Molecular and histopathological investigation of stress fracture healing and effects of anti-inflammatory drugs.

应力性骨折是一种使人衰弱的损伤，影响儿童、青少年和成年人的运动和军队新兵。它们也发生在赛马和灰狗比赛中，通常导致相关动物的安乐死。他们在医疗费用、体育运动时间损失和军事训练中断方面付出了相当大的代价。但是，几乎没有关于这些骨折愈合机制的信息。非甾体类抗炎药（NSAID）仍然是最广泛使用的药物在管理肌肉骨骼损伤，但其对应力性骨折愈合的影响是未知的。非甾体抗炎药延缓骨折愈合，但直到最近还没有标准化的方法来研究应力性骨折。我们第一次在大鼠前臂中创建了一个特征良好的非侵入性应力性骨折模型，该模型与临床情况非常相似。这提供了一个新的和独特的机会，以确定应力骨折愈合的组织学和分子机制，并研究抗炎镇痛药物对这一过程的影响。大鼠的一只前肢将产生实验性应力性骨折，其愈合将通过显微镜检查和对启动该过程的关闭或打开的基因的分析进行长达10周的检查。一组大鼠也将接受布洛芬等抗肿瘤药物、特异性考克斯-2抑制剂和一类称为C5 a受体拮抗剂的靶向早期免疫反应的新型药物的治疗。还将研究镇痛药对乙酰氨基酚作为上述NSAID的替代品。有广泛使用的抗炎药在管理应力性骨折，所以它是至关重要的，他们对应力性骨折愈合的影响进行检查。该项目对于优化应力性骨折的临床管理方法以及了解抗炎或镇痛剂在该过程中的相互作用具有重大意义。

Stress fractures are debilitating injuries affecting children, adolescents and adults in sport, and army recruits. They also occur in horse and greyhound racing, often resulting in euthanasia of the animals involved. They incur considerable costs in medical expenses, time lost from sport and interruption to military training. But, there is almost no information on the mechanism of healing of these fractures. Non-steroidal anti-inflammatory drugs (NSAIDs) are still the most widely used medication in management of musculoskeletal injuries, yet their effect on healing of stress fractures is unknown. NSAIDs delay fracture healing, but until recently there has been no standardised way of studying stress fractures. We have created, for the first time, a well-characterised, non-invasive model of stress fractures in the forearm of rats that closely resembles the clinical situation. This provides a novel and unique opportunity to determine the histological and molecular mechanism of stress fracture healing, and to investigate effects of antiinflammatory-analgesic medications on this process. Rats will have an experimental stress fracture produced in one forelimb, and its healing will be examined up to ten weeks using microscopic investigation and analysis of the genes that are turned off or on to initiate the process. Groups of rats will also be treated with antiinflammatory drugs such as ibuprofen, specific COX-2 inhibitors and a new class of drugs that target early immune responses called C5a receptor antagonists. The analgesic Paracetamol will also be investigated as an alternative to the NSAIDs described above. There is widespread use of anti-inflammatory agents in managing stress fractures, so it is vital that their effects on stress fracture healing be examined. This project has enormous significance for optimising approaches for clinical management of stress fractures and for understanding the interaction of anti-inflammatory or analgesic agents in that process.