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Safety study: is there a pathologic IGF-1, PDGF and TGF-ß cytokine expression caused by adjunct BMP-7 in tibial and femoral non-union therapy?

Authors Fischer C, Reiner C, Schmidmaier G, Doll J, Child C, Grützner PA, Biglari B, Boxriker S, Moghaddam A

Received 16 December 2017

Accepted for publication 22 February 2018

Published 16 April 2018 Volume 2018:14 Pages 691—697

DOI https://doi.org/10.2147/TCRM.S160064

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Lucy Goodman

Peer reviewer comments 3

Editor who approved publication: Professor Garry Walsh

Christian Fischer,1 Christian Reiner,2 Gerhard Schmidmaier,1 Julian Doll,1 Christopher Child,3 Paul Alfred Grützner,4 Bahram Biglari,4 Sonja Boxriker,5 Arash Moghaddam5

1Center for Orthopedics, Trauma Surgery and Spinal Cord Injury, HTRG – Heidelberg Trauma Research Group, Heidelberg University Hospital, Heidelberg, Germany; 2Department of Trauma and Orthopedic Surgery, Paracelsus Medical University, Nuremberg Hospital South, Nuremberg, Germany; 3Department of Trauma Surgery, University Hospital Zurich, Zurich, Switzerland; 4Trauma and Orthopedics, BG Trauma Center Ludwigshafen, Ludwigshafen, Germany; 5Center of Orthopedics, Trauma Surgery and Sport Medicine, ATORG Aschaffenburg-Alzenau, Aschaffenburg, Germany


Background: In this prospective safety study, we investigated if the characteristic cytokine expression during bone regeneration is manipulated by the local application of bone morphogenetic protein-7 (BMP-7) in non-union surgery. Therefore, the levels of insulin like growth factor 1 (IGF-1), platelet-derived growth factor AB (PDGF-AB) and transforming growth factor beta (TGF-β) were compared between patients with the gold standard use of autologous bone graft (ABG) and those with additional application of BMP-7 as part of the diamond concept.
Patients and methods: Between 2009 and 2014, of the 153 patients with tibial and femoral non-unions, a matched pair analysis was performed to compare the serological cytokine expressions. Blood samples were collected preoperatively, 1, 2 and 6 weeks as well as 3 and 6 months after non-union surgery. Matching criteria were smoking status, fracture location, gender, age and body mass index (BMI). Patients in G1 (n=10) were treated with ABG and local BMP-7 while their matching partners in G2 (n=10) received ABG only. The routine clinical and radiologic follow-up was 1 year.
Results: Although the IGF-1 quantification in G2 showed higher pre- and postoperative values compared to G1 (p<0.05), the courses of both groups were similar. Likewise, PDGF-AB and TGF-β expressions appeared similar in G1 and G2 with peaks in both groups at 2 weeks follow-up. Osseous consolidation was assessed in all operated non-unions. The adjunct application of BMP-7 did not cause any pathologic cytokine expression.
Conclusion: Similar expressions of the serum cytokines IGF-1, PDGF-AB and TGF-β were demonstrated in non-union patients treated with ABG and additional application of BMP-7 according to the diamond concept. Our findings indicate that the local application of BMP-7, which imitates the physiologic secretion of growth factors during bone regeneration, is safe and without the risk of abnormal systemic cytokine expression. Studies with higher patient numbers will have to validate these assumptions.

Keywords: bone morphogenetic protein, cytokine, non-union, safety

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