The novel bisphosphonate disodium dihydrogen-4-[(methylthio) phenylthio] methanebisphosphonate increases bone mass in post-ovariectomy rats

Aiko Takizawa; Mirei Chiba; Takeru Ota; Mayumi Yasuda; Keiko Suzuki; Takuya Kanemitsu; Takashi Itoh; Hisashi Shinoda; Kaoru Igarashi

doi:10.1016/j.jphs.2016.04.011

Journal of Pharmacological Sciences (May 2016)

The novel bisphosphonate disodium dihydrogen-4-[(methylthio) phenylthio] methanebisphosphonate increases bone mass in post-ovariectomy rats

Aiko Takizawa,
Mirei Chiba,
Takeru Ota,
Mayumi Yasuda,
Keiko Suzuki,
Takuya Kanemitsu,
Takashi Itoh,
Hisashi Shinoda,
Kaoru Igarashi

Affiliations

Aiko Takizawa: 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
Mirei Chiba: 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
Takeru Ota: 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
Mayumi Yasuda: 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
Keiko Suzuki: Department of Pharmacology, School of Dentistry, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan
Takuya Kanemitsu: 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
Takashi Itoh: 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
Hisashi Shinoda: Center for Environmental Dentistry, Graduate School of Dentistry, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan
Kaoru Igarashi: 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

DOI: https://doi.org/10.1016/j.jphs.2016.04.011
Journal volume & issue: Vol. 131, no. 1
pp. 37 – 50

Abstract

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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.

Published in Journal of Pharmacological Sciences

ISSN: 1347-8613 (Print)
Publisher: Elsevier
Country of publisher: Japan
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: http://www.journals.elsevier.com/journal-of-pharmacological-sciences

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