Background <p>Obesity and osteoporosis (OP) are becoming more prevalent and endangering people’s health. As the most commonly used indicator for assessing obesity, body mass index (BMI) has its limitations. The health issues caused by central obesity in the non-overweight state need to be addressed. The relationship between waist circumference (WC), a traditional indicator of central obesity, and bone health is controversial. To date, the association between WC and OP in non-overweight populations has been unclear. Our study therefore aimed to assess the association between WC and risk of OP in non-overweight U.S. adults.</p> Methods <p>This cross-sectional study included subjects aged 18&#xa0;years or older with a BMI ≤ 25&#xa0;kg/m² from National Health and Nutrition Examination Survey 1999–2018. A multivariable logistic regression model was used to assess the association between WC and risk of OP. Restricted cubic spline curves were used to evaluate the potential non-linear association. Subgroup and sensitivity analysis were conducted to assess the robustness of the results.</p> Results <p>3606 participants were included. A higher WC was associated with a reduced risk of OP, regardless of traditional confounders. Each 1&#xa0;cm increase in WC was associated with a 4% decrease in the risk of OP. Moreover, a non-linear association was observed. The association remaining consistent in sensitivity and subgroup analyses.</p> Conclusion <p>In non-overweight US adults, there is a negative association between WC and the risk of OP. The association between WC and OP exhibits a non-linear relationship.</p>