BACKGROUND: Although bisphosphonates are useful in the management of osteoporosis, patients often discontinue treatment. OBJECTIVES: The aims of this study were to investigate persistence with bisphosphonates, and to assess whether the dose intervainfluenced persistence, among women with postmenopausal osteoporosis. METHODS: Data were obtained from the PHARMO Record Linkage System, which includes, among other databases, drug-dispensing records from community pharmacies linked to hospital discharge records of > 1 million subjects in defined areas in The Netherlands. Women who were new users of alendronate (daily or weekly), etidronate (daily), or risedronate (daily) during the period from January 2000 through September 2003 were eligible for inclusion in the study if they were aged > or = 55 years or had been hospitalized for a menopausal disorder. One-year rates of persistence with treatment (defined as the percentage of patients who used the drug for > or = 365 days without failure to continuerenewals) were determined by using episodes of bisphosphonate treatment. The association between persistence and dose intervals, type of bisphosphonate, and other determinants (including age, occurrence of gastrointestinal adverse events as measured byuse of concomitant medications [eg, antacids, proton pump inhibitors, histamine2 (H2)-receptor antagonists, misoprostol, laxatives, antidiarrheals, bowel motility enhancers] and fractures) was assessed. To study whether persistence with bisphosphonates was associated with the former use of other antiosteoporosis medication or the presence of drug-induced osteoporosis, the use of hormone replacement therapy, raloxifene, and systemic corticosteroids in the 6 months before the index date were included as determinants. RESULTS: The study sample included 2124 women who were new users of bisphosphonates. The mean (SD) age of the study population was 71.6 (8.7) years. After 1 year, 51.9% of weekly alendronate users and 30.1% to 42.2% of daily bisphosphonate users were persistent. In the multivariate analysis (which included age, concomitant medication, and fractures), patients using alendronate weekly were significantly more likely to persist than those using alendronate daily (relative risk [RR], 1.56 [95%CI, 1.32-1.85]). The likelihood of persistence was similar among those who used the daily regimens of risedronate, etidronate, and alendronate. The occurrence of gastrointestinal adverse events was associated with decreased persistence with bisphosphonates (H2)-receptor antagonists: RR, 0.71 [95% CI, 0.53-0.94]; bowel motility enhancers: RR, 0.78 [95% CI, 0.65-0.94]). CONCLUSIONS: In this study, dose interval and the occurrence of gastrointestinal adverse events were independent determinants of persistence with bisphosphonate therapy. Although the likelihood of persistence with bisphosphonate use was significantly higher among those who used a less frequently administered regimen, persistence rates were still suboptimal.