The study results showed that ESR2 RsaI was not significantly correlated with osteoporosis; however, when stratified analysis by ethnicity was performed, a significant correlation was observed between the loci and osteoporosis in Asians (OR = 0.69, 95% CI = 0.58–0.82, P value < 0.001) but not in Caucasians. Here, ESR2 is linked to osteoporosis.