Age, bone mineral density may predict 5-year fracture risk after stopping bisphosphonate

When postmenopausal women stop bisphosphonate therapy, their age and hip bone mineral density (BMD) can help predict the likelihood of fractures over the next 5 years, a study found.

The prospective Fracture Intervention Trial Long-term Extension (FLEX) study looked at 1,099 postmenopausal women age 61 to 86 years who were previously treated with 4 to 5 years of alendronate sodium, 5 or 10 mg/d. The women were randomized to either 5 more years of alendronate (60%) or placebo (40%) from 1998 through 2003. Women were offered a daily supplement of 500 mg of calcium and 250 IU of vitamin D.

This substudy specifically focused on the placebo group. The report appeared online May 5 at JAMA Internal Medicine.

Hip and spine dual-energy X-ray absorptiometry (DXA) were measured for 1 to 3 years of follow-up. Two biochemical markers of bone turnover, urinary type 1 collagen cross-linked N-telopeptide (NTX) and serum bone-specific alkaline phosphatase (BAP), were measured at baseline and after 1 and 3 years.

During 5 years of follow-up of the placebo group, 82 women had fractures after 1 year and 94 women (22%) had fractures over the entire time span. After adjustment for age, the risk of total hip fracture in women in the lowest tertile of baseline total hip BMD was higher than that in the other 2 tertiles (relative hazard ratio, 1.87; 95% CI, 1.20 to 2.92).

Results were similar for femoral neck BMD (relative hazard ratio, 2.17; 95% CI, 1.38 to 3.41). Older age was independently associated with a greater risk of fracture (relative hazard ratio, 1.54; 95% CI, 1.26 to 1.85 per 5-year increase) after stopping alendronate. Baseline levels of NTX (relative hazard ratio, 1.33; 95% CI, 0.84 to 2.10) and BAP (relative hazard ratio, 1.39, 95% CI, 0.89 to 2.17) were not associated with fracture outcomes.

The authors noted, “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.”

In an invited commentary, editorialists noted the study is convincing because it relies on a clinical, symptomatic fracture outcome rather than surrogate measures such as rates of BMD loss or changes in bone turnover marker levels.

“In an era when we know much more about how to start alendronate therapy than how to stop it, the results of [the current study] 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.