title: Effects of eldecalcitol on bone and skeletal muscles in glucocorticoid-treated rats.
abstract: Glucocorticoids cause secondary osteoporosis and myopathy, characterized by type II muscle fiber atrophy. We examined whether a new vitamin D3 analogue, eldecalcitol, could inhibit glucocorticoid-induced osteopenia or myopathy in rats, and also determined the effects of prednisolone (PSL) and/or eldecalcitol on muscle-related gene expression. Six-month-old female Wistar rats were randomized into four groups: PSL group (10 mg/kg PSL); E group (0.05 µg/kg eldecalcitol); PSL + E group; and control group. PSL, eldecalcitol, and vehicles were administered daily for 2 or 4 weeks. Right calf muscle strength, muscle fatigue, cross-sectional areas (CSAs) of left tibialis anterior muscle fibers, and bone mineral density (BMD) were measured following administration. Pax7, MyoD, and myogenin mRNA levels in gastrocnemius muscles were also determined. Muscle strength was significantly higher in the PSL + E group than in the PSL group (p < 0.05) after 4 weeks, but not after 2 weeks. No significant difference in muscle fatigue was seen between groups at 2 or 4 weeks. CSAs of type II muscle fibers were significantly larger in the E group and the PSL + E group than in the PSL group at 4 weeks (p = 0.0093, p = 0.0443, respectively). Eldecalcitol treatment for 4 weeks maintained the same BMD as the PSL + E group. After 2 weeks, but not 4 weeks, eldecalcitol treatment significantly increased Pax7 and myogenin mRNA expression in gastrocnemius muscle, and PSL also stimulated myogenin expression. Eldecalcitol appears to increase muscle volume and to protect against femur BMD loss in PSL-administered rats, and it may also stimulate myoblast differentiation into early myotubes.
authors.affiliation: Department of Orthopedic Surgery, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita, 010-8543, Japan.
authors.forename: Hayato
authors.initials: H
authors.lastname: Kinoshita
authors.affiliation: Department of Orthopedic Surgery, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita, 010-8543, Japan. miyakosh@doc.med.akita-u.ac.jp.
authors.forename: Naohisa
authors.initials: N
authors.lastname: Miyakoshi
authors.affiliation: Department of Orthopedic Surgery, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita, 010-8543, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kasukawa
authors.affiliation: Product Research Department, Chugai Pharmaceutical Co., Ltd., 1-135 Komakado, Gotemba, Shizuoka, 412-8513, Japan.
authors.forename: Sadaoki
authors.initials: S
authors.lastname: Sakai
authors.affiliation: Medical Plan Management Department, Chugai Pharmaceutical Co., Ltd., 1-1 Nihonbashi-Muromachi 2-Chome, Chuo-ku, Tokyo, 103-8324, Japan.
authors.forename: Ayako
authors.initials: A
authors.lastname: Shiraishi
authors.affiliation: Department of Orthopedic Surgery, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita, 010-8543, Japan.
authors.forename: Toyohito
authors.initials: T
authors.lastname: Segawa
authors.affiliation: Department of Orthopedic Surgery, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita, 010-8543, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Ohuchi
authors.affiliation: Department of Orthopedic Surgery, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita, 010-8543, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Fujii
authors.affiliation: Department of Orthopedic Surgery, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita, 010-8543, Japan.
authors.forename: Chie
authors.initials: C
authors.lastname: Sato
authors.affiliation: Department of Orthopedic Surgery, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita, 010-8543, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Shimada
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D015519:Bone Density / Q000187:drug effects; D005260:Female; D005269:Femur / Q000187:drug effects* / Q000502:physiology; D005938:Glucocorticoids / Q000494:pharmacology*; D006614:Hindlimb / Q000187:drug effects; D053580:Muscle Strength / Q000187:drug effects; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000502:physiology; D017208:Rats, Wistar; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D005938:Glucocorticoids; D014807:Vitamin D; C547512:eldecalcitol
keywords: Bone; Eldecalcitol; Muscle fatigue; Muscle strength; Muscle-related gene