title: Bone marrow-derived cell mobilization by G-CSF to enhance osseointegration of bone substitute in high tibial osteotomy.
abstract: OBJECTIVE
  To evaluate granulocyte colony-stimulating factor (G-CSF) efficacy in accelerating bone regeneration following opening-wedge high tibial valgus osteotomy for genu varum.
  
  
  METHODS
  A phase II trial was conducted for evaluating the preoperative administration of G-CSF given at 10 μg/kg/day for 3 consecutive days with an additional half-dose 4 h before the opening-wedge high tibial valgus osteotomy. Overall, 12 patients (Group A) received G-CSF treatment, and the subsequent 12 patients (Group B) underwent surgery without G-CSF. The osteotomy gap was filled by a bone graft substitute. Bone marrow cell (BMC) mobilization was monitored by CD34+ve cell and clonogenic progenitor cell analysis. All patients underwent a clinical (Lysholm Knee Scale and SF-36) and radiographic evaluation preoperatively, as well as at given intervals postsurgery.
  
  
  RESULTS
  All patients completed the treatment program without major side effects; G-CSF was well tolerated. BMC mobilization occurred in all Group A patients, with median peak values of circulating CD34+ve cells of 110/μL (range 29-256). Circulating clonogenic progenitors paralleled CD34+ve cell levels. A significant improvement in Lysholm Knee Scale was recorded at follow-up in Group A compared to Group B. At the radiographic evaluation, there was a significant increase in osseointegration at the bone-graft junction in Group A at 1, 2, 3 and 6 months postsurgery compared to Group B. The computerized tomography scan of the grafted area at 2 months postsurgery showed no significant difference in the quality of the newly formed bone between the two Groups.
  
  
  CONCLUSIONS
  Although the limited number of patients does not allow firm conclusions, the study suggests that G-CSF can be safely administered preoperatively in subjects undergoing opening-wedge high tibial valgus osteotomy; in addition, the clinical, radiographic and CT monitoring indicate that G-CSF and/or mobilized BMCs may hasten bone graft substitute osseointegration.
  
  
  METHODS
  I.
authors.affiliation: Department of Orthopaedics and Traumatology, Ordine Mauriziano, Umberto I Hospital, University of Torino, Turin, Italy. antonio.marmotti@inwind.it
authors.forename: A
authors.initials: A
authors.lastname: Marmotti
authors.forename: F
authors.initials: F
authors.lastname: Castoldi
authors.forename: R
authors.initials: R
authors.lastname: Rossi
authors.forename: S
authors.initials: S
authors.lastname: Marenco
authors.forename: A
authors.initials: A
authors.lastname: Risso
authors.forename: M
authors.initials: M
authors.lastname: Ruella
authors.forename: A
authors.initials: A
authors.lastname: Tron
authors.forename: A
authors.initials: A
authors.lastname: Borrè
authors.forename: D
authors.initials: D
authors.lastname: Blonna
authors.forename: C
authors.initials: C
authors.lastname: Tarella
mesh_terms: D000328:Adult; D000368:Aged; D018786:Bone Substitutes; D004334:Drug Administration Schedule; D005240:Feasibility Studies; D005260:Female; D005500:Follow-Up Studies; D056305:Genu Varum / Q000150:complications / Q000000981:diagnostic imaging / Q000601:surgery*; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000494:pharmacology*; D006305:Health Status Indicators; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods*; D006801:Humans; D007719:Knee Joint / Q000000981:diagnostic imaging / Q000187:drug effects / Q000502:physiology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D016348:Osseointegration / Q000187:drug effects*; D020370:Osteoarthritis, Knee / Q000150:complications / Q000000981:diagnostic imaging / Q000601:surgery; D010027:Osteotomy / Q000295:instrumentation / Q000379:methods*; D011300:Preoperative Care; D011446:Prospective Studies; D013977:Tibia / Q000000981:diagnostic imaging / Q000187:drug effects / Q000502:physiology / Q000601:surgery*; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
chemical_list: D018786:Bone Substitutes; D016179:Granulocyte Colony-Stimulating Factor