FPIN's Help Desk Answers

Duration of Bisphosphonate Therapy


Am Fam Physician. 2018 Apr 1;97(7):online.

Clinical Question

What is the optimal duration of bisphosphonate therapy for the treatment of osteoporosis in post-menopausal women?

Evidence-Based Answer

Oral bisphosphonates significantly reduce clinical fracture risk at four years in women with postmenopausal osteoporosis (T-score less than −2.5). (Strength of Recommendation [SOR]: B, based on a randomized controlled trial [RCT] with subgroup analysis.) Treatment beyond five years is associated with further reductions in fractures in women with persistent femoral neck T-scores less than −2.5. (SOR: C, based on a post-hoc analysis of RCTs.) Treatment beyond five years in other women with osteopenia or osteoporosis does not result in further decreases in rates of clinical vertebral fractures, nonvertebral fractures, or mortality. (SOR: C, based on a meta-analysis of two small RCTs reporting fracture as a secondary outcome.)

Evidence Summary

A 2011 meta-analysis of three RCTs in post-menopausal women with primary osteoporosis (N = 1,443) evaluated continual oral bisphospho-nate treatment vs. discontinuation at five years.1 Study participants had a bone mineral density (BMD) of 0.68 g per cm2 or less (corresponding to a T-score of −1.6) in one trial or a T-score of −2.5 or less in two trials, or a history of fracture. Oral bisphosphonates included alendronate (Fosamax), 5 or 10 mg per day, or etidronate (Didronel), 400 mg per day. Outcomes included change in BMD, rates of bone turnover, mortality, and adverse events. Fracture rates were reported but were not primary outcomes in any of the trials. Comparing a discontinuation group (patients who stopped bisphosphonate therapy after five years) with a continuation group (extended bisphosphonate treatment for seven to 10 years), pooled analysis of two of the trials (N = 1,346) showed no difference in the risk of vertebral fracture (relative risk [RR] = 0.61; 95% confidence interval [CI], 0.32 to 2.1), nonvertebral fracture (RR = 0.91; 95% CI, 0.77 to 1.2) or mortality (RR

Address correspondence to Julia M. Shaver, MD, at Julia.M.Shaver@kp.org. Reprints are not available from the authors.

Author disclosure: No relevant financial affiliations.

Copyright © Family Physicians Inquiries Network. Used with permission.


1. Fraser LA, Vogt KN, Adachi JD, Thabane L. Fracture risk associated with continuation versus discontinuation of bisphosphonates after 5 years of therapy in patients with primary osteoporosis: a systematic review and meta-analysis. Ther Clin Risk Manag. 2011;7:157–166.

2. Cummings SR, Black DM, Thompson DE, et al. Effect of alendronate on risk of fracture in women with low bone density but without vertebral fractures: results from the Fracture Intervention Trial. JAMA. 1998;280(24):2077–2082.

3. Schwartz AV, Bauer DC, Cummings SR, et al.; FLEX Research Group. Efficacy of continued alendronate for fractures in women with and without prevalent vertebral fracture: the FLEX trial. J Bone Miner Res. 2010;25(5):976–982.

Help Desk Answers provides answers to questions submitted by practicing family physicians to the Family Physicians Inquiries Network (FPIN). Members of the network select questions based on their relevance to family medicine. Answers are drawn from an approved set of evidence-based resources and undergo peer review. The strength of recommendations and the level of evidence for individual studies are rated using criteria developed by the Evidence-Based Medicine Working Group (http://www.cebm.net).

The complete database of evidence-based questions and answers is copyrighted by FPIN. If interested in submitting questions or writing answers for this series, go to http://www.fpin.org or e-mail: questions@fpin.org.

This series is coordinated by John E. Delzell Jr., MD, MSPH, Associate Medical Editor.

A collection of FPIN's Help Desk Answers published in AFP is available at http://www.aafp.org/afp/hda.



Want to use this article elsewhere? Get Permissions

CME Quiz

More in AFP

Editor's Collections

Related Content

More in Pubmed


Mar 15, 2019

Access the latest issue of American Family Physician

Read the Issue

Email Alerts

Don't miss a single issue. Sign up for the free AFP email table of contents.

Sign Up Now

Navigate this Article