Exploratory study on mechanism of influence of age at the onset to prognostic femoral head deformity in patients with Perthes disease

• Project/Area Number: 19K18534
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56020:Orthopedics-related
• Research Institution: Kyushu University
• Principal Investigator: Yamaguchi Ryosuke 九州大学, 大学病院, 助教 (30826152)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2022: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000); Fiscal Year 2021: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2019: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: ペルテス病 / 骨壊死 / 軟骨肥厚 / 成長 / 加齢 / 動物実験 / ＭＲＩ / 大腿骨頭壊死症 / 年齢 / 軟骨代謝 / 骨代謝

Outline of Research at the Start

小児の虚血性大腿骨頭壊死症であるペルテス病は、学童期に数年間の治療を要し、大腿骨頭変形遺残により青年期に重度の股関節障害を引き起こす疾患である。発症時年齢が若いほど股関節予後が良いことは広く認識されているが、その基礎的なメカニズムはほとんどわかっていない。本研究では骨頭虚血後に生じる軟骨肥厚変化に着目し、年齢によって軟骨形成能や骨形成能が異なることが股関節予後に関わる一因ではないかと仮説をたて、画像的検討「MRIによる三次元的軟骨性大腿骨頭の検討」と動物実験「骨壊死マウスモデルにおける骨軟骨形成能の検討」という二つのアプローチから仮説を検討する。

Outline of Final Research Achievements

Age at the onset is important prognostic factor for femoral head deformity in patients with Perthes disease. However, its' mechanism has still been unknown. In this study, three-dimensional analysis of cartilage hypertrophy of the femoral head using Perthes MRI, and assessment of repair process of cartilage and bone using a mouse model of ischemic osteonecrosis were conducted. In patients with Perthes disease, multidirectional hypertrophy of the femoral head cartilage was observed and that was well correlated with age and femoral head deformity at bone maturity age. Also, ischemic osteonecrosis was significantly well repaired in younger age of the mouse model.

Academic Significance and Societal Importance of the Research Achievements

本研究の結果、ペルテス病では軟骨肥厚による骨頭肥大が生じ、その軟骨肥厚の部位と程度により将来的な骨頭変形が生じている可能性が示唆された。ペルテス病に対する基本的治療コンセプトとされているcontainment（封じ込め）療法の基礎的メカニズム解明につながる世界で初めての研究成果である。また若年齢であるほど、虚血性骨壊死修復が速やかであることがわかり、そのメカニズム解明に向けて今後の発展が期待される結果が得られた。

Research Products

• [Journal Article] Relationship between the degree of subchondral collapse and articular surface irregularities in osteonecrosis of the femoral head (2023)
  • Author(s): Yamamoto N, Motomura G, Ikemura S, Yamaguchi R, Utsunomiya T, Kawano K, Xu M, Tanaka H, Ayabe Y, Nakashima Y
  • Journal Title: Journal of Orthopaedic Research Volume: - Issue: 9 Pages: 1996-2006
  • DOI: 10.1002/jor.25539
  • Peer Reviewed
• [Journal Article] Effects of the location of both anterior and lateral boundaries of the necrotic lesion on collapse progression in osteonecrosis of the femoral head (2023)
  • Author(s): Utsunomiya T, Motomura G, Yamaguchi R, Hamai S, Sato T, Kawahara S, Hara D, Kitamura K, Nakashima Y
  • Journal Title: Journal of Orthopaedic Science Volume: - Issue: 2 Pages: 552-558
  • DOI: 10.1016/j.jos.2023.01.011
  • Peer Reviewed
• [Journal Article] Hip Prognosis in Patients With Congenital Diastasis of the Pubic Symphysis (2022)
  • Author(s): Yamaguchi Ryosuke、Nakamura Tomoyuki、Yanagida Haruhisa、Yamaguchi Toru、Takamura Kazuyuki、Wada Akifusa、Nakashima Yasuharu
  • Journal Title: Journal of Pediatric Orthopaedics Volume: 42 Issue: 5 Pages: 246-252
  • DOI: 10.1097/bpo.0000000000002114
  • Peer Reviewed
• [Journal Article] Does Flexion Varus Osteotomy Improve Radiographic Findings Compared With Patients Treated in a Brace for Late-onset Legg-Calv?-Perthes Disease? (2022)
  • Author(s): Nakamura Tomoyuki、Wada Akifusa、Yamaguchi Ryosuke、Iwamoto Miho、Takamura Kazuyuki、Yanagida Haruhisa、Yamaguchi Toru、Ishikawa Chinatsu
  • Journal Title: Clinical Orthopaedics & Related Research Volume: 481 Issue: 4 Pages: 808-819
  • DOI: 10.1097/corr.0000000000002450
  • Peer Reviewed
• [Journal Article] Posterior Pelvic Tilt in the Standing Position Might Be Associated with Collapse Progression in Post‐Collapse Stage Osteonecrosis of the Femoral Head (2022)
  • Author(s): Xu Mingjian、Motomura Goro、Ikemura Satoshi、Yamaguchi Ryosuke、Kawano Koichiro、Yamamoto Noriko、Tanaka Hidenao、Ayabe Yusuke、Nakashima Yasuharu
  • Journal Title: Orthopaedic Surgery Volume: 14 Issue: 12 Pages: 3201-3208
  • DOI: 10.1111/os.13544
  • Peer Reviewed / Open Access
• [Journal Article] The influence of bone marrow edema for the assessment of the boundaries of necrotic lesions in patients with osteonecrosis of the femoral head (2022)
  • Author(s): Ikemura Satoshi、Motomura Goro、Yamaguchi Ryosuke、Utsunomiya Takeshi、Hamai Satoshi、Fujii Masanori、kawahara Shinya、Sato Taishi、Hara Daisuke、shiomoto Kyohei、Yamamoto Takuaki、Nakashima Yasuharu
  • Journal Title: Scientific Reports Volume: 12 Issue: 1
  • DOI: 10.1038/s41598-022-23427-y
  • Peer Reviewed / Open Access
• [Journal Article] Development of a murine model of ischemic osteonecrosis to study the effects of aging on bone repair (2021)
  • Author(s): Yamaguchi Ryosuke、Kamiya Nobuhiro、Kuroyanagi Gen、Ren Yinshi、Kim Harry K. W.
  • Journal Title: Journal of Orthopaedic Research Volume: - Issue: 12 Pages: 2663-2670
  • DOI: 10.1002/jor.25006
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] A longitudinal study for the prediction of the mature acetabular morphology using childhood magnetic resonance imaging (2020)
  • Author(s): Nakamura Tomoyuki、Yamaguchi Ryosuke、Wada Akifusa、Takamura Kazuyuki、Yanagida Haruhisa、Yamaguchi Toru
  • Journal Title: Journal of Orthopaedic Science Volume: - Issue: 4 Pages: 644-649
  • DOI: 10.1016/j.jos.2020.05.002
  • Peer Reviewed
• [Journal Article] Subchondral fracture of the femoral head in children: Differential diagnosis of pediatric hip pain (2020)
  • Author(s): Yamaguchi Ryosuke、Nakamura Tomoyuki、Yamamoto Takuaki、Takamura Kazuyuki、Yanagida Haruhisa、Yamaguchi Toru、Nakashima Yasuharu
  • Journal Title: Journal of Orthopaedic Surgery Volume: 28 Issue: 2
  • DOI: 10.1177/2309499020937862
  • Peer Reviewed
• [Presentation] Transtrochanteric rotational osteotomy (Sugioka Osteotomy) (2022)
  • Author(s): Ryosuke Yamaguchi, Yasuharu Nakashima
  • Organizer: 第61回日本小児股関節研究会
  • Invited
• [Presentation] The effect of aging on bone repair against ischemic osteonecrosis in a mouse model (2022)
  • Author(s): Ryosuke Yamaguchi, Nobuhiro Kamiya, Gen Kuroyanagi, Yinshi Ren, Harry KW Kim
  • Organizer: ARCO 2022
  • Int'l Joint Research
• [Presentation] Morphological analysis of articular surface of the femoral head with osteonecrosis (2022)
  • Author(s): Noriko Yamamoto, Goro Motomura, Ryosuke Yamaguchi, Takeshi Utsunomiya, Xu Mingjian, Hidenao Tanaka, Yusuke Ayabe, Kosei Sakamoto, Yasuharu Nakashima
  • Organizer: ARCO 2022
  • Int'l Joint Research
• [Presentation] Multidirectional hypertrophy of the femoral head cartilage in Legg-Calve-Perthes disease (2022)
  • Author(s): Hidenao Tanaka, Ryosuke Yamaguchi, Tomoyuki Nakamura, Akifusa Wada, Goro Motomura, Takeshi Utsunomiya, Noriko Yamamoto, Yusuke Ayabe, Kosei Sakamoto, Yasuharu Nakashima
  • Organizer: ARCO 2022
  • Int'l Joint Research
• [Presentation] Management of AVN after unstable SCFE (2021)
  • Author(s): Ryosuke Yamaguchi, Tomoyuki Nakamura, Goro Motomura, Satoshi Hamai, Satoshi Ikemura, Masanori Fujii, Shinya Kawahara, Taishi Sato, Yasuharu Nakashima
  • Organizer: APSS-APPOS 2021
  • Int'l Joint Research / Invited
• [Presentation] Role of periacetabular osteotomy (2021)
  • Author(s): Ryosuke Yamaguchi, Masanori Fujii, Goro Motomura, Satoshi Hamai, Satoshi Ikemura, Shinya Kawahara, Taishi Sato, Yasuharu Nakashima
  • Organizer: APSS-APPOS 2021
  • Int'l Joint Research / Invited
• [Presentation] Closed repositioning following lower-extremity traction for developmental dysplasia of the hip in walking age (2021)
  • Author(s): Ryosuke Yamaguchi, Tomoyuki Nakamura, Akifusa Wada, Kazuyuki Takamura, Yasuharu Nakashima
  • Organizer: APSS-APPOS 2021
  • Int'l Joint Research
• [Presentation] 3D-MRI analysis of articular cartilage thickness in the femoral head of children with Legg-Calve-Perthes disease (2021)
  • Author(s): Hidenao Tanaka, Ryosuke Yamaguchi, Tomoyuki Nakamura, Akifusa Wada, Goro Motomura, Satoshi Ikemura, Koichiro Kawano, Mingjian Xu, Noriko Yamamoto, Yasuharu Nakashima
  • Organizer: APSS-APPOS 2021
  • Int'l Joint Research
• [Presentation] Long-term outcomes of soft tissue surgery for the prevention of hip displacement in children with severe cerebral palsy: Comparison with the natural course (2021)
  • Author(s): akashi Hatano, Ryosuke Yamaguchi, Mitsuru Saeki, Kiyoyuki Torigoe, Yoshika Kawamura, Mihoko Hatano, Ken Sugita, Keisuke Matsuo
  • Organizer: APSS-APPOS 2021
  • Int'l Joint Research
• [Presentation] Surveillance study on reasons for the cessation of Botulinum toxin-A therapyin spastic patients (2021)
  • Author(s): Yoshika Kawamura, Keisuke Matsuo, Takashi Hatano, Mihoko Hatano, Ken Sugita, Ryosuke Yamaguchi, Kiyoyuki Torigoe
  • Organizer: APSS-APPOS 2021
  • Int'l Joint Research
• [Presentation] Multidirectional hypertrophy of the femoral head cartilage in Legg-Calve-Perthes disease (2021)
  • Author(s): Hidenao Tanaka, Ryosuke Yamaguchi, Tomoyuki Nakamura, Akifusa Wada, Yasuharu Nakashima
  • Organizer: 第32回日本小児整形外科学会学術集会
• [Presentation] 小児期MRIを用いた軟骨性臼蓋の評価－予後予測と術前評価について－ (2019)
  • Author(s): 中村幸之、和田晃房、山口亮介、高村和幸、柳田晴久、山口徹、李容承、高橋宗志、石川千夏、川口健悟
  • Organizer: 第30回日本小児整形外科学会学術集会
• [Presentation] 股関節MRIを用いた乳児股関節脱臼における軟骨性寛骨臼形態の検討 (2019)
  • Author(s): 岩本美帆、山口亮介、中村幸之、和田晃房、高村和幸、中島康晴
  • Organizer: 第30回日本小児整形外科学会学術集会