Epidemiological observations support a positive relationship between cardiovascular diseases (CVD) and osteoporosis, where cholesterol has been indicated to be a possible link. Only a few studies have investigated the relation between lipids and BMD, but the association remains unclear. We studied the relationship between serum lipids and BMD of the calcaneus. A cross-sectional population-based study was performed, based on data from the Longitudinal Aging Study Amsterdam, including 620 men and 635 women, 65-88 yr of age. BMD was measured by quantitative ultrasound (QUS), velocity of sound (VOS; m/s), and broadband ultrasound attenuation (BUA; dB/MHz). Models were adjusted for age, body mass index, physical activity, smoking, alcohol, diabetes mellitus, hypertension, testosterone, and 25-hydroxyvitamin D. No association was found between total cholesterol (TC) and QUS. Men and women in the highest quartile of high-density lipoprotein cholesterol (HDL-c) had a significantly lower QUS (men-VOS: beta = -20.8, p = 0.00; BUA: beta = -5.2, p = 0.02; women-VOS: beta = -18.6, p = 0.00) compared with men and women in the lowest quartile. An even stronger positive association was seen between TC/HDL-c ratio and QUS (men-VOS: beta = 21.8, p = 0.00; BUA: beta = 5.5, p = 0.01; women-VOS: beta = 19.2, p = 0.00; BUA: beta = 3.6, p = 0.05). Our analysis shows that the lipid profile that is favorable in the prevention of CVD (i.e., high levels of HDL-c and low TC/HDL-c ratio) is unfavorable for QUS. These results indicate that HDL-c levels do not explain the association between osteoporosis and CVD.