title: Adverse effects of hyperlipidemia on bone regeneration and strength.
abstract: Hyperlipidemia increases the risk for generation of lipid oxidation products, which accumulate in the subendothelial spaces of vasculature and bone. Atherogenic high-fat diets increase serum levels of oxidized lipids, which are known to attenuate osteogenesis in culture and to promote bone loss in mice. In this study, we investigated whether oxidized lipids affect bone regeneration and mechanical strength. Wild-type (WT) and hyperlipidemic (Ldlr(-/-)) mice were placed on a high-fat (HF) diet for 13 weeks. Bilateral cranial defects were introduced on each side of the sagittal suture, and 5 weeks postsurgery on the respective diets, the repair/regeneration of cranial bones and mechanical properties of femoral bones were assessed. MicroCT and histological analyses demonstrated that bone regeneration was significantly impaired by the HF diet in WT and Ldlr(-/-) mice. In femoral bone, cortical bone volume fraction (bone volume [BV]/tissue volume [TV]) was significantly reduced, whereas cortical porosity was increased by the HF diet in Ldlr(-/-) but not in WT mice. Femoral bone strength and stiffness, measured by three-point bending analysis, were significantly reduced by the HF diet in Ldlr(-/-), but not in WT mice. Serum analysis showed that the HF diet significantly increased levels of parathyroid hormone, tumor necrosis factor (TNF)-α, calcium, and phosphorus, whereas it reduced procollagen type I N-terminal propeptide, a serum marker of bone formation, in Ldlr(-/-), but not in WT mice. The serum level of carboxyl-terminal collagen crosslinks, a marker for bone resorption, was also 1.7-fold greater in Ldlr(-/-) mice. These findings suggest that hyperlipidemia induces secondary hyperparathyroidism and impairs bone regeneration and mechanical strength.
authors: Division of Diagnostic and Surgical Sciences, School of Dentistry, University of California, Los Angeles, Los Angeles, CA, USA.
authors: Flavia
authors: F
authors: Pirih
authors: Jinxiu
authors: J
authors: Lu
authors: Fei
authors: F
authors: Ye
authors: Olga
authors: O
authors: Bezouglaia
authors: Elisa
authors: E
authors: Atti
authors: Maria-Grazia
authors: MG
authors: Ascenzi
authors: Sotirios
authors: S
authors: Tetradis
authors: Linda
authors: L
authors: Demer
authors: Tara
authors: T
authors: Aghaloo
authors: Yin
authors: Y
authors: Tintut
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D001696:Biomechanical Phenomena / Q000502:physiology; D001786:Blood Glucose / Q000378:metabolism; D001861:Bone Regeneration / Q000502:physiology*; D001862:Bone Resorption / Q000097:blood / Q000150:complications / Q000000981:diagnostic imaging / Q000503:physiopathology; D001842:Bone and Bones / Q000503:physiopathology*; D059305:Diet, High-Fat; D005269:Femur / Q000000981:diagnostic imaging / Q000503:physiopathology; D005786:Gene Expression Regulation; D006949:Hyperlipidemias / Q000097:blood / Q000150:complications / Q000000981:diagnostic imaging / Q000503:physiopathology*; D008055:Lipids / Q000097:blood; D051379:Mice; D008810:Mice, Inbred C57BL; D055114:X-Ray Microtomography
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D008055:Lipids