title: 22-Oxacalcitriol attenuates bone loss in nonobese type 2 diabetes.
abstract: Active vitamin D is a major therapeutic agent for bone disease. Although some studies have reported that vitamin D ameliorates bone disease related to diabetes, the mechanism remains unclear. Our study investigated the effect of the vitamin D receptor activator 22-oxacalcitriol (OCT) on bone disease in a rat model of diabetes. OCT was administered at a dose of 0.2μg/kg three times per week for 10weeks. We performed blood and urine analyses, single energy X-ray absorptiometry, micro-computed tomography, bone histomorphometry, and oxidative stress assessment in rats at 30weeks of age. OCT did not affect hemoglobin A1c or serum calcium levels. Bone mineral density (BMD), bone volume in the cortical and trabecular bones, and bone turnover were decreased in rats with diabetes. OCT treatment increased BMD and bone formation and tended to increase bone volume in the trabecular bone, but did not change bone volume in the cortical bone or bone resorption. The urinary oxidative stress marker 8-hydroxydeoxyguanosine (8-OHdG) excretion and the number of 8-OHdG-positive cells in bone were increased in rats with diabetes, and OCT treatment suppressed these increases. Our data suggest that OCT attenuated bone loss in a rat model of diabetes. This attenuation may be partially mediated by improved bone formation resulting from the antioxidative effect of OCT.
authors: Division of Nephrology and Kidney Center, Kobe University Graduate School of Medicine, Kobe, Japan.
authors: Shunsuke
authors: S
authors: Goto
authors: Division of Nephrology and Kidney Center, Kobe University Graduate School of Medicine, Kobe, Japan. Electronic address: fhideki@med.kobe-u.ac.jp.
authors: Hideki
authors: H
authors: Fujii
authors: Division of Nephrology and Kidney Center, Kobe University Graduate School of Medicine, Kobe, Japan.
authors: Keiji
authors: K
authors: Kono
authors: Division of Nephrology and Kidney Center, Kobe University Graduate School of Medicine, Kobe, Japan.
authors: Kentaro
authors: K
authors: Nakai
authors: Division of Nephrology and Kidney Center, Kobe University Graduate School of Medicine, Kobe, Japan.
authors: Rie
authors: R
authors: Awata
authors: Division of Nephrology and Kidney Center, Kobe University Graduate School of Medicine, Kobe, Japan.
authors: Yuriko
authors: Y
authors: Yonekura
authors: Product Research Department, Fuji Gotemba Research Laboratories, Chugai Pharmaceutical Co., Ltd., Shizuoka, Japan.
authors: Michinori
authors: M
authors: Hirata
authors: Tokyo Animal & Diet Dept., CLEA Japan, Inc., Tokyo, Japan.
authors: Masami
authors: M
authors: Shinohara
authors: Division of Nephrology and Kidney Center, Kobe University Graduate School of Medicine, Kobe, Japan.
authors: Shinichi
authors: S
authors: Nishi
authors: Division of Nephrology and Kidney Center, Kobe University Graduate School of Medicine, Kobe, Japan; Division of Nephrology, Endocrinology, and Metabolism, Department of Medicine, Tokai University School of Medicine, Isehara, Japan.
authors: Masafumi
authors: M
authors: Fukagawa
mesh_terms: D015502:Absorptiometry, Photon; D000818:Animals; D015519:Bone Density / Q000187:drug effects; D001862:Bone Resorption / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D005269:Femur / Q000000981:diagnostic imaging / Q000187:drug effects / Q000503:physiopathology; D007328:Insulin / Q000008:administration & dosage / Q000627:therapeutic use; D008297:Male; D009765:Obesity / Q000150:complications / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D017207:Rats, Sprague-Dawley; D013977:Tibia / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology; D055114:X-Ray Microtomography
chemical_list: D007328:Insulin; D002117:Calcitriol; C051883:maxacalcitol
keywords: 22-Oxacalcitriol; Active vitamin D; Diabetes mellitus; Diabetic bone disease