Hypercholesterolemia promotes an osteoporotic phenotype.

A role for hypercholesterolemia in the development of osteoporosis has been suggested in published reports. However, few studies contain direct evidence of a role for maintenance of cholesterol homeostasis in bone health. Using isocaloric high-fat/high-cholesterol and low-fat/no-cholesterol diets in a 4-month feeding study combined with micro computed tomography analysis, we demonstrated in two different mouse strains that mice with hypercholesterolemia lose cortical and trabecular bone in the femurs and vertebrae (bone mineral density was decreased on average by ≈90 mg/mL in the cortical vertebrae in one strain) and cortical bone in the calvariae (bone mineral density was decreased on average by ≈60 mg/mL in one strain). Mechanical testing of the femurs demonstrated that loss of bone in the mice with hypercholesterolemia caused changes in the mechanical properties of the bone including loss of failure load (failure load was decreased by ≈10 N in one strain) and energy to failure. Serologic and histomorphologic analyses suggested that hypercholesterolemia promotes osteoclastogenesis. These studies support a role for hypercholesterolemia in the development of osteoporosis and provide a model with which to test intervention strategies to reduce the effects of hypercholesterolemia on bone health.

Actinobacillus actinomycetemcomitans lipopolysaccharide-mediated experimental bone loss model for aggressive periodontitis.

BACKGROUND: Bacterial constituents, such as Gram-negative derived lipopolysaccharide (LPS), can initiate inflammatory bone loss through induction of host-derived inflammatory cytokines. The aim of this study was to establish a model of aggressive inflammatory alveolar bone loss in rats using LPS derived from the periodontal pathogen Actinobacillus actinomycetemcomitans. METHODS: Eighteen female Sprague-Dawley rats were divided into LPS test (N = 12) and saline control (N = 6) groups. All animals received injections to the palatal molar gingiva three times per week for 8 weeks. At 8 weeks, linear and volumetric alveolar bone loss was measured by micro-computed tomography (microCT). The prevalence of inflammatory infiltrate, proinflammatory cytokines, and osteoclasts was assessed from hematoxylin and eosin, immunohistochemical, or tartrate-resistant acid phosphatase (TRAP)-stained sections. Statistical analysis was performed. RESULTS: A. actinomycetemcomitans LPS induced severe bone loss over 8 weeks, whereas control groups were unchanged. Linear and volumetric analysis of maxillae by microCT indicated significant loss of bone with LPS administration. Histologic examination revealed increased inflammatory infiltrate, significantly increased immunostaining for interleukin IL-6 and -1beta and tumor necrosis factor-alpha, and more TRAP-positive osteoclasts in the LPS group compared to controls. CONCLUSION: Oral injections of LPS derived from the periodontal pathogen A. actinomycetemcomitans can induce severe alveolar bone loss and proinflammatory cytokine production in rats by 8 weeks.