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J Inflamm (Lond). 2016 Jan 22;13:3. doi: 10.1186/s12950-016-0111-x. eCollection 2016.

Non-unions treated with bone morphogenic protein 7: introducing the quantitative measurement of human serum cytokine levels as promising tool in evaluation of adjunct non-union therapy.

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HTRG - Heidelberg Trauma Research Group, Trauma and Reconstructive Surgery, Center of Orthopaedics, Traumatology and Paraplegiology, Heidelberg University Hospital, Schlierbacher Landstraße 200a, D-69118 Heidelberg, Germany.
Department of Orthopaedics and Traumatology, St. Marienkrankenhaus, Salzburger Str. 15, 67067 Ludwigshafen, Germany.
Department for anesthesiology, Stadtklinik Frankenthal, Elsa-Brändenström Str. 1, D-67227 Frankenthal, Germany.
Berufsgenossenschaftliche Unfallklinik Ludwigshafen, Department of Paraplegiology, Ludwig-Guttmann-Straße-13, D-67071 Ludwigshafen, Germany.
Berufsgenossenschaftliche Unfallklinik Ludwigshafen, Trauma Center, Ludwig-Guttmann-Straße-13, D-67071 Ludwigshafen, Germany.
Department for Trauma Surgery, Theresienkrankenhaus und St. Hedwigs-Klinik GmbH, Bassermannstr. 1, D-68165 Mannheim, Germany.



In this study we sought to determine if application of bone morphogenic protein 7 (BMP-7) promotes physiological bone healing of non-unions and to investigate if serum cytokine analysis may serve as a promising tool in the analysis of adjunct non-union therapy. Therefore we analyzed the influence of BMP-7 application on the serum cytokine expression patterns on patients with impaired bone healing compared to patients that showed proper bone healing.


Our study involved analyzing blood samples from 208 patients with long bone fractures together with patients that subsequently developed non-unions. From this large pool, 15 patients with atrophic non-union were matched to 15 patients with atrophic non-union treated with local application of BMP-7 as well as normal bone healing. Changes in the cytokine expression patterns were monitored during the 1st, 2nd, 4th, 8th, 12th and 52nd week. The patients were followed both clinically and radiologically for the entire duration of the study. Serum cytokine expression levels of transforming growth factor beta (TGF-β), platelet-derived growth factor (PDGF) and basic fibroblast growth factor (bFGF) were analyzed and compared.


Serum expression of TGF-β were nearly parallel in all three groups, however serum concentrations were significantly higher in patients with proper bone healing and those treated with BMP-7 than in patients with non-unions (p < 0.05). bFGF serum concentrations increased initially in patients with proper bone healing and in those treated with BMP-7. Afterwards, values decreased; bFGF serum concentrations in the BMP-7 group were significantly higher than in the other groups (p < 0.05). PDGF serum concentration levels were nearly parallel in all groups, serum concentrations were significantly higher in patients with proper bone healing and those treated with BMP-7 than in patients with non-unions (p < 0.05).


Treatment with BMP-7 in patients with former non-unions led to similar cytokine expression patterns after treatment as those found in patients with proper bone healing. Our results suggest that treatment with BMP-7 promote healing of non-unions. Furthermore, quantitative measurement of serum cytokine expression is a promising tool for evaluating the effectiveness of additional non-union therapies such as adjunct application of growth factors.


BMP-7; Cytokines; Fracture healing; Non-union; PDGF; Pseudarthrosis; TGF- β; bFGF

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