Association of innate immune abnormalities with the development and collapse of idiopathic osteonecrosis of the femoral head.

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K17984
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56020:Orthopedics-related
• Research Institution: Hokkaido University
• Principal Investigator: Shimizu Tomohiro 北海道大学, 大学病院, 助教 (60784246)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 特発性大腿骨頭壊死症 / 好中球 / 全身MRI

Outline of Final Research Achievements

Whole-body MRI proved to be a useful screening for osteonecrosis in idiopathic osteonecrosis of the femoral head, as it identified asymptomatic osteonecrosis compared to bone scintigraphy.
In all cases of idiopathic osteonecrosis of the femoral head, histological expression of NETs was confirmed in the soft tissues of the periprosthetic femoral head, and when a rat model with strong NETs expression was created, expression of NETs was confirmed in the periprosthetic femoral head tissue as in clinical specimen samples. In addition, osteonecrosis and positive expression of HIF1α, a marker of ischemia, could be partially confirmed. This could not be confirmed in the controls. These findings suggest that the expression of NETs is associated with the development of osteonecrosis of the femoral head.

Free Research Field

整形外科

Academic Significance and Societal Importance of the Research Achievements

特発性大腿骨頭壊死症(ONFH)は国の定める難病であり、現在のところ発生及び圧潰のメカニズムは十分に解明されていない。本研究の目的は、疫学的にONFHと関連するSLEやネフローゼ症候群の発症に深い関わりを持つことが近年明らかとなった好中球トラップ(NETs)に注目し、ONFH発生とNETsの関連性を明らかにすることである。本研究は、人工股関節全置換術を行うONFH症例の臨床サンプルを用いて自然免疫異常とONFHの発生の関連を調査する前向き観察研究である。本研究によりONFHの発生メカニズムの一部が解明されれば、発生・圧潰予測因子の解明や予防法の確立につながり治療成績向上に繋がる。