Use of oral bisphosphonates and the risk of aseptic osteonecrosis: a nested case-control study.
OBJECTIVE
To determine whether use of oral bisphosphonates is associated with an increased risk of aseptic osteonecrosis (AON) among a cohort of elderly cardiovascular patients.


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.


CONCLUSIONS
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.
Etminan
Mahyar
M
Center for Clinical Epidemiology and Evaluation, Vancouver General Hospital, Vancouver, BC, Canada. metminan@shaw.ca
Aminzadeh
Kevin
K
Matthew
Ian R
IR
Brophy
James M
JM
D000368:Aged; D050071:Bone Density Conservation Agents / Q000009:adverse effects*; D016022:Case-Control Studies; D004164:Diphosphonates / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007568:Jaw / Q000473:pathology; D007571:Jaw Diseases / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D016017:Odds Ratio; D010020:Osteonecrosis / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D012189:Retrospective Studies; D012307:Risk Factors
D050071:Bone Density Conservation Agents; D004164:Diphosphonates