Relationship between compliance and persistence with osteoporosis medications and fracture risk in primary health care in France: A retrospective case—control analysis

Background: Nonadherence to treatment is an important determinant of long-term outcomes in women with osteoporosis.Objectives: This study was conducted to investigate the association between adherence and osteoporotic fracture risk and to identify optimal thresholds for good compliance and persistence. A secondary objective was to perform a preliminary evaluation of the cost consequences of adherence.Method: This was a retrospective case-control analysis. Data were derived from the Thales prescription database, which contains information on >1.6 million patients in the primary health care setting in France. Cases were women aged ≥50 years who had an osteoporosis-related fracture in 2006. For each case, 5 matched controls were randomly selected. Both compliance and persistence aspects of treatment adherence were examined. Compliance was estimated based on the medication possession ratio (MPR). Persistence was calculated as the time from the initial filling of a prescription for osteoporosis medication until its discontinuation.Results: The mean (SD) MPR was lower in cases compared with controls (58.8% [34.7%] vs 72.1% [28.8%], respectively; P < 0.001). Cases were more likely than controls to discontinue osteoporosis treatment (50.0% vs 25.3%; P < 0.001), yielding a significantly lower proportion of patients who were still persistent at 1 year (34.1% vs 40.9%; P < 0.001). MPR was the best predictor of fracture risk, with an area under the receiver-operating-characteristic curve that was higher than that for persistence (0.59 vs 0.55). The optimal MPR threshold for predicting fracture risk was ≥68.0%. Compared with less-compliant women, women who achieved this threshold had a 51% reduction in fracture risk. The difference in annual drug expenditure between women achieving this threshold and those who did not was approximately €300. The optimal threshold for persistence with therapy was at least 6 months. Attaining this threshold was associated with a 28% reduction in fracture risk compared with less-persistent women.Conclusions: In this study, better treatment adherence was associated with a greater reduction in fracture risk. Compliance appeared to predict fracture risk better than did persistence.