Receptor activator of nuclear factor κB ligand is a biomarker for osteitis of chronic rhinosinusitis

• Published in: International forum of allergy & rhinology Vol. 10; no. 3; pp. 364 - 373
• Main Authors: Kong, Il Gyu, Kim, Dong‐Kyu, Eun, Kyoung Mi, Yang, Seung Koo, Kim, Minju, Oh, Heonjeong, Kim, Dae Woo
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.03.2020
• Subjects: Adult; Animal models; Animals; biomarker; Biomarkers; Biomarkers - metabolism; Bone remodeling; Chronic Disease; chronic rhinosinusitis; Computed tomography; Cytokines - metabolism; Disease Models, Animal; Eosinophilia; Female; Humans; Inflammation; Leukocytes (eosinophilic); Ligands; Male; Mice; Middle Aged; mRNA; Mucosa; Nasal Polyps - complications; Nasal Polyps - metabolism; Nasal Polyps - pathology; Osteitis; Osteitis - complications; Osteitis - drug therapy; Osteitis - metabolism; Osteitis - pathology; Osteoprotegerin; Osteoprotegerin - metabolism; Patients; Phenotypes; Polyps; RANK Ligand - antagonists & inhibitors; RANK Ligand - metabolism; RANKL; Rhinitis; Rhinitis - complications; Rhinitis - metabolism; Rhinitis - pathology; Rhinosinusitis; Sinusitis; Sinusitis - complications; Sinusitis - metabolism; Sinusitis - pathology; TRANCE protein; chronic rhinosinusitis; sinusitis; RANKL; osteitis; biomarker
• ISSN: 2042-6976; 2042-6984; 2042-6984
• DOI: 10.1002/alr.22481

Background Evidence of osteitis is frequently observed in patients with chronic rhinosinusitis (CRS), especially in recalcitrant cases. However, studies focusing on biological markers of osteitis are limited and it remains unclear whether osteitis is associated with different phenotypes of CRS. This study aimed to analyze the expression and assess the roles of receptor activator of nuclear factor κB ligand (RANKL) in patients with CRS and osteitis. Methods CRS patients with nasal polyps (CRSwNP, n = 63), CRS patients without nasal polyps (CRSsNP, n = 8), and control subjects (n = 12) were enrolled. Histologic phenotypes, clinical information, and computed tomography (CT) scores were investigated. The Global Osteitis Scoring Scale (GOSS) and RANKL, a molecular marker of bone remodeling, were analyzed in each type of CRS. CRS mouse models were treated with anti‐RANKL. Results GOSS values were significantly higher in all CRS patients than in the control group. The GOSS value in non‐eosinophilic CRSwNP was higher than in eosinophilic CRSwNP. RANKL was upregulated whereas decoy receptor osteoprotegerin (OPG) was downregulated in CRS. RANKL messenger RNA (mRNA) and protein levels were positively correlated with GOSS. RANKL/OPG was increased in recurrent cases compared with primary cases. Multiple inflammatory mediators were positively correlated with the protein level of RANKL in CRS tissues. In the mouse CRSwNP model, anti‐RANKL treatment abrogated mucosal inflammation and bone remodeling. Conclusion RANKL expression is associated with clinical osteitis and disease severity in CRSwNP. These findings shed light on the importance of RANKL as a potential biomarker of CRS and a key player in CRS pathogenesis.