title: The efficacy of targeted intraarterial delivery of concentrated autologous bone marrow containing mononuclear cells in the treatment of osteonecrosis of the femoral head: a five year follow-up study.
abstract: OBJECTIVE
  To investigate the efficacy and safety of targeted delivery of autologous bone marrow mononuclear cells (BMMCs), which are highly enriched with mesenchymal stem cells (BMMSCs), via medial circumflex femoral artery in the treatment of osteonecrosis of the femoral head (ONFH).
  
  
  METHODS
  62 patients (78 hips) with ONFH were recruited in this study. All of these patients were treated with BMMCs perfusion via medial circumflex femoral artery. The concentrated BMMCs (30-60ml) were gained from autologous bone marrow (100-200ml) harvested from anterior iliac crest and then were intra-arterially perfused into the femoral head. Ficat stage was used to classify the radiological stage of ONFH. Harris hip score was used to evaluate the clinical symptoms of osteonecrosis. Ficat stage and Harris hip scores were assessed at onset of treatment at 6, 12, 24, 36, 48 and 60months after the initial treatment. Total hip arthroplasty (THA) was also assessed as an endpoint at each follow-up.
  
  
  RESULTS
  A follow-up on the patient was done at the end of five years, and 92.31% (72 of 78) of hips achieved a satisfactory clinical result while only 6 hips (7.69%) progressed to clinical failure and required THA. Radiological progression was noted in 34 of 78 hips (43.59%); the overall rate of collapse was 38.24% (26 of 68 hips) in stage-I and stage-II hip combinations and 12.5% (2 of 16) in stage-I hips and 46.15% (24 of 52) in stage-II hips. The mean time of conversion to THA was 3years (1 to 5years) and the average time to collapse were 3.5years (1-5years). The mean Harris hip score increased from 59 points at baseline to 75 points at 12months, 82 points at 24months, 81 points at 36months, 79 points at 48months and 74 points at 60months. Five years after the treatment, 3 of 10 hips (30%) in stage-III had deteriorated to clinical failure whereas only 3 of 68 hips (4.41%) in stage-I and II combination had progressed to clinical failure (p<0.05). Kaplan-Meier survival analysis showed a significant difference in the time to failure between the pre-collapse hips (Ficat stage-I and II) and the post-collapse hips (Ficat stage-III) at five years follow-up (Log-rank test; p<0.01). No complication was found in any patients.
  
  
  CONCLUSIONS
  Autologous BMMSC perfusion via the medial circumflex femoral artery can relieve symptoms, improve hip function and delay the progression of ONFH. The clinical outcome is better when it is applied prior to the collapse. This work demonstrates that autologous BMMSC perfusion via the medial circumflex femoral artery is a safe, effective and minimally invasive treatment strategy for early-stage ONFH.
authors.affiliation: Zhejiang Chinese Medical University, Hangzhou 310053 Zhejiang Province, China; Department of Orthopaedic Surgery, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006 Zhejiang Province, China; Institute of Orthopaedics and Traumatology of Zhejiang Province, Hangzhou 310053 Zhejiang Province, China. Electronic address: peijiantongzy@126.com.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Mao
authors.forename: Hongting
authors.initials: H
authors.lastname: Jin
authors.forename: Fei
authors.initials: F
authors.lastname: Liao
authors.forename: Luwei
authors.initials: L
authors.lastname: Xiao
authors.forename: Di
authors.initials: D
authors.lastname: Chen
authors.forename: Peijian
authors.initials: P
authors.lastname: Tong
mesh_terms: D000328:Adult; D019644:Arthroplasty, Replacement, Hip; D001854:Bone Marrow Cells / Q000166:cytology*; D016026:Bone Marrow Transplantation; D005260:Female; D005271:Femur Head Necrosis / Q000000981:diagnostic imaging / Q000473:pathology / Q000628:therapy*; D005500:Follow-Up Studies; D006615:Hip / Q000473:pathology; D006801:Humans; D007269:Injections, Intra-Arterial; D007963:Leukocytes, Mononuclear / Q000637:transplantation*; D008297:Male; D008875:Middle Aged; D014057:Tomography, X-Ray Computed; D014182:Transplantation, Autologous; D016896:Treatment Outcome; D055815:Young Adult
keywords: Bone marrow; Intraarterial delivery; Medial circumflex femoral artery; Mesenchymal stem cells; Osteonecrosis of the femoral head