Department of Biomedical Engineering, Wayne State University, 818 West Hancock, Detroit, MI 48201, USA.
Clin Orthop Relat Res. 2011 Aug;469(8):2399-403. doi: 10.1007/s11999-011-1918-7. Epub 2011 May 17.
Persistent inflammatory reaction to wear debris causes periprosthetic osteolysis and loosening. Some authors have advocated pharmaceutical approaches to reduce the inflammatory reaction. Erythromycin has antiinflammatory effects independent of its antimicrobial properties. Although oral erythromycin reportedly inhibits periprosthetic tissue inflammation in patients with aseptic loosening, long-term systematic erythromycin treatment is not recommended owing to its side effects. Therefore, it would be advantageous to restrict erythromycin delivery to the inflammatory periprosthetic tissue without causing side effects.
QUESTIONS/HYPOTHESES: Erythromycin eluted from hydroxyapatite-coated titanium (Ti) pins inhibits periprosthetic tissue inflammation and osteolysis.
We propose restricting erythromycin delivery to the inflammatory periprosthetic site. A previously described rat model of ultrahigh molecular weight polyethylene (UHMWPE) particle-induced periprosthetic tissue inflammation and osteolysis will be used to test the effect of local delivery of erythromycin via Peri-Apatite(TM)-coated Ti implants. The outcome measures will include bone ingrowth (μCT), implant stability (pullout test), and histologic analysis of periprosthetic tissues.
Pharmacologic intervention aimed at slowing, preventing, or reversing the aseptic loosening process would represent an advance in the management of joint replacement. Erythromycin may be appropriate for prophylactically treating patients who have repeated revision surgery and/or show early signs of progressive osteolysis after arthroplasty.
对磨损颗粒的持续炎症反应导致假体周围骨溶解和松动。一些作者主张采用药物方法来减少炎症反应。红霉素具有独立于其抗菌特性的抗炎作用。尽管口服红霉素据称可抑制无菌性松动患者的假体周围组织炎症,但由于其副作用,不建议长期系统使用红霉素治疗。因此,将红霉素的释放限制在炎症性假体周围组织而不引起副作用将是有利的。
问题/假设:从羟基磷灰石涂层钛(Ti)钉中洗脱的红霉素可抑制假体周围组织炎症和骨溶解。
我们建议将红霉素的释放限制在炎症性假体周围部位。将使用先前描述的超高分子量聚乙烯(UHMWPE)颗粒诱导的假体周围组织炎症和骨溶解大鼠模型来测试通过 Peri-Apatite(TM)涂层 Ti 植入物局部递送红霉素的效果。将包括骨内生长(μCT)、植入物稳定性(拔出试验)和假体周围组织的组织学分析作为结果测量。
旨在减缓、预防或逆转无菌性松动过程的药物干预将代表关节置换管理的进步。红霉素可能适合预防性治疗反复接受翻修手术的患者,或在关节置换术后出现进行性骨溶解的早期迹象的患者。