{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T14:47:47Z","timestamp":1787755667930,"version":"build-2784847793"},"reference-count":29,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"11","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,6,4]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>We previously established a small animal model of femoral head-neck cam-type hip deformity by inducing physeal injury in immature rabbits. We investigated whether this induced deformity led to hip osteoarthritis (OA) within 4 months.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>Six-week-old immature New Zealand White rabbits underwent surgery to induce physeal injury in the right femoral head, causing growth arrest and secondary head-neck deformity. Animals were divided into early-pre-OA (4 weeks) and late-OA (16 weeks) groups. Left hips served as (nonsurgical) controls. Radiographs were made to visualize deformities and OA progression. The Beck classification was used to assess macroscopic cartilage damage and OA on the acetabulum and femoral head. Micro-computed tomography (CT), histological scoring, and gene expression were used to evaluate OA progression. The Wilcoxon signed-rank test was used for group comparisons. Significance was set at p &lt; 0.05.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      At 16 weeks, the injured hips showed radiographic evidence of joint space narrowing and a higher OA grade than the control hips (p = 0.0002). Micro-CT confirmed degenerative OA changes and a higher femoral head bone volume fraction (BV\/TV) and trabecular thickness (Tb.Th) in the injured hips than in the control hips (BV\/TV: p = 0.0001, Tb.Th: p = 0.0007). Macroscopically, the injured hips exhibited a greater prevalence and severity of chondral lesions at 4 weeks (85.7%, p = 0.015) and 16 weeks (100.0%, p = 0.002) post-injury compared with the control hips (0%), with worsening over time (4 versus 16 weeks: p = 0.016). The Osteoarthritis Research Society International (OARSI) score and synovitis score increased from 4 to 16 weeks post-injury. Compared with the control hips, the injured hips showed decreased\n                      <jats:italic toggle=\"yes\">Col2<\/jats:italic>\n                      expression and increased\n                      <jats:italic toggle=\"yes\">Col10<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">MMP13<\/jats:italic>\n                      expression at 16 weeks post-injury (p = 0.062, p = 0.016, p = 0.041, respectively), confirming catabolism and OA progression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>To our knowledge, we have created the first small animal model of hip OA secondary to experimentally induced head-neck deformity. In this model, the deformity resulted in hip OA at 16 weeks post-injury.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical Relevance:<\/jats:title>\n                    <jats:p>This model can be used to test future interventional therapies and study mechanisms of femoroacetabular impingement-mediated hip OA.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.2106\/jbjs.24.00248","type":"journal-article","created":{"date-parts":[[2025,4,22]],"date-time":"2025-04-22T14:01:48Z","timestamp":1745330508000},"page":"1200-1209","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":2,"title":["Experimentally Induced Femoroacetabular Impingement Results in Hip Osteoarthritis"],"prefix":"10.2106","volume":"107","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6191-674X","authenticated-orcid":false,"given":"Tomoyuki","family":"Kamenaga","sequence":"first","affiliation":[{"name":"Department of Orthopaedic Surgery, Washington University in St. Louis School of Medicine, St. Louis, Missouri"},{"name":"Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6235-3990","authenticated-orcid":false,"given":"Kenichi","family":"Kikuchi","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Washington University in St. Louis School of Medicine, St. Louis, Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Regis J.","family":"O\u2019Keefe","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Washington University in St. Louis School of Medicine, St. Louis, Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John C.","family":"Clohisy","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Washington University in St. Louis School of Medicine, St. Louis, Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7487-4753","authenticated-orcid":false,"given":"Cecilia","family":"Pascual-Garrido","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Washington University in St. Louis School of Medicine, St. Louis, Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2025,4,22]]},"reference":[{"issue":"7","key":"bib1-20260205","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1302\/0301-620X.87B7.15203","article-title":"Hip morphology influences the pattern of damage to the acetabular cartilage: femoroacetabular impingement as a cause of early osteoarthritis of the hip","volume":"87","author":"Beck","year":"2005","journal-title":"J Bone Joint Surg Br."},{"key":"bib2-20260205","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1097\/01.blo.0000096804.78689.c2","article-title":"Femoroacetabular impingement: a cause for osteoarthritis of the hip","volume":"417","author":"Ganz","year":"2003","journal-title":"Clin Orthop Relat Res."},{"issue":"10","key":"bib3-20260205","doi-asserted-by":"crossref","first-page":"2481","DOI":"10.1177\/0363546520935440","article-title":"Distinct Pattern of Inflammation of Articular Cartilage and the Synovium in Early and Late Hip Femoroacetabular Impingement","volume":"48","author":"Haneda","year":"2020","journal-title":"Am J Sports Med."},{"issue":"7","key":"bib4-20260205","doi-asserted-by":"crossref","first-page":"1647","DOI":"10.1177\/0363546520918804","article-title":"Inflammatory Response of Articular Cartilage to Femoroacetabular Impingement in the Hip","volume":"48","author":"Haneda","year":"2020","journal-title":"Am J Sports Med."},{"issue":"16","key":"bib5-20260205","doi-asserted-by":"crossref","first-page":"1457","DOI":"10.2106\/JBJS.L.00497","article-title":"Molecular characterization of articular cartilage from young adults with femoroacetabular impingement","volume":"95","author":"Hashimoto","year":"2013","journal-title":"J Bone Joint Surg Am."},{"issue":"2","key":"bib6-20260205","doi-asserted-by":"crossref","first-page":"135","DOI":"10.2106\/JBJS.O.00443","article-title":"Inflammation and Degeneration in Cartilage Samples from Patients with Femoroacetabular Impingement","volume":"98","author":"Chinzei","year":"2016","journal-title":"J Bone Joint Surg Am."},{"issue":"7S","key":"bib7-20260205","doi-asserted-by":"crossref","first-page":"S391","DOI":"10.1016\/j.arth.2022.03.013","article-title":"Otto Aufranc Award: Identification of Key Molecular Players in the Progression of Hip Osteoarthritis Through Transcriptomes and Epigenetics","volume":"37","author":"Pascual-Garrido","year":"2022","journal-title":"J Arthroplasty."},{"issue":"1","key":"bib8-20260205","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.joca.2021.09.010","article-title":"How does hip osteoarthritis differ from knee osteoarthritis?","volume":"30","author":"Hall","year":"2022","journal-title":"Osteoarthritis Cartilage."},{"issue":"9","key":"bib9-20260205","doi-asserted-by":"crossref","first-page":"2450","DOI":"10.1002\/art.38713","article-title":"Characterization of the cartilage DNA methylome in knee and hip osteoarthritis","volume":"66","author":"Rushton","year":"2014","journal-title":"Arthritis Rheumatol."},{"issue":"12","key":"bib10-20260205","doi-asserted-by":"crossref","first-page":"2208","DOI":"10.1136\/annrheumdis-2014-205980","article-title":"Knee and hip articular cartilage have distinct epigenomic landscapes: implications for future cartilage regeneration approaches","volume":"73","author":"den Hollander","year":"2014","journal-title":"Ann Rheum Dis."},{"issue":"4","key":"bib11-20260205","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1002\/jor.22273","article-title":"Experimentally induced cam impingement in the sheep hip","volume":"31","author":"Siebenrock","year":"2013","journal-title":"J Orthop Res."},{"issue":"7","key":"bib12-20260205","doi-asserted-by":"crossref","first-page":"1919","DOI":"10.1177\/03635465221090645","article-title":"A Novel Model of Hip Femoroacetabular Impingement in Immature Rabbits Reproduces the Distinctive Head-Neck Cam Deformity","volume":"50","author":"Kamenaga","year":"2022","journal-title":"Am J Sports Med."},{"issue":"1","key":"bib13-20260205","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1080\/17453670610045678","article-title":"Deformity of the femoral head following vascular infarct in piglets","volume":"77","author":"Rowe","year":"2006","journal-title":"Acta Orthop."},{"issue":"4","key":"bib14-20260205","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1302\/0301-620X.84B4.0840556","article-title":"The contour of the femoral head-neck junction as a predictor for the risk of anterior impingement","volume":"84","author":"N\u00f6tzli","year":"2002","journal-title":"J Bone Joint Surg Br."},{"issue":"1","key":"bib15-20260205","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1038\/laban0112-20","article-title":"A proposed model of naturally occurring osteoarthritis in the domestic rabbit","volume":"41","author":"Arzi","year":"2011","journal-title":"Lab Anim (NY)."},{"issue":"2","key":"bib16-20260205","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.joca.2010.11.002","article-title":"In vivo structural analysis of subchondral trabecular bone in osteoarthritis of the hip using multi-detector row CT","volume":"19","author":"Chiba","year":"2011","journal-title":"Osteoarthritis Cartilage."},{"issue":"4","key":"bib17-20260205","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods."},{"issue":"Suppl 3","key":"bib18-20260205","doi-asserted-by":"crossref","first-page":"S53","DOI":"10.1016\/j.joca.2010.05.029","article-title":"The OARSI histopathology initiative - recommendations for histological assessments of osteoarthritis in the rabbit","volume":"18","author":"Laverty","year":"2010","journal-title":"Osteoarthritis Cartilage."},{"issue":"4","key":"bib19-20260205","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1111\/j.1365-2559.2006.02508.x","article-title":"Synovitis score: discrimination between chronic low-grade and high-grade synovitis","volume":"49","author":"Krenn","year":"2006","journal-title":"Histopathology."},{"issue":"8","key":"bib20-20260205","doi-asserted-by":"crossref","first-page":"1678","DOI":"10.1002\/jor.25513","article-title":"Epigenetic dysregulation of articular cartilage during progression of hip femoroacetabular impingement disease","volume":"41","author":"Kamenaga","year":"2023","journal-title":"J Orthop Res."},{"key":"bib21-20260205","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1097\/00003086-200401000-00010","article-title":"Abnormal extension of the femoral head epiphysis as a cause of cam impingement","volume":"418","author":"Siebenrock","year":"2004","journal-title":"Clin Orthop Relat Res."},{"issue":"2","key":"bib22-20260205","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1177\/0363546517697689","article-title":"Origin of Cam Morphology in Femoroacetabular Impingement","volume":"46","author":"Morris","year":"2018","journal-title":"Am J Sports Med."},{"issue":"9","key":"bib23-20260205","doi-asserted-by":"crossref","first-page":"1299","DOI":"10.1007\/s00256-016-2417-4","article-title":"Asymmetric epiphyseal closure of the femoral head as a potential cause of the primary cam lesion: a case report","volume":"45","author":"Cho","year":"2016","journal-title":"Skeletal Radiol."},{"issue":"4","key":"bib24-20260205","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1177\/0363546514524364","article-title":"A cam deformity is gradually acquired during skeletal maturation in adolescent and young male soccer players: a prospective study with minimum 2-year follow-up","volume":"42","author":"Agricola","year":"2014","journal-title":"Am J Sports Med."},{"key":"bib25-20260205","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1097\/00003086-198110000-00002","article-title":"Patterns of deformity of the developing hip","volume":"160","author":"Siffert","year":"1981","journal-title":"Clin Orthop Relat Res."},{"issue":"7","key":"bib26-20260205","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1016\/j.joca.2019.04.001","article-title":"Proof of concept: hip joint damage occurs at the zone of femoroacetabular impingement (FAI) in an experimental FAI sheep model","volume":"27","author":"Zurm\u00fchle","year":"2019","journal-title":"Osteoarthritis Cartilage."},{"issue":"5","key":"bib27-20260205","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1097\/CORR.0000000000000649","article-title":"The Pattern of Acetabular Cartilage Wear Is Hip Morphology-dependent and Patient Demographic-dependent","volume":"477","author":"Pascual-Garrido","year":"2019","journal-title":"Clin Orthop Relat Res."},{"key":"bib28-20260205","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1186\/1471-2474-15-309","article-title":"Type X collagen levels are elevated in serum from human osteoarthritis patients and associated with biomarkers of cartilage degradation and inflammation","volume":"15","author":"He","year":"2014","journal-title":"BMC Musculoskelet Disord."},{"issue":"7","key":"bib29-20260205","doi-asserted-by":"crossref","first-page":"1517","DOI":"10.1002\/jor.25485","article-title":"Whole-genome RNA sequencing identifies distinct transcriptomic profiles in impingement cartilage between patients with femoroacetabular impingement and hip osteoarthritis","volume":"41","author":"Kuhns","year":"2023","journal-title":"J Orthop Res."}],"updated-by":[{"DOI":"10.2106\/jbjs.er.24.00248","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T00:00:00Z","timestamp":1768953600000}}],"container-title":["Journal of Bone and Joint Surgery"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/10.2106\/JBJS.24.00248","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T13:45:47Z","timestamp":1787751947000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.2106\/JBJS.24.00248"}},"subtitle":["A Novel Platform to Study Mechanisms of Hip Disease"],"short-title":[],"issued":{"date-parts":[[2025,4,22]]},"references-count":29,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2025]]}},"URL":"https:\/\/doi.org\/10.2106\/jbjs.24.00248","relation":{},"ISSN":["0021-9355","1535-1386"],"issn-type":[{"value":"0021-9355","type":"print"},{"value":"1535-1386","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,22]]}}}