Osteomyelitis (OM), characterized by heterogeneity and complexity in treatment, has a high risk of infection recurrence which may cause limb disability. Management of chronic inactive osteomyelitis (CIOM) without typical inflammatory symptoms is a great challenge for orthopedic surgeons. On the basis of data analysis of 1091 OM cases, we reported that latent osteogenic decline in CIOM patients was the main cause of secondary surgery. Our research shows that impairment of osteoblasts capacity in CIOM patients is associated with ferroptosis of osteoblasts caused by internalization of Staphylococcus aureus. Further studies show that melatonin could alleviate ferroptosis of osteoblasts in infected states through Nox4/ROS/P38 axis and protect the osteogenic ability of CIOM patients. Knockout of NADPH oxidase 4 (Nox4) in vivo could effectively relieve ferroptosis of osteoblasts in the state of infection and promote osteogenesis. Through a large number of clinical data analyses combined with molecular experiments, this study clarified that occult osteogenic disorders in CIOM patients were related to ferroptosis of osteoblasts. We revealed that melatonin might be a potential therapeutic drug for CIOM patients and provided a new insight for the treatment of OM.

中文翻译：

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褪黑素，一种治疗感染性骨不连的潜在有效药物

骨髓炎（OM）具有治疗的异质性和复杂性，感染复发的风险很高，可能导致肢体残疾。对于骨科医生来说，治疗没有典型炎症症状的慢性非活动性骨髓炎（CIOM）是一个巨大的挑战。通过对1091例OM病例的数据分析，我们发现CIOM患者潜在的成骨能力下降是二次手术的主要原因。我们的研究表明，CIOM 患者的成骨细胞能力受损与金黄色葡萄球菌内化引起的成骨细胞铁死亡有关。进一步研究表明，褪黑素可以通过Nox4/ROS/P38轴缓解感染状态下成骨细胞的铁死亡，保护CIOM患者的成骨能力。体内敲除NADPH氧化酶4（Nox4）可有效缓解感染状态下成骨细胞的铁死亡，促进成骨。本研究通过大量临床数据分析结合分子实验，阐明CIOM患者隐匿性成骨障碍与成骨细胞铁死亡有关。我们发现褪黑激素可能是 CIOM 患者的潜在治疗药物，为 OM 的治疗提供了新的见解。