Bone fragility induced by tissue disoreder of mineral crystals and collargen in chronic kidney disease

• Project/Area Number: 17K16670
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Orthopaedic surgery
• Research Institution: Hokkaido University
• Principal Investigator: Shimizu Tomohiro 北海道大学, 大学病院, 助教 (60784246)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 骨脆弱性 / 慢性腎臓病 / 骨質 / ラット動物モデル / 骨質異常 / CKD / ビスフォスフォネート / テリパラチド / 細胞・組織

Outline of Final Research Achievements

We clarified the mechanism of bone fragility by chronic kidney disease and investigated efficacy and safety of bisphosphonate (BP) and terparatide (TPD). We found the deterioration of bone quality including material parameters and high bone turnover. We next investigated the efficacy and safety of medicine. BP was safe and improved osteoporosis and bone fragility via suppression of bone turnover and there were no significant differences between different dose and frequency. TPD improved low bone volume and bone microstructure via promoting the bone turnover.

Academic Significance and Societal Importance of the Research Achievements

慢性腎臓病（Chronic kidney disease: CKD）罹患患者は，本邦では非常に多くなっており，その早期から骨折リスクが上昇するためCKDを原因とする続発性骨粗鬆症患者は相当数いると推定されている．CKD患者の骨脆弱性発症には骨質劣化が関与しているが，詳細についてはまた十分に解明されていない．また，進行期CKD患者に対して，腎排泄である既存の骨粗鬆症治療薬の有効性と安全性の検証は行われていない．本研究は前臨床研究として、動物モデルを作成して、骨代謝調整薬を投与し、骨質を含めた評価と安全性について検証を行った。この知見は臨床での薬剤投与法に参考になりうるものと考えられる。

Research Products

• [Journal Article] Ten years change in post-fracture care for hip fracture patients. (2020)
  • Author(s): Shimodan S, Sato D, Takahashi K, Nakamura Y, Hyakkan R, Watanabe T, Hishimura R, Ota M, Shimizu H, Hojo Y, Hasegawa Y, Chubachi T, Yasui K, Tsujimoto T, Tsukuda Y, Asano T, Takahashi D, Takahata M, Iwasaki N, Shimizu T.
  • Journal Title: J Bone Miner Metab. Volume: 38(2) Pages: 222-229
  • NAID: 120006980047
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Potential association with early changes in serum calcium level after starting or switching to denosumab combined with eldecalcitol. (2019)
  • Author(s): Asano T, Shimizu T, Takahashi D, Ota M, Sato D, Hamano H, Hiratsuka S, Takahata M, Iwasaki N.
  • Journal Title: J Bone Miner Metab. Volume: 37(2) Pages: 351-357
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Potential association with early changes in serum calcium level after starting or switching to denosumab combined with eldecalcitol (2018)
  • Author(s): Asano Tsuyoshi、Shimizu Tomohiro、Takahashi Daisuke、Ota Masahiro、Sato Dai、Hamano Hiroki、Hiratsuka Shigeto、Takahata Masahiko、Iwasaki Norimasa
  • Journal Title: Journal of Bone and Mineral Metabolism Volume: 37 Issue: 2 Pages: 351-357
  • DOI: 10.1007/s00774-018-0928-x
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Optimal administration frequency and dose of teriparatide for acceleration of biomechanical healing of long-bone fracture in a mouse model (2018)
  • Author(s): Ota Masahiro、Takahata Masahiko、Shimizu Tomohiro、Momma Daisuke、Hamano Hiroki、Hiratsuka Shigeto、Amizuka Norio、Hasegawa Tomoka、Iwasaki Norimasa
  • Journal Title: Journal of Bone and Mineral Metabolism Volume: 37 Issue: 2 Pages: 256-263
  • DOI: 10.1007/s00774-018-0930-3
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Efficacy and safety of osteoporosis medications in a rat model of late-stage chronic kidney disease accompanied by secondary hyperparathyroidism and hyperphosphatemia. (2017)
  • Author(s): Ota M, Takahata M, Shimizu T, Kanehira Y, Kimura-Suda H, Kameda Y, Hamano H, Hiratsuka S, Sato D, Iwasaki N.
  • Journal Title: Osteoporosis International Volume: 28 Issue: 4 Pages: 1481-1490
  • DOI: 10.1007/s00198-016-3861-7
  • Peer Reviewed / Int'l Joint Research
• [Presentation] 手術加療を施行した脆弱性骨折における術後骨粗鬆症検査・治療介入率の検証 －北海道10年多施設後ろ向きコホート－ (2018)
  • Author(s): 太田昌博, 清水智弘，菱村亮介, 高橋要, 佐藤大, 辻本武尊, 岸本隆史, 林晴久, 宮本守孝, 佃幸憲, 髙橋大介, 高畑雅彦, 岩崎倫政
  • Organizer: 第20回日本骨粗鬆症学会
• [Presentation] 新規骨粗鬆症治療薬が骨粗鬆症性骨脆弱性骨折に及ぼす影響の検討：10年2747例の検討 (2018)
  • Author(s): 佐藤大，清水智弘，菱村亮介，高橋要，太田昌博，辻本武尊，佃幸憲，髙橋大介，高畑雅彦，岩崎倫政
  • Organizer: 第20回日本骨粗鬆症学会，長崎市，2018年10月26日-28日