title: Eldecalcitol, a second-generation vitamin D analog, drives bone minimodeling and reduces osteoclastic number in trabecular bone of ovariectomized rats.
abstract: To elucidate the histological events that follow administration of eldecalcitol, a second-generation of vitamin D analog currently awaiting approval as a drug for treatment of osteoporosis, we employed the ovariectomy (OVX) rat model. OVX rats received vehicle or 30ng/kg of eldecalcitol, and sham-operated animals received vehicle only. Rats were sacrificed after 12weeks and had their femora and tibiae removed and processed for histochemical and histomorphometrical analyses. When compared with OVX group, osteoclastic number and bone resorption parameters were significantly reduced in eldecalcitol-treated rats, accompanied by decreased bone formation parameters. The preosteoblastic layer, with which osteoclastic precursors interact for mutual differentiation, was poorly developed in the eldecalcitol group, indicating less cell-to-cell contact between preosteoblasts and osteoclast precursors. Interestingly, eldecalcitol did promote a type of focal bone formation that is independent of bone resorption, a process known as bone minimodeling. While the number of ED-1-positive macrophages was higher in the bone marrow of treated rats, though osteoclastic number was deceased. Taken together, our findings suggest that eldecalcitol stimulates preosteoblastic differentiation rather than their proliferation, which in turn may prevent or diminish cell-to-cell contact between preosteoblasts and osteoclastic precursors, and therefore, lead to lower osteoclast numbers and decreased bone resorption.
authors.affiliation: Division of Oral Health Science, Graduate School of Dental Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Paulo Henrique Luiz
authors.initials: PH
authors.lastname: de Freitas
authors.forename: Tomoka
authors.initials: T
authors.lastname: Hasegawa
authors.forename: Satoshi
authors.initials: S
authors.lastname: Takeda
authors.forename: Muneteru
authors.initials: M
authors.lastname: Sasaki
authors.forename: Chihiro
authors.initials: C
authors.lastname: Tabata
authors.forename: Kimimitsu
authors.initials: K
authors.lastname: Oda
authors.forename: Minqi
authors.initials: M
authors.lastname: Li
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Saito
authors.forename: Norio
authors.initials: N
authors.lastname: Amizuka
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015519:Bone Density; D001862:Bone Resorption; D001842:Bone and Bones / Q000166:cytology* / Q000187:drug effects* / Q000502:physiology*; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology* / Q000187:drug effects* / Q000502:physiology; D010012:Osteogenesis; D010052:Ovariectomy; D051381:Rats; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D014807:Vitamin D; C547512:eldecalcitol