Bone marrow-derived cell mobilization by G-CSF to enhance osseointegration of bone substitute in high tibial osteotomy

Knee Surg Sports Traumatol Arthrosc. 2013 Jan;21(1):237-48. doi: 10.1007/s00167-012-2150-z. Epub 2012 Aug 8.


Purpose: 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.

Level of evidence: I.

Publication types

  • Clinical Trial, Phase II
  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Bone Substitutes*
  • Drug Administration Schedule
  • Feasibility Studies
  • Female
  • Follow-Up Studies
  • Genu Varum / complications
  • Genu Varum / diagnostic imaging
  • Genu Varum / surgery*
  • Granulocyte Colony-Stimulating Factor / administration & dosage
  • Granulocyte Colony-Stimulating Factor / pharmacology*
  • Health Status Indicators
  • Hematopoietic Stem Cell Mobilization / methods*
  • Humans
  • Knee Joint / diagnostic imaging
  • Knee Joint / drug effects
  • Knee Joint / physiology
  • Knee Joint / surgery
  • Male
  • Middle Aged
  • Osseointegration / drug effects*
  • Osteoarthritis, Knee / complications
  • Osteoarthritis, Knee / diagnostic imaging
  • Osteoarthritis, Knee / surgery
  • Osteotomy / instrumentation
  • Osteotomy / methods*
  • Preoperative Care
  • Prospective Studies
  • Tibia / diagnostic imaging
  • Tibia / drug effects
  • Tibia / physiology
  • Tibia / surgery*
  • Tomography, X-Ray Computed
  • Treatment Outcome


  • Bone Substitutes
  • Granulocyte Colony-Stimulating Factor