Telephone call intervention did not improve alendronate persistence in Fracture Liaison Service (FLS) patients in this study. A bone turnover marker cut-off point for alendronate persistence is proposed for individual FLS patients. FLS aims to prevent subsequent fractures, which should include improving patients' persistence with prescribed oral bisphosphonates. We studied the influence of telephone calls and the predictive value of changes in bone turnover markers (BTMs) for evaluating persistence with alendronate. Postmenopausal women with a recent fracture and osteoporosis who started alendronate were randomized to receive three phone calls (PC) (after 1, 4, and 12 months) or no phone calls (no PC). s-CTX and P1NP were measured at baseline and after 3, 6, 9, and 12 months. As a reference group, 30 postmenopausal osteopenic patients with a recent fracture were analyzed as well. Persistence was assessed using the Dutch National Switch Point Pharmacies-GPs database and cross-referenced with PC, no PC, and BTM changes. Cut-off values of BTMs were calculated based on least significant change (LSC) and also on underrunning median values of the untreated osteopenic postmenopausal reference group with a recent fracture. Out of 119 patients, 93 (78%) completed 12 months follow-up (45 PC and 48 no PC). Mean age was 69 years. Persistence was similar in PC and no PC participants. The cut-off value > 29% (<415 ng/L) as LSC of s-CTX and > 36% (<53.1 mu g/L) as LSC of P1NP was determined optimally showing alendronate persistence after 1 year (being 93 and 88%, respectively). In this context, telephone calls did not improve persistence. In around 90% of patients, 1-year alendronate persistence was confirmed by achieving LSC of s-CTX and of P1NP at 12 months.