IMPORTANCE Discontinuation of bisphosphonate therapy after 3 to 5 years is increasingly considered, but methods to monitor fracture risk after discontinuation have not been established. OBJECTIVE To test methods of predicting fracture risk among women who have discontinued alendronate therapy after 4 to 5 years. DESIGN, SETTING, AND PARTICIPANTS The prospective Fracture Intervention Trial Long-term Extension (FLEX) study randomized 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. MAIN OUTCOMES AND MEASURES Symptomatic spine and nonspine fractures occurring after the follow-up measurement of DXA or bone turnover. RESULTS 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]). CONCLUSIONS AND RELEVANCE Among postmenopausal women who discontinue alendronate therapy after 4 to 5 years, age and hip BMD at discontinuation predict clinical fractures during the subsequent 5 years. Follow-up measurements of DXA 1 year after discontinuation and of BAP or NTX 1 to 2 years after discontinuation are not associated with fracture risk and cannot be recommended. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00398931.