Authors: Keshishian A, Boytsov N, Burge R, Krohn K, Lombard L, Zhang X, Xie L, Baser O.

Background: In the United States, osteoporosis affects approximately 10 million people, of whom 80% are women, and it contributes a significant clinical burden to the community. Poor adherence to osteoporosis medications adds to the overall burden of illness.

Objective: To examine the association of osteoporosis medication adherence and the risk of a subsequent fracture among Medicare-enrolled women with a previous fragility fracture.

Methods: This study was a retrospective observational analysis of U.S. administrative claims data among female Medicare beneficiaries who had a nontrauma closed fragility fracture between January 1, 2011, and December 31, 2011. Patients were required to have continuous medical and pharmacy enrollment 12 months pre- and postfracture date. In addition, patients were required to have an osteoporosis medication prescription for a bisphosphonate (alendronate, risedronate, pamidronate, etidronate, zoledronate, and tiludronate), calcitonin, denosumab, raloxifene, or teriparatide during the follow-up period. Adherence was calculated using cumulative medication possession ratio (MPR) from the treatment initiation date in 30-day increments. MPR was stratified into high adherence (MPR ≥ 80%), moderate adherence (50%≤MPR>80%), and low adherence (MPR<50%). Outcomes included first subsequent fracture after treatment initiation; patients were censored at treatment discontinuation, or end of the 12-month period posttreatment initiation. Covariates included demographics, comorbidities, osteoporosis medications, medications associated with falls, and health care utilization. Cox regression was used to model subsequent fractures with time-dependent cumulative MPR.

Results: Of the 1,292,248 Medicare enrollees who had a fracture in 2011, a total of 103,852 (8.0%) women aged ≥65 years with a fragility fracture were identified. Overall, 27,736 (26.7%) patients were treated with osteoporosis medication within 12 months of the fragility fracture (mean time to treatment initiation was 85.0 ± 84.6 days). Over half of the patients were highly adherent (MPR≥80%) to osteoporosis medications during the follow-up (n=14,112; 50.9%). Almost a third of the patients had low adherence (MPR<50%; n=9,022, 32.5%), followed by patients with moderate adherence (50%≤MPR>80%; n=4,602, 16.6%). After adjusting for demographics and clinical characteristics, patients with low and moderate adherence to osteoporosis medications were 33% (hazard ratio [HR]=1.33; 95% CI=1.17-1.50, P<0.001) and 19% (HR=1.19; 95% CI=1.02-1.38, P=0.026) more likely to have a subsequent fracture, respectively, compared with patients with high adherence. Low adherence patients had a 32% and 34% increased risk for a hip/pelvis/femur fracture (HR=1.32; 95% CI=1.09-1.59, P=0.005) and a clinical vertebral fracture (HR=1.34; 95% CI=1.09-1.63, P=0.005), respectively, compared with high adherence patients.

Conclusions: Medicare-enrolled women with low and moderate adherence to osteoporosis medications had a higher risk of a subsequent fracture compared with high adherence patients. These results highlight the importance of improving osteoporosis medication adherence among women enrolled in Medicare.

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