Bissinger Oliver, Kreutzer Kilian, Götz Carolin, Hapfelmeier Alexander, Pautke Christoph, Vogt Stephan, Wexel Gabriele, Wolff Klaus-Dietrich, Tischer Thomas, Prodinger Peter Michael
Department of Oral and Maxillofacial Surgery, Klinikum rechts der Isar der Technischen Universität München, Ismaninger Str. 22, 81675, Munich, Germany.
Institute of Medical Statistics and Epidemiology, Klinikum rechts der Isar der Technischen Universität München, Ismaninger Str. 22, 81675, Munich, Germany.
BMC Musculoskelet Disord. 2016 Sep 5;17(1):383. doi: 10.1186/s12891-016-1241-2.
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.
Femura of diclofenac-, prednisolone- or placebo-treated rats were pinned and a closed transverse fracture was generated. After 21 days, biomechanics, micro-CT (μCT) and histology were examined.
The diclofenac group showed significantly impaired fracture healing compared with the control group by biomechanics and μCT (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 μCT and histology.
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.
长期以来，非甾体抗炎药（NSAIDs）一直被怀疑会对骨折愈合产生负面影响，尽管仍存在众多争议，且关于双氯芬酸的数据很少。糖皮质激素通过类似甚至更广泛的作用机制干扰这一过程。由于许多先前进行的研究仅评估了治疗后骨骼的形态变化或生物力学特性，因此完全缺乏这两种结构测量方法的结合。因此，我们的目的是通过生物力学、形态学以及三维（3D）微观结构分析来评估双氯芬酸和泼尼松龙对骨折痂的影响。
对双氯芬酸、泼尼松龙或安慰剂治疗的大鼠股骨进行穿针，并造成闭合性横断骨折。21天后，检查生物力学、显微CT（μCT）和组织学。
与对照组相比，双氯芬酸组在生物力学和μCT方面显示骨折愈合明显受损（例如，刚度：57.31±31.11N/mm对122.44±81.16N/mm，p = 0.030；骨痂体积：47.05±15.67mm³对67.19±14.90mm³，p = 0.037，小梁厚度：0.0937mm±0.003对0.0983mm±0.003，p = 0.023），组织学证实了这一点。泼尼松龙组的生物力学绝对值明显低于对照组。这些改变通过μCT和组织学得到证实。
这两种物质的抑制作用不仅由绝对参数（例如断裂负荷、骨体积）介导，而且我们首次表明，骨微观结构网络中还发生了其他变化。特别是对于有骨愈合延迟风险的患者（动脉硬化、糖尿病、吸烟），应仔细权衡这些药物的使用。
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