Does the alcohol flushing response modify the relationship between alcohol consumption and the risk of developing osteonecrosis of the femoral head? A multicenter case-control study in Japan

Objectives Alcohol consumption is a recognized risk factor for osteonecrosis of the femoral head (ONFH), as well as hypertension, and malignant tumors. Aldehyde dehydrogenase 2 (ALDH2) activity influences alcohol-associated risks by modulating acetaldehyde metabolism; however, its role in ONFH remains unclear. This study aimed to investigate whether the alcohol flushing response, a proxy for ALDH2, modifies the relationship between alcohol consumption and ONFH. Methods A hospital-based case-control study was conducted on newly diagnosed patients with ONFH and controls recruited. Information on alcohol flushing responses was collected using a self-administered questionnaire and categorized into current/former flushers (inactive ALDH2) and never flushers (active ALDH2). Odds ratios (OR) and their 95% confidence intervals (CI) of various levels of alcohol consumption (habitual drinking, heavy drinking, and drinking of ≥320 g/week) were assessed for ONFH using a logistic regression model. Stratified analysis and multiplicative interaction were used to investigate the effect modification by the alcohol flushing response on the association between alcohol consumption and ONFH. Results A total of 118 cases with ONFH and 213 controls were included (mean age, 45 years; 197 men and 134 women). The adjusted ORs of alcohol consumption for the development of ONFH were 1.5 (95% CI: 0.4–6.0) and 3.7 (0.3–41.3) for habitual drinking, 1.6 (0.4–5.6) and 2.0 (0.1–24.2) for heavy drinking, and 3.8 (0.8–17.6) and 4.5 (0.4–49.2) for drinking of ≥320 g/week among current/former and never flushers, respectively. No significant multiplicative interactions were observed. Conclusion Alcohol flushing response may not modify the relationship between alcohol consumption and the risk of ONFH.