Abstract
BackgroundIn 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.MethodsOur 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.ResultsSerum 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).ConclusionTreatment 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.
Highlights
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
Basic fibroblast growth factor (BFGF) basic fibroblast growth factor (bFGF) serum concentrations increased in between the first and the second week in patients with proper bone healing and in those treated with Bone morphogenic protein (BMP)-7 (BMP-7 week 1: 7.96 ± 2.03 ng/ml, week 2: 36.77 ± 10.12 ng/ml; Nonunion week 1: 5.94 ± 1.59 ng/ml, week 2: 6.60 ± 1.08 ng/ ml; Union week 1: 5.09 ± 1.03 ng/ml, week 2: 13.12 ± 1.92 ng/ml) (Fig. 3)
In non-union patients, values did not change significantly during the whole course but varied around. In this prospective, controlled clinical study, we analyzed the serum concentrations of Transforming growth factor beta (TGF-β), platelet-derived growth factor (PDGF) and bFGF during a 1 year follow-up in non-union patients treated with BMP-7 and compared them to the cytokine expression pattern of patients with failed as well as with physiological bone healing to determine whether the local application of BMP-7 modulates the microenvironment in the fracture gap and thereby influences secondary bone regeneration
Summary
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. There are various surgical treatment options for non-unions [2], including revision surgery, medullary reaming, and dynamisation of nails. Patients who do not respond to such therapies require further surgical interventions, such as adjunct application of bone morphogenic protein 7 (BMP-7) during revision surgery. BMP-7 was documented as being 80–90 % effective in healing non-unions, showing comparable or even better results as autologous bone grafting [7, 8]
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