Predicting Fractures After Patients Stop Bisphosphonate

A new study indicates that age and testing of hip bone mineral density (BMD) when postmenopausal women discontinue bisphosphonate therapy can help predict the likelihood of fractures over the next five years. The study, performed by Douglas Bauer, M.D. of the University of California, San Francisco, tested methods for predicting fracture risk by measuring BMD using hip and spine duel-energy x-ray absorptiometry (DXA) and also bone turnover markers (BTMs) when women discontinue bisphosphonate therapy and a few years afterward.

Dr. Bauer and his colleagues examined data from the Fracture Intervention Trial Long-term Extension (FLEX), and randomly assigned postmenopausal women (ages 61 to 86 years) previously treated with the bisphosphonate alendronate sodium (for four to five years) to five additional years of alendronate or placebo from 1998 through 2003. This analysis included only the placebo group. Hip and spine DXA were measured when the placebo was started and after one to three years of follow-up. Two different BTMs also were measured at baseline and after one and three years.

During five years of placebo, 22% of women (94 of 437) had one or more fractures; 82 had fractures after one year. Older age and lower hip BMD at the time alendronate therapy was discontinued were associated with higher rates of clinical fractures during the subsequent five years. However, neither BMD measures after one year nor BTM levels one to two years after discontinuing alendronate were associated with fracture risk.

The authors say in the May 5, 2014 news release, “Women with greater total hip bone loss two or three 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. … In the meantime, short-term monitoring with BMD, BAP or NTX [two bone turnover markers] after discontinuation of four to five years of alendronate therapy does not appear to improve fracture prediction.”

Dr. Bauer told OTW, “It was surprising the bone turnover markers did not predict fracture risk after discontinuation of alendronate, as we believe the offset of efficacy should be reflected by a rise in bone turnover that translates into higher fracture risk. We know that changes in BMD do not reliably predict treatment efficacy when starting bisphosphonates, so the observations that short term changes in BMD did not predict fracture risk after discontinuation was not particularly surprising. Future studies should look at newer and perhaps more accurate bone turnover markers which might be more helpful.”