Arthritis and Arthroplasty Design Group, The Bone and Joint Center, Magee-Womens Hospital of the University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Infect Immun. 2020 Jun 22;88(7). doi: 10.1128/IAI.00932-19.
Osteomyelitis, or inflammation of bone, is most commonly caused by invasion of bacterial pathogens into the skeleton. Bacterial osteomyelitis is notoriously difficult to treat, in part because of the widespread antimicrobial resistance in the preeminent etiologic agent, the Gram-positive bacterium Bacterial osteomyelitis triggers pathological bone remodeling, which in turn leads to sequestration of infectious foci from innate immune effectors and systemically delivered antimicrobials. Treatment of osteomyelitis therefore typically consists of long courses of antibiotics in conjunction with surgical debridement of necrotic infected tissues. Even with these extreme measures, many patients go on to develop chronic infection or sustain disease comorbidities. A better mechanistic understanding of how bacteria invade, survive within, and trigger pathological remodeling of bone could therefore lead to new therapies aimed at prevention or treatment of osteomyelitis as well as amelioration of disease morbidity. In this minireview, we highlight recent developments in our understanding of how pathogens invade and survive within bone, how bacterial infection or resulting innate immune responses trigger changes in bone remodeling, and how model systems can be leveraged to identify new therapeutic targets. We review the current state of osteomyelitis epidemiology, diagnostics, and therapeutic guidelines to help direct future research in bacterial pathogenesis.
骨髓炎，即骨骼炎症，通常是由细菌病原体入侵骨骼引起的。细菌性骨髓炎的治疗极具挑战性，部分原因在于主要病原体革兰氏阳性菌的广泛抗菌药物耐药性。细菌性骨髓炎会引发病理性骨重塑，进而导致感染灶与先天免疫效应物和全身递送的抗菌药物隔离。因此，骨髓炎的治疗通常包括长期使用抗生素联合手术清创坏死感染组织。即使采取了这些极端措施，许多患者仍会发展为慢性感染或持续存在疾病合并症。因此，更好地了解细菌如何入侵、在骨骼内存活以及引发病理性重塑，可能会带来新的治疗方法，旨在预防或治疗骨髓炎，并改善疾病的发病率。在这篇简评中，我们强调了最近在理解病原体如何入侵和在骨骼内存活、细菌感染或由此产生的先天免疫反应如何引发骨重塑变化，以及如何利用模型系统来确定新的治疗靶点方面的进展。我们回顾了骨髓炎的流行病学、诊断和治疗指南的现状，以帮助指导细菌发病机制的未来研究。
