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J Orthop Sci. 2012 Nov;17(6):730-6. doi: 10.1007/s00776-012-0293-x. Epub 2012 Aug 29.

Pronounced risk of nontraumatic osteonecrosis of the femoral head among cigarette smokers who have never used oral corticosteroids: a multicenter case-control study in Japan.

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  • 1Department of Public Health, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan.



Cigarette smoking has been linked to an increased risk of nontraumatic osteonecrosis of the femoral head (ONFH) in previous studies. However, the effect of smoking amount, duration and cessation, and interaction with corticosteroids remains unclear. The purpose of this study was to precisely evaluate the effects of smoking and the interaction with corticosteroid use.


This was a multicenter, matched case-control study in Japan. Cases were defined as patients who were newly diagnosed with ONFH at an initial visit or during the previous year if they were referred patients. For each case, matched controls were selected from patients without ONFH. The matching conditions were sex, age, and ethnicity. A logistic regression model was used to compute odds ratios (OR) and 95 % confidence intervals (95 % CI).


We compared 72 cases with 244 matched controls. ORs were 3.89 (95 % CI 1.46-10.4) for current smokers, 3.89 (1.22-12.4) for smokers consuming more than 20 cigarettes per day, 4.26 (1.32-13.7) for smokers with 26 pack-years or more, and 3.11 (0.92-11.5) for smokers with a history of 29 years or more, with significant or marginally significant dose-response relationships. OR for current smokers was 10.3 among those who had never used corticosteroids and 1.56 among past or current corticosteroid users (P for interaction 0.010).


Our results revealed that heavier cigarette smoking was associated with a higher risk of ONFH. The elevated risk from cigarette smoking was markedly pronounced among those who had never used oral corticosteroids.

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