Compromised vertebral structural and mechanical properties associated with progressive XXXX and the effects of traditional pharmacological interventions.

@entity1 @entity8 @entity171 @entity740 @entity460 @entity4381 @entity461
BACKGROUND/AIMS: @entity1 with @entity740 ( @entity740 ) have a significantly higher vertebral and non-vertebral fracture risk than the general population. Several preclinical models have documented altered skeletal properties in long bones, but few data exist for vertebral bone. The goal of this study was to examine the effects of progressive CKD on vertebral bone structure and mechanics and to determine the effects of treatment with either @entity171 or anti-sclerostin antibody in groups of animals with high or low @entity461 . METHODS: Animals with progressive @entity8 were left untreated, treated with @entity460 to lower @entity461 , @entity4381 to lower remodeling without affecting @entity461 , anti-sclerostin antibody, or anti-sclerostin antibody plus @entity460 . Non-diseased, untreated littermates served as controls. Vertebral bone morphology (trabecular and cortical) and mechanical properties (structural and material-level) were assessed at 35weeks of age by microCT and mechanical testing, respectively. RESULTS: CKD with high @entity461 resulted in 6-fold higher bone formation rate, significant reductions in the amount of trabecular and cortical bone, and compromised whole bone mechanical properties in the vertebra compared to normal animals. Treatments that reduced bone remodeling were effective in normalizing vertebral structure and mechanical properties only if the treatment reduced serum @entity461 . Similarly, treatment with anti-sclerostin antibody was effective in enhancing bone mass and mechanical properties but only if combined with @entity461 -suppressive treatment. CONCLUSIONS: CKD significantly altered both cortical and trabecular bone properties in the vertebra resulting in compromised mechanical properties and these changes can be normalized by interventions that involve reductions in @entity461 levels.
