title: Individual and combining effects of anti-RANKL monoclonal antibody and teriparatide in ovariectomized mice.
abstract: We examined the individual and combined effects of teriparatide and anti-RANKL (receptor activator of nuclear factor κB ligand) monoclonal antibody in ovariectomized mice. Three-month-old female C57BL/6 mice were ovariectomized (OVX) or sham operated. Four weeks after OVX, they were assigned to 3 different groups to receive anti-RANKL monoclonal antibody (Ab) alone (5 mg/kg single injection at 4 weeks after OVX, Ab group), teriparatide alone (80 μg/kg daily injection for 4 weeks from 4 weeks after OVX, PTH group), or mAb plus teriparatide (Ab + PTH group). Mice were sacrificed 8 weeks after OVX. Bone mineral density (BMD) was measured at the femur and lumbar spine. Hind limbs were subjected to histological and histomorphometric analysis. Serum osteocalcin and CTX-I levels were measured to investigate the bone turnover. Compared with Ab group, Ab + PTH group showed a significant increase in BMD at distal femur and femoral shaft. Cortical bone volume was significantly increased in PTH and Ab + PTH groups compared with Ab group. Bone turnover in Ab + PTH group was suppressed to the same degree as in Ab group. The number of TRAP-positive multinucleated cells was markedly reduced in Ab and Ab + PTH groups. These results suggest that combined treatment of teriparatide with anti-RANKL antibody has additive effects on BMD in OVX mice compared with individual treatment.
authors.affiliation: Department of Orthopaedic Surgery, Faculty of Medicine, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-8655,Japan.
authors.forename: Naoto
authors.initials: N
authors.lastname: Tokuyama
authors.affiliation: Department of Orthopaedic Surgery, Faculty of Medicine, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-8655,Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Hirose
authors.affiliation: Department of Orthopaedic Surgery, Faculty of Medicine, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-8655,Japan.
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Omata
authors.affiliation: Department of Orthopaedic Surgery, Faculty of Medicine, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-8655,Japan.
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Yasui
authors.affiliation: Department of Orthopaedic Surgery, Faculty of Medicine, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-8655,Japan.
authors.forename: Naohiro
authors.initials: N
authors.lastname: Izawa
authors.affiliation: Department of Orthopaedic Surgery, Faculty of Medicine, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-8655,Japan.
authors.forename: Takumi
authors.initials: T
authors.lastname: Matsumoto
authors.affiliation: Department of Orthopaedic Surgery, Faculty of Medicine, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-8655,Japan.
authors.forename: Hironari
authors.initials: H
authors.lastname: Masuda
authors.affiliation: Department of Orthopaedic Surgery, Faculty of Medicine, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-8655,Japan.
authors.forename: Toshinobu
authors.initials: T
authors.lastname: Ohmiya
authors.affiliation: Bioindustry Division, Oriental Yeast Co., Ltd., Azusawa 3-6-10, Itabashi-ku, Tokyo 174-8505, Japan.
authors.forename: Hisataka
authors.initials: H
authors.lastname: Yasuda
authors.affiliation: Department of Orthopaedic Surgery, Faculty of Medicine, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-8655,Japan.
authors.forename: Taku
authors.initials: T
authors.lastname: Saito
authors.affiliation: Department of Orthopaedic Surgery, Faculty of Medicine, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-8655,Japan.
authors.forename: Yuho
authors.initials: Y
authors.lastname: Kadono
authors.affiliation: Department of Orthopaedic Surgery, Faculty of Medicine, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-8655,Japan.
authors.forename: Sakae
authors.initials: S
authors.lastname: Tanaka
keywords: Combination therapy; Mouse; Osteoporosis; Ovariectomy; Parathyroid hormone; RANKL