Type I Angiotensin II Receptor Blockade Reduces Uremia-Induced Deterioration of Bone Material Properties

Abstract

Chronic kidney disease (CKD) is associated with a high incidence of fractures. However, the pathophysiology of this disease is not fully understood, and limited therapeutic interventions are available. This study aimed to determine the impact of type 1 angiotensin II receptor blockade (AT‐1RB) on preventing CKD‐related fragility fractures and elucidate its pharmacological mechanisms. AT‐1RB use was associated with a lower risk of hospitalization due to fractures in 3276 patients undergoing maintenance hemodialysis. In nephrectomized rats, administration of olmesartan suppressed osteocyte apoptosis, skeletal pentosidine accumulation, and apatite disorientation, and partially inhibited the progression of the bone elastic mechanical properties, while the bone mass was unchanged. Olmesartan suppressed angiotensin II‐dependent oxidation stress and apoptosis in primary cultured osteocytes in vitro. In conclusion, angiotensin II‐dependent intraskeletal oxidation stress deteriorated the bone elastic mechanical properties by promoting osteocyte apoptosis and pentosidine accumulation. Thus, AT‐1RB contributes to the underlying pathogenesis of abnormal bone quality in the setting of CKD, possibly by oxidative stress. © 2020 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Periodontal Tissue as a Biomaterial for Hard-Tissue Regeneration following bmp-2 Gene Transfer

“…The effect of a gene transfer on the anisotropic micro-arrangement of the bone matrix in regenerated bone is unknown, in spite of the importance of the bone matrix quality for the mechanical function of bone. Impaired bone mechanical function, owing to disturbed collagen/apatite orientation, has been shown in various bone disorders, such as osteoporosis [44], osteopetrosis [45], cancer metastasis [46], and chronic kidney disease [47]. Thus, the maintenance of an intact collagen/apatite orientation during bone regeneration is imperative for realizing proper bone mechanical function.…”

Superior Alignment of Human iPSC-Osteoblasts Associated with Focal Adhesion Formation Stimulated by Oriented Collagen Scaffold

“…Several bone disorders in humans have limited treatment possibilities because of the inaccessibility of the affected bones. Genetic disorders, such as osteopetrosis [45] and osteogenesis imperfecta [46]; acquired disorders, including osteoporosis [47,48], cancer bone metastasis [49,50], and chronic kidney disease (CKD) [51]; regenerated bone [13,52]; and drug treatment [53,54] affect bone matrix microstructures, demonstrating the involvement of various biological mechanisms, including the autonomous or mutual activity of bone cells and their related biomolecules, in the formation of bone microstructure [55]. The biological mechanism underlying changes in the bone microstructure upon the emergence of bone disorders may be revealed in the future by an iPSC-based disease model composed of patient-derived hiPSC-Obs and the culture platform introduced in this study.…”

Ibandronate Suppresses Changes in Apatite Orientation and Young's Modulus Caused by Estrogen Deficiency in Rat Vertebrae

“…The degree of preferential orientation of the c -axis in the apatite crystals was determined as the relative intensity ratio of the (002) diffraction peak to the (310) peak in the X-ray profile. This was previously reported as a suitable index for evaluating the degree of apatite orientation [ 16 , 24 , 25 ]. The intensity ratios calculated from the upper and lower parts of the Debye ring were averaged.…”