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

  • Knee
  • Published:
Knee Surgery, Sports Traumatology, Arthroscopy Aims and scope

Abstract

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.

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Acknowledgments

Authors are grateful to Prof. Paolo Rossi for his precious help in the planning and fulfilment of the study program and his continuous encouragement during the data collection and analysis. This work was supported in part by grants from the Ministero Italiano Università e Ricerca (MIUR) (PRIN 2006), Rome, Italy and by Regione Piemonte (Ricerca Sanitaria Finalizzata and Ricerca Scientifica Applicata), Torino. AR is supported with a grant from PiSTEM Project-Regione Piemonte. The laboratory assays on stem/progenitor cell mobilization have been performed at the Hematology laboratory of the Molecular Biotechnology Center (MBC) in Torino. G-CSF (Myelostim®) was kindly provided free of charge by Italfarmaco, Milano, Italy. The authors would also like to thank Prof. Paolo Provero, for the assistance in the statistics, and Radhika Srinivasan, PhD, for editing the manuscript.

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Authors and Affiliations

  1. Department of Orthopaedics and Traumatology, Ordine Mauriziano, Umberto I Hospital, University of Torino, Turin, Italy

    A. Marmotti, F. Castoldi, R. Rossi, S. Marenco, A. Tron & D. Blonna

  2. Department of Haematology and Cell Therapy, Ordine Mauriziano, Umberto I Hospital, University of Torino, Turin, Italy

    M. Ruella & C. Tarella

  3. Molecular Biotechnology Centre, University of Torino, Turin, Italy

    A. Risso, M. Ruella & C. Tarella

  4. Department of Orthopaedic Radiology, Maria Adelaide Hospital, University of Torino, Turin, Italy

    A. Borrè

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  1. A. Marmotti
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Marmotti, A., Castoldi, F., Rossi, R. et al. Bone marrow-derived cell mobilization by G-CSF to enhance osseointegration of bone substitute in high tibial osteotomy. Knee Surg Sports Traumatol Arthrosc 21, 237–248 (2013). https://doi.org/10.1007/s00167-012-2150-z

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