Consequences of poor compliance with bisphosphonates Becky A. Briesacher a,b, ⁎ , Susan E. Andrade b , Robert A. Yood b , Kristijan H. Kahler c a University of Massachusetts Medical School, Division of Geriatric Medicine, Biotech Four, Suite 315, 377 Plantation Street, Worcester, MA 01605, USA b Meyers Primary Care Institute (University of Massachusetts Medical School, The Fallon Clinic Foundation, and Fallon Community Health Plan), Worcester, Massachusetts, USA c Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA Received 7 March 2007; revised 29 June 2007; accepted 10 July 2007 Available online 18 July 2007 Abstract Background: Prior research on the ability of bisphosphonates to prevent fractures and related health care utilization has been based on high levels of compliance achievable in clinical trial settings. This study was undertaken to assess rates of osteoporotic fractures and health care utilization as a function of bisphosphonate compliance in usual clinical practice. Methods: This retrospective cohort study used 2000–2004 pharmacy and medical claims data from 45 large U.S. employers. Our sample included persons diagnosed with osteoporosis, aged 40 years or older, and who initiated use of either alendronate or risedronate. Main outcome measures were medication compliance, rates of osteoporotic fracture, and costs for inpatient care, outpatient services, and prescription drugs. Results: We identified 17,988 new users of bisphosphonate therapy. After 1 to 3 years of follow-up, only 30.6% to 42.9% of patients could achieve high compliance (80%–100%), 17.4%–23.0% moderate compliance (79%–40%), and 33.8%–52.0% had low compliance (0%–39%). Multivariate models of fracture risk showed benefits ( p b 10) with compliance levels of at least 60%, after which no risk benefit could be detected. Multivariate models of health care costs showed statistically significant ( p b .05) total costs savings of $859 to $366 per year with high to moderate compliance levels. However, individuals achieving less than 40% compliance had no detectable decrease in inpatient or outpatient costs to offset the increase in drug costs. Conclusions: Reductions in fracture risk and overall health costs can be detected in individuals achieving as little as 60% to 40% compliance with bisphosphonates. However, as many as 34% of patients in the first year of therapy and 52% by the third year will not reach even the minimal compliance levels required to receive benefits. Published by Elsevier Inc. Keywords: Patient compliance; Bisphosphonates; Health care costs Introduction Most patients who initiate a medication for osteoporosis do not continue to take it as prescribed [7,14,20]. For example, 1 year after initiating drug therapy for osteoporosis, 45.2% of over 40,000 Medicare patients did not continue filling prescriptions, and 52.1% stopped their therapy within 5 years [20]. Prior research on the ability of osteoporosis medications to prevent fractures and related health care utilization has been based on higher levels of compliance (N 75%) as achievable in clinical trial settings [3,2]. Studies on the relationship between compliance with bisphosphonate therapy (BPs) or estrogens and change in bone density have found statistically significant differences for patients with compliance above 66% compared to those with lower compliance [10,23]. We examined the rates of osteoporotic fractures and health care utilization as a function of compliance with BPs in a large population with employer-sponsored health insurance. Our analysis assessed the entire range of compliance from 0% to 100% because there is no accepted standard for establishing when enough medication has been taken to achieve clinical targets [8]. Furthermore, we assessed fracture rates and health care utilization as a function of the previous year's compliance with BPs. Randomized clinical trials of BPs versus placebo showed statistically significant reductions in fracture risk after 12–18 months of initiating therapy [4,12]. We hypothesized that the benefits of BP therapy in reducing osteoporotic fractures and Bone 41 (2007) 882 – 887 www.elsevier.com/locate/bone ⁎ Corresponding author. University of Massachusetts Medical School, Division of Geriatric Medicine, Biotech Four, Suite 315, 377 Plantation Street, Worcester, MA 01605, USA. Fax: +1 508 856 5024. E-mail address: Becky.Briesacher@umassmed.edu (B.A. Briesacher). 8756-3282/$ - see front matter. Published by Elsevier Inc. doi:10.1016/j.bone.2007.07.009