title: Effect of combined teriparatide and monthly minodronic acid therapy on cancellous bone mass in ovariectomized rats: a bone histomorphometry study.
abstract: The purpose of the present study was to determine whether teriparatide and monthly minodronic acid would have an additive effect on cancellous bone mass in ovariectomized rats. Seven-week-old female Sprague-Dawley rats were randomized into five groups of 10 animals each, including a sham-operation+vehicle group, an ovariectomy (OVX)+vehicle group, an OVX+minodronic acid (6 μg/kgs.c., every 4 weeks) group, an OVX+teriparatide (20 μg/kgs.c., daily) group, and an OVX+minodronic acid+teriparatide group. After the 12-week experimental period, static and dynamic histomorphometric analyses were performed on the cancellous bone of the tibial proximal metaphysis. OVX decreased the bone volume per total volume (BV/TV) and the trabecular number (Tb.N) and increased the trabecular separation (Tb.Sp) as a result of increased bone remodeling. Minodronic acid prevented the OVX-induced decreases in BV/TV, while teriparatide increased the BV/TV and trabecular width (Tb.Wi) beyond the values of the sham controls. Minodronic acid prevented, but teriparatide only mitigated, the OVX-induced decrease in Tb.N, although both drugs similarly prevented the OVX-induced increase in Tb.Sp. A combination of teriparatide and minodronic acid further increased the BV/TV and Tb.N and decreased the Tb.Sp as a result of the suppression of bone remodeling, compared with teriparatide alone. These results suggest the differential effect of teriparatide and monthly minodronic acid on cancellous bone structure and the additive effect of the two drugs on cancellous bone mass in OVX rats.
authors.affiliation: Institute for Integrated Sports Medicine, Keio University School of Medicine, Tokyo, Japan. Electronic address: jiwamoto@a8.keio.jp.
authors.forename: Jun
authors.initials: J
authors.lastname: Iwamoto
authors.affiliation: Hamri Co., Ltd., Ibaraki, Japan.
authors.forename: Azusa
authors.initials: A
authors.lastname: Seki
authors.affiliation: Department of Neurology, Mitate Hospital, Fukuoka, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Sato
mesh_terms: D000818:Animals; D050071:Bone Density Conservation Agents / Q000008:administration & dosage* / Q000494:pharmacology; D001842:Bone and Bones / Q000033:anatomy & histology / Q000187:drug effects*; D004164:Diphosphonates / Q000008:administration & dosage* / Q000494:pharmacology; D004359:Drug Therapy, Combination; D005260:Female; D007093:Imidazoles / Q000008:administration & dosage* / Q000494:pharmacology; D009929:Organ Size / Q000187:drug effects*; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D019379:Teriparatide / Q000008:administration & dosage* / Q000494:pharmacology
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D019379:Teriparatide; C087958:YM 529
keywords: Bone histomorphometry; Cancellous bone; Minodronic acid; Ovariectomized rats; Teriparatide