A biomechanical, micro computertomographic and histological analysis of the influence of diclofenac and prednisolone on fracture healing in vivo

作者:Bissinger Oliver; Kreutzer Kilian; Goetz Carolin; Hapfelmeier Alexander; Pautke Christoph; Vogt Stephan; Wexel Gabriele; Wolff Klaus Dietrich; Tischer Thomas; Prodinger Peter Michael
来源:BMC Musculoskeletal Disorders, 2016, 17(1): 383.
DOI:10.1186/s12891-016-1241-2

摘要

Background: Non-steroidal anti-inflammatory drugs (NSAIDs) have long been suspected of negatively affecting fracture healing, although numerous disputes still exist and little data are available regarding diclofenac. Glucocorticoids interfere in this process over a similar and even broader mechanism of action. As many previously conducted studies evaluated either morphological changes or biomechanical properties of treated bones, the conjunction of both structural measures is completely missing. Therefore, it was our aim to evaluate the effects of diclofenac and prednisolone on the fracture callus biomechanically, morphologically and by 3-dimensional (3D) microstructural analysis. Methods: Femura of diclofenac-, prednisolone- or placebo-treated rats were pinned and a closed transverse fracture was generated. After 21 days, biomechanics, micro-CT (mu CT) and histology were examined. Results: The diclofenac group showed significantly impaired fracture healing compared with the control group by biomechanics and mu CT (e.g. stiffness: 57.31 +/- 31.11 N/mm vs. 122.44 +/- 81.16 N/mm, p = 0.030; callus volume: 47.05 +/- 15. 67 mm3 vs. 67.19 +/- 14.90 mm3, p = 0.037, trabecular thickness: 0.0937 mm +/- 0.003 vs. 0.0983 mm +/- 0.003, p = 0.023), as confirmed by histology. Biomechanics of the prednisolone group showed obviously lower absolute values than the control group. These alterations were confirmed in conjunction with mu CT and histology. Conclusions: The inhibiting effects of both substances were not only mediated by absolute parameters (e.g. breaking load, BV), but we have shown, for the first time, that additional changes occurred in the microstructural bony network. Especially in patients at risk for delayed bone healing (arteriosclerosis, diabetes mellitus, smoking), the administration of these drugs should be weighed carefully.