OBJECTIVES Osteoporosis treatment involves several therapeutic tools, including long-term drug therapy. Subjects with chronic disorders are more likely to be non-adherent and/or non-persistent to treatment than those with other diseases. Adherence is the extent to which patients take medication as prescribed by their physicians, whereas persistence is the time from treatment initiation to discontinuation. Lack of persistence is common among subjects using oral anti-osteoporotic drugs, and leads to increased risk of fragility fracture. The aim of our study is to analyze the rates and reasons for discontinuation of anti-osteoporotic drugs in the Campania Region. METHODS The study was a retrospective cohort study. Patients, aged ≥ 40 years, were enrolled if at least one prescription for any antiosteoporotic drugs had been filled from July 1, 2009 through June 30,2010. Data were retrieved from an administrative database of medications prescription in Campania region. Patients were followed from the index date until the antiosteoporotic therapy discontinuation or end of the observation period (June, 30, 2011). RESULTS A total of 30,048 were incident users of anti-osteoporotic drugs:1,731 (5.8%) males and 28,317 (94.2%) females. The mean age [SD] of the cohort was 69.0 [10.0] years. Weekly bisphosphonate (51.1%), was the most commonly prescribed drug. In the overall cohort study, persistence rates were 34,8% after 6 months, 13,4% at one year. A multivariate Cox proportional hazard analysis showed that daily regimen (HR 1,9) treatments remained at a higher risk of early discontinuation compared to weekly regimen therapies. Patients who started treatment with a co-prescription with calcium and vitamin D had a lower risk of early discontinuation (HR 0.7). CONCLUSIONS Our data showed that the persistence to osteoporosis therapy is significantly worse than reported in literature. A better osteoporosis management should include drugs with less frequent dosing, to obtain both an increase in rate of persistence and a reduction in side-effect.