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Age, BMD predicted fracture risk after bisphosphonates
Age and hip bone mineral density are two factors that could help predict the likelihood of fractures for up to 5 years after postmenopausal women discontinue bisphosphonates, according to research published in JAMA Internal Medicine.
In the Fracture Intervention Trial Long-term Extension (FLEX), Douglas C. Bauer, MD, of the University of California, San Francisco, and colleagues randomly assigned 437 postmenopausal women aged 61 to 86 years — previously treated with bisphosphonate alendronate sodium for 4 to 5 years — to an additional 5 years of alendronate or placebo to examine the relationships among age, BMD and fracture risk after therapy discontinuation.
Douglas C. Bauer
The researchers analyzed DXA scans in the placebo group at baseline and again after 1 to 3 years of follow-up. During the same start and follow-up points, urinary type 1 collagen cross-linked N-telopeptide (NTX) and serum bone-specific alkaline phosphatase (BAP) were measured to assess bone turnover.
During 5 years, 94 participants (22%) experienced one or more symptomatic fractures; 82 had fractures after 1 year. Changes in hip DXA, NTX and BAP at the 1-year mark were not related to subsequent fracture risk. However, older age and lower hip DXA upon discontinuation were significant predictors of increased fracture risk.
Women in the lowest tertile of femoral neck DXA at baseline had elevated risk compared with those in the two higher tertiles (HR=2.17; 95%CI, 1.38-3.41). Results corresponded in respective tertiles for total hip DXA (HR=1.87; 95%CI, 1.2-2.92).
“Women with greater total hip bone loss 2 or 3 years after discontinuation may be at increased risk of fracture,” the researchers wrote. “But these results need to be confirmed in other studies before routine measurement of BMD after discontinuation of alendronate therapy can be recommended.”
In an attached commentary, Margaret L. Gourlay, MD, of the University of North Carolina-Chapel Hill, and Kristine E. Ensrud, MD, of the University of Minnesota Medical School, Minneapolis, called the study “convincing” because it relies on clinical fracture outcome rather than surrogate measures.
“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,” they wrote.
Disclosure: The FLEX study was supported by contracts from Merck & Co, and some of the researchers have consulted or worked for Merck. The analysis was designed and conducted by the non-Merck investigators without additional financial support. The study drug was manufactured and packaged by Merck.