Department of Women's & Children's Health, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, United Kingdom.
Department of Pediatric Radiology, University Children's Hospital Basel UKBB, Basel, Switzerland.
J Bone Miner Res. 2024 Oct 29;39(11):1523-1538. doi: 10.1093/jbmr/zjae141.
Chronic nonbacterial osteomyelitis (CNO) is an autoinflammatory bone disease that primarily affects children and young people. It can cause significant pain, reduced function, bone swelling, and even (vertebral body) fractures. Because of a limited understanding of its pathophysiology, the treatment of CNO remains empiric and is based on relatively small case series, expert opinion, and personal experience. Several studies have linked pathological NOD-kike receptor (NLR) family pyrin domain containing 3 (NLRP3) inflammasome activation and the resulting imbalance between pro- and anti-inflammatory cytokine expression with CNO. This agrees with elevated pro-inflammatory (mostly) monocyte-derived protein signatures in the blood of CNO patients that may be used as future diagnostic and/or prognostic biomarkers. Recently, rare variants in the P2RX7 gene, encoding for an ATP-dependent transmembrane channel, were linked with increased NLRP3 inflammasome assembly and prolonged monocyte/macrophage survival in CNO. Although the exact molecular mechanisms remain unclear, this will inform future target-directed and individualized treatment. This manuscript reviews most recent developments and their impact on diagnostic and therapeutic strategies in CNO.
慢性非细菌性骨髓炎（CNO）是一种自身炎症性骨病，主要影响儿童和年轻人。它可导致明显的疼痛、功能下降、骨肿胀，甚至（椎体）骨折。由于对其病理生理学的认识有限，CNO 的治疗仍然是经验性的，主要基于相对较小的病例系列、专家意见和个人经验。几项研究将病理性 NOD 样受体（NLR）家族吡咯烷域包含 3（NLRP3）炎性小体激活以及由此导致的促炎和抗炎细胞因子表达失衡与 CNO 联系起来。这与 CNO 患者血液中升高的促炎（主要是）单核细胞衍生蛋白特征一致，这些特征可能被用作未来的诊断和/或预后生物标志物。最近，编码 ATP 依赖性跨膜通道的 P2RX7 基因的罕见变异与 NLRP3 炎性小体组装增加和 CNO 中单核细胞/巨噬细胞存活时间延长有关。尽管确切的分子机制尚不清楚，但这将为未来的靶向和个体化治疗提供信息。本文综述了 CNO 中最新的发展及其对诊断和治疗策略的影响。
