Hidradenitis Suppurativa-Related Autoinflammatory Syndromes: An Updated Review on the Clinics, Genetics, and Treatment of Pyoderma gangrenosum, Acne and Suppurative Hidradenitis (PASH), Pyogenic Arthritis, Pyoderma gangrenosum, Acne and Suppurative Hidradenitis (PAPASH), Synovitis, Acne, Pustulosis, Hyperostosis and Osteitis (SAPHO), and Rarer Forms.

Hidradenitis suppurativa (HS) is an autoinflammatory skin disorder of the terminal hair follicle, which can present in sporadic, familial, or syndromic form. A classification has been proposed for the latter, distinguishing cases associated with a known genetic condition, with follicular keratinization disorders or with autoinflammatory diseases. This review focuses on the clinical and genetic features of those entities (ie, pyoderma gangrenosum [PG], acne and HS; PG, acne, pyogenic arthritis and HS; psoriatic arthritis, PG, acne and HS; synovitis, acne, pustulosis, hyperostosis, osteitis; and so forth) for which the collective term HS-related autoinflammatory syndromes is proposed.

Postoperative mediastinitis and sternal osteitis after cardiac surgery caused by Mycoplasma hominis: A case report.

BACKGROUND: Mediastinitis and sternal osteitis are critical complications in cardiac surgery. Cases of these complications caused by Mycoplasma hominis are extremely rare. CASE PRESENTATION: We present a case of mediastinitis and sternal osteitis caused by M. hominis infection following ascending aortic replacement surgery. Whole gene sequencing analysis suggested the genitourinary tract as the most likely source of this M. hominis infection. Successful infection control was achieved through a regimen of moxifloxacin treatment. Additionally, a notable correlation was observed between serum levels of interleukin-6 and M. hominis infection. CONCLUSIONS: The significance of M. hominis as a potential cause of postoperative infection in cardiac surgery is still not fully recognized. Special attention should be paid to patients with bacteriologically negative infections, as M. hominis should not be disregarded, despite its rarity.

Treatment and monitoring of SAPHO syndrome: a systematic review.

BACKGROUND AND OBJECTIVES: Synovitis acne pustulosis hyperostosis osteitis (SAPHO) is a rare heterogeneous disease of unknown aetiopathology. Externally validated and internationally agreed diagnostic criteria or outcomes and, as a result, prospective randomised controlled trials in SAPHO are absent. Consequently, there is no agreed treatment standard. This study aimed to systematically collate and discuss treatment options in SAPHO. METHODS: Following 'Preferred Reporting Items for Systematic Reviews and Meta-Analyses' guidance, a systematic literature search was conducted using PubMed, Scopus and Web of Science databases. Prospective clinical studies and retrospective case collections discussing management and outcomes in SAPHO involving five or more participants were included. Articles not published in English, studies not reporting defined outcomes, and studies solely relying on patient-reported outcomes were excluded. RESULTS: A total of 28 studies (20 observational, 8 open-label clinical studies) reporting 796 patients of predominantly European ethnicity were included. Reported therapies varied greatly, with many centres using multiple treatments in parallel. Most patients (37.1%) received non-steroidal anti-inflammatory drugs alone or in combination. Bisphosphonates (22.1%), conventional (21.7%) and biological (11.3%) disease-modifying antirheumatic drugs were the next most frequently reported treatments. Reported outcomes varied and delivered mixed results, which complicates comparisons. Bisphosphonates demonstrated the most consistent improvement of osteoarticular symptoms and were associated with transient influenza-like symptoms. Paradoxical skin reactions were reported in patients treated with TNF inhibitors, but no serious adverse events were recorded. Most treatments had limited or mixed effects on cutaneous involvement. A recent study investigating the Janus kinase inhibitor tofacitinib delivered promising results in relation to skin and nail involvement. CONCLUSIONS: No single currently available treatment option sufficiently addresses all SAPHO-associated symptoms. Variable, sometimes descriptive outcomes and the use of treatment combinations complicate conclusions and treatment recommendations. Randomised clinical trials are necessary to generate reliable evidence.

Utility of nailfold capillary assessment for predicting pustulotic arthro-osteitis in palmoplantar pustulosis based on a prospective cohort study.

BACKGROUND: Pustulotic arthro-osteitis (PAO) is 1 of the most serious comorbidities associated with palmoplantar pustulosis (PPP). Risk factors of PAO development are not well-known. OBJECTIVE: To evaluate the clinical significance of nailfold capillary (NFC) changes in patients with PPP. METHODS: We conducted a prospective cohort study in a population of 102 PPP patients. Correlations of NFC abnormalities, including nailfold bleeding and enlarged capillaries, with the prevalence of PAO, the incidence of new PAO, and serum levels of cytokines were analyzed. RESULTS: Detailed examination revealed that of 102 PPP patients, 52 without PAO and 50 with PAO. Both nailfold bleeding and enlarged capillaries were significantly more frequent in patients with PAO (50.0% vs 92.0%, P < .0001; 50.0% vs 94.0%, P < .0001). In addition, PPP patients without PAO were prospectively observed before they developed PAO (mean 28 months [1-52 months]). Multivariate analysis suggested that these NFC abnormalities were predictors of PAO development (hazard ratio 3.37, 95% confidence interval 1.13-10.07; 3.37, 1.13-10.07) and guselkumab prevent PAO development (0.093, 0.012-0.76). The degree of NFC abnormalities correlated with the severity of PAO and serum cytokine levels. LIMITATIONS: All participants were Japanese. CONCLUSION: NFC abnormalities could be predictors of PAO in PPP patients, and their degree indicators of disease severity.

The Impact of Spray Cryotherapy on Lesion-Induced Osteitis in a New Murine Experimental Model.

Background and Objectives: Endoscopic sinus surgery is considered the gold management strategy for difficult-to-treat chronic rhinosinusitis. The inflammatory bony process is incriminated as being involved in the unfavorable evolution and recurrence of the disease. Osteitis is significantly increased in patients that have been previously submitted to surgery, and it is more often present in patients with extended radiological disease and in patients undergoing revision surgery. The aim of the research is to demonstrate the presence of inflammations and neo-osteogenesis associated with nasal mucosal surgical injury and the correlation between their severity and to evaluate the efficacy of low-pressure spray cryotherapy in reducing inflammation and bone remodeling. Materials and Methods: The experimental murine model was conducted over a period of 80 days and included a total of 60 adult female Wistar rats, with three periods of withdrawal of 20 individuals each from the experiment. After inducing a bilateral mechanical injury by brushing, low-pressure spray cryotherapy application was performed unilaterally, and tissue samples were prepared specifically for histological analysis. The scores for inflammation and osteitis were compared over time and between the two nasal fossae. Results: Osteitis and inflammation were induced by a simple mucosal brushing lesion, similar to surgical injury. We identified the presence of inflammation in 95% of the specimens, and it was present over time. Moreover, criteria for bone remodeling were clearly highlighted in a percentage of 72% of the specimens. There was a direct correlation between the severity of inflammation and neo-osteogenesis, with a statistical significance of p = 0.050. Low-pressure spray cryotherapy was safe and effective in reducing inflammation (p = 0.020) and osteitis (p = 0.000) with a safety profile. Conclusions: Low-pressure cryotherapy reduces the severity of mucosal inflammation and osteitis in lesion-induced neo-osteogenesis.

Inflammation, bone loss and 2-year bone formation at the same vertebra in axial spondyloarthritis: a multilevel MRI and low-dose CT analysis.

OBJECTIVE: To investigate whether in radiographic axial spondyloarthritis (r-axSpA) inflammation is associated with lower trabecular bone density (TBD), and subsequently, if a lower TBD increases the likelihood of 2-year bone formation at the same vertebra. METHODS: Whole spine (C3-L5) data from patients included in the multicentre 2-year Sensitive Imaging in Ankylosing Spondylitis cohort was used. Two readers measured baseline TBD by Hounsfield units (HU) on low-dose CT (ldCT). Baseline MRI bone marrow oedema (BME) status scores and ldCT syndesmophyte formation and/or growth change-from-baseline scores were assessed by three and two readers, respectively. Average of readers' continuous measurements or readers' agreement in binary scores generated within the same vertebra (1-present in ≥1 quadrant/0-absent in all quadrants) were used. Multilevel generalised estimating equations models were used, the unit of analysis being the vertebra. RESULTS: In 50 patients with r-axSpA, TBD HU decreased from cranial to caudal vertebrae. Baseline MRI-BME was present in 300/985 (30%) and syndesmophytes in 588/910 (65%) vertebrae, both most prevalent at thoracolumbar region. Syndesmophyte formation or growth was observed in 18% of at-risk vertebrae (124/691). A significant confounder-adjusted association was found between inflammation and lower TBD (regression coefficient=-51; 95% CI-63 to -39). TBD was not associated with 2-year syndesmophyte formation or growth (adjusted OR 1.00; 95% CI 0.99 to 1.00). CONCLUSION: In r-axSpA, while vertebral inflammation was associated with lower vertebral TBD, lower vertebral TBD itself did not increase the risk for new bone formation at the same vertebra. In preventing syndesmophyte progression, targeting local inflammation seems more important than targeting vertebral trabecular bone loss.

Computed Tomography Evaluation of Unilateral Chronic Maxillary Sinusitis With Osteitis.

BACKGROUND: Computed tomography (CT) is the preferred noninvasive method for the evaluation of osteitis in chronic sinusitis. Some scholars believe that the bone changes associated with chronic sinusitis always show high attenuation (high density) and are positively correlated with the severity of the disease. However, sinus bone remodeling is a complex process that may cause high or low attenuation. There have been few reports on the spread of osteitis. Therefore, additional research on sinus CT is necessary. OBJECTIVE: To observe bony changes in chronic maxillary sinusitis (CMS) by CT and reveal the mechanism. METHODS: A retrospective study was conducted in 45 patients with unilateral CMS with bony changes in the sinus walls. The patients' clinical data and CT results were analyzed and compared between the affected and normal sides. We propose the location, involvement, attenuation, and thickness method to evaluate CMS with osteitis. RESULTS: Of the 45 patients, 40 (88.9%), 2, 12, and 7 had posterior external, medial, anterior, and superior lesions, respectively. The nasal region, sphenoid bone, palatine bone, and zygomatic arch were involved in 3, 12, 8, and 18 (40%) patients, respectively. Computed tomography indicated high attenuation in 30 (75.0%) and low attenuation in 10 (25.0%) patients; 6 (15.0%) showed new bone marrow cavities. The bone thickness was significantly different between the affected and normal sides in 40 patients (P < .001), including members of both the high- and low-attenuation groups (high-attenuation group: P < .001; low-attenuation group: P < .01). However, there was no significant difference in the thickness of the affected side between the high- and low-attenuation groups (P > .05). CONCLUSIONS: Chronic rhinosinusitis with bony changes may occur in the maxillary sinus walls and spread to adjacent bones. Both increased and decreased attenuation may occur in these circumstances. Analyzing the CT features of bone changes in unilateral CMS can improve the accuracy of disease diagnosis.

Nail lesions in palmoplantar pustulosis and pustulotic arthro-osteitis impairs patients' quality of life: Suggesting new assessment tool of PPP nail lesions.

BACKGROUND: Palmoplantar pustulosis (PPP) sometimes presents with nail lesions, which affect the patients' quality of life (QOL). However, little is known about nail lesions in PPP, and there is currently no established method for assessing them. OBJECTIVE: This study aimed to analyze the impact of PPP-related nail lesions with the patients' QOL. In addition, we considered whether they might constitute a risk factor of pustulotic arthro-osteitis (PAO).' METHODS: A total of 178 patients with PPP were enrolled. Among the 178 patients, 66 patients participated in the following quality of life questionnaires; GHQ28, DLQI, and Skindex-16. The severity of the nail lesions was classified according to the Nail Psoriasis Severity Index (NAPSI), and the types of nail lesion were investigated. RESULTS: The DLQI, Skindex-16 and PPPASI scores were significantly higher in patients with nail lesions than in those without them. Indentions, transverse ridging, and nail thickening were relatively common in PPP. Nail lesions were unrelated to the presence of PAO complications, but leukonychia and discoloration were likely to be related to PAO lesion site. CONCLUSIONS: The study demonstrated that the presence of nail lesions is associated with a decreased QOL regardless of the severity of the skin lesions. The nail lesions were not a risk factor of PAO, but a predictor of skin lesion severity and PAO lesion site. Given this association, indention, transverse ridging, and thickening of the nail, currently not included in the NAPSI, should be added as an assessment item in the evaluation of PPP nail lesions.

[Arthroscopically assisted minimally invasive symphysioplasty for the treatment of pubic related groin pain]. / Arthroskopisch assistierte minimal-invasive Symphysioplastik zur Behandlung des schambeinbezogenen Leistenschmerzes.

OBJECTIVE: Therapy of pubic related groin pain via minimally invasive symphysioplasty. INDICATIONS: Therapy of refractory pubic related groin pain based on osteitis pubis. CONTRAINDICATIONS: Groin pain from causes other than pubic related groin pain. SURGICAL TECHNIQUE: After a minimally invasive approach, an incision in the anterior capsule is made while protecting the dorsal capsule parts and the arcuate pubic ligament. The symphysis end plates are remodeled arthroscopically assisted using a surgical burr. The newly created pubic symphysis joint is filled with autogenous fibrin to support the formation of a new discus interpubicus. POSTOPERATIVE MANAGEMENT: Partial weight-bearing for 4 weeks with 20 kg using crutches is recommended. During the first 4 weeks the range of motion should be restricted. RESULTS: Since 2010, 10 athletes (7 men, 3 women; average age 34.1 ± 7.8 (23-47) years) have undergone arthroscopically assisted minimally invasive symphysioplasty and treatment of femoroacetabular impingement syndrome. The average follow-up time was 5.1 (2-9) years. All patients returned to their sport level. The mean preoperative Nonarthritic Hip Score (NAHS) of 64.4 ± 15.1 (32.1-86.5) points improved to a mean postoperative NAHS of 91.4 ± 9.8 (62.4-98.75) points (p < 0.0001). The average patient satisfaction (scale 0 to 10; 10 highest satisfaction) was 9.8 ± 0.4 (9-10).

Osteitis in Systemic Sclerosis: A Nationwide Case-Control Retrospective Study.

OBJECTIVE: Systemic sclerosis (SSc) is an autoimmune connective tissue disorder characterized by skin fibrosis, vasculopathy, and dysimmunity. Data regarding osteitis in SSc are scarce. METHODS: We performed a nationwide multicenter, retrospective, case-control study including patients with SSc, according to the 2013 American College of Rheumatology/European Alliance of Associations for Rheumatology classification, with a diagnosis of osteitis. The objectives of the study were to describe, to characterize, and to identify associated factors for osteitis in patients with SSc. RESULTS: Forty-eight patients were included. Twenty-six patients (54.1%) had osteitis beneath digital tip ulcers. Physical symptoms included pain (36 of 48, 75%), erythema (35 of 48, 73%), and local warmth (35 of 48, 73%). Thirty-one (65%) patients had median (interquartile range) C-reactive protein levels >2 mg/liter of 8 (2.7-44.3) mg/liter. On radiography, computed tomography, or magnetic resonance imaging, osteitis was characterized by swelling or abscess of soft tissues, with acro-osteolysis or lysis in 28 patients (58%). Microbiological sampling was performed in 45 (94%) patients. Most pathogens were Staphylococcus aureus (43.8%), anaerobes and Enterobacteriaceae (29.1%), and Pseudomonas aeruginosa (10.4%). Management comprised antibiotics in 37 (77.1%) patients and/or surgery in 26 (54.2%). Fluoroquinolones were used in 22 (45.8%) patients, and amoxicillin plus ß-lactamase inhibitor in 7 (14.6%). Six (12.6%) patients relapsed, 6 (12.6%) patients had osteitis recurrence, 15 (32%) sequelae, and 2 patients had septic shock and died. CONCLUSION: This study confirmed digital tip ulcers as an associated factor for osteitis and revealed a high rate of functional sequelae. Antimicrobial therapy with oral fluoroquinolone or intravenous amoxicillin and ß-lactamase inhibitor are used as first-line antibiotic therapy in SSc patients with osteitis.

Radical versus Functional Endoscopic Sinus Surgery for Osteitis in Chronic Rhinosinusitis.

INTRODUCTION: Osteitis in chronic rhinosinusitis (CRS) is a predictive factor of disease severity and an important potential reason for disease recalcitrance. Other than medical treatment, transnasal endoscopic surgery could be another choice to deal with osteitis in CRS. OBJECTIVE: In this study, 2 different surgical outcomes and influence in patients with osteitis in CRS were discussed. METHODS: A retrospective analysis of 51 cases was carried out. Osteitis in CRS was confirmed by sinus computed tomography (CT). According to surgical management, patients were divided into the radical endoscopic sinus surgery (RESS) group (n = 24) and functional endoscopic sinus surgery (FESS) group (n = 27). Baseline measures and postoperative outcomes were evaluated by symptom visual analog scale (VAS), peripheral blood eosinophil percentage, serum total IgE, skin prick test, endoscopy Lund-Kennedy score, CT scan Lund-Mackay score, and global osteitis scoring scale (GOSS) in 2 groups. RESULTS AND CONCLUSIONS: There was no significant difference between the 2 groups in age, gender, and complicated with allergic rhinitis and asthma. The preoperative symptom VAS score and endoscopy Lund-Kennedy score were higher in the RESS group than in the FESS group, and the Lund-Mackay score and GOSS score were similar in the 2 groups. One year after surgery, symptom VAS scores, endoscopy Lund-Kennedy score, and Lund-Mackay score were significantly lower in the 2 groups. The endoscopy Lund-Kennedy score and Lund-Mackay score were lower in the RESS group than in the FESS group 1 year after surgery. RESS was more effective in reducing inflammatory load of sinuses in patients with osteitis in CRS.

18F-Sodium Fluoride PET/CT Findings in Osteitis Condensans Ilii.

ABSTRACT: Osteitis condensans ilii (OCI) is a benign cause of low back pain for which no clear etiology has been identified. We report cases of 2 women with breast cancer referred for 18F-NaF PET/CT for skeletal staging. Both cases show characteristic findings of OCI on CT images, with 18F-NaF PET uptake in symptomatic patient and no uptake in asymptomatic. 18F-NaF PET CT can be useful in evaluating back pain and may be used as an adjunctive biological maker for assessing OCI as a potential cause of pain.

Cutaneous odontogenic sinus: an inflammatory mimicker of squamous cell carcinoma and epidermal cysts.

An odontogenic cutaneous sinus tract (OCST) of dental origin is an uncommon and frequently misdiagnosed lesion that is caused by chronic periodontitis. Given that OCSTs often lack symptoms, are located on the lower face, and can have notable variations in clinical appearance, they can be mistaken for more common dermatologic diagnoses such as squamous cell carcinomas (SCCs) and cysts. We present 2 patients with OCSTs who were referred for cutaneous surgery for a rendered diagnosis of an SCC and epidermal cyst. A proper diagnosis was rendered after a high index of suspicion, and clinicopathologic correlation led to additional testing and eventual referral to oral surgery for an OCST.

Do Bisphosphonates Alleviate Pain in Children? A Systematic Review.

PURPOSE OF REVIEW: The goal of this systematic review is to analyze the effectiveness of bisphosphonates (BPs) to treat bone pain in children and adolescents who have diseases with skeletal involvement. RECENT FINDINGS: We included 24 studies (2 randomized controlled trials, 3 non-randomized controlled trials, 10 non-randomized open-label uncontrolled studies, 8 retrospective studies, and 1 study with design not specified). The majority of included studies assessed pain from a unidimensional approach, with pain intensity the most frequently evaluated dimension. Only 38% of studies used validated tools; visual analogue scale was the most frequently employed. BPs were used to alleviate bone pain in a wide variety of pediatrics conditions such as osteogenesis imperfecta, secondary osteoporosis, osteonecrosis related to chemotherapy, chronic non-bacterial osteitis, idiopathic juvenile osteoporosis, unresectable benign bone tumor, and cancer-related pain. Twenty of the 24 studies reported a positive effect of BPs for alleviating pain in different pathologies, but 58% of the studies were categorized as having high risk of bias. Intravenous BPs are helpful in alleviating bone pain in children and adolescents. It is advised that our results be interpreted with caution due to the heterogeneity of the doses used, duration of treatments, and types of pathologies included. In addition, this review shows the paucity of high-quality evidence in the available literature and further research is needed. TRIAL REGISTRATION: Before the completion of this review, the protocol was registered to PROSPERO (International prospective register of systematic reviews), PROSPERO 2020 ID # CRD42020158316. Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020158316.

A new sequential animal model for infection-related non-unions with segmental bone defect.

BACKGROUND: The treatment of fracture-related infections (FRI) is still a challenge for orthopedic surgeons. The prevalence of FRI is particularly high in open fractures with extensive soft-tissue damage. This study aimed to develop a new two-step animal model for non-unions with segmental bone defects, which could be used to evaluate new innovative bone substitutes to improve the therapeutic options in humans with FRI and bone defects. METHODS: After randomization to infected or non-infected groups, 30 Sprague-Dawley rats underwent a transverse osteotomy of the mid-shaft femur with a 5 mm defect. Additionally, the periosteum at the fracture zone was cauterized at both sides. After intramedullary inoculation with 103 CFU Staphylococcus aureus (infected group) or PBS (non-infected group), a fracture stabilization was done by intramedullary K-wires. After 5 weeks, the bone healing process was evaluated, and revision surgery was performed in order to obtain increased bone healing. The initial K-wires were removed, and debridement of the osteotomy-gap was done followed by a more stable re-osteosynthesis with an angle-stable plate. After further 8 weeks all rats were euthanized and the bone consolidation was tested biomechanically and the callus formation quantitatively by micro-CT analysis. RESULTS: We developed and presented a new two-stage non-union animal model through a targeted S. aureus infection. After 5 weeks, all animals showed a non-union irrespective of assignment to the infected and non-infected group. Lane and Sandhu score showed a higher callus formation in the infected group. In all infected animals, the inoculated S. aureus strain was detected in the revision surgery. The second surgery did not improve bone healing, as shown by the Lane Sandhu score and in the µ-CT analysis. Similarly, biomechanical testing showed in both groups a significantly lower maximum torque as compared to the contralateral side (p < 0.0001). CONCLUSIONS: We were able to successfully develop a new two-stage non-union animal model, which reflects a genuine clinical situation of an infection-related non-union model with segmental bone defects. This model could be used to evaluate various therapeutic anti-infectious and osteoinductive strategies in FRIs.

Relationship Between Sever Disease and Skeletal Maturity.

BACKGROUND: Sever disease is a common condition in active, growing children. This condition presents as pain in the heel and is thought to be an overuse condition of the calcaneal apophysis. There are currently no defined radiographic diagnostic criteria for evaluation of Sever disease, with radiographs generally showing normal appearance of the calcaneal apophysis. A better understanding of the relationship of Sever disease and skeletal maturity may allow for improved interpretation of radiographs when trying to diagnose this condition. METHODS: ICD-9 code 732.5 was used to search for patients diagnosed with Sever disease from 2007 to 2015 at a single hospital. For every patient with Sever disease with available calcaneal imaging within 40 days of diagnosis, heel x-rays were staged for calcaneal maturity score using a previously described calcaneal skeletal maturity assessment system. Controls matched by age, race, and sex were evaluated for calcaneal stage to compare with the Sever patients. RESULTS: The chart review yielded 78 patients diagnosed with Sever disease by the orthopaedic attending, 39 of which have x-rays around the time of diagnosis. Calcaneal scores averaged 2.2±0.8 for all patients, 2.1±0.9 for male individuals, and 2.3±0.8 for female individuals. The average age for male individuals was 10.4±1.9 years and for female individuals, 9.2±2.2 years. The ages of diagnosis were similar for patients with and without x-rays. Twenty-two of 39 patients with Sever disease were calcaneal stage 2, and 37 of 39 were stages 1, 2, or 3. We calculated the absolute difference from stage 2 for the Sever and control groups. Mean difference from stage 2 was 0.51±0.68 for the Sever patients and 0.95±0.79 for control patients (P=0.01). CONCLUSION: Sever disease occurs in a very narrow range of skeletal maturity, as measured by the calcaneal skeletal maturity assessment system and our observations with chronological age. When compared with age-matched and race-matched controls, stage 2 was seen more frequently in the Sever patients. If a child is not within calcaneal stages 1, 2, or 3, then a different diagnosis should be considered. LEVEL OF EVIDENCE: Level III-retrospective case-control study.

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

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.