Distinction in the mechanism for administration of PTH and bisphosphonate in bone mineral metabolism induced by osteocytes

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K17011
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 57010:Oral biological science-related
• Research Institution: Hokkaido University
• Principal Investigator: Hongo Hiromi 北海道大学, 歯学研究院, 学術研究員 (00778970)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Keywords: 骨代謝 / 骨細胞性骨溶解 / PTH / ビスホスホネート

Outline of Final Research Achievements

PTH-administered mice showed an outflow of bone minerals in the periphery of the osteocytic lacunae, resulting in the enlargement of the lacunae. However, when mice were injected with calcein or 42Ca (stable Ca isotope) after the PTH administration, thus treated mice demonstrated calcium deposition onto the peripheral region of the osteocytic lacunae which previously showed an outflow of bone minerals. Therefore, PTH appears to reversibly erode and deposit calcium phosphates in the periphery of the osteocytic lacunae. In contrast, after ALN administration, many osteocytes seemed to be damaged, and the connectivity by cytoplasmic processes of osteocytic network was disrupted. Taken together, osteocytes seem to respond to PTH to erode and deposit calcium phosphates onto the lacunae, while osteocytes would be damaged by an excess amount of ALN, disrupting the connectivity of cytoplasmic processes of their network.

Free Research Field

骨代謝

Academic Significance and Societal Importance of the Research Achievements

副甲状腺ホルモン(PTH)およびビスホスホネート製剤の1つであるアレンドロネート(ALN)は骨粗鬆症の治療薬、あるいは転移性骨腫瘍による骨吸収抑制剤として広く使用されている薬剤である。しかしその一方で、これらの薬剤が骨細胞に及ぼす影響について明らかにした報告はほとんどない。したがって、これらの頻用性の高い薬剤が及ぼす骨ミネラル代謝を明らかにすることは、今後の薬剤の使用において大きな意義をなすと考えられる。