The Potential Effects on Fracture Outcomes of Improvements in Persistence and Compliance with Bisphosphonates

Background: Osteoporotic fractures are a substantial public health burden worldwide. Evidence from studies show that treatments, such as bisphosphonates, which reduce the risk of fractures when taken regularly and long term, are being used irregularly and suboptimally. The objective of this study was to quantify the additional number of hip fractures prevented by improving persistence and compliance with bisphosphonates.

Methods: The study population included patients prescribed alendronate or risedronate in the UK General Practice Research Database. Individualized probabilities of fracture and death during bisphosphonate therapy and of treatment persistence and compliance were estimated by age, gender, dosage, calendar year and clinical risk factors using Cox regression. Persistence was calculated by measuring repeat prescribing and compliance by estimating the medication possession ratio. A unique patient-based decision model was then developed using these probabilities. By varying the persistence and compliance probabilities in the simulation, the fracture outcomes with different scenarios were then evaluated. The outcomes were simulated over a 4-year period (maximum of three years of bisphosphonate use followed by 1 year of offset). It was assumed that the bisphosphonate users had experienced similar fracture reductions as observed in clinical trials.

Results: The study population included 44 531 patients. Modelling showed that improvement of the 3-year persistence by 10% (over current persistence) would prevent an additional 14.4 hip fractures per 10 000 patients with weekly treatment. If weekly was substituted with yearly treatment (refill once a year), an additional 68.4 hip fractures (per 10 000 patients) would be prevented. If 3-year persistence improved by 10% with yearly treatment, an additional 78.5 hip fractures would be prevented compared to monthly bisphosphonates. The effects of this substitution were largest in elderly patients and in women.

Conclusion: Improvements in treatment persistence and compliance may improve the impact of bisphosphonates in reducing the risk of fractures. Yearly administration may also improve the impact on fracture risk reduction, unless long-term persistence is substantially reduced.