title: The novel bisphosphonate disodium dihydrogen-4-[(methylthio) phenylthio] methanebisphosphonate increases bone mass in post-ovariectomy rats.
abstract: The novel bisphosphonate (BP) disodium dihydrogen-4-[(methylthio) phenylthio] methanebisphosphonate (MPMBP) is a non-nitrogen-containing BP with an antioxidant side chain that possesses anti-inflammatory properties. We investigated the systemic effects of this compound on bone loss induced by ovariectomy (OVX) in adult rats. Micro-computed tomography revealed that MPMBP increased bone mass and density in both the metaphysis and diaphysis, and improved the structural properties important for mechanical strength of osteoporotic bone. Sequential bone labeling with tetracycline and calcein indicated that MPMBP decreased longitudinal growth of the primary spongiosa (PS), but stimulated cortical bone formation in the diaphysis. MPMBP increased type I collagen accumulation in the PS, and decreased the number and size of adipocytes in the bone marrow, suggesting inhibition of increased bone marrow adipogenesis induced by OVX. Furthermore, MPMBP reduced the number of bone resorbing cathepsin K-positive osteoclasts induced by OVX. These results suggest that MPMBP could improve bone loss induced by estrogen deficiency. Both stimulation of bone formation and inhibition of bone resorption might play a role in the increase in bone mass and bone density after MPMBP treatment.
authors.affiliation: Division of Oral Dysfunction Science, Department of Oral Health and Development Science, Graduate School of Dentistry, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan; Division of Oral Physiology, Department of Oral Function and Morphology, Graduate School of Dentistry, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.
authors.forename: Aiko
authors.initials: A
authors.lastname: Takizawa
authors.affiliation: Division of Oral Physiology, Department of Oral Function and Morphology, Graduate School of Dentistry, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan. Electronic address: mirei@m.tohoku.ac.jp.
authors.forename: Mirei
authors.initials: M
authors.lastname: Chiba
authors.affiliation: Division of Oral Physiology, Department of Oral Function and Morphology, Graduate School of Dentistry, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.
authors.forename: Takeru
authors.initials: T
authors.lastname: Ota
authors.affiliation: Division of Oral Dysfunction Science, Department of Oral Health and Development Science, Graduate School of Dentistry, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan; Division of Oral Physiology, Department of Oral Function and Morphology, Graduate School of Dentistry, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Yasuda
authors.affiliation: Department of Pharmacology, School of Dentistry, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Suzuki
authors.affiliation: Division of Organic and Bioorganic Chemistry, Department of Medicinal Chemistry, School of Pharmacy, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Kanemitsu
authors.affiliation: Division of Organic and Bioorganic Chemistry, Department of Medicinal Chemistry, School of Pharmacy, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Itoh
authors.affiliation: Center for Environmental Dentistry, Graduate School of Dentistry, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Shinoda
authors.affiliation: Division of Oral Dysfunction Science, Department of Oral Health and Development Science, Graduate School of Dentistry, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.
authors.forename: Kaoru
authors.initials: K
authors.lastname: Igarashi
mesh_terms: D050156:Adipogenesis / Q000187:drug effects; D000818:Animals; D015519:Bone Density / Q000187:drug effects*; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D001851:Bone Diseases, Metabolic / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism; D024042:Collagen Type I / Q000378:metabolism; D004164:Diphosphonates / Q000494:pharmacology*; D005260:Female; D010010:Osteoclasts / Q000187:drug effects / Q000378:metabolism; D010052:Ovariectomy / Q000009:adverse effects; D017207:Rats, Sprague-Dawley; D013977:Tibia / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000502:physiology; D055114:X-Ray Microtomography
chemical_list: D050071:Bone Density Conservation Agents; D024042:Collagen Type I; D004164:Diphosphonates; C109548:TRK 530
keywords: Anti-inflammatory; Bone formation; Bone resorption; Disodium dihydrogen-4-[(methylthio) phenylthio] methanebisphosphonate (MPMBP); Ovariectomy