Nonbacterial Osteomyelitis Research Articles

Response of Different Treatment Protocols to Treat Chronic Non-Bacterial Osteomyelitis (CNO) of the Mandible in Adult Patients: A Systematic Review.

(1) Background: Chronic non-bacterial osteomyelitis (CNO) is an autoinflammatory bone disease of finally unknown etiology, which can occur alone or related with syndromes (chronic recurrent multifocal osteomyelitis—CRMO; synovitis, acne, pustulosis, hyperostosis and osteitis syndrome—SAPHO). The involvement of the mandible is rather rare. (2) Methods: We carried out a systematic literature search on CNO with mandibular involvement, according to the “Preferred Reporting Items for Systematic Reviews and Meta-Analyses” (PRISMA) guidelines, considering the different synonyms for CNO, with a special focus on therapy. (3) Results: Finally, only four studies could be included. A total of 36 patients were treated in these studies—therefore, at most, only tendencies could be identified. The therapy in the included works was inconsistent. Various therapies could alleviate the symptoms of the disease. A complete remission could only rarely be observed and is also to be viewed against the background of the fluctuating character of the disease. The success of one-off interventions is unlikely overall, and the need for long-term therapies seems to be indicated. Non-steroidal anti-inflammatory drugs (NSAIDs) were not part of any effective therapy. Surgical therapy should not be the first choice. (4) Conclusions: In summary, no evidence-based therapy recommendation can be given today. For the future, systematic clinical trials on therapy for CNO are desirable.

Prevalence of cranial involvement in a cohort of Italian patients with chronic non-bacterial osteomyelitis

Chronic non-bacterial osteomyelitis (CNO) is a non-infectious inflammatory disease characterised by uni- or multi-focal bone lytic lesions. CNO mainly affects metaphysis of long bones, pelvis and shoulder girdle. Neurocranium lesions are extremely rare. The objective of the study is to describe the prevalence and clinical manifestations of CNO patients with neurocranium involvement in an Italian cohort of CNO patients. This is a retrospective study. Medical records of patients with CNO admitted to eight paediatric rheumatology centres were reviewed. Among 86 patients with CNO enrolled in the study, three of them were female and presented neurocranium involvement - multifocal lesions. Two out of the 3 patients were completely asymptomatic for cranial involvement, while one of the 3 complained of cranial bossing. Cranial involvement was detected with bone scintigraphy and then confirmed by magnetic resonance imaging and/or computed tomography. Two patients presented fever and two with skin manifestations. Laboratory inflammatory markers were increased in two of them. All patients underwent bone biopsy confirming the diagnosis. They all received NSAIDs. Two patients received corticosteroids and then methotrexate and achieved clinical remission, while one patient received pamidronate. This is the first report of neurocranium involvement in a cohort of patients affected by CNO. In our cohort no patient showed significant signs attributable to cranial involvement.

A Targeted Genetic Association Study of the Rare Type of Osteomyelitis

Chronic nonbacterial osteomyelitis is a rare bone disorder that can be found in the jaw. It is often associated with systemic conditions, including autoimmune deficiencies. However, little is known about how the genetic and immunologic background of patients influences the disease. Here, we focus on human leukocyte antigen (HLA), killer cell immunoglobulin-like receptors (KIRs), and their specific combinations that have been difficult to analyze owing to their high diversity. We employed a recently developed technology of simultaneous typing of HLA alleles and KIR haplotype and investigated alleles of the 35 HLA loci and KIR haplotypes composed of centromeric and telomeric motifs in 18 cases and 18 controls for discovery and 472 independent controls for validation. We identified an amino acid substitution of threonine at position 94 of HLA-C in combination with the telomeric KIR genotype of haplotype tA01/tB01 that had significantly higher frequency (>20%) in the case population than in both control populations. Multiple logistic regression analysis based on a dominant model with adjustments for age and sex revealed and validated its statistical significance and high predictive accuracy (C-statistic ≥0.85). Structure-based analysis revealed that the combination of the amino acid change in HLA-C and the telomeric genotype tA01/tB01 could be associated with lower stability of HLA-C. This is the first case-control study of a rare disease that employed the latest sequencing technology enabling simultaneous typing and investigated amino acid polymorphisms at HLA loci in combination with KIR haplotype.

Pediatric chronic nonbacterial osteomyelitis of the mandible: Seattle Children\u2019s hospital 22-patient experience

BackgroundStudies evaluating treatment responses for chronic nonbacterial osteomyelitis (CNO) are lacking. We aimed to measure and compare response rates of medical treatments, time to response of medical treatments among patients with CNO of the mandible, and describe bacterial contamination rates from biopsy.MethodsWe conducted a retrospective chart review of all patients diagnosed with CNO of mandible between 2003 and 2017 and extracted demographic, clinical, laboratory, imaging and surgical data. Detailed medication use and response to medications were recorded. The primary outcome was response to medical treatments defined as improvement of presenting symptoms, inflammatory markers, and imaging if available. Medical treatments included nonsteroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, disease modifying anti rheumatic drugs (DMARDs), anti-tumor necrosis factor (TNF) therapy, and pamidronate. Descriptive analysis was performed when appropriate. Multivariable logistic regression and Kaplan-Meier curves were applied to compare the responses to medical treatments and time to full response.ResultsWe identified 22 patients with a median age of 11 and 36% were female. Four patients (18%) had multifocal bone lesions. CT findings (n = 21) showed lytic lesions (62%) and sclerosis (90%). MRI (n = 14) revealed hyperintensity within bone marrow (100%), soft tissue (71%) and bony expansion (71%). Non-antibiotic treatments including NSAIDs (n = 18), glucocorticoids (n = 10), DMARDs (n = 9), anti-TNF therapy (n = 5) and pamidronate (n = 6) were applied. Rates of full responses to anti-TNF therapy (60%) and pamidronate (67%) were higher than that to NSAIDs (11%) (p < 0.05). Patients receiving pamidronate responded more rapidly than those receiving anti-TNF therapy (median two vs 17 months, p = 0.01) when there was a full response. All had bone biopsies. Intraoral biopsy was performed in 12 of 13 operated in our center and the most common contaminants were Neisseria spp and Streptococcus viridians.ConclusionBoth anti-TNF and pamidronate appeared superior to NSAIDs alone in treating mandibular CNO. Patients receiving pamidronate responded faster than those receiving anti-TNF therapy.

Possibilities of differentiation of various processes that cause focal destruction of small and flat bones in children

Purpose of the study. Systematize Rg, CT and MRI semi-otics of destructive processes in flat and spongy bones in children and determine the diagnostic significance of various X-ray signs for differentiating tuberculosis and other destructive processes and the statistical relation-ship between them. Material and methods. 123 children with suspected tuberculous osteitis were selected for the study. Tuberculous osteomyelitis was detected in 80 (65.1%) patients, nonspecific osteomyelitis in 27 (21.9%), non-bacterial osteomyelitis and oncological processes in 8 (6.5%), respectively. Results. Fistulous process is more common in tuberculous osteomyelitis. Temperature rise to febrile numbers — in patients with nonspecific osteo-myelitis. Their combination was found only with tubercu-losis. Tuberculosis was characterized by large (&gt;10 mm), single cavities with a clear contour, with the presence of sequesters. Nonspecific osteomyelitis was characterized by smaller (5–10 mm), single cavities without destroying the cortical closing plate. In case of non-bacterial osteo-myelitis, multiple cavities with a clear contour, with the presence of sequesters, were more oftenly detected. Oncological processes were characterized by swelling of the bone with the presence of periostitis, as well as large single cavities with a clear contour, with sclerotic chan-ges in the surrounding bone tissue. In some cases, a solid component in soft tissues was visualized. Conclusion.The radiological and cli nical picture is often non-specific for the pathology in question, however, the identification of some symptoms makes it possible to suspect a certain pathological process with a certain degree of probability, which ultimately should lead to a shortening of the diag-nostic pause

The off-label use of anakinra in pediatric systemic autoinflammatory diseases.

Interleukin 1 (IL-1), a central mediator of innate immunity, is considered a master cytokine of local and systemic inflammation. IL-1 has emerged as pivotal in the pathogenesis of autoinflammatory diseases (AIDs), and blockade of its pathway has become a crucial target for therapy. Anakinra (ANA), a recombinant IL-1β receptor antagonist, was the first anti-IL-1 agent employed in clinical practice. ANA is currently approved for the treatment of rheumatoid arthritis, systemic juvenile idiopathic arthritis, adult-onset Still’s disease, and cryopyrin-associated autoinflammatory syndrome. It has also been successfully used for off-label treatment of various monogenic, polygenic, or undefined etiology systemic AIDs.This review describes currently available evidence for the off-label use of ANA in pediatric rheumatologic diseases. Specifically, the use of ANA in Kawasaki disease, idiopathic recurrent pericarditis, Behçet disease, monogenic AIDs, undifferentiated AIDs, chronic non-bacterial osteomyelitis, macrophage activation syndrome, and febrile infection-related epilepsy, in terms of its safety and efficacy. In selected pediatric rheumatic disorders, the off-label administration of ANA appears to be effective and safe. In order to control severe and/or relapsing disease, ANA should be considered as a valuable treatment option in children suffering from rare inflammatory diseases. However, currently available data consist of retrospective studies and short case series; thus, randomized controlled trials and larger series with long-term follow up are mandatory to better assess the efficacy and cost effectiveness of ANA in these challenging patients.

The peculiarities and treatment outcomes of the spinal form of chronic non-bacterial osteomyelitis in children: a retrospective cohort study.

Chronic non-bacterial osteomyelitis (CNO) is a group of immune-mediated diseases which appears in bone inflammation, destruction and some orthopaedic consequences, especially in the cases of spinal involvement. This study is to compare characteristics and treatment outcomes of CNO patients with spinal involvement. The retrospective cohort study included data from 91 pediatric patients with CNO. The diagnosis is based on Jannson's criteria with morphological confirmation (nonspecific chronic inflammation). Spine involvement detected by X-ray, computed tomography, magnetic resonance imaging, and bone scan in 29 (31.9%) patients. No differences in the family history, concomitant immune-mediated diseases between spinal (SpCNO) and peripheral (pCNO) forms of CNO have been revealed. Only 5 (10.2%) SpCNO patients (10.2%) had monofocal monovertebral involvement. The main risk factors of spinal involvement were female sex: RR = 2.0 (1.1; 3.9), sensitivity (Se) = 0.66, specificity (Sp) = 0.6; multifocal involvement: RR = 2.1 (0.9; 5.0), Se = 0.83, Sp = 0.37; no foot bones involvement: RR = 3.1 (1.3; 7.5), Se = 0.83, Sp = 0.5; sternum involvement RR = 2.3 (1.3; 4.1), Se = 0.24, Sp = 0.94. In the linear regression analysis only female sex (p = 0.005), multifocal involvement (p = 0.000001) and absence of foot bones involvement (p = 0.000001) were independent risk factors of spinal involvement (p = 0.000001). The response rate on bisphosphonates and tumor necrosis factor-a inhibitors was 90.9% and 66.7%, consequently. Only 4/29 (13.8%) SpCNO patients underwent surgery due to severe spinal instability or deformities. The spinal involvement is frequent in CNO and could be crucial for choosing a treatment strategy. Bisphosphonates and TNFa-inhibitors could be effective treatment options for severe SpCNO.

Proceedings From the Clinical and Scientific Innovations in Oral and Maxillofacial Surgery Conference 2019

Proceedings From the Clinical and Scientific Innovations in Oral and Maxillofacial Surgery Conference 2019

A Pilot Study of Infrared Thermal Imaging to Detect Active Bone Lesions in Children With Chronic Nonbacterial Osteomyelitis

Chronic nonbacterial osteomyelitis (CNO) is an autoinflammatory bone disease. An inexpensive and rapid imaging tool, infrared thermal imaging, was evaluated for its utility to detect active bone lesions in extremities of children with CNO. Children with suspected active CNO and healthy controls were enrolled. All subjects underwent infrared thermal imaging of the lower extremities. Patients in the CNO group also received a magnetic resonance imaging (MRI) examination. Hyperintensity within bone marrow on a fluid-sensitive T2-weighted MRI sequence was considered confirmatory for inflammation. Infrared thermal data were analyzed using custom software by dividing the leg below the knee into 3 equal segments longitudinally and adding the distal femur segment as an equal length above the knee. Median and 95th percentile temperatures were recorded for each leg segment. Temperature differences between inflamed and uninflamed segments in all subjects (both intersubject and intrasubject) were evaluated using a linear mixed-effects model. Thirty children in the suspected/known CNO group and 31 healthy children were enrolled. In the healthy control group, males had significantly higher temperature in their lower extremities than females (P < 0.05). There was no difference in temperature detected between inflamed leg segments of patients with CNO versus uninflamed leg segments of the healthy control group. However, within the CNO group, significantly higher temperatures were detected for inflamed versus uninflamed distal tibia/fibula segments (P < 0.01). Children with active CNO lesions in the distal tibia/fibula exhibited higher regional temperatures on average than healthy extremities. Larger studies are warranted to further evaluate the clinical utility of infrared thermal imaging for CNO detection.

Chronic non-bacterial osteomyelitis of clavicle

The patient was a 10-year-old girl with pain and swelling of the left clavicle. The physical examination was normal except swelling and tenderness of the left clavicular region. All the...

Development of a Scoring Tool for Chronic Nonbacterial Osteomyelitis Magnetic Resonance Imaging and Evaluation of its Interrater Reliability

Serial magnetic resonance imaging (MRI) examinations are often needed in chronic nonbacterial osteomyelitis (CNO) to determine the objective response to treatment. Our objectives in this study were (1) to develop a consensus-based MRI scoring tool for clinical and research use in CNO; and (2) to evaluate interrater reliability and agreement using whole-body (WB)-MRI from children with CNO. Eleven pediatric radiologists discussed definitions and grading of signal intensity, size of signal abnormality within bone marrow, and associated features on MRI through monthly conference calls and a consensus meeting, using a nominal group technique in July 2017. WB-MRI scans from children with CNO were deidentified for training reading and an interrater reliability study. The reading by each radiologist was conducted in a randomized order. Interrater reliability for abnormal signal and severity were assessed using free-marginal κ statistics. Radiologists reached a consensus on grading CNO-specific MRI findings and on describing bone units based on anatomy. A total of 45 sets of WB-MRI scans, including 4 sets of non-CNO MRI examinations, were selected for the final reading. The mean κ of each category of bones was > 0.7 with majority > 0.9 demonstrating substantial/almost perfect interrater reliability of readings among radiologists. The agreement on signal intensity and the size of signal abnormality within the most commonly affected bones (femur and tibia) were lower than those of other bones. The chronic nonbacterial osteomyelitis magnetic resonance imaging scoring (CROMRIS) tool is a comprehensive standardized scoring tool for MRI in children with CNO. Our interrater study demonstrated good interrater reliability and agreement of readings.

Chronic nonbacterial osteomyelitis in children: a multicenter case series.

Chronic nonbacterial osteomyelitis (CNO) is a primary autoinflammatory bone disease that presents more frequently in children and is characterized by inflammatory bone lesions in the absence of an infectious etiology. There is little information of this disease in Latin America. The objective of the study was to evaluate demographic, clinical, laboratory, imaging, histopathology characteristics, and treatment responses of pediatric CNO patients. The clinical records of 19 patients with CNO diagnosed between 2007 and 2019 at three tertiary centers in Santiago, Chile were reviewed. The median age of onset was 10years and 47% were female. Median delay in diagnosis was 12months. All patients had a pattern of recurrent multifocal disease. 37% of patients had positive antinuclear antibodies and 16% HLA-B27 positivity. 21% of patients presented arthritis or other rheumatologic comorbidity, although no association with psoriasis, inflammatory bowel disease (IBD) or palmoplantar pustulosis (PPP) was observed. Eighteen patients received treatment with nonsteroidal anti-inflammatory drugs with partial response. Twelve patients received methotrexate, and half of them received steroids at the same time reaching remission in 50%. Of the five patients who received bisphosphonates, 60% achieved remission. All four patients who received adalimumab had comorbid arthritis and 75% achieved remission. In a series of Chilean children with CNO, all patients presented with multifocal lesions. Comorbid autoimmune diseases including arthritis were frequent, but no association was observed with psoriasis, IBD, or PPP.

Mast cells enhance sterile inflammation in chronic nonbacterial osteomyelitis.

ABSTRACTChronic nonbacterial osteomyelitis (CNO) is an autoinflammatory bone disease, and patients with active or recurrent bone inflammation at multiple sites are diagnosed with chronic recurrent multifocal osteomyelitis (CRMO). The Chronic multifocal osteomyelitis (CMO) mouse model develops IL-1β-driven sterile bone lesions reminiscent of severe CRMO. The goal of this study was to evaluate the potential involvement of mast cells in CMO/CRMO. Here, we show that mast cells accumulate in inflamed tissues from CMO mice and that mast cell protease Mcpt1 can be detected in the peripheral blood. A transgenic model of connective tissue mast cell depletion (Mcpt5-Cre:Rosa26-Stopfl/fl-DTa) was crossed with CMO mice and the resulting mice (referred to as CMO/MC–) showed a significant delay in disease onset compared with age-matched CMO mice. At 5-6 months of age, CMO/MC– mice had fewer bone lesions and immune infiltration in the popliteal lymph nodes that drain the affected tissues. In bone marrow-derived mast cell cultures from CMO mice, cytokine production in response to the alarmin IL-33 was elevated compared with wild-type cultures. To test the relevance of mast cells to human CRMO, we tested serum samples from a cohort of healthy controls and from CRMO patients at diagnosis. Interestingly, mast cell chymase was elevated in CRMO patients as well as in patients with oligoarticular juvenile arthritis. Tryptase-positive mast cells were also detected in bone lesions from CRMO patients and patients with bacterial osteomyelitis. Together, our results identify mast cells as cellular contributors to bone inflammation in CMO/CRMO and provide rationale for further study of mast cells as therapeutic targets.

Next-generation sequence and biomarker levels in the patients with early-onset chronic non-bacterial osteomyelitis from North Caucasian region of Russia

Next-generation sequence and biomarker levels in the patients with early-onset chronic non-bacterial osteomyelitis from North Caucasian region of Russia

A prospective study of 17 consecutive pediatric patients with chronic non-bacterial osteomyelitis treated with intravenous pamidronate over a 15 year period at a single center reveals excellent clinical and radiologic outcome initially and after flare

Searchable abstracts of presentations at key conferences on calcified tissues ISSN 2052-1219 (online)

Chronic non-bacterial osteomyelitis: a comparative study between children and adults

BackgroundTo compare clinical presentation, diagnostic and treatment strategies, and outcome between pediatric and adult patients with chronic non-bacterial osteomyelitis (CNO).MethodsRetrospective single-centre comparative study of pediatric and adult patients diagnosed with chronic recurrent multifocal osteomyelitis (CRMO)/CNO or synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome treated at the Medical University of Graz.Results24 pediatric patients diagnosed with CRMO/CNO and 10 adult patients diagnosed with SAPHO syndrome were compared. Median age at diagnosis was 12.3 years (range 7.9–18.9) in the pediatric group and 32.5 years (range 22–56) in the adult group. Median time to diagnosis was shorter in children than in adults (0.3 vs. 1.0 years). Initial clinical presentation, laboratory and histopathological findings were similar in children and adults. Mean numbers of bone lesions were comparable between pediatric and adult patients (3.1 vs. 3.0), as were rates of skin involvement (33% vs. 30%). Sternal involvement was more frequent in adults whereas involvement of clavicle and long bones was more frequent in children (41.7% vs.10, 33% vs. 10%). Computerized tomography (CT) was used more often in adults, whereas whole-body magnetic resonance imaging (MRI) was used only in children. Bisphosphonates were applied more often in children and outcome was better in children than in adults (62.5% vs.30%).ConclusionResults of our study suggest that CNO/CRMO and SAPHO syndrome in children and adults might represent a single clinical syndrome that needs a similar diagnostic and therapeutic approach.

Physical activity and health-related quality of life in chronic non-bacterial osteomyelitis

BackgroundChronic non-bacterial osteomyelitis (CNO) is an autoinflammatory disorder of the skeletal system of yet unknown etiology. Patients present with local bone pain and inflammation and - to our experience - often suffer from functional impairment with significant disabilities of daily life. The objective of this study was to assess physical activity, fitness and health-related quality of life (HRQOL) in adolescents with established diagnosis of CNO versus healthy controls (HC).Methods15 patients with CNO and 15 age and gender matched HC aged 13–18 years, completed questionnaires, performed an incremental exercise test with gas exchange measures up to voluntary fatigue and wore an accelerometer over 7 days at home to assess physical activity behavior.ResultsAt the time of assessment, 5 CNO patients were in clinical, one in radiological and 5 in clinical and radiological remission. 7 did not receive any therapy at the time of assessment. The results of the exercise test and of the accelerometry did not show any significant difference between CNO and HC. However, reported sports participation was lower in patients with CNO and PedsQL3.0 and 4.0 showed significant lower values in most of the scores indicating reduced HRQOL.ConclusionAlthough most CNO patients showed a favorable course of disease without any relevant differences in objective measurements of physical activity and fitness versus HC at the time of assessment, questionnaires revealed perceived limitations. Further studies are needed to measure HRQOL and to validate questionnaires in patients with CNO against objective measures including more participants with a higher level of disease activity.

The Role of Epigenetics in Autoimmune/Inflammatory Disease.

Historically, systemic self-inflammatory conditions were classified as either autoinflammatory and caused by the innate immune system or autoimmune and driven by adaptive immune responses. However, it became clear that reality is much more complex and that autoimmune/inflammatory conditions range along an “inflammatory spectrum” with primarily autoinflammatory vs. autoimmune conditions resembling extremes at either end. Epigenetic modifications influence gene expression and alter cellular functions without modifying the genomic sequence. Methylation of CpG DNA dinucleotides and/or their hydroxymethylation, post-translational modifications to amino termini of histone proteins, and non-coding RNA expression are main epigenetic events. The pathophysiology of autoimmune/inflammatory diseases has been closely linked with disease causing gene mutations (rare) or a combination of genetic susceptibility and epigenetic modifications arising from exposure to the environment (more common). Over recent years, progress has been made in understanding molecular mechanisms involved in systemic inflammation and the contribution of innate and adaptive immune responses. Epigenetic events have been identified as (i) central pathophysiological factors in addition to genetic disease predisposition and (ii) as co-factors determining clinical pictures and outcomes in individuals with monogenic disease. Thus, a complete understanding of epigenetic contributors to autoimmune/inflammatory disease will result in approaches to predict individual disease outcomes and the introduction of effective, target-directed, and tolerable therapies. Here, we summarize recent findings that signify the importance of epigenetic modifications in autoimmune/inflammatory disorders along the inflammatory spectrum choosing three examples: the autoinflammatory bone condition chronic nonbacterial osteomyelitis (CNO), the “mixed pattern” disorder psoriasis, and the autoimmune disease systemic lupus erythematosus (SLE).

Total clavicle reconstruction with free peroneal graft for the surgical management of chronic nonbacterial osteomyelitis of the clavicle: a case report

BackgroundChronic nonbacterial osteomyelitis (CNO) is a rare chronic autoinflammatory syndrome affecting mainly children and young adults. The natural history of the disease is marked by recurrent pain as the mainstay of inflammatory outbreaks. Typical radiographic findings are osteosclerosis and hyperostosis of the medial clavicle, sternum and first rib. Compression of the brachial plexus is exceedingly rare and one of the few surgical indications. Literature on total clavicle reconstruction is scarce. While claviclectomy alone has been associated with fair functional and cosmetic outcomes, several reconstruction techniques with autograft, allograft or even cement (“Oklahoma prosthesis”) have been reported with the aim of achieving better pain control, cosmetic outcome and protecting the brachial plexus and subclavian vessels. We herewith report a unique case of complicated CNO of the clavicle treated with total clavicle reconstruction using a free peroneal graft.Case presentationA 21-year-old female patient presented with CNO of her left clavicle, associated with recurrent, progressive and debilitating pain as well as limited range of motion. In recent years, she started complaining of paresthesia, weakness and pain radiating to her left arm during arm abduction. The clavicle diameter reached 6 cm on computed tomography, with direct compression of the brachial plexus and subclavian vessels. Following surgical biopsy for diagnosis confirmation, she further developed a chronic cutaneous fistula. Therefore, a two-stage total clavicle reconstruction using a vascularized peroneal graft stabilized by ligamentous reconstruction was performed. At two-year follow-up, complete pain relief and improvement of her left shoulder Constant-Murley score were observed, along with satisfactory cosmetic outcome.ConclusionsThis case illustrates a rarely described complication of CNO with direct compression of the brachial plexus and subclavian vessels, and chronic cutaneous fistula. To our knowledge, there is no consensus regarding the optimal management of this rare condition in this context. Advantages and complications of clavicle reconstruction should be carefully discussed with patients due to limited evidence of superior clinical outcome and potential local and donor-site complications. While in our case the outcomes met the patient’s satisfaction, it remains an isolated case and further reports are awaited to help surgeons and patients in their decision process.

Response to Early-onset Pamidronate Treatment in Chronic Nonbacterial Osteomyelitis: A Retrospective Single-center Study.

Chronic nonbacterial osteomyelitis (CNO) is a sterile inflammatory bone disorder with an unpredictable disease course. The objective was to assess clinical and radiological disease activity in children with CNO including response to early-onset pamidronate treatment. A single-center retrospective study was conducted of children fulfilling the Bristol Criteria for CNO. At the time of diagnosis, whole-body magnetic resonance imaging (WB-MRI) or local MRI was performed to assess radiological disease activity. Children with multifocal or spinal bone inflammation and clinical disease activity not responding to nonsteroidal antiinflammatory drugs were categorized as having extended CNO. Clinical disease activity was assessed annually. Fifty-one children were included. Median followup time was 4 years (interquartile range 3-7). Children categorized with extended CNO (n = 32) were treated in an early-onset 2-year pamidronate regimen. In extended CNO, WB-MRI was performed at time of diagnosis, and at years 1 and 2 in 88%, 84%, and 91% of cases, respectively. During the first year, the total number of radiologically active lesions and number of spinal lesions per patient declined (p = 0.01). Clinically inactive disease was recorded in 12/32 children (38%). However, 8/12 children (67%) experienced clinical relapse. In limited CNO (n = 19), 10/19 children (53%) presented with clinically inactive disease after 1 year and did not experience clinical relapse. Pamidronate might contribute to improvement in clinical and radiological disease activity in extended CNO, especially after 1 year of treatment. However, children with continuously active disease after 2 years of pamidronate treatment were seen.