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Alcohol-induced osteonecrosis of the femoral head (ONFH) is an important pathogenesis of nontraumatic ONFH. However, the mechanisms of the pathogenesis are still unknown. Osteoprotegerin (OPG) and receptor activator of nuclear factor-kappa B ligand (RANKL) have been implicated in multiple functions including blocking osteoclast maturation, controlling vascular calcifications, and promoting tumor growth and metastasis. The purpose of this article was to explore the association between  OPG  and  RANKL  gene variants and alcohol-induced ONFH. Six hundred seventy male subjects (335 patients and 335 normal individuals) were enrolled in our study. We selected 24 single-nucleotide polymorphisms (SNPs) to evaluate the association between genetic susceptibility variants and alcohol-induced ONFH using the chi-square test and gene model analysis. Overall, the  OPG  SNPs (rs1032128 and rs11573828) were associated with the strongest increased risk of alcohol-induced ONFH in the recessive model (rs1032128: odds ratio [OR] 1.49, 95% confidence interval [CI] 1.00–2.22,  P  = 0.04 for G/A; rs11573828: OR 3.32, 95% CI 1.07–10.30,  P  = 0.03 for T/C). The  RANKL  SNP rs2200287 was also an increased risk factor (OR 3.65, 95% CI 1.53–8.47,  P  = 0.003 for T/C) in the recessive model. The rs11573856, rs3134056, and rs1564861 SNPs were considered protective factors for alcohol-induced ONFH. We concluded that  OPG  and  RANKL  polymorphisms were associated with the occurrence of alcohol-induced ONFH.

OPG and RANKL polymorphisms are associated with alcohol-induced osteonecrosis of the femoral head in the north area of China population in men