Evaluting Effectiveness and Safety of Long-Term BisphosphonateI Use among Women Aged 50 or Older

Backgrounds Osteoporosis is a prevalent illness among women in Taiwan and around the world. Complications resulting from osteoporosis fractures increase patients’ health resource utilization, morbidity, and mortality. Pharmacotherapy, including bisphosphonates, is effective to treat osteoporosis and often recommended for patients with a history of fractures. Although bisphosphonates often serve as the first-line therapy, studies evaluating the long-term effect (i.e., treatment duration > 5 years) of bisphosphonate use are limited, given that most efficacy data are from trials conducted in short study period and with relatively small sample sizes. Side effects such as osteoporosis of the jaw, atypical fractures, and esophageal cancer are suspected to be induced by long-term bisphosphonate use. Furthermore, whether taking a low dose bisphosphonate among long-term users could provide the same protection effect for fractures and lower the risk of adverse events are still unclear. Objectives The purpose of this study is to evaluate the effectiveness and safety of long-term bisphosphonate use (i.e., bisphosphonate treatment > 5 years) among women aged 50 years or older. The study will compare time to fractures between long-term bisphosphonate users and regular bisphosphonate users. The study will further evaluate whether a low dose bisphosphonate use can prevent osteoporosis fractures when compared to a guideline (The National Osteoporosis Foundation: Clinician's Guide to Prevention and Treatment of Osteoporosis) recommended bisphosphonate dose among long term bisphosphonate users. Methods This will be a retrospective cohort study with a new drug user design. Outcomes are time to fractures and time to severe side effects. Propensity score matching will be used to balance measurable confounders between study groups. Kaplan-Meier survival curves and Cox-proportional hazard models will be used to compare rate of fractures and side effects between long-term bisphosphonate users and regular users. Furthermore, the time to fractures and time to severe side effects will also be compared between patients receiving low bisphosphonate doses and patients receiving recommended doses among long-term bisphosphonate users. Anticipated Outcomes Using National Health Insurance Research Database, the results of this study are highly generalizable to routine clinical practice and provide rich clinical evidence for clinicians to evaluate the appropriateness of long-term bisphosphonate use. The results also provide clinical evidence to help clinicians to improve treatment safety and treatment outcomes for long-term bisphosphonate users with osteoporosis.