Low-density lipoprotein cholesterol (LDL-C) plays an essential part in bone metabolism. However, the correlation between LDL-C levels and bone mineral density (BMD) is still controversial. This study aimed to explore the relationship between LDL-C levels and lumbar BMD in young- and middle-aged people.We conducted a cross-sectional study comprising 4,441 participants aged 20-59 from the National Health and Nutrition Examination Survey (NHANES). LDL-C levels and lumbar BMD were used as independent and dependent variables, respectively. We evaluated the correlation between LDL-C levels and lumbar BMD through a weighted multivariate linear regression model. We performed a subgroup analysis of the relationship between LDL-C levels and lumbar BMD based on age, gender, and body mass index (BMI).After adjusting for confounding factors, LDL-C levels were negatively correlated with lumbar BMD. In subgroup analyses stratified by gender, this negative association was statistically significant in men and women. In the subgroup analysis stratified by age, a negative connection existed in people aged 30-49 years. In the subgroup analysis divided by BMI, there was an inverse correlation in overweight people (25 ≤ BMI < 30).Our research observed an inverse association between LDL-C levels and lumbar BMD in young- and middle-aged people, especially in people aged 30-49 years and who are overweight. Close monitoring of BMD and early intervention may be required for these people.Copyright © 2022 Xiao, Peng, Gao, Lin, Fang and He.