Alendronate Holiday: Women May Not Need Annual Monitoring

Lara C. Pullen, PhD

May 07, 2014

Multiple dual-energy X-ray absorptiometry (DXA) scans do not improve prediction of clinical fracture among postmenopausal women who discontinue alendronate therapy after 4 to 5 years. Instead, age and hip bone mineral density (BMD) at discontinuation are most predictive of clinical fractures during the subsequent 5 years.

Follow-up measures of DXA at 1 year after discontinuation or bone turnover marker (BTM) measurements at 1 to 2 years after discontinuation also do not appear to add useful information to the clinical picture.

Douglas C. Bauer, MD, from the University of California, San Francisco, and colleagues present an analysis of data from the Fracture Intervention Trial Long-term Extension (FLEX) study in an article published online May 5 in JAMA Internal Medicine. The results expand on previously reported results from the FLEX study.

FLEX enrolled postmenopausal women aged 61 to 86 years from 1998 to 2003.

In the current analysis, the investigators found that lower hip DXA at the time of discontinuation of alendronate therapy was significantly related to increased fracture risk: The hazard ratio of the lowest tertile of baseline femoral neck DXA vs other 2 tertiles was 2.17 (95% confidence interval [CI], 1.38 - 3.41), and the total hip DXA relative hazard ratio was 1.87 (95% CI, 1.20 - 2.92).

"We found that after discontinuation of 4 to 5 years of alendronate therapy, 22% of women experience fracture during the subsequent 5 years. Older age and lower hip BMD at the time of discontinuation strongly predict fracture risk after discontinuation, but neither 1-year change in hip BMD nor 1- or 3-year change in [urinary type 1 collagen cross-linked N-telopeptide or bone-specific alkaline phosphatase] are associated with the risk of fracture after discontinuation," the authors write. "Women with greater total hip bone loss 2 or 3 years after discontinuation may be at increased risk of fracture, but these results need to be confirmed in other studies before routine measurement of BMD after discontinuation of alendronate therapy can be recommended."

On the basis of the newly reported data, Brian Neuman, MD, from Johns Hopkins University in Baltimore, Maryland, told Medscape Medical News that the patients clinicians should "keep a close eye on" are older women with lower BMD at the time of discontinuation.

Bisphosphonates are frequently prescribed to women with osteoporosis as an antifracture treatment. They have a well-documented effect on bone turnover and BMD.

This is the first study to examine the value of serial BMD and BTM monitoring after discontinuation of bisphosphonate use, and it suggests such tests may not be useful. The number of fractures during FLEX follow-up was relatively small, however, and the authors did note that the study had limited power to detect significant associations.

"In an era when we know much more about how to start alendronate therapy than how to stop it, the results of Bauer and colleagues suggest that identification of patients at high risk of fracture after treatment discontinuation is best accomplished by BMD measurement at the time of discontinuation rather than frequent short-term monitoring with BMD or bone turnover marker measurements after treatment discontinuation. Longer-term research studies are warranted to determine the best clinical practice strategy for management of patients who remain at high fracture risk after discontinuation of 3 to 5 years of bisphosphonate treatment," write Margaret L. Gourlay, MD, MPH, from the University of North Carolina-Chapel Hill, and Kristen E. Ensrud, MD, MPH, from the University of Minnesota Medical School in Minneapolis, in an accompanying invited commentary.

The FLEX study was supported by contracts from Merck & Co; this analysis was designed and conducted by the non-Merck investigators (including Dr. Bauer) without additional financial support. Several coauthors have consulted for Merck, Nycomed, Amgen, GlaxoSmithKline, and/or Eli Lilly. One coauthor is employed by Merck. Another coauthor has received honoraria from Amgen, Merck, and Novartis. The other authors have disclosed no relevant financial relationships. Dr. Ensrud serves as a consultant on a Data Monitoring Committee for Merck Sharpe & Dohme. Neither Dr. Gourlay nor Dr. Neuman report conflicts of interest.

JAMA Intern Med. Published online May 5, 2014. Article abstract, Commentary extract

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