Department of Rheumatology, Maastricht University Medical Center, Maastricht, The Netherlands.
Curr Opin Rheumatol. 2013 Jul;25(4):524-31. doi: 10.1097/BOR.0b013e32836200b8.
Published data raise concerns about the use of nonselective NSAIDs and selective cyclo-oxygenase (COX)-2 inhibitors as anti-inflammatory or analgesic drugs in patients after a recent fracture or who are undergoing (uncemented) arthroplasty or osteotomy. However, clinical reports on the effect of COX-2 inhibition on fracture healing in humans have been variable and inconclusive. This review gives an overview of the published data and an advice when to avoid NSAIDs.
Prostaglandins play an important role as mediators of inflammation and COX are required for their production. Inflammation is an essential step in the fracture healing process in which prostaglandin production by COX-2 is involved. Data from animal studies suggest that NSAIDs, which inhibit COX-2, can impair fracture healing due to the inhibition of the endochondral ossification pathway. Animal data suggest that the effects of COX-2 inhibitors are dependent on the timing, duration, and dose, and that these effects are reversible.
These animal data, together with the view of limited scientifically robust clinical evidence in humans, indicate that physicians consider only short-term administration of COX-2 inhibitors or other drugs in the pain management of patients who are in the phase of fracture or other bone defect healing. COX-2-inhibitors should be considered a potential risk factor for fracture healing, and therefore to be avoided in patients at risk for delayed fracture healing.
近期骨折或正在接受（非骨水泥型）关节置换术或截骨术的患者，使用非选择性非甾体抗炎药和选择性环氧化酶（COX）-2 抑制剂作为抗炎或镇痛药物，相关的已发表数据令人担忧。然而，关于 COX-2 抑制对人类骨折愈合影响的临床报告结果不一且尚无定论。本文综述了已发表的数据，并就何时应避免使用 NSAIDs 提供了相关建议。
前列腺素作为炎症介质发挥重要作用，而 COX 是其产生所必需的。炎症是骨折愈合过程中的一个重要步骤，其中 COX-2 产生的前列腺素参与其中。动物研究数据表明，COX-2 抑制剂（如 NSAIDs）可通过抑制软骨内骨化途径来损害骨折愈合，因为它们抑制 COX-2 的产生。动物数据表明，COX-2 抑制剂的作用取决于时间、持续时间和剂量，并且这些作用是可逆的。
这些动物数据，以及人类中有限的具有科学稳健性的临床证据，表明在骨折或其他骨缺损愈合阶段的患者的疼痛管理中，医生仅考虑短期使用 COX-2 抑制剂或其他药物。COX-2 抑制剂被认为是骨折愈合的潜在风险因素，因此应避免在有延迟骨折愈合风险的患者中使用。
