Chronic Non-bacterial Osteitis Research Articles

Neuropathic and Nociplastic Pain Profiles are Common in Adult Chronic Nonbacterial Osteitis (CNO).

Chronic nonbacterial osteitis (CNO) is a rare musculoskeletal disease causing chronic bone pain. It is known that chronic musculoskeletal pain may involve other mechanisms than nociceptive pain only. We investigate the prevalence of neuropathic and nociplastic pain in adult CNO and their association with clinical characteristics and treatment outcomes. Survey study among the Dutch adult CNO cohort (n = 84/195 participated), including PAIN-detect for neuropathic pain, and the Central Sensitization Inventory (CSI), Fibromyalgia Rapid Screening Tool (FiRST), and ACTTION-APS Pain Taxonomy (AAPT) for nociplastic pain. Clinical characteristics and CNO-related bone pain scores were compared between patients with exclusive nociceptive pain and those with nociceptive pain plus neuropathic and/or nociplastic pain (mixed pain). 31% (95% CI 21-41) of patients classified as likely having neuropathic pain according to PAIN-detect. 53% (41-64) of patients displayed central sensitization on CSI, 61% (50-72) screened positive for fibromyalgia on FiRST and 14% (7-23) of patients fulfilled the AAPT criteria, all indicative of nociplastic pain. Mixed pain was associated with longer diagnostic delay (mean difference 2.8years, 95% CI 0.4-5.2, p = 0.023), lower educational level (72% versus 20%, p < 0.001), and opioid use (37% versus 13%, p = 0.036). Despite comparable disease severity and extent, patients with mixed pain reported significantly higher CNO-related bone pain scores. This study demonstrates the high prevalence of mixed pain in adult CNO, in which neuropathic and nociplastic pain exist alongside nociceptive inflammatory bone pain. Disease burden in CNO may extend beyond inflammatory activity, highlighting the need for a multifaceted management approach.

Defining the imaging diagnostic criteria for adult chronic non-bacterial osteitis.

Osteitis of the sternocostoclavicular (SCC) region, referred to as sternocostoclavicular hyperostosis (SCCH), is the clinical expression of chronic non-bacterial osteitis (CNO) in adults with this rare chronic auto-inflammatory disorder of the axial skeleton. The diagnosis is based on distinctive computerized tomography (CT) features of sclerosis and hyperostosis of the SCC region, and local increases in osteoid formation visualized by high radiopharmacon uptake on skeletal scintigraphy but clear radiologic diagnostic criteria are lacking. In a cross-sectional study, CT scans and whole-body skeletal scintigraphy images obtained in 169 patients seen at the Center for Bone Quality of the Leiden University Medical Center between 2008 and 2018 with a suspected diagnosis of CNO of the SCC region were re-evaluated by 2 skeletal radiologists and 2 nuclear physicians. The diagnosis was confirmed in 118 (70%) predominantly female patients (n= 103, 89.2%); median age at first symptoms 45years (range 20-73). The diagnosis was excluded in the remaining 51 "non-CNO" patients. Increased radiopharmacon uptake at the SCC region was observed in 82% CNO patients, with the manubrium sterni having the highest predictive ability to discriminate on both imaging modalities. The prevalence of sclerosis of the clavicles, manubrium and first ribs was significantly higher in CNO patients (P< 0.001). Hyperostosis was not observed in non-CNO patients. 46 CNO versus only 2 non-CNO patients had costoclavicular ligament calcification. Our findings identify CT scan features of sclerosis and hyperostosis of manubrium sterni, medial end of clavicles and first ribs, and calcification of costoclavicular ligaments, associated with increased tracer uptake on skeletal scintigraphy at the SCC region, specifically manubrium sterni, as well-defined imaging diagnostic criteria for adult CNO. Pitfalls encountered in the diagnosis of CNO are highlighted. These defined imaging diagnostic criteria for adult CNO should facilitate the diagnosis of this rare auto-inflammatory bone disease across the spectrum of its early to late stages.

18F-Sodium fluoride PET-CT visualizes disease activity in chronic nonbacterial osteitis in adults.

Chronic nonbacterial osteitis (CNO) is a rare disease spectrum, which lacks biomarkers for disease activity. Sodium fluoride-18 positron emission tomography/computed tomography ([18F]NaF-PET/CT) is a sensitive imaging tool for bone diseases and yields quantitative data on bone turnover. We evaluated the capacities of [18F]NaF-PET/CT to provide structural and functional assessment in adult CNO. A coss-sectional study was performed including 43 adult patients with CNO and 16 controls (patients referred for suspected, but not diagnosed with CNO) who underwent [18F]NaF-PET/CT at our expert clinic. Structural features were compared between patients and controls, and maximal standardized uptake values (SUVmax [g/mL]) were calculated for bone lesions, soft tissue/joint lesions, and reference bone. SUVmax was correlated with clinical disease activity in patients. Structural assessment revealed manubrial and costal sclerosis/hyperostosis and calcification of the costoclavicular ligament as typical features associated with CNO. SUVmax of CNO lesions was higher compared with in-patient reference bone (mean paired difference: 11.4; 95% CI: 9.4-13.5; p < .001) and controls (mean difference: 12.4; 95%CI: 9.1-15.8; p < .001). The highest SUVmax values were found in soft tissue and joint areas such as the costoclavicular ligament and manubriosternal joint, and these correlated with erythrocyte sedimentation rate in patients (correlation coefficient: 0.546; p < .002). Our data suggest that [18F]NaF-PET/CT is a promising imaging tool for adult CNO, allowing for detailed structural evaluation of its typical bone, soft-tissue, and joint features. At the same time, [18F]NaF-PET/CT yields quantitative bone remodeling data that represent the pathologically increased bone turnover and the process of new bone formation. Further studies should investigate the application of quantified [18F]NaF uptake as a novel biomarker for disease activity in CNO, and its utility to steer clinical decision making.

Cachexia, chorea, and pain in chronic nonbacterial osteitis and inflammatory bowel disease: a case report

BackgroundInflammatory bowel disease is an inflammatory disorder that primarily impacts the gastrointestinal tract, leading to malnutrition and chronic microscopic intestinal blood loss. Uncontrolled systemic inflammation can impact other parts of the body, known as extraintestinal manifestations. Up to 25% of patients with inflammatory bowel disease are reported to have these complications in their skin, joints, bones, eyes, liver, lung, and pancreas (Rogler et al. in Gastroenterology 161(4):1118–1132, 2021). Neurologic involvement as extraintestinal manifestations are less common, reported at 3–19%, including neuropathies, demyelination, and cerebrovascular events (Morís in World J Gastroenterol. 20(5):1228–1237, 2014).Case presentationA 13-year-old Caucasian boy presented with 1 month of progressive lower-extremity pain, weakness, and weight loss. His physical examination was notable for cachexia, lower-extremity weakness, and chorea. Labs revealed normocytic anemia and systemic inflammation. Imaging revealed symmetric abnormal marrow signal in the pelvis and upper femurs. Pathologic examination of the bone revealed chronic inflammation consistent with chronic nonbacterial osteitis. Endoscopy revealed colonic inflammation consistent with inflammatory bowel disease.ConclusionsChildren and adolescents with musculoskeletal pain lasting more than 2 weeks with systemic signs or symptoms like weight loss should prompt evaluation for systemic inflammatory disorders such as chronic nonbacterial osteitis, which can occur in isolation or associated with inflammatory bowel disease. This patient also had a nonspecific neurologic abnormality, chorea, which resolved with treatment of underlying inflammatory disorder. These extraintestinal manifestations may be concurrent with or precede intestinal inflammation, requiring a high index of suspicion when investigating nonspecific systemic inflammation.

Diffusion-weighted MR imaging in chronic non-bacterial osteitis: Proof-of-concept of the apparent diffusion coefficient as an outcome measure.

BackgroundThe apparent diffusion coefficient (ADC), as determined by whole-body diffusion-weighted MRI, may be useful as an outcome measure for monitoring response to treatment in chronic non-bacterial osteitis.PurposeTo test and demonstrate the feasibility of ADC-measurement methods for use as outcome measure in chronic non-bacterial osteitis.Materials and MethodsUsing data from a randomized pilot study, feasibility of change-score ADC between baseline and second MRI (ΔADC12) and third MRI (ΔADC13) as outcome measure was assessed in three settings: “whole-lesion,” “single-slice per lesion,” and “index-lesion per patient”. Bone marrow edema lesions were depicted on short tau inversion recovery sequence at baseline and copied to ADC maps at the three time-points. Correlations between the three settings were measured as were analysis of variances. Discriminant validity was assessed as inter- and intra-observer reproducibility and smallest detectable change.Results12 subjects were enrolled, and MRI was performed at baseline and weeks 12 and 36. Pearson correlation was high (r > 0.86; p ≤ 0.01) for ΔADC between single-slice—whole-lesion and whole-lesion—index-lesion and tended to be significant for single-slice—index-lesion settings (p = 0.06). For ΔADC12 and ΔADC13, Bland–Altman plots showed small differences (0.02, 0.03) and narrow 95% limits-of-agreement (−0.13–0.09, −0.07–0.05 μm2/s) between whole-lesion and single-slice ROI settings. Inter-observer reproducibility measured by intra-class correlation coefficient was poor-to-fair (range: 0.09–0.31), whereas intra-observer reproducibility was good-to-excellent (range: 0.67–0.90). Smallest detectable changes were between 0.21–0.28 μm2/s.ConclusionADC change-score as outcome measure was feasible, and the single-slice per lesion ROI setting performed almost equally to whole-lesion setting resulting in reduced assessment time.

Whole-body MRI Imaging Is an Essential Tool in Diagnosing and Monitoring Patients With Sterile Osteomyelitis

From the first description in 1972 as "subacute and chronic recurrent osteomyelitis" to the currently recognized chronic recurrent multifocal osteomyelitis (CRMO) or chronic nonbacterial osteitis (CNO), diagnosis and monitoring of patients with this disease has been and continues to be a challenge1,2 While the most common presenting symptom is focal bone pain, its waxing and waning nature tends to contribute to the diagnostic odyssey that many patients must endure.

Do Bisphosphonates Alleviate Pain in Children? A Systematic 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. 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. 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.

Efficacy of pamidronate in children with chronic non-bacterial osteitis using whole body MRI as a marker of disease activity

BackgroundTo study the response to pamidronate using whole body magnetic resonance imaging (WB-MRI) in children with chronic non-bacterial osteitis (CNO) in a tertiary health centre.MethodsThe medical records of children under the age of sixteen with a diagnosis of chronic non-bacterial osteitis between 2005 and 2018 were reviewed. All those who were treated with pamidronate were included and relevant data was collected. Response to therapy was determined based on the status of lesions on WB- MRI.ResultsForty six patients were included in the study. Pre- and post-treatment WB-MRI was available in forty patients. Cumulative lesions pre-treatment were 150 and reduced to 45 (30%) post-treatment. Seventeen patients (42.5%) had a good response with complete resolution of all lesions and nine patients (22.5%) worsened during or following treatment with pamidronate. Vertebral disease had a good response and 82.3% of the lesions resolved completely.ConclusionOur study describes the experience with pamidronate in a tertiary health centre using WB-MRI as a marker of disease activity. Pamidronate was well tolerated in our cohort and treatment response was fairly good.Significance and innovation1. Bisphosphonates can be used in the treatment of CNO when response to NSAIDs is suboptimal. 2. In the presence of spinal or mandibular lesions bisphosphonates were used as first line. 3. Treatment was escalated to a TNF blocker when response to bisphosphonates was suboptimal.

Chronic non bacterial osteitis- a multicentre study

ObjectiveTo understand the demographics, clinical features and treatment outcomes of Chronic Non-bacterial Osteitis (CNO) from three tertiary paediatric rheumatology services in the United Kingdom.MethodsChildren less than 18 years of age diagnosed with CNO between 2001 to 2016 from one tertiary service and between 2001 to 2017 from two tertiary services were included. Clinical notes were reviewed and all pertinent data were collected on a pre-defined proforma. One hundred and thirty one patients were included in the study. The Bristol diagnostic criteria were applied retrospectively.ResultsRetrospective analysis of the data showed that the disease was more common in girls than boys (2.5:1), median age at onset of symptoms was 9.5 years (IQR 8 to 11 years). Bone pain was the predominant symptom in 118/129 (91.4%) followed by swelling in 50/102 (49.01%). Raised inflammatory markers were present in 39.68% of the patients. Whole body Magnetic Resonance Imaging (MRI) was a useful diagnostic tool. Metaphyses of long bones were most often involved and the distal tibial metaphyses 65/131 (49.6%) was the most common site. Non-steroidal anti-inflammatory drugs were used as first line (81.67%) followed by bisphosphonates (61.79%). Treatment was escalated to a TNF blocker when response to bisphosphonates was suboptimal. The disease was in remission in 82.4% of the patients during the last follow up.ConclusionOur multicentre study describes features and outcomes of CNO in a large number of patients in the United Kingdom.Significance and innovationRaised inflammatory markers were present in 39.68% of our patients.Whole body MRI is useful for diagnosis and also determining response to treatment.A greater number of lesions were detected on radiological imaging compared to clinical assessment.Metaphyses of long bones were most often involved and the distal tibial metaphyses (49.6%) were the most common site.Non-steroidal anti-inflammatory drugs were used as first line (81.67%) followed by bisphosphonates (61.79%).There was no difference in number of medications used for management in unifocal versus multifocal disease.TNF blockers were used with good effect in our cohort.

Chronic non-bacterial osteitis from the patient perspective: a health services research through data collected from patient conferences

ObjectiveAlthough chronic non-bacterial osteitis (CNO) is an ever-increasingly recognised illness in the paediatric community and the adult healthcare community, a study to assess diagnosing, treatment and the psychosocial aspect of...

Characteristics and outcomes of chronic non-bacterial osteitis in children.

To determine patient characteristics, clinical presentation, pattern of involvement, treatment, and outcome of patients with chronic non-bacterial osteitis (CNO). Consecutive cases of CNO were analyzed at a single center for pediatrics and adolescent medicine from 2006 to 2013 in terms of patient characteristics, clinical presentation, pattern of involvement, treatment, and outcome. We identified 32 children aged 1.5-15 years who were diagnosed with CNO between 2006 and 2013. A maximum of 12 bones per patient were affected in a total of 114 documented locations. The pelvis and clavicle (affecting 34% of patients each) were the most frequently affected bones. The foot skeleton was the most commonly affected region in 60% of patients. Skin manifestations were found in 7 (21%) patient. Increased inflammatory signs at presentation were detected in 18 patients. Pathological findings were found in all 30 children examined using magnetic resonance imaging (MRI), in 10 of 11 children examined using radiography, and in 8 of 10 patients examined using skeletal scintigraphy. Bone biopsy was performed in 9 patients. For initial treatment, non-steroidal anti-inflammatory drugs (NSAIDs) or coxibs were used in 28 (87.5%) patients. Remission or satisfactory follow-up was achieved in all patients. Today, CNO is increasingly diagnosed using MRI and rarely through histological examinations. Therapeutic strategies include NSAIDs, which are often highly effective. All patients in the present study showed good clinical outcomes.

Succesful treatment of diffuse sclerosing osteomyelitis of the mandible/mandibular chronic non-bacterial osteitis with intravenous pamidronate: resolution of pain and radiographic bone inflammation with improved cosmetic appearance - a case study

Diffuse sclerosing osteomyelitis of the manidble ( DSMO) is a form of chronic non-bacterial osteitis (CNO) and predominantly affects patients < 18 years. It can result in cosmetic disfigurement. No uniformly effective treatment exists. Intravenous pamidronate (IV-PAM) has been reported to be effective in multifocal CNO.

Efficacy of pamidronate therapy in children with chronic non-bacterial osteitis: disease activity assessment by whole body magnetic resonance imaging.

The aim of this study was to describe the efficacy of pamidronate therapy on disease activity in children with chronic non-bacterial osteitis (CNO) using whole body MRI (WB-MRI). Clinical assessment and WB-MRI were obtained in 11 children before and after 1 year of pamidronate therapy using a 1.5 T MRI scanner and short tau inversion recovery sequences. The images were reported by a paediatric radiologist. WB-MRI identified 75 lesions in 11 patients; 16 of these lesions had not been detected by clinical examination. Follow-up MRI after 1 year of pamidronate showed complete resolution of inflammation in 45 lesions, moderate improvement in 10 lesions and no change in 20 lesions. Two new lesions developed while on treatment. WB-MRI allows a more accurate assessment of the disease extent in CNO than clinical examination alone and is useful in the objective measurement of treatment efficacy. Pamidronate appears to be an effective treatment in children with CNO unresponsive to NSAIDs.

FRI0541 Imaging of Chronic Recurrent Multifocal Osteitis: A French National Cohort of 178 Cases

BackgroundThe radiological assessment of CRMO is currently the subject of countless works and the recent use of whole-body MRI leads to discuss the respective roles of the various imaging techniques.ObjectivesThis...

PReS-FINAL-2206: Clinical experiences in patients with chronic recurrent multifocal osteomyelitis (CRMO)

Chronic recurrent multifocal osteomyelitis (CRMO) is a form of chronic nonbacterial osteitis (CNO) characterized by one or more lytic bone lesions with no identifiable cause. (CRMO) is a rare (prevalence less than 1/1,000,000) auto-inflammatory disorder, characterized by relapsing and remitting episodes of pain related to the presence of foci of sterile bone inflammation.

Combination Therapy with Methotrexate and Etanercept for Refractory Chronic Recurrent Multifocal Osteomyelitis: Figure 1.

To the Editor: Chronic recurrent multifocal osteomyelitis (CRMO) is a form of chronic nonbacterial osteitis (CNO) characterized by one or more lytic bone lesions with no identifiable cause1. The metaphyses of long bones and the clavicle are most frequently affected, although any bone may be involved. Most cases begin in childhood, and follow an intermittent course. Pain is the most common presenting symptom. Affected individuals are sometimes febrile, and acute-phase reactants may be increased, pointing to the inflammatory expression of this condition. Lesions may resolve at or before the time of puberty, but in some cases skeletal deformity and/or disability may occur2. We describe 2 children with CRMO whose symptoms persisted after trials of nonsteroidal antiinflammatory medication, glucocorticoids, and methotrexate (MTX). Combination therapy with MTX and etanercept resulted in amelioration of pain, accompanied in one patient by radiographic improvement in a lytic bone lesion. A 4-year-old boy developed pain in his right foot and refused to walk for 2 months. Plain radiographs showed normal-appearing vertebra. A bone scan disclosed increased uptake in the right talus and navicular bone. He received several courses of intravenous and oral antimicrobials, without improvement. Fever was absent, C-reactive protein was normal, and erythrocyte sedimentation rate (ESR) was mildly increased to 23 mm/h. A second bone scan performed 2 months later showed increased radionuclide uptake in the L4 and L5 vertebra. Focal magnetic resonance imaging (MRI) revealed vertebral abnormalities consistent with CRMO including increased signal intensity of the vertebral marrow (Figure 1A). Talar biopsy was nonrevealing, showing bone fragments with myxoid-appearing fibrous stroma. Naproxen 10 mg/kg/day was given, without improvement. Prednisone 2 mg/kg/day was added for 3 weeks, … [↵][1]Address correspondence to Dr. Eisenstein; E-mail: emeisenstein{at}gmail.com [1]: #xref-corresp-1-1