{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T13:59:29Z","timestamp":1788962369271,"version":"build-2803163510"},"reference-count":53,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,10,23]],"date-time":"2022-10-23T00:00:00Z","timestamp":1666483200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JPM"],"abstract":"<jats:p>Objective: The aim of this meta-analysis was to investigate the impact of intravenous iloprost therapy on pain, function, edema changes, and follow-up surgery in bone marrow edema syndrome of the proximal femur. Methods: A systematic literature search up to May 2022 was performed to find relevant papers that made a statement about the outcome of intravenous iloprost therapy alone. Factors such as the Visual Analog Scale (VAS), Harris Hip Score (HHS), edema reduction, and follow-up interventions were considered. These were compared using Forest plots. Results: In 11 studies, 190 proximal femora with bone marrow edema syndrome that received intravenous iloprost therapy without further therapeutic intravenous or surgical intervention such as core decompression were studied. There was a significant mean improvement in VAS by 3.3 cm (2.07\u20134.5 cm) (p &lt; 0.001) and HHS by 24.36 points (18.23\u201330.49) (p &lt; 0.001) 3\u20136 months after receiving iloprost therapy. Only in 9.3% of cases (1.1\u201324.3%) did no clinical or radiological improvement occur. Conclusions: It could be shown that the existing publications support intravenous therapy with iloprost in patients with bone marrow edema syndrome and result in good clinical outcomes.<\/jats:p>","DOI":"10.3390\/jpm12111757","type":"journal-article","created":{"date-parts":[[2022,10,24]],"date-time":"2022-10-24T04:40:36Z","timestamp":1666586436000},"page":"1757","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["The Use of Iloprost in the Treatment of Bone Marrow Edema Syndrome of the Proximal Femur: A Review and Meta-Analysis"],"prefix":"10.3390","volume":"12","author":[{"given":"Timo","family":"Zippelius","sequence":"first","affiliation":[{"name":"Department of Orthopedic Surgery, University of Ulm, Oberer Eselsberg 45, 89081 Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Strube","sequence":"additional","affiliation":[{"name":"Orthopedic Department, Jena University Hospital, Campus Eisenberg, 07607 Eisenberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Rohe","sequence":"additional","affiliation":[{"name":"Orthopedic Department, Jena University Hospital, Campus Eisenberg, 07607 Eisenberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Schlattmann","sequence":"additional","affiliation":[{"name":"Institute of Medical Statistics, Computer Sciences and Documentation, Jena University Hospital, 07743 Jena, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver","family":"Dobrindt","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, University of Ulm, Oberer Eselsberg 45, 89081 Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9468-2089","authenticated-orcid":false,"given":"Thomas","family":"Caffard","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, University of Ulm, Oberer Eselsberg 45, 89081 Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hassan","family":"Awan Malik","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, University of Ulm, Oberer Eselsberg 45, 89081 Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris","family":"Lindemann","sequence":"additional","affiliation":[{"name":"Orthopedic Department, Jena University Hospital, Campus Eisenberg, 07607 Eisenberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georg","family":"Matziolis","sequence":"additional","affiliation":[{"name":"Orthopedic Department, Jena University Hospital, Campus Eisenberg, 07607 Eisenberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6976-8953","authenticated-orcid":false,"given":"Sabrina","family":"B\u00f6hle","sequence":"additional","affiliation":[{"name":"Orthopedic Department, Jena University Hospital, Campus Eisenberg, 07607 Eisenberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1080\/14740338.2018.1424828","article-title":"The role of Iloprost on bone edema and osteonecrosis: Safety and clinical results","volume":"17","author":"Pountos","year":"2018","journal-title":"Expert Opin. Drug Saf."},{"key":"ref_2","first-page":"172","article-title":"Long-term effects of intravenous iloprost therapy in patients with bone marrow oedema of the hip","volume":"84","author":"Zippelius","year":"2018","journal-title":"Acta Orthop. Belg."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1050","DOI":"10.1302\/0301-620X.84B7.0841050","article-title":"Juvenile bone-marrow oedema of the acetabulum treated by iloprost","volume":"84","author":"Aigner","year":"2002","journal-title":"J. Bone Jt. Surg. Br. Vol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1007\/s00264-001-0311-7","article-title":"Core decompression in early stages of femoral head osteonecrosis\u2014An MRI-controlled study","volume":"26","author":"Aigner","year":"2002","journal-title":"Int. Orthop."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1007\/s00508-005-0322-2","article-title":"The painful bone marrow edema syndrome of the hip joint","volume":"117","author":"Hofmann","year":"2005","journal-title":"Wien. Klin. Wochenschr."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1302\/0301-620X.87B4.15658","article-title":"The management of necrosis-associated and idiopathic bone-marrow oedema of the proximal femur by intravenous iloprost","volume":"87","author":"Disch","year":"2005","journal-title":"J. Bone Jt. Surg. Br. Vol."},{"key":"ref_7","first-page":"1609","article-title":"Effects of intravenous iloprost therapy in patients with bone marrow oedema of the foot and ankle","volume":"24","author":"Zippelius","year":"2013","journal-title":"Eur. J. Orthop. Surg. Traumatol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"17","DOI":"10.55095\/achot2018\/002","article-title":"Long-Term Effects of Intravenous Iloprost Therapy in Patients with Bone Marrow Oedema of the Knee Joint","volume":"85","author":"Zippelius","year":"2018","journal-title":"Acta Chir. Orthop. Traumatol. Cechoslov."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1080\/02841850802161023","article-title":"Bone marrow edema: Pathophysiology, differential diagnosis, and imaging","volume":"49","author":"Starr","year":"2008","journal-title":"Acta Radiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/j.ocl.2004.04.005","article-title":"Painful bone marrow edema of the knee: Differential diagnosis and therapeutic concepts","volume":"35","author":"Hofmann","year":"2004","journal-title":"Orthop. Clin. N. Am."},{"key":"ref_11","unstructured":"Urbaniak, J.R., and Jones, J.P. (1997). Osteonecrosis and bone marrow edema syndrome: Similar etiology but a different pathogenesis. Osteonecrosis: Etiology, Diagnosis, and Treatment, American Academy of Orthopaedic Surgeons."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1007\/s00508-005-0326-y","article-title":"MRI-controlled analysis of 104 patients with painful bone marrow edema in different joint localizations treated with the prostacyclin analogue iloprost","volume":"117","author":"Meizer","year":"2005","journal-title":"Wien. Klin. Wochenschr."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1007\/s00117-005-1304-0","article-title":"Differential diagnosis of bone marrow edema of the knee joint","volume":"46","author":"Breitenseher","year":"2006","journal-title":"Radiologe"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1007\/s00264-007-0320-2","article-title":"Avascular necrosis of the femoral head: Inter- and intraobserver variations of Ficat and ARCO classifications","volume":"32","author":"Kirchhoff","year":"2008","journal-title":"Int. Orthop."},{"key":"ref_15","first-page":"403","article-title":"Osteonecrosis: Natural course and conservative therapy","volume":"29","author":"Hofmann","year":"2000","journal-title":"Orthopade"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"897","DOI":"10.3233\/BMR-171043","article-title":"Effects of iloprost on human mature osteoblasts in vitro","volume":"32","author":"Zippelius","year":"2019","journal-title":"J. Back Musculoskelet. Rehabil."},{"key":"ref_17","first-page":"761","article-title":"Efficiency of iloprost treatment for osseous malperfusion","volume":"35","author":"Zilkens","year":"2010","journal-title":"Int. Orthop."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1561","DOI":"10.1007\/s00296-012-2597-8","article-title":"Infusion, core decompression, or infusion following core decompression in the treatment of bone edema syndrome and early avascular osteonecrosis of the femoral head","volume":"33","author":"Beckmann","year":"2012","journal-title":"Rheumatol. Int."},{"key":"ref_19","first-page":"488","article-title":"S3 guideline. Part 2: Non-traumatic avascular femoral head necrosis in adults-untreated course and conservative treatment","volume":"153","author":"Roth","year":"2015","journal-title":"Z. Orthop. Unf."},{"key":"ref_20","first-page":"6150","article-title":"Long-term clinical results after iloprost treatment for bone marrow edema and avascular necrosis","volume":"8","author":"Becker","year":"2016","journal-title":"Orthop. Rev."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.ocl.2018.08.008","article-title":"Technologies in the Treatment of Bone Marrow Edema Syndrome","volume":"50","author":"Ghasemi","year":"2018","journal-title":"Orthop. Clin. N. Am."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1007\/s00132-018-3616-6","article-title":"Conservative treatment of atraumatic femoral head necrosis","volume":"47","author":"Maus","year":"2018","journal-title":"Orthopade"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"889","DOI":"10.2165\/00003495-199243060-00008","article-title":"Iloprost. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in peripheral vascular disease, myocardial ischemia and extracorporeal circulation procedures","volume":"43","author":"Grant","year":"1992","journal-title":"Drugs"},{"key":"ref_24","first-page":"ED000142","article-title":"Updated guidance for trusted systematic reviews: A new edition of the Cochrane Handbook for Systematic Reviews of Interventions","volume":"10","author":"Cumpston","year":"2019","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"36","DOI":"10.4103\/0019-5413.45321","article-title":"Outcome of painful bone marrow edema of the femoral head following treatment with parenteral iloprost","volume":"43","author":"Meizer","year":"2009","journal-title":"Indian J. Orthop."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1007\/s00508-005-321-3","article-title":"Bone marrow edema syndrome of the femoral head: Treatment with the prostacyclin analogue iloprost vs. core decompression: An MRI-controlled study","volume":"117","author":"Aigner","year":"2005","journal-title":"Wien. Klin. Wochenschr."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/j.ocl.2008.10.007","article-title":"Bone Marrow Edema Syndrome in Postpartal Women: Treatment with Iloprost","volume":"40","author":"Aigner","year":"2009","journal-title":"Orthop. Clin. N. Am."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1055\/s-0037-1614202","article-title":"Intravenous Iloprost treatment for severe bone pain caused by sickle cell crisis","volume":"91","author":"Disch","year":"2004","journal-title":"Thromb. Haemost."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1016\/j.itjm.2012.05.003","article-title":"Proposal of early retreatment with iloprost in partially responsive patients with bone marrow edema syndrome: A case report","volume":"6","author":"Meini","year":"2012","journal-title":"Ital. J. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"R120","DOI":"10.1186\/ar2526","article-title":"Rationale for prostaglandin I2 in bone marrow oedema--from theory to application","volume":"10","author":"Tillmann","year":"2008","journal-title":"Arthritis Res. Ther."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1455","DOI":"10.1517\/14656566.5.7.1455","article-title":"Pharmacological management of aseptic osteonecrosis in children","volume":"5","author":"Petje","year":"2004","journal-title":"Expert Opin. Pharmacother."},{"key":"ref_32","first-page":"481","article-title":"Pain management in non-juvenile, aseptic osteonecrosis","volume":"18","author":"Jager","year":"2004","journal-title":"Schmerz"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1302\/0301-620X.83B6.0830855","article-title":"Treatment of bone-marrow oedema of the talus with the prostacyclin analogue iloprost. An MRI-controlled investigation of a new method","volume":"83","author":"Aigner","year":"2001","journal-title":"J. Bone Jt. Surg. Br. Vol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1177\/107110070202300513","article-title":"Bone Marrow Edema of the Forefoot after Chevron Osteotomy\u2014A Rare Cause of Metatarsalgia: A Case Report","volume":"23","author":"Aigner","year":"2002","journal-title":"Foot Ankle Int."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1016\/S1083-7515(03)00145-1","article-title":"Iloprost for the treatment of bone marrow edema in the hindfoot","volume":"8","author":"Aigner","year":"2003","journal-title":"Foot Ankle Clin."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.fas.2005.01.003","article-title":"Bone marrow edema in the foot\u2014MRI findings after conservative therapy","volume":"11","author":"Aigner","year":"2005","journal-title":"Foot Ankle Surg."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Aigner, N., Meizer, R., Petje, G., Meizer, E., Abdelkafy, A., and Landsiedl, F. (2008). Natural course of intra-articular shifting bone marrow edema syndrome of the knee. BMC Musculoskelet. Disord., 9.","DOI":"10.1186\/1471-2474-9-45"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e1283","DOI":"10.3928\/01477447-20130920-21","article-title":"Role of Serum Lipoprotein at the Site of Iloprost Therapy in the Treatment of Painful Bone Marrow Edema","volume":"36","author":"Anagnostakos","year":"2013","journal-title":"Orthopedics"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"909.e1","DOI":"10.1016\/j.arthro.2006.05.011","article-title":"Be aware of bone marrow edema syndrome in ankle arthroscopy: A case successfully treated with iloprost","volume":"22","author":"Arazi","year":"2006","journal-title":"Arthroscopy"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1007\/s00590-010-0650-4","article-title":"Bone marrow edema syndrome of the third metatarsal bone: A rare cause of metatarsalgia treated with Iloprost","volume":"21","author":"Arazi","year":"2010","journal-title":"Eur. J. Orthop. Surg. Traumatol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1397","DOI":"10.1007\/s00296-012-2584-0","article-title":"Bisphosphonates or prostacyclin in the treatment of bone-marrow oedema syndrome of the knee and foot","volume":"33","author":"Baier","year":"2012","journal-title":"Rheumatol. Int."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.1177\/1071100718778557","article-title":"Treatment of Bone Marrow Edema of the Foot and Ankle With the Prostacyclin Analog Iloprost","volume":"39","author":"Baumbach","year":"2018","journal-title":"Foot Ankle Int."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2529","DOI":"10.1007\/s00264-020-04697-5","article-title":"Bone marrow lesion on magnetic resonance imaging indicates the last chance for hip osteonecrosis treated with vascularized fibular grafting before collapse","volume":"44","author":"Huang","year":"2020","journal-title":"Int. Orthop."},{"key":"ref_44","first-page":"3433","article-title":"Efficiency of iloprost treatment for chemotherapy-associated osteonecrosis after childhood cancer","volume":"29","author":"Zilkens","year":"2009","journal-title":"Anticancer Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1097\/01.mph.0000163215.37147.13","article-title":"Aseptic osteonecrosis in children and adolescents treated for hemato-oncologic diseases: A 13-year longitudinal observational study","volume":"27","author":"Lackner","year":"2005","journal-title":"J. Pediatr. Hematol. Oncol."},{"key":"ref_46","unstructured":"Mahmoudi, M. (2009). Therapie der Nicht-Juvenilen, Aseptischen Osteonekrose und des Symptomatischen Knochenmark\u00f6dems mit dem Prostazyklin-Analogon Iloprost: Eie MRT-Kontrollierte Klinische. [Ph.D. Thesis, Heinrich Heine University D\u00fcsseldorf]."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1460","DOI":"10.1093\/rheumatology\/kem172","article-title":"Short-term outcome of painful bone marrow oedema of the knee following oral treatment with iloprost or tramadol: Results of an exploratory phase II study of 41 patients","volume":"46","author":"Mayerhoefer","year":"2007","journal-title":"Rheumatology"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1097\/JSM.0b013e31817f3e1c","article-title":"MRI-demonstrated outcome of subchondral stress fractures of the knee after treatment with iloprost or tramadol: Observations in 14 patients","volume":"18","author":"Mayerhoefer","year":"2008","journal-title":"Clin. J. Sport Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1007\/s00132-002-0387-9","article-title":"Aseptic osteonecrosis in childhood: Diagnosis and treatment","volume":"31","author":"Petje","year":"2002","journal-title":"Orthopade"},{"key":"ref_50","first-page":"6902","article-title":"Bone marrow aspirate concentrate in combination with intravenous iloprost increases bone healing in patients with avascular necrosis of the femoral head: A matched pair analysis","volume":"8","author":"Pilge","year":"2016","journal-title":"Orthop. Rev."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1111\/j.1600-6143.2007.01662.x","article-title":"Intravenous iloprost: A new therapeutic option for patients with post-transplant distal limb syndrome (PTDLS)","volume":"7","author":"Tillmann","year":"2007","journal-title":"Am. J. Transplant"},{"key":"ref_52","first-page":"e10547","article-title":"Effectiveness of Iloprost in the Treatment of Bone Marrow Edema","volume":"12","author":"Tosun","year":"2020","journal-title":"Cureus"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/0197-2456(86)90046-2","article-title":"Meta-analysis in clinical trials","volume":"7","author":"Laird","year":"1986","journal-title":"Control. Clin. Trials"}],"container-title":["Journal of Personalized Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4426\/12\/11\/1757\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:01:15Z","timestamp":1760144475000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4426\/12\/11\/1757"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,23]]},"references-count":53,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2022,11]]}},"alternative-id":["jpm12111757"],"URL":"https:\/\/doi.org\/10.3390\/jpm12111757","relation":{},"ISSN":["2075-4426"],"issn-type":[{"value":"2075-4426","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,23]]}}}