Atherogenic high-fat diet reduces bone mineralization in mice

The epidemiological correlation between osteoporosis and cardiovascular dis ease is independent of age, but the basis for this correlation is unknown. We previously found that atherogenic oxidized lipids inhibit osteoblastic d ifferentiation in vitro and ex vivo, suggesting that an atherogenic diet ma y contribute to both diseases. In this study, effects of an atherogenic hig h-fat diet versus control chow diet on bone were tested in two strains of m ice with genetically different susceptibility to atherosclerosis and lipid oxidation, After 4 months and 7 months on the diets, mineral content and de nsity were measured in excised femurs and lumbar vertebrae using peripheral quantitative computed tomographic (pQCT) scanning. In addition, expression of osteocalcin in marrow isolated from the mice after 4 months on the diet s was examined. After 7 months, femoral mineral content in C57BL/6 atherosc lerosis-susceptible mice on the high-fat diet was 43% lower (0.73 +/- 0.09 mg vs. 1.28 +/- 0.42 mg; p = 0.008), and mineral density was 15% lower comp ared with mice on the chow diet. Smaller deficits were observed after 4 mon ths. Vertebral mineral content also was lower in the fat-fed C57BL/6 mice. These changes in the atherosclerosis-resistant, C3H/HeJ mice were smaller a nd mostly not significant. Osteocalcin expression was reduced in the marrow of high fat-fed C57BL/6 mice, These findings suggest that an atherogenic d iet inhibits bone formation by blocking differentiation of osteoblast proge nitor cells.