Type I angiotensin II receptor blockade reduces uremia‐induced deterioration of bone material properties

Wakamatsu, Takuya; Iwasaki, Yoshiko; Yamamoto, Suguru; Matsuo, Koji; Goto, Shin; Narita, Ichiei; Kazama, Junichiro J.; Tanaka, Kennichi; Ito, Akemi; Ozasa, Ryosuke; Nakano, Takayoshi; Miyakoshi, Chisato; Onishi, Yoshihiro; Fukuma, Shingo; Fukuhara, Shunichi; Yamato, Hideyuki; Fukagawa, Masafumi; Akizawa, Tadao

Affiliations

¹Division of Clinical Nephrology and Rheumatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan

²Department of Health Sciences, Oita University of Nursing and Health Sciences, Oita, Japan

³Department of Nephrology and Hypertension, Fukushima Medical University, Fukushima, Japan

⁴Ito Bone Histomorphometry Institute, Niigata, Japan

⁵Division of Materials and Manufacturing Science, Graduate School of Engineering, Osaka University, Suita, Japan

⁶Department of Healthcare Epidemiology, School of Public Health in the Graduate School of Medicine, Kyoto University, Kyoto, Japan

⁷Department of Pediatrics, Kobe City Medical Center General Hospital, Kobe, Japan

⁸Institute for Health Outcomes and Process Evaluation Research (iHope International), Kyoto, Japan

⁹The Keihanshin Consortium for Fostering the Next Generation of Global Leaders in Research (K-CONNEX), Kyoto, Japan

¹⁰Division of Nephrology, Endocrinology, and Metabolism, Tokai University School of Medicine, Isehara, Japan

¹¹Division of Nephrology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan

Abstract and keywords

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.

Keywords: BONE MATERIAL PROPERTIES; CHRONIC KIDNEY DISEASE; OLMESARTAN; RENIN‐ANGIOTENSIN‐ALDOSTERONE SYSTEM

Links

DOI: 10.1002/jbmr.4159

PubMed: 32786093

WoS: 000574215600001

History

Received: 2019-12-19

Revised: 2020-07-15

Accepted: 2020-07-27

Online: 2020-10-2

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Cited By (2)

Year	Entry
2022	Ozasa R, Matsugaki A, Ishimoto T, Kamura S, Yoshida H, Magi M, Matsumoto Y, Sakuraba K, Fujimura K, Miyahara H, Nakano T. Bone fragility via degradation of bone quality featured by collagen/apatite micro-arrangement in human rheumatic arthritis. Bone. February 2022;155:116261.
2022	Ozasa R, Saito M, Ishimoto T, Matsugaki A, Matsumoto Y, Nakano T. Combination treatment with ibandronate and eldecalcitol prevents osteoporotic bone loss and deterioration of bone quality characterized by nano-arrangement of the collagen/apatite in an ovariectomized aged rat model. Bone. April 2022;157:116309.