Long-term impact of adherence to oral bisphosphonates on osteoporotic fracture incidence.

Adherence to osteoporosis treatments is a critical parameter resulting in suboptimal effectiveness in real-life practice. The long-term effect of adherence on fracture risk has not been assessed. This was a retrospective study using provincial health insurance claims databases to assess the association between adherence to oral bisphosphonates (OBP) and incidence of osteoporotic fractures in all Ontario patients with osteoporosis between April 1996 and December 2009. Multivariate logistic regression models were used to assess the association between OBP adherence and fracture risk. Treatment duration was classified into 2-year intervals. Compliance was estimated with the medication possession ratio (MPR), and persistence was defined as the length of continuous therapy without a gap in refills >30 days. The study cohort was composed of 636,114 patients, among whom 36.1% were prescribed OBPs for 0 to 2 years, 19.7% for 2 to 4 years, 15.1% for 4 to 6 years, 12% for 6 to 8 years, 9.1% for 8 to 10 years, 6.1% for 10 to 12 years, and 1.9% for 12 to 14 years. Overall, the mean (SD) compliance for the cohort was 0.72 (0.30) with 53.5% of the patients having compliance >80% and 24.6% being persistent with treatment during the 14-year follow-up period. Significant associations between high adherence and reduced fracture risk over the entire 14-year period were observed; the overall odds ratio for categorical compliance (MPR >80% or MPR ≤80%), continuous compliance, and persistence were 0.909 (95% confidence interval [CI] 0.893-0.925), 0.918 (95% CI 0.893-0.944), and 0.804 (95% CI 0.787-0.821), respectively. In conclusion, adherence to OBP in osteoporosis management is suboptimal in a real-life setting. A significant positive association exists between poor adherence and increased risk of osteoporotic fractures, which becomes augmented with longer treatment duration.