title: Eldecalcitol improves mechanical strength of cortical bones by stimulating the periosteal bone formation in the senescence-accelerated SAM/P6 mice - a comparison with alfacalcidol.
abstract: Eldecalcitol (ELD), a 2β-hydroxypropyloxy derivative of 1α,25(OH)2D3, is a potent inhibitor of bone resorption that has demonstrated a greater effect at reducing the risk of fracture in osteoporotic patients than alfacalcidol (ALF). In the present study, we used the senescence-accelerated mouse strain P6 (SAM/P6), which has low bone mass caused by osteoblast dysfunction, to evaluate the effect of ELD on cortical bone in comparison with ALF. Four-month-old SAM/P6 mice were given either ELD (0.025 or 0.05μg/kg) or ALF (0.2 or 0.4μg/kg) by oral gavage 5 times/week for 6 weeks. Both ELD and ALF increased serum calcium (Ca) in a dose-dependent manner. Serum Ca levels in the ELD 0.05μg/kg group were comparable to those of the ALF 0.2μg/kg group. ELD 0.05μg/kg significantly improved the bone biomechanical properties of the femur compared with the vehicle control group (p<0.001) and the ALF 0.2μg/kg group (p<0.05) evaluated by 3-point bending test. The cortical area of the mid-femur in the ELD 0.05μg/kg group but not the ALF 0.2μg/kg group was significantly higher than those of the vehicle control group (p<0.001). Bone histomorphometry revealed that in the femoral endocortical surface, the suppression of bone resorption parameters (N.Oc/BS) and bone formation parameters (MS/BS) by ELD (0.05μg/kg) was greater than that by ALF (0.2μg/kg). In contrast, in the femoral periosteal surface, ELD 0.05μg/kg significantly increased bone formation parameters (BFR/BS, MS/BS) compared with the vehicle control group (p<0.05, p<0.01, respectively), whereas ALF 0.2μg/kg did not alter these parameters. These results indicate that ELD improved the biomechanical properties of femoral cortical bone not only by inhibiting endocortical bone resorption but also by stimulating the periosteal bone formation in SAM/P6 mice. This article is part of a Special Issue entitled '16th Vitamin D Workshop'.
authors.affiliation: Medical Plan Management Department, Chugai Pharmaceutical Co., Ltd., Tokyo 103-8324, Japan. Electronic address: shiraishiayk@chugai-pharm.co.jp.
authors.forename: Ayako
authors.initials: A
authors.lastname: Shiraishi
authors.affiliation: Product Research Department, Chugai Pharmaceutical Co., Ltd., Tokyo 103-8324, Japan.
authors.forename: Sadaoki
authors.initials: S
authors.lastname: Sakai
authors.affiliation: Medical Science Department, Chugai Pharmaceutical Co., Ltd., Tokyo 103-8324, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Saito
authors.affiliation: Primary Product Lifecycle Management Department, Chugai Pharmaceutical Co., Ltd., Tokyo 103-8324, Japan.
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Takahashi
mesh_terms: D000818:Animals; D015519:Bone Density / Q000187:drug effects*; D050071:Bone Density Conservation Agents / Q000494:pharmacology; D001842:Bone and Bones / Q000166:cytology* / Q000187:drug effects*; D016922:Cellular Senescence / Q000187:drug effects* / Q000502:physiology; D006887:Hydroxycholecalciferols / Q000494:pharmacology*; D051379:Mice; D008815:Mice, Inbred Strains; D010012:Osteogenesis / Q000187:drug effects*; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D050071:Bone Density Conservation Agents; D006887:Hydroxycholecalciferols; D014807:Vitamin D; C547512:eldecalcitol; C008088:alfacalcidol
keywords: Alfacalcidol; BMD; Bone formation; Eldecalcitol; Osteoporosis