A systematic review and meta-analysis of the effect of bisphosphonate drug holidays on bone mineral density and osteoporotic fracture risk
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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.
We performed a systematic review and meta-analysis on the effect of drug holidays (discontinuation) on BMD and fracture risk.
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.
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.
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.
KeywordsBisphosphonates Drug holiday Meta-analysis Osteoporosis Systematic review
Compliance with ethical standards
Conflicts of interest
- 2.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, 2004Google Scholar
- 3.Osteoporosis prevention, diagnosis, and therapy. NIH Consens Statement 2000;17(1):1–45Google Scholar
- 9.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
- 11.Wells GA SB, O’Connell D, Peterson J, Welch V, Losos M, Tugwell P The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp. Accessed June 2018
- 17.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 350:1189–1199CrossRefGoogle Scholar
- 20.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)Google Scholar
- 23.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 103:468–476CrossRefGoogle Scholar