title: Intermittent Ibandronate Maintains Bone Mass, Bone Structure, and Biomechanical Strength of Trabecular and Cortical Bone After Discontinuation of Parathyroid Hormone Treatment in Ovariectomized Rats.
abstract: Although parathyroid hormone (PTH) expresses an anabolic effect on bone mass, the increased bone mass disappears once PTH treatment is withdrawn. Therefore, sequential treatment with anti-bone-resorptive agents is required to maintain bone mass after PTH treatment. We examined the effect of sequential treatment with ibandronate (IBN), a nitrogen-containing bisphosphonate, following PTH in ovariectomized (OVX) rats. Wistar-Imamichi rats (27 weeks old) were ovariectomized and treated with PTH (10 µg/kg, s.c.; 5 times/week; PTH group) for 8 weeks from 8 weeks after OVX. Thereafter, PTH was withdrawn and rats were administered IBN (10 µg/kg, s.c.; every 4 weeks; PTH-IBN group) or vehicle (PTH-Veh group) for another 8 weeks. PTH increased bone mineral density (BMD) measured by dual-energy X-ray absorptiometry and biomechanical strength in the lumbar spine and femur as compared to the disease control rats. BMD and biomechanical strength in the PTH-Veh group were lower than in the PTH group, whereas in the PTH-IBN group they were maintained at the level of the PTH group. Microstructure of the trabecular and cortical bone in the PTH-IBN group was not significantly different from that in the PTH group. In histomorphometric analysis of the lumbar vertebra, eroded surface and osteoclast surface in the PTH-Veh group were no different from those in the PTH group, whereas they were lower in the PTH-IBN group. Osteoid surface, osteoblast surface, and mineralize surface decreased in both PTH-IBN and PTH-Veh groups compared to the PTH group, and these parameters in the PTH-IBN group were lower than in the PTH-Veh group. These results indicated that intermittent IBN after PTH treatment suppressed bone turnover and maintained BMD, biomechanical strength, and microstructure in the lumbar spine and femur of OVX rats.
authors.affiliation: Fuji Gotemba Research Laboratories, Product Research Department, Chugai Pharmaceutical Co., Ltd, 1-135 Komakado, Gotemba, Shizuoka, 412-8513, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Takeda
authors.affiliation: Fuji Gotemba Research Laboratories, 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: Fuji Gotemba Research Laboratories, Product Research Department, Chugai Pharmaceutical Co., Ltd, 1-135 Komakado, Gotemba, Shizuoka, 412-8513, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Tanaka
authors.affiliation: Fuji Gotemba Research Laboratories, Product Research Department, Chugai Pharmaceutical Co., Ltd, 1-135 Komakado, Gotemba, Shizuoka, 412-8513, Japan.
authors.forename: Haruna
authors.initials: H
authors.lastname: Tomizawa
authors.affiliation: Fuji Gotemba Research Laboratories, Product Research Department, Chugai Pharmaceutical Co., Ltd, 1-135 Komakado, Gotemba, Shizuoka, 412-8513, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Serizawa
authors.affiliation: Fuji Gotemba Research Laboratories, Product Research Department, Chugai Pharmaceutical Co., Ltd, 1-135 Komakado, Gotemba, Shizuoka, 412-8513, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Yogo
authors.affiliation: Product Marketing and Management Department, Taisho Toyama Pharmaceutical Co., Ltd, 3-25-1 Takada, Toshima-ku, Tokyo, 170-8635, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Urayama
authors.affiliation: Primary Lifecycle Management Department, Chugai Pharmaceutical Co., Ltd, 2-1-1 Nihombashi Muromachi, Chuo-ku, Tokyo, 103-8324, Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Hashimoto
authors.affiliation: Medical Science Department, Chugai Pharmaceutical Co., Ltd, 2-1-1 Nihombashi Muromachi, Chuo-ku, Tokyo, 103-8324, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Endo
authors.affiliation: Fuji Gotemba Research Laboratories, Product Research Department, Chugai Pharmaceutical Co., Ltd, 1-135 Komakado, Gotemba, Shizuoka, 412-8513, Japan. matsumotoyosh@chugai-pharm.co.jp.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Matsumoto
mesh_terms: D045930:Anabolic Agents / Q000494:pharmacology*; D000818:Animals; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D016723:Bone Remodeling; D001842:Bone and Bones / Q000187:drug effects*; D004164:Diphosphonates / Q000494:pharmacology*; D005260:Female; D000077557:Ibandronic Acid; D010052:Ovariectomy; D010281:Parathyroid Hormone / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar
chemical_list: D045930:Anabolic Agents; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D010281:Parathyroid Hormone; D000077557:Ibandronic Acid
keywords: Bone biomechanical strength; Bone mineral density; Histomorphometry; Ibandronate; Parathyroid hormone