Miner Res 22:781–788CrossRefPubMed
6.
Zurück zum Zitat Blume SW, Curtis JR (2011) Medical costs of osteoporosis in the elderly Medicare population. Osteoporos Int 22:1835–1844CrossRefPubMed Blume SW, Curtis JR (2011) Medical costs of osteoporosis in the elderly Medicare population. Osteoporos Int 22:1835–1844CrossRefPubMed
7.
Zurück zum Zitat Cosman F, de Beur SJ, LeBoff MS, Lewiecki EM, Tanner B, Randall S, Lindsay R, National Osteoporosis F (2014) Clinician’s guide to prevention and treatment of osteoporosis. Osteoporos Int 25:2359–2381CrossRefPubMedPubMedCentral Cosman F, de Beur SJ, LeBoff MS, Lewiecki EM, Tanner B, Randall S, Lindsay R, National Osteoporosis F (2014) Clinician’s guide to prevention and treatment of osteoporosis. Osteoporos Int 25:2359–2381CrossRefPubMedPubMedCentral
8.
Zurück zum Zitat Adler RA, El-Hajj Fuleihan G, Bauer DC et al (2016) Managing osteoporosis in patients on long-term bisphosphonate treatment: report of a task force of the American Society for Bone and Mineral Research. J Bone Miner Res 31:16–35CrossRefPubMed Adler RA, El-Hajj Fuleihan G, Bauer DC et al (2016) Managing osteoporosis in patients on long-term bisphosphonate treatment: report of a task force of the American Society for Bone and Mineral Research. J Bone Miner Res 31:16–35CrossRefPubMed
9.
Zurück zum Zitat Higgins JPT, Green S (editors). Cochrane handbook for systematic reviews of interventions Version 5.1.0 [updated March 2011]. Box 6.4.b: Cochrane Highly Sensitive Search Strategy for identifying randomized trials in MEDLINE: sensitivity- and precision-maximizing version; PubMed format. The Cochrane Collaboration, 2011. Available from www.handbook.cochrane.org. Accessed Jan 2018 Higgins JPT, Green S (editors). Cochrane handbook for systematic reviews of interventions Version 5.1.0 [updated March 2011]. Box 6.4.b: Cochrane Highly Sensitive Search Strategy for identifying randomized trials in MEDLINE: sensitivity- and precision-maximizing version; PubMed format. The Cochrane Collaboration, 2011. Available from www.​handbook.​cochrane.​org. Accessed Jan 2018
10.
Zurück zum Zitat Higgins JP, Altman DG, Gotzsche PC et al (2011) The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ 343:d5928CrossRefPubMedPubMedCentral Higgins JP, Altman DG, Gotzsche PC et al (2011) The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ 343:d5928CrossRefPubMedPubMedCentral
12.
Zurück zum Zitat DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7:177–188CrossRefPubMed DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7:177–188CrossRefPubMed
13.
Zurück zum Zitat Adams AL, Adams JL, Raebel MA, Tang BT, Kuntz JL, Vijayadeva V, McGlynn EA, Gozansky WS (2018) Bisphosphonate drug holiday and fracture risk: a population-based cohort study. J Bone Miner Res 33:1252–1259CrossRefPubMed Adams AL, Adams JL, Raebel MA, Tang BT, Kuntz JL, Vijayadeva V, McGlynn EA, Gozansky WS (2018) Bisphosphonate drug holiday and fracture risk: a population-based cohort study. J Bone Miner Res 33:1252–1259CrossRefPubMed
14.
Zurück zum Zitat Black D, Reid I, Boonen S et al (2012) The effect of 3 versus 6 years of zoledronic acid treatment of osteoporosis: a randomized extension to the HORIZON-Pivotal Fracture Trial (PFT). J Bone Miner Res 27:243–254CrossRefPubMed Black D, Reid I, Boonen S et al (2012) The effect of 3 versus 6 years of zoledronic acid treatment of osteoporosis: a randomized extension to the HORIZON-Pivotal Fracture Trial (PFT). J Bone Miner Res 27:243–254CrossRefPubMed
15.
Zurück zum Zitat Black D, Reid I, Cauley J et al (2015) The effect of 6 versus 9 years of zoledronic acid treatment in osteoporosis: a randomized second extension to the HORIZON-Pivotal Fracture Trial (PFT). J Bone Miner Res 30:934–944CrossRefPubMed Black D, Reid I, Cauley J et al (2015) The effect of 6 versus 9 years of zoledronic acid treatment in osteoporosis: a randomized second extension to the HORIZON-Pivotal Fracture Trial (PFT). J Bone Miner Res 30:934–944CrossRefPubMed
16.
Zurück zum Zitat Black D, Schwartz A, Ensrud K et al (2006) Effects of continuing or stopping alendronate after 5 years of treatment: the Fracture Intervention Trial Long-term Extension (FLEX): a randomized trial. JAMA 296:2927–2938CrossRefPubMed Black D, Schwartz A, Ensrud K et al (2006) Effects of continuing or stopping alendronate after 5 years of treatment: the Fracture Intervention Trial Long-term Extension (FLEX): a randomized trial. JAMA 296:2927–2938CrossRefPubMed
17.
Zurück zum Zitat Bone H, Hosking D, Devogelaer J, Tucci JR, Emkey RD, Tonino RP, Rodriguez-Portales JA, Downs RW, Gupta J, Santora AC, Liberman UA, Alendronate Phase III Osteoporosis Treatment Study Group (2004) Ten years’ experience with alendronate for osteoporosis in postmenopausal women. N Engl J Med 350:1189–1199CrossRefPubMed Bone H, Hosking D, Devogelaer J, Tucci JR, Emkey RD, Tonino RP, Rodriguez-Portales JA, Downs RW, Gupta J, Santora AC, Liberman UA, Alendronate Phase III Osteoporosis Treatment Study Group (2004) Ten years’ experience with alendronate for osteoporosis in postmenopausal women. N Engl J Med 350:1189–1199CrossRefPubMed
18.
Zurück zum Zitat Cosman F, Cauley J, Eastell R, Boonen S, Palermo L, Reid I, Cummings S, Black D (2014) Reassessment of fracture risk in women after 3 years of treatment with zoledronic acid: when is it reasonable to discontinue treatment? J Clin Endocrinol Metab 99:4546–4554CrossRefPubMed Cosman F, Cauley J, Eastell R, Boonen S, Palermo L, Reid I, Cummings S, Black D (2014) Reassessment of fracture risk in women after 3 years of treatment with zoledronic acid: when is it reasonable to discontinue treatment? J Clin Endocrinol Metab 99:4546–4554CrossRefPubMed
19.
Zurück zum Zitat Curtis JR, Westfall AO, Cheng H, Delzell E, Saag KG (2008) Risk of hip fracture after bisphosphonate discontinuation: implications for a drug holiday. Osteoporos Int 19:1613–1620CrossRefPubMedPubMedCentral Curtis JR, Westfall AO, Cheng H, Delzell E, Saag KG (2008) Risk of hip fracture after bisphosphonate discontinuation: implications for a drug holiday. Osteoporos Int 19:1613–1620CrossRefPubMedPubMedCentral
20.
Zurück zum Zitat Curtis JR, Chen R, Li Z, Arora T, Saag K, Wright NC, Daigle S, Kilgore M, Delzell E (2017) The impact of the duration of bisphosphonate drug holidays on hip fracture rates [abstract]. Arthritis Rheumatol 69(suppl 10) Curtis JR, Chen R, Li Z, Arora T, Saag K, Wright NC, Daigle S, Kilgore M, Delzell E (2017) The impact of the duration of bisphosphonate drug holidays on hip fracture rates [abstract]. Arthritis Rheumatol 69(suppl 10)
21.
Zurück zum Zitat Ensrud K, Barrett-Connor E, Schwartz A et al (2004) Randomized trial of effect of alendronate continuation versus discontinuation in women with low BMD: results from the Fracture Intervention Trial long-term extension. J Bone Miner Res 19:1259–1269CrossRefPubMed Ensrud K, Barrett-Connor E, Schwartz A et al (2004) Randomized trial of effect of alendronate continuation versus discontinuation in women with low BMD: results from the Fracture Intervention Trial long-term extension. J Bone Miner Res 19:1259–1269CrossRefPubMed
22.
Zurück zum Zitat Mignot MA, Taisne N, Legroux I, Cortet B, Paccou J (2017) Bisphosphonate drug holidays in postmenopausal osteoporosis: effect on clinical fracture risk. Osteoporos Int 28:3431–3438CrossRefPubMed Mignot MA, Taisne N, Legroux I, Cortet B, Paccou J (2017) Bisphosphonate drug holidays in postmenopausal osteoporosis: effect on clinical fracture risk. Osteoporos Int 28:3431–3438CrossRefPubMed
23.
Zurück zum Zitat Miller PD, Watts NB, Licata AA, Harris ST, Genant HK, Wasnich RD, Ross PD, Jackson RD, Hoseyni MS, Schoenfeld SL, Valent DJ, Chesnut CH 3rd (1997) Cyclical etidronate in the treatment of postmenopausal osteoporosis: efficacy and safety after seven years of treatment. Am J Med 103:468–476CrossRefPubMed Miller PD, Watts NB, Licata AA, Harris ST, Genant HK, Wasnich RD, Ross PD, Jackson RD, Hoseyni MS, Schoenfeld SL, Valent DJ, Chesnut CH 3rd (1997) Cyclical etidronate in the treatment of postmenopausal osteoporosis: efficacy and safety after seven years of treatment. Am J Med 103:468–476CrossRefPubMed
24.
Zurück zum Zitat Schwartz A, Bauer D, Cummings S et al (2010) Efficacy of continued alendronate for fractures in women with and without prevalent vertebral fracture: the FLEX trial. J Bone Miner Res 25:976–982CrossRefPubMed Schwartz A, Bauer D, Cummings S et al (2010) Efficacy of continued alendronate for fractures in women with and without prevalent vertebral fracture: the FLEX trial. J Bone Miner Res 25:976–982CrossRefPubMed
25.
Zurück zum Zitat Tonino R, Meunier P, Emkey R et al (2000) Skeletal benefits of alendronate: 7-year treatment of postmenopausal osteoporotic women. Phase III Osteoporosis Treatment Study Group. J Clin Endocrinol Metab 85:3109–3115PubMed Tonino R, Meunier P, Emkey R et al (2000) Skeletal benefits of alendronate: 7-year treatment of postmenopausal osteoporotic women. Phase III Osteoporosis Treatment Study Group. J Clin Endocrinol Metab 85:3109–3115PubMed
Metadaten
Titel
A systematic review and meta-analysis of the effect of bisphosphonate drug holidays on bone mineral density and osteoporotic fracture risk
verfasst von
S. Nayak
S. L. Greenspan
Publikationsdatum
08.01.2019
Verlag
Springer London
Erschienen in
Osteoporosis International / Ausgabe 4/2019
Print ISSN: 0937-941X
Elektronische ISSN: 1433-2965
DOI
https://doi.org/10.1007/s00198-018-4791-3

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