Discontinuation of bisphosphonate therapy after 3 to 5 years is increasingly considered, but methods to monitor fracture risk after discontinuation have not been established.
Dr Douglas C. Bauer from the University of California and colleagues set out to test methods of predicting fracture risk among women who have discontinued alendronate therapy after 4 to 5 years.
The prospective Fracture Intervention Trial Long-term Extension (FLEX) study randomised postmenopausal women aged 61 to 86 years previously treated with 4 to 5 years of alendronate therapy to 5 more years of alendronate or placebo from 1998 through 2003; the present analysis includes only the placebo group.
Hip and spine dual-energy x-ray absorptiometry (DXA) were measured when placebo was begun (FLEX baseline) and after 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 FLEX baseline and after 1 and 3 years.
that symptomatic spine and nonspine fractures occurring after the follow-up measurement of DXA or bone turnover.
The results showed during 5 years of placebo, 94 of 437 women (22%) experienced 1 or more symptomatic fractures; 82 had fractures after 1 year.
One-year changes in hip DXA, NTX, and BAP were not related to subsequent fracture risk, but older age and lower hip DXA at time of discontinuation were significantly related to increased fracture risk (lowest tertile of baseline femoral neck DXA vs other 2 tertiles relative hazard ratio, 2.17 [95% CI, 1.38-3.41]; total hip DXA relative hazard ratio, 1.87 [95% CI, 1.20-2.92]).
The researchers 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.
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.
Bauer DC, Schwartz A, Palermo L, Cauley J, Hochberg M, Santora A, Cummings SR, Black DM. Fracture Prediction After Discontinuation of 4 to 5 Years of Alendronate Therapy JAMA Intern Med. Published online May 05, 2014. doi:10.1001/jamainternmed.2014.1232
Content updated 5 May 2014