{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T05:24:16Z","timestamp":1783488256380,"version":"3.55.0"},"reference-count":37,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2025,6,24]],"date-time":"2025-06-24T00:00:00Z","timestamp":1750723200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Daewoong Biologics Indonesia"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec039\">\n<jats:title>Background<\/jats:title>\n<jats:p>Avascular necrosis (AVN) of the hip is a disease characterized by vascular disruptions, where 67% of untreated cases may lead to the collapse of the femoral head. None of the current approaches, such as core decompression (CD), vascularized bone grafting, osteotomy, tissue implantation, and other methods, have been proven fully effective in delaying the progression of osteonecrosis. Recent findings indicate that bone marrow stem cells (BMSCs) have significant potential to regenerate necrotic tissue and prevent the progression of AVN in the hip. This study aims to evaluate the efficacy, side effects, treatment failure rate, most effective treatment stage of AVN hip, and application technique to treat AVN hip.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec040\">\n<jats:title>Method<\/jats:title>\n<jats:p>We performed this systematic review and meta-analysis from randomized controlled trials (RCTs) and sources published between 2013 and 2023 from six databases. The literature searching method was based on predetermined PICOS, study eligibility criteria, and PRISMA guidelines. The extracted data were then assessed quantitatively using R Studio with Harris hip score (HHS), Visual analog scale (VAS), the collapse of the femoral head, and conversion of total hip arthroplasty (THA) as the outcomes of interest, then qualitatively using RoB Tool, the extracted data were analyzed using R Studio.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec041\">\n<jats:title>Result<\/jats:title>\n<jats:p>A total of 12,939 records were identified through database searching. After the removal of duplicates and non-randomized studies using automation tools, 4,846 articles were screened. Following title and abstract review, 10 studies met the eligibility criteria and were included in the systematic review and meta-analysis, comprising 593 patients and 779 hips.<\/jats:p>\n<jats:p>The included studies originated from China (n\u2009=\u20094), France (n\u2009=\u20091), South Korea (n\u2009=\u20091), Australia (n\u2009=\u20091), Iran (n\u2009=\u20091), India (n\u2009=\u20091), and Spain (n\u2009=\u20091). Risk of bias assessment using RoB 2.0 tool revealed 70% of the RCTs were rated as having a low risk of bias, while 30% were judged to have some concerns.<\/jats:p>\n<jats:p>Meta-analysis demonstrated that BMSC therapy significantly reduced the risk of femoral head collapse (OR = 0.15; 95% CI: 0.09\u20130.25; P\u2009&lt;\u20090.00001; I\u00b2\u2009=\u20090%) and conversion to THA (OR = 0.20; 95% CI: 0.13\u20130.31; P\u2009&lt;\u20090.00001; I\u00b2\u2009=\u200983%). Functional outcomes, as measured by the HHS, were significantly improved in the BMSC group (MD\u2009=\u200910.70; 95% CI: 9.70\u201311.69; P\u2009&lt;\u20090.00001; I\u00b2\u2009=\u200951%). Pain reduction, assessed using the VAS, also favored BMSC therapy (MD\u2009=\u2009\u22128.04; 95% CI: \u22128.66 to \u22127.42; P\u2009&lt;\u20090.00001; I\u00b2\u2009=\u200999%).<\/jats:p>\n<jats:p>Meta-regression analyses explored the influence of study-level covariates on outcomes. No predictor reached statistical significance for HHS or THA conversion. However, mean age showed a borderline significant association with VAS (coefficient\u2009=\u2009\u22120.8029; P\u2009=\u20090.065), suggesting a possible trend of more significant pain reduction in older patients.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec042\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>Currently established AVN hip treatments are proven to be less effective. The findings strongly support that giving a BMSC at the early-stage AVN hip could improve the patient\u2019s clinical outcome and have fewer side effects and treatment failure compared to conventional treatment.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0297319","type":"journal-article","created":{"date-parts":[[2025,6,24]],"date-time":"2025-06-24T17:28:32Z","timestamp":1750786112000},"page":"e0297319","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["Assessing the latest advances in bone marrow stem cell therapy for Avascular Necrosis hip: A comprehensive systematic review, meta-analysis, and meta-regression of randomized controlled trial studies"],"prefix":"10.1371","volume":"20","author":[{"given":"Robin","family":"Novriansyah","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanti Ajoe","family":"Kesoema","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3821-8446","authenticated-orcid":true,"given":"Kevin Christian","family":"Tjandra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0434-8421","authenticated-orcid":true,"given":"I. Nyoman Sebastian","family":"Sudiasa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1480-6155","authenticated-orcid":true,"given":"Shakira","family":"Amirah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-2506-6546","authenticated-orcid":true,"given":"Imke Maria Del Rosario","family":"Puling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prudence","family":"Lucianus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-4123-980X","authenticated-orcid":true,"given":"Revina","family":"Maharani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danendra Rakha Putra","family":"Respati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-1495-5293","authenticated-orcid":true,"given":"Laksmana Adi Krista","family":"Nugraha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6202-0918","authenticated-orcid":true,"given":"Ismail Hadisoebroto","family":"Dilogo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,6,24]]},"reference":[{"key":"pone.0297319.ref001","volume-title":"Hip Osteonecrosis (Archived)","author":"H Hsu","year":"2025"},{"issue":"12","key":"pone.0297319.ref002","doi-asserted-by":"crossref","first-page":"7348","DOI":"10.3390\/ijerph19127348","article-title":"Avascular Necrosis of Femoral Head-Overview and Current State of the Art","volume":"19","author":"W Konarski","year":"2022","journal-title":"Int J Environ Res Public Health"},{"key":"pone.0297319.ref003","volume-title":"Avascular necrosis","author":"AH Matthews","year":"2023"},{"key":"pone.0297319.ref004","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.jot.2019.12.004","article-title":"Guidelines for clinical diagnosis and treatment of osteonecrosis of the femoral head in adults (2019 version)","volume":"21","author":"D Zhao","year":"2020","journal-title":"J Orthop Translat"},{"issue":"5","key":"pone.0297319.ref005","article-title":"Treatment of non\u2011traumatic avascular necrosis of the femoral head (Review)","volume":"23","author":"N Liu","year":"2022","journal-title":"Exp Ther Med"},{"issue":"3","key":"pone.0297319.ref006","doi-asserted-by":"crossref","first-page":"226","DOI":"10.2174\/1574888X13666181025120252","article-title":"New Advances in Stem Cell Therapy for Osteonecrosis of the Femoral Head","volume":"14","author":"W 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