Background: Hypercholesterolaemia has been associated with low bone mineral density (BMD) in some but not all studies. Objectives: To examine the influence of age, menopausal status and hormone replacement therapy (HRT) on the relationship between serum cholesterol and BMD in women. Patients and measurements: 497 female participants (age range 20-81) comprising 224 premenopausal and 273 postmenopausal women (156 on HRT and 117 no HRT) underwent measurements of bone mineral density (BMD) and serum lipid profile. Results: Total serum cholesterol (TC) and low density lipoprotein (LDL) levels were higher and lumbar spine BMD was lower in postmenopausal women not taking HRT compared to those taking HRT. TC and LDL were negatively associated with BMD at all measured sites among postmenopausal women not taking HRT in univariate regression analysis (all p<0.05). High density lipoprotein (HDL) had inverse relationships with BMD at all sites in pre-menopausal women and those who were exposed to HRT (p<0.05). In fully adjusted regression models the relationships between TC and BMD remained significant at the lumbar spine and whole body (p<0.05) and between LDL and lumbar spine BMD only (p<0.05). For subjects in the other groups, no significant associations between TC or LDL and BMD were found. Significant interactions between total cholesterol and LDL levels with HRT were detected among post-menopausal women in the regression analyses (all p<0.05). No such interactions were found between HDL levels and HRT. Conclusion: There is a modest inverse relationship between lumbar spine and whole body BMD and serum TC and LDL levels and in post-menopausal women and HDL in pre-menopausal women. HRT use appears to modify these relationships. The mechanisms of this relationship require further study. (C) 2008 Elsevier Inc. All rights reserved.