ABSTRACTObjective: Non-adherence to oral bisphosphonate medications is a pervasive problem that blunts their potential to prevent fractures. Using multivariate modeling, we assessed the unique contribution of six classes of variables as drivers of non-adherence to bisphosphonates: (1) beliefs about osteoporosis and its prescription drug treatment, (2) ratings of the affordability of the prescription osteoporosis medications, (3) evaluations of the convenience of the bisphosphonate dosing frequency, (4) reports of troublesome side effects, (5) ratings of aspects of the bisphosphonate dosing regimen, and (6) risk factors for fracture. These categories of predictor variables were selected for investigation because they have been suggested by clinical-trial, survey, and observational studies in osteoporosis as reasons for non-adherence among patients taking prescription osteoporosis therapy.Methods: Women aged 45 or older who filled a prescription for an oral bisphosphonate in January or February of 2006 were identified through a dispensing database of 3300 US retail pharmacies. Subjects received a mailed pre-notification letter from the retail pharmacy chain informing them that someone would be calling them to invite them to participate in a telephone survey about osteoporosis medications. Trained interviewers used a standardized telephone script to recruit patients. Our definition of adherence was provisionally based on database records across a 7-month period and then cross-validated using patient self-report during the telephone recruitment. We measured beliefs regarding bisphosphonate effectiveness and safety, osteoporosis health concerns, concerns regarding drug costs, dosing frequency convenience, and experienced side effects using multi-item scales. Data were collected by telephone interview. Bivariate analyses were conducted using χ2 and t-tests, and multivariate analyses were conducted using logistic regression.Results: Of the 3274 women contacted for study participation, 1092 (33%) completed the interview and 1015 had analyzable data. Multivariate analyses showed that those most symptomatic in terms of side effects and those with the most skeptical beliefs in drug effectiveness and drug safety had odds ratios for non-adherence of 6.78 (95% CI 4.67–9.86), 5.70 (95% CI 3.65–8.92), and 2.26 (95% CI 1.49–3.42), respectively. In multivariate models, osteoporosis health concerns, dosing frequency convenience, and concerns regarding medication costs were not statistically associated with non-adherence to bisphosphonate therapy.Conclusions: The experience of troublesome side effects and patient beliefs regarding the effectiveness and safety of oral bisphosphonate medications prescribed for them are strongly associated with bisphosphonate non-adherence. Improving adherence to oral bisphosphonates may require providers to solicit and address patients’ medication beliefs and to proactively address side effects. Limitations of our study include: (1) the study sample is not likely to be a national random sample of bisphosphonate users, and (2) some evidence of non-response bias was observed.