Original Article

Osteoporosis International

, Volume 24, Issue 10, pp 2639-2647

First online:

Association between refill compliance to oral bisphosphonate treatment, incident fractures, and health care costs—an analysis using national health databases

  • K. R. OlsenAffiliated withGSK Pharma A/S, Nykær 68
  • , C. HansenAffiliated withResearch Unit of Nursing, Institute of Clinical Research, Faculty of Health Sciences, University of Southern DenmarkDepartment of Medicine C, Gentofte University Hospital
  • , B. AbrahamsenAffiliated withDepartment of Medicine F, Gentofte University HospitalOdense Patient Data Exploratory Network, Institute of Clinical Research, Faculty of Health Sciences, University of Southern Denmark Email author 

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The study estimates the cost of poor and suboptimal refill compliance by estimating fracture costs and assessing the association between refill compliance with oral bisphosphonates and incident fractures using Danish health registers. Patients with poor and suboptimal refill compliance had more major osteoporotic fractures, and the direct costs related to hospital care, primary care, and pharmaceutical treatment for these excess fractures reached almost 14 M DKK (2.5 M USD) for the study population which compares to a national annual excess cost of around 17 M DKK (3.1 M USD) using 2011 prescription prevalence.


Adherence to oral anti-osteoporosis treatment has been shown in several studies to be relatively low and the potential impact on fracture burden is high. The aim of the study was to assess the association between refill compliance and all-cause health care costs.


A national dataset was extracted with all treatment-naive patients who began oral bisphosphonate (BP) treatment for osteoporosis in Denmark between 1997 and 2006 (N = 54,876, 87 % women). Patients who survived for at least 2 years (N = 47,176) were divided into groups based on Medication Possession Ratio (MPR). Logistic regressions were used to derive difference in the probability of incident fractures between the three MPR groups. Fracture costs (related to medication use, primary care practice, specialists, and hospitals) were derived by comparing cost 12 months before and after fracture.


For alendronate, the adjusted risk of major osteoporotic fractures was significantly reduced (OR 0.768; 0.686–0.859), including fractures of the hip (0.718; 0.609–0.846) and humerus (0.54; 0.431–0.677) with MPR ≥ 0.8. The risk reduction was lower with etidronate. Over 2 years, a total of 171 hip fractures and 53 other major osteoporotic fractures were attributed to suboptimal or poor refill compliance, with an excess cost of 13.7 M DKK (2.5 M USD).


Poor refill compliance is not unusual in patients on oral bisphosphonates, and we demonstrate that this is accompanied by excess major osteoporotic fractures and health care costs at the societal level.


Bisphophonates Epidemiology Fractures Health economics Osteoporosis