{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T14:45:15Z","timestamp":1787755515002,"version":"build-2784847793"},"reference-count":38,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:sec>\n                    <jats:title>Case:<\/jats:title>\n                    <jats:p>Atraumatic avascular necrosis (AVN) of the humeral head is a debilitating condition with an insidious onset and progressively worsening pain. We report a case of a woman who presented with left shoulder pain with a medical history of a rare genetic polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene. Advanced imaging demonstrated focal AVN of her humeral head. Treatment varies based on the stage of the disease, which, in this case, included an ultrasound-guided intra-articular corticosteroid injection and oral methylated supplementation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>In patients with no other known risk factors presenting with AVN of the humeral head, MTHFR polymorphism should be strongly considered a possible cause of AVN.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.2106\/jbjs.cc.19.00486","type":"journal-article","created":{"date-parts":[[2020,7,31]],"date-time":"2020-07-31T11:54:35Z","timestamp":1596196475000},"page":"e19.00486-e19.00486","source":"Crossref","is-referenced-by-count":0,"title":["Avascular Necrosis of the Humeral Head in a Patient with Methylenetetrahydrofolate Reductase 1 Gene Polymorphism"],"prefix":"10.2106","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2743-7806","authenticated-orcid":false,"given":"Irshad","family":"Shakir","sequence":"first","affiliation":[{"name":"Department of Orthopedic Surgery, 99th Medical Group, Nellis Air Force Base, Las Vegas, Nevada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7988-2020","authenticated-orcid":false,"given":"Andrew","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery & Rehabilitation, Loyola University Health System, Maywood, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dane","family":"Salazar","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery & Rehabilitation, Loyola University Health System, Maywood, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2020]]},"reference":[{"issue":"6","key":"bib1-20230720","doi-asserted-by":"crossref","first-page":"345","DOI":"10.5435\/00124635-200906000-00003","article-title":"Osteonecrosis of the humeral head","volume":"17","author":"Harreld","year":"2009","journal-title":"J Am Acad Orthop Surg."},{"issue":"1","key":"bib2-20230720","doi-asserted-by":"crossref","first-page":"47","DOI":"10.3928\/0147-7447-19950101-10","article-title":"Steroid-induced osteonecrosis of the humeral head","volume":"18","author":"Usher","year":"1995","journal-title":"Orthopedics."},{"issue":"6","key":"bib3-20230720","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1016\/S1058-2746(99)90089-7","article-title":"Osteonecrosis of the humeral head: relationship of disease stage, extent, and cause to natural history","volume":"8","author":"Hattrup","year":"1999","journal-title":"J Shoulder Elbow Surg."},{"key":"bib4-20230720","first-page":"499","article-title":"Concepts of etiology and early pathogenesis of osteonecrosis","volume":"43","author":"Jones","year":"1994","journal-title":"Instr Course Lect."},{"key":"bib5-20230720","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1097\/00003086-197110000-00015","article-title":"Necrosis of the humeral head associated with sickle cell anemia and its genetic variants","volume":"80","author":"Chung","year":"1971","journal-title":"Clin Orthop Relat Res."},{"key":"bib6-20230720","first-page":"51","article-title":"Epidemiology of traumatic and nontraumatic osteonecrosis","volume":"130","author":"Jacobs","year":"1978","journal-title":"Clin Orthop Relat Res."},{"issue":"3","key":"bib7-20230720","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1302\/0301-620X.58B3.956247","article-title":"Steroid-induced avascular necrosis of the head of the humerus. Natural history and management","volume":"58","author":"Cruess","year":"1976","journal-title":"J Bone Joint Surg Br."},{"issue":"1","key":"bib8-20230720","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ejmg.2014.10.004","article-title":"Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism: epidemiology, metabolism and the associated diseases","volume":"58","author":"Liew","year":"2015","journal-title":"Eur J Med Genet."},{"issue":"130","key":"bib9-20230720","first-page":"86","article-title":"Experience with steroid-induced avascular necrosis of the shoulder and etiologic considerations regarding osteonecrosis of the hip","author":"Cruess","year":"1978","journal-title":"Clin Orthop Relat Res."},{"issue":"4","key":"bib10-20230720","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1016\/S0030-5898(20)30444-2","article-title":"Corticosteroid-induced osteonecrosis of the humeral head","volume":"16","author":"Cruess","year":"1985","journal-title":"Orthop Clin N Am."},{"issue":"7","key":"bib11-20230720","doi-asserted-by":"crossref","first-page":"1809","DOI":"10.1007\/s11999-009-1094-1","article-title":"The natural progression of shoulder osteonecrosis related to corticosteroid treatment","volume":"468","author":"Hernigou","year":"2010","journal-title":"Clin Orthop Relat Res."},{"key":"bib12-20230720","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1007\/s12178-015-9277-8","article-title":"Pathophysiology and risk factors for osteonecrosis","volume":"8","author":"Shah","year":"2015","journal-title":"Curr Rev Musculoskelet Med."},{"key":"bib13-20230720","first-page":"1766","article-title":"Atraumatic osteonecrosis of the humeral head","volume":"27","author":"Mont","year":"2000","journal-title":"J Rheumatol."},{"issue":"10","key":"bib14-20230720","doi-asserted-by":"crossref","first-page":"3270","DOI":"10.1007\/s00167-016-4169-z","article-title":"Surgical management of osteonecrosis of the humeral head: a systematic review","volume":"25","author":"Franceschi","year":"2017","journal-title":"Knee Surg Sports Traumatol Arthrosc."},{"issue":"9","key":"bib15-20230720","doi-asserted-by":"crossref","first-page":"1442","DOI":"10.1016\/j.jse.2016.01.022","article-title":"Core decompression and arthroplasty outcomes for atraumatic osteonecrosis of the humeral head","volume":"25","author":"Kennon","year":"2016","journal-title":"J Shoulder Elbow Surg."},{"issue":"22","key":"bib16-20230720","doi-asserted-by":"crossref","first-page":"1473","DOI":"10.1056\/NEJM199205283262206","article-title":"Nontraumatic necrosis of bone (osteonecrosis)","volume":"326","author":"Mankin","year":"1992","journal-title":"N Engl J Med."},{"issue":"4","key":"bib17-20230720","doi-asserted-by":"crossref","first-page":"943","DOI":"10.2106\/JBJS.H.01144","article-title":"Quantitative assessment of the vascularity of the proximal part of the humerus","volume":"92","author":"Hettrich","year":"2010","journal-title":"J Bone Joint Surg Am."},{"issue":"18","key":"bib20-20230720","doi-asserted-by":"crossref","first-page":"2507","DOI":"10.1161\/CIRCULATIONAHA.108.808675","article-title":"MTHFR 677 C>T polymorphism reveals functional importance for 5-methyltetrahydrofolate, not homocysteine, in regulation of vascular redox state and endothelial function in human atherosclerosis","volume":"119","author":"Antoniades","year":"2009","journal-title":"Circulation."},{"issue":"3","key":"bib21-20230720","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1016\/j.jvs.2008.10.004","article-title":"Peripheral arterial disease and methylenetetrahydrofolate reductase (MTHFR) C677T mutations: a case-control study and meta-analysis","volume":"49","author":"Khandanpour","year":"2009","journal-title":"J Vasc Surg."},{"issue":"22","key":"bib22-20230720","doi-asserted-by":"crossref","first-page":"1775","DOI":"10.1001\/jama.1997.03540460039030","article-title":"Plasma homocysteine as a risk factor for vascular disease. The European Concerted Action Project","volume":"277","author":"Graham","year":"1997","journal-title":"JAMA."},{"issue":"2","key":"bib23-20230720","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1258\/vasc.2011.oa0320","article-title":"Higher incidence of C677T polymorphism of the MTHFR gene in North Indian patients with vascular disease","volume":"20","author":"Bhargava","year":"2012","journal-title":"Vascular."},{"key":"bib24-20230720","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1001\/archinte.167.5.497","article-title":"No association between the common MTHFR 677C->T polymorphism and venous thrombosis: results from the MEGA study","volume":"167","author":"Bezemer","year":"2007","journal-title":"Arch Intern Med."},{"key":"bib25-20230720","doi-asserted-by":"crossref","first-page":"196495","DOI":"10.1155\/2015\/196495","article-title":"Genetic association between methylenetetrahydrofolate reductase gene polymorphism and risk of osteonecrosis of the femoral head","volume":"2015","author":"Chai","year":"2015","journal-title":"Biomed Res Int."},{"key":"bib26-20230720","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1186\/1471-2474-14-264","article-title":"Prevalence of genetic risk factors related with thrombophilia and hypofibrinolysis in patients with osteonecrosis of the femoral head in Poland","volume":"14","author":"Gagala","year":"2013","journal-title":"BMC Musculoskelet Disord."},{"issue":"6","key":"bib27-20230720","doi-asserted-by":"crossref","first-page":"7089","DOI":"10.1007\/s11033-012-1540-0","article-title":"Association between MTHFR C677T polymorphism and osteonecrosis of the femoral head: a meta-analysis","volume":"39","author":"Shang","year":"2012","journal-title":"Mol Biol Rep."},{"issue":"11","key":"bib28-20230720","first-page":"2360","article-title":"Genotyping method for methylenetetrahydrofolate reductase (C677T thermolabile variant) using heteroduplex technology","volume":"44","author":"Clark","year":"1998","journal-title":"Clin Chem."},{"issue":"13","key":"bib29-20230720","doi-asserted-by":"crossref","first-page":"1506","DOI":"10.1161\/01.CIR.101.13.1506","article-title":"Hyperhomocysteinemia increases risk of death, especially in type 2 diabetes: 5-year follow-up of the Hoorn Study","volume":"101","author":"Hoogeveen","year":"2000","journal-title":"Circulation."},{"issue":"2","key":"bib30-20230720","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1080\/13816810.2017.1401087","article-title":"The relationship between methylenetetrahydrofolate reductase C677T polymorphism and diabetic retinopathy: a meta-analysis in multiethnic groups","volume":"39","author":"Chen","year":"2018","journal-title":"Ophthalmic Genet."},{"issue":"8","key":"bib31-20230720","first-page":"1195","article-title":"Association of C677T gene polymorphisms of methylenetetrahydrofolate reductase and plasma homocysteine level with hyperlipidemia","volume":"34","author":"Liang","year":"2014","journal-title":"Nan Fang Yi Ke Da Xue Xue Bao."},{"issue":"3","key":"bib32-20230720","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1177\/1076029615609686","article-title":"Individual and joint associations of methylenetetrahydrofolate reductase C677T genotype and plasma homocysteine with dyslipidemia in a Chinese population with hypertension","volume":"23","author":"Liu","year":"2017","journal-title":"Clin Appl Thromb Hemost."},{"key":"bib33-20230720","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1186\/s12944-015-0099-x","article-title":"Joint associations of folate, homocysteine and MTHFR, MTR and MTRR gene polymorphisms with dyslipidemia in a Chinese hypertensive population: a cross-sectional study","volume":"14","author":"Li","year":"2015","journal-title":"Lipids Health Dis."},{"issue":"5","key":"bib34-20230720","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.1016\/j.jstrokecerebrovasdis.2017.12.025","article-title":"The methylenetetrahydrofolate reductase C677T (rs1801133) and apolipoprotein A5-1131T>C (rs662799) polymorphisms, and anemia are independent risk factors for ischemic stroke","volume":"27","author":"Escobedo","year":"2018","journal-title":"J Stroke Cerebrovasc Dis."},{"key":"bib35-20230720","doi-asserted-by":"crossref","first-page":"1162","DOI":"10.3389\/fneur.2018.01162","article-title":"Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and subacute combined degeneration: revealing a genetic predisposition","volume":"9","author":"Zhang","year":"2019","journal-title":"Front Neurol."},{"issue":"5","key":"bib36-20230720","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1007\/s11914-018-0469-1","article-title":"The effects of homocysteine on the skeleton","volume":"16","author":"Saito","year":"2018","journal-title":"Curr Osteoporos Rep."},{"issue":"4","key":"bib37-20230720","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1016\/S0030-5898(20)30431-4","article-title":"Fat embolism and osteonecrosis","volume":"16","author":"Jones","year":"1985","journal-title":"Orthop Clin N Am."},{"issue":"3","key":"bib38-20230720","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/j.ocl.2004.03.004","article-title":"Pathogenesis and treatment of osteonecrosis of the shoulder","volume":"35","author":"Sarris","year":"2004","journal-title":"Orthop Clin N Am."},{"issue":"6","key":"bib39-20230720","doi-asserted-by":"crossref","first-page":"339","DOI":"10.5435\/00124635-199711000-00006","article-title":"Osteonecrosis of the humeral head","volume":"5","author":"Cushner","year":"1997","journal-title":"J Am Acad Orthop Surg."},{"issue":"6","key":"bib40-20230720","doi-asserted-by":"crossref","first-page":"7089","DOI":"10.1007\/s11033-012-1540-0","article-title":"Association between MTHFR C677T polymorphism and osteonecrosis of the femoral head: a meta-analysis","volume":"39","author":"Shang","year":"2012","journal-title":"Mol Biol Rep."}],"container-title":["JBJS Case Connector"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/10.2106\/JBJS.CC.19.00486","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T13:44:18Z","timestamp":1787751858000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.2106\/JBJS.CC.19.00486"}},"subtitle":["A Case Report"],"short-title":[],"issued":{"date-parts":[[2020]]},"references-count":38,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2020]]}},"URL":"https:\/\/doi.org\/10.2106\/jbjs.cc.19.00486","relation":{},"ISSN":["2160-3251"],"issn-type":[{"value":"2160-3251","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020]]}}}