Combination Therapy with Teriparatide and Denosumab Contributes to Fracture Healing on Rat Femoral Fracture Model

• Project/Area Number: 16K12939
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Rehabilitation science/Welfare engineering
• Research Institution: Oita University
• Principal Investigator: Kataoka Masashi 大分大学, 福祉健康科学部, 教授 (40301379)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2018: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000); Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: 骨リモデリング / 骨粗鬆症 / 骨折早期治癒 / 難治性骨折 / 仮骨形成 / 骨吸収抑制 / 骨形成促進 / テリパラチド / デノスマブ / ゾレドロネート / ラット / 骨癒合 / 同種骨移植 / 骨折治癒

Outline of Final Research Achievements

Delay in fracture healing or non-union can be devastating complication. Recent studies have reported that Teriparatide (TP) demonstrated effectively on callus formation and mechanical strength and Denosumab (DM) increased the callus size and resistance at the fracture site in rat fracture model. In this study the effects of combination therapy with low dose TP and DM on fracture healing was evaluated. From 1 week post-operation, TP (5 times a week administration) and DM (0.1 mg/kg single administration) were administered by dividing the rats into the following five groups: TP 1μg group, DM group, TP1μg+DM group, TP10μg+DM group, and control group. It is suggested that administration of low dose TP and DM in combination may lead to the treatment of delayed union of fracture. We hope the combination treatment may become one of new therapeutic strategy.

Academic Significance and Societal Importance of the Research Achievements

ヒト大腿骨骨折後の偽関節など難治性骨折を臨床においてしばしば遭遇する。本研究では難治性骨折に対する治療法を新たに樹立することを目的とした。本治療法は他の難治性骨疾患へも応用できる可能性が高い点が重要である。テリパラチド＋デノスマブの協調作用の有効性が確率すると骨折のみでなく、関節リウマチの骨破壊、骨壊死症、ぺルテス病、人工関節周囲の緩み、骨延長術、骨移植術、難治性骨折治療に対しても臨床応用可能になる可能性が十分あると考えている。

Research Products

• [Journal Article] Combination therapy with low-dose teriparatide and zoledronate contributes to fracture healing on rat femoral fracture model (2018)
  • Author(s): Yuta Tsubouchi, Shinichi Ikeda, Masashi Kataoka, Hiroshi Tsumura
  • Journal Title: Journal of Orthopaedic Surgery and Research Volume: 13 Pages: 267-272
  • DOI: 10.1186/s13018-018-0917-8
  • Peer Reviewed / Open Access
• [Presentation] The influence of combination therapy with zoledronate and treadmill training in ovariectomised rats. (2019)
  • Author(s): Tsubouchi Y, Kataoka M,Ikeda S, Tsumura H.
  • Organizer: 8th FFN Global Congress 2019, PE3-5, August 2019.
  • Int'l Joint Research
• [Presentation] 卵巣摘出ラットに対するzoledronateとtreadmill trainingの併用療法が皮質骨微細構造および骨強度に与える影響 (2019)
  • Author(s): 坪内 優太, 片岡 晶志, 池田 真一, 津村 弘
  • Organizer: 第34回日本整形外科学会基礎学術集会
• [Presentation] ラット骨粗鬆症モデルに対するZoledronateと運動療法の併用が骨微細構造および骨強度に与える影響 (2019)
  • Author(s): 坪内優太, 片岡晶志, 池田真一, 津村弘
  • Organizer: 第6回日本予防理学療法学会学術大会
• [Presentation] The effects of combined low dose Teriparatide and Zoledronate treatment on fracture healing in rats fracture model. (2018)
  • Author(s): Tsubouchi Y, Kataoka M, Ikeda S, Tsumura H
  • Organizer: 6th FFN Global Congress
  • Int'l Joint Research
• [Presentation] ラット難治性大腿骨骨折モデルにおける低用量teriparatideとzoledronateの協調効果 (2018)
  • Author(s): 坪内優太, 片岡晶志, 池田真一, 津村弘
  • Organizer: 第32回日本整形外科学会基礎学術集会