High-fat diet decreases cancellous bone mass but has no effect on cortical bone mass in the tibia in mice

Body mass has a positive effect on bone health. Whether mass derived from an obesity condition or excessive fat accumulation is beneficial to bone has not been established; neither have the mechanisms by which obesity affects bone metabolism. The aim of this study was to examine the effects of obesity on bone structure and osteoblastic expression of key markers involved in bone formation and resorption in a diet-induced obesity mouse model. Six-wk-old male C57BL/6 mice (n=21) were assigned to two groups and fed either a control (10 kcal% energy as fat) or high-fat diet (HFD, 45 kcal% energy as fat) for 14 weeks. Bone marrow stromal/osteoblastic cells (BMSC) were cultured. Osteoprogenitor activity [alkaline phosphatase (ALP) positive colonies] and mineralization (calcium nodule formation) were determined. Gene expression was measured using quantitative real-time PCR. Bone structure of proximal and midshaft tibia was evaluated by micro-computed tomography. Mice fed the HFD were 31% heavier (P<0.01) than those fed the control diet. There were more ALP positive colony forming units at d 14 and calcium nodules at d 28 of culture by BMSC from HFD mice than from control mice (P<0.01). Receptor activator of NF-kappaB ligand (RANKL) mRNA levels and the ratio of RANKL to osteoprotegerin expression in HFD animals was higher (P<0.01) than in control diet animals. Serum tartrate-resistant acid phosphatase levels were higher in HFD fed mice when compared to control diet fed mice (P<0.05). There were no significant differences in tibial fat-free weight, length, and cortical parameters of midshaft between the two groups. Compared with control mice, tibial trabecular bone volume was reduced, and trabecular separation was increased in HFD mice. Trabecular number was lower (P<0.05) and connectivity density tended to be less (P=0.07) in HFD mice than in control mice. In conclusion, our data indicate that obesity induced by a high-fat diet decreases cancellous bone mass but has no effect on cortical bone mass in the tibia in mice.