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Use of Oral Bisphosphonates and the Risk of Aseptic Osteonecrosis: A Nested Case-Control Study
MAHYAR ETMINAN, KEVIN AMINZADEH, IAN R. MATTHEW, and JAMES M. BROPHY
ABSTRACT. Methods. We conducted a nested case-control study within a previously defined cardiovascular cohort of elderly Quebec patients using linked administrative health databases. Cases were defined as those with the diagnosis of hospitalization secondary to AON at a nonspecified site. For each case, 10 controls were randomly selected and matched to the cases by age, calendar time, and length of followup. The main outcome measure was the risk ratio (RR) of AON among ever-users of oral bisphosphonates compared to that among nonusers. As a quality measure, RR for AON among users of statin and angiotensin-converting enzyme inhibitors (ACE-I) compared to nonusers were also calculated. Results. The initial cohort consisted of 87,837 subjects. In the primary analysis, the adjusted RR for AON among bisphosphonate users was 2.87 (95% CI 1.71-5.05). The adjusted RR for alendronate, etidronate, and risedronate were 2.87 (95% CI 1.46-5.67), 2.43 (95% CI 1.05-5.62), and 3.34 (95% CI 1.04-10.67), respectively. There were no significant differences in RR for AON among current users (most recent drug exposure within 90 days of diagnosis) and past users (drug exposure between 91 and 365 days before diagnosis) of bisphosphonates. The adjusted RR for both statins and ACE-I were 0.79 (95% CI 0.49-1.07) and 1.16 (95% CI 0.79-1.70), respectively. Conclusion. In this cohort of elderly cardiovascular patients, an association was observed between oral bisphosphonate use and aseptic osteonecrosis. Further research into this putative association is required. (J Rheumatol First Release Jan 15 2008) Key Indexing Terms:
OSTEONECROSIS From the Center for Clinical Epidemiology and Evaluation, Vancouver General Hospital; Eagle Creek Dental Center; Department of Oral and Maxillofacial Surgery, University of British Columbia, Vancouver, BC; and the Department of Medicine, McGill University and University of Montreal, Montreal, Quebec, Canada. Dr. Brophy receives financial support from le Fonds de la Recherche en Santé du Québec. M. Etminan, PharmD, MSc, Center for Clinical Epidemiology and Evaluation, Vancouver General Hospital; K. Aminzadeh, DDS, Eagle Creek Dental Center; I.R. Matthew, PhD, MDentSc, BDS, FDSRCS (Eng & Ed), Department of Oral and Maxillofacial Surgery, University of British Columbia; J.M. Brophy, MD, PhD, FRCPC, Department of Medicine, McGill University and University of Montreal. Address reprint requests to Dr. M. Etminan, Center for Clinical Epidemiology and Evaluation, Vancouver General Hospital, 800 West 12th Avenue, Vancouver, British Columbia V7L 1M1, Canada. E-mail: metminan@shaw.ca Accepted for publication October 10, 2007. |
