A Comprehensive Review of the Pathogenesis, Diagnosis, and Management of Diabetic Foot Infections.

GENERAL PURPOSE: To review an approach to diabetic foot infections (DFIs), including acute osteomyelitis, while also discussing current practices and the challenges in diagnosis and management. TARGET AUDIENCE: This continuing education activity is intended for physicians, physician assistants, nurse practitioners, and nurses with an interest in skin and wound care. LEARNING OBJECTIVES/OUTCOMES: After participating in this educational activity, the participant will1. Identify the risk factors for developing DFIs.2. Outline diagnostic techniques for assessing DFIs.3. Select the assessment techniques that support a diagnosis of osteomyelitis.4. Choose the appropriate pharmacologic and nonpharmacologic treatment options for patients who have DFIs. ABSTRACT: Diabetic foot ulcers result from a combination of peripheral neuropathy, vascular compromise, and repetitive trauma. Approximately 50% of individuals with diabetic foot ulcers will develop a diabetic foot infection (DFI), and 20% of individuals with a DFI will develop osteomyelitis. Herein, the authors review an approach to DFIs including acute osteomyelitis and discuss current practices and challenges in diagnosis and management.The diagnosis of a skin and soft tissue DFI is based on clinical criteria. A bone biopsy is considered the criterion standard for diagnosis of osteomyelitis; however, biopsy is not always feasible or available. Consequently, diagnosis can be made using a combination of clinical, biochemical, and radiographic findings. X-ray is the recommended imaging modality for initial evaluation; however, because of its lower relative sensitivity, advanced imaging may be used when clinical suspicion remains after negative initial testing.The microbiology of skin and soft tissue DFIs and osteomyelitis is similar. Staphylococcus aureus and other Gram-positive cocci are the most common pathogens identified. Deep cultures are preferred in both DFI and osteomyelitis to identify the etiologic pathogens implicated for targeted antimicrobial therapy. Management also requires a multidisciplinary approach. Surgical debridement in those with deep or severe infections is necessary, and surgical resection of infected bone is curative in cases of osteomyelitis. Finally, appropriate wound care is critical, and management of predisposing factors, such as peripheral neuropathy, peripheral arterial disease, tinea, and edema, aids in recovery and prevention.

Application and Clinical Effectiveness of Antibiotic-Loaded Bone Cement to Promote Soft Tissue Granulation in the Treatment of Neuropathic Diabetic Foot Ulcers Complicated by Osteomyelitis: A Randomized Controlled Trial.

This study explored the clinical effectiveness of antibiotic-loaded bone cement on primary treatment of diabetic foot infection. This is a randomized controlled study, including thirty-six patients with diabetic foot ulcer complicated by osteomyelitis who had undergone treatment between May 2018 and December 2019. Patients were randomly divided into control group (group A) and study group (group B). Patients in the intervention group received antibiotic-loaded bone cement repair as primary treatment, while patients in the control group received conventional vacuum sealing draining treatment. Clinical endpoints were assessed and compared between the two groups, including wound healing time, wound bacterial conversion, NRS pain score, number of wound dressing changes, and average hospitalization time. All patients were followed up for a period of 12 months after discharge. Results show that compared with the control group, patients in the study group had significant difference in the number of patients for baseline pathogens eradication, short NRS pain score, hospital length of stay and cost, wound surface reduction, healing time, low rate of complications, and infection recurrence. Based on the findings, we conclude that antibiotic-loaded bone cement can be used for treatment of wound in patient with diabetic foot infection. It can help to control wound infections, shorten hospital length of stay, reduce medical cost, and relieve both doctors' and patients' burden. The application of antibiotic-loaded bone cement is suitable for diabetic wound with soft tissue infection or osteomyelitis.

Personalized three-dimensional printed polyether-ether-ketone prosthesis for reconstruction after subtotal removal of chronic clavicle osteomyelitis: A case report.

RATIONALE: Three-dimensional (3D) printing has attracted wide attention for its potential and abilities in the assistance of surgical planning and the development of personalized prostheses. We herewith report a unique case of chronic clavicle osteomyelitis treated with a two-stage subtotal clavicle reconstruction using a 3D printed polyether-ether-ketone (PEEK) prosthesis. PATIENT CONCERNS: A 23-year-old Chinese female presented to our clinic complaining about a progressive pain of her right clavicle for about 1 year. DIAGNOSES: Chronic clavicle osteomyelitis confirmed by percutaneous biopsy and lesion biopsy. INTERVENTIONS: This patient accepted a long-term conservative treatment, which did not gain satisfactory outcomes. Thus, a subtotal removal and two-stage reconstruction of the right clavicle with a 3D-printed polyether-ether-ketone prosthesis stabilized by screw fixation system was performed. OUTCOMES: At 2-year follow-up, complete pain relief and satisfactory functional recovery of her right shoulder were observed. LESSONS: Personalized 3D printed prosthesis is an effective and feasible method for reconstruction of complex bone defects.

Skull base osteomyelitis: Comprehensive analysis and a new clinicoradiological classification system.

OBJECTIVE: Skull baseosteomyelitis (SBO) is a rare phenomenon that typically occurs in diabetic or immunocompromised patients, causing significant morbidity and mortality. This study aimed to analyze a single institution's treatment results in SBO patients and propose anew integrated clinicoradiological classification system. METHODS: The medical records of 32 SBO patients that were treated at a tertiary care center between 2006 and 2017 were retrospectively reviewed. A scoring system based on anatomical involvement according to MRI was created. Subsequently, the scoring system was integrated with cranial nerve dysfunction status and a clinical grading system (CGS) was proposed. RESULTS: Among the 32 patients, 78.1% were diabetic and 63% had cranial nerve dysfunction at presentation. Bone erosion based on CT was greater in the patients without regression (P = 0.046). The regression rate decreased from clinical grade (CG)1 to CG3 (P = 0.029). Duration of hospitalization increased as CG increased (P = 0.047). Surgery had no effect on regression status at the time of discharge (P = 0.41). The 1-year, 2-year, and 5-year overall survival rates were 82.2%, 70.8%, and 45.8%, respectively. CG was significantly correlated with overall survival but not with disease-specific survival (log-rank; P = 0.017, P = 0.362, respectively). CONCLUSION: SBO continues to pose a challenge to clinicians, and causes significant morbidity and mortality. The proposed new classification system can be an option for grouping SBO patients according to clinical and radiological findings, helping clinicians estimate prognosis.

Genomic Expression Profiling and Bioinformatics Analysis of Chronic Recurrent Multifocal Osteomyelitis.

OBJECTIVE: Chronic nonbacterial osteomyelitis (CNO) is an autoinflammatory bone disorder. Its most severe form is referred to as chronic recurrent multifocal osteomyelitis (CRMO). Currently, the exact molecular pathophysiology of CNO/CRMO remains unknown. No uniform diagnostic standard and treatment protocol were available for this disease. The aim of this study was to identify the differentially expressed genes (DEGs) in CRMO tissues compared to normal control tissues to investigate the mechanisms of CRMO. MATERIALS: Microarray data from the GSE133378 (12 CRMO and 148 matched normal tissue samples) data sets were downloaded from the Gene Expression Omnibus (GEO) database. DEGs were identified using the limma package in the R software. Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and protein-protein interaction (PPI) network analysis were performed to further investigate the function of the identified DEGs. RESULTS: This study identified a total of 1299 differentially expressed mRNAs, including1177 upregulated genes and 122 downregulated genes, between CRMO and matched normal tissue samples. GO analyses showed that DEGs were enriched in immune-related terms. KEGG pathway enrichment analyses showed that the DEGs were mainly related to oxidative phosphorylation, ribosome, and Parkinson disease. Eight modules were extracted from the gene expression network, including one module constituted with immune-related genes and one module constituted with ribosomal-related genes. CONCLUSION: Oxidative phosphorylation, ribosome, and Parkinson disease pathways were significantly associated with CRMO. The immune-related genes including IRF5, OAS3, and HLA-A, as well as numerous ribosomal-related genes, might be implicated in the pathogenesis of CRMO. The identification of these genes may contribute to the development of early diagnostic tools, prognostic markers, or therapeutic targets in CRMO.

Rare case of osteomyelitis caused by Gardnerella vaginalis and Streptococcus parasanguinis in a postmenopausal woman.

Vertebral osteomyelitis is an infection of the vertebrae that can lead to spinal degeneration, most commonly caused by Staphylococcus aureus Here, we report an unusual case of pyogenic osteomyelitis caused by Gardnerella vaginalis and Streptococcus parasanguinis in a 61-year-old postmenopausal woman. The patient presented with a 2-week history of worsening lower back pain and fever and a recent episode of cystitis following re-engagement of sexual activity. Imaging revealed a deterioration of vertebrae discs and spinal canal stenosis at the L3-L4 levels with a formation of abscess in the right psoas muscle. Needle aspiration of the abscess identified G. vaginalis and S. parasanguinis and the patient was successfully treated with a 6-week course of ceftriaxone and metronidazole. This case describes an unusual coinfection of two pathogens that normally reside in the urogenital tract and oral cavity, respectively, and highlights the risk posed when these organisms breach the body's normal barriers.

Osteomyelitis, Venous Thrombosis, and Septic Emboli in a Pediatric Patient: A Case Report.

New virulence factors, such as the Panton-Valentine leukocidin (PVL), are appearing during Staphylococcus aureus infections occurring in the pediatric population. Such factors increase the aggressiveness and risk of dissemination of the bacteria, causing infections to be life-threatening. An early diagnosis is thus especially important. We present a case of osteomyelitis, venous thrombosis, and septic emboli occurring in a pediatric patient that should trigger suspicion of a PVL-positive strain. A multidisciplinary approach is necessary to enable rapid diagnosis and early treatment, which is essential for successful management of these infections. Management is based on broad-spectrum antibiotics, in combination with aggressive surgical treatment and antithrombotic therapy. In patients infected with S. aureus whose condition worsens quickly, PVL gene sequencing should be considered.

Acute osteomyelitis of the distal fibula in children: Treatment options and long-term follow-up.

INTRODUCTION: Acute osteomyelitis of the distal fibula is a rare disease in children and is characterized by special features compared with other sites. The objective of this study was to report the functional outcome at long-term follow-up. METHODS: We reviewed retrospectively, between January 2000 and December 2010, all cases of acute osteomyelitis of the distal fibula. Epidemiological and bacteriological data as well as therapy and outcome factors were analyzed. At the last follow-up, functional outcome was studied based on ankle motion, growth disturbance, and radiological sequelae. RESULTS: Seven cases of acute osteomyelitis of the distal fibula were found. The mean age was patients was 7.71 years and the sex ratio was 2.5. The portal of entry of the pathogen was a skin injury in 57% of cases. Staphylococcusaureus was identified in 71% of cases. The mean duration of antibiotic therapy was 33.2 days. At a mean of 12.85 years of follow-up, no growth disturbance was found. The mean plantar and dorsal flexion was 41° and 27.7°, respectively. The mean postoperative American Orthopedics Foot and Ankle score (AOFAS) was 96.71 points. CONCLUSION: Acute osteomyelitis of the distal fibula in children is scarce and rarely reported in the literature. It occurs more often in boys at an average age of 7 years. Local symptoms are usually more obvious than general symptoms. Surgical debridement of the subperiosteal abscess without bone trepanation seems to lead to a satisfactory outcome. LEVEL OF EVIDENCE: Level IV - case series. IRB: Sahloul Hospital Human Research Ethics Committee.

A case report of a novel compound heterozygous mutation in a Brazilian patient with deficiency of Interleukin-1 receptor antagonist (DIRA).

BACKGROUND: Deficiency of the natural antagonist of interleukin-1 was first described in 2009 and so far 20 patients has been reported. In Brazil just two cases have been reported both carrying the same homozygous 15 bp deletion. Blocking interleukin-1 has changed rate survival for DIRA patients. The use of anakinra and rilonacept has been reported safe and efficient, whereas the selective blockade of interleukin-1 beta, using the monoclonal antibody canakinumab has been reported in a single case only. CASE PRESENTATION: Here we report a case of a 7 years old Brazilian boy that presented with recurrent episodes of systemic inflammation with severe disabling osteomyelitis with mild pustular skin rash. A Next Generation Sequencing gene panel allowed to detect two pathogenic mutations in the IL1RN gene, described in compound heterozygosity. Corticosteroids was effective in controlling inflammation and anti-IL1 beta blocker triggered disease flare. Complete clinical control could be achieved using IL-1 receptor antagonist. CONCLUSIONS: DIRA is a severe, life threatening autoinflammatory condition with low numbers of patients described all over the world. The mutation p.Asp72_Ile76del in IL1RN is presented in all Brazilian DIRA patients already described and p.Q45* (rs1019766125) is a new mutation affecting the IL1RN gene. Following the pathogenesis of DIRA, blocking both subunits of interleukin one as well as antagonizing the receptor using anakinra or rilonacept seems to be effective. There is just one report using canakinumab for the treatment of DIRA and this is the first report of disease flare using this drug.

Foot and Ankle Surgery for Chronic Nonhealing Wounds.

Chronic wounds often are the result of bone deformities, compounded by musculotendinous and ligamentous imbalance. Sensory neuropathy places patients at greater risk for acute wounds to develop into chronic wounds. Etiologies of these deforming forces include Charcot neuroarthropathy, trauma, and congenital and acquired neuromuscular disorders. Management of these deformities ranges from simple relief of pressure with soft inserts to bracing for mechanical instability. Correction of more complex deformities requires resection of bone, osteotomies, fusions, and external fixation. Tendon and ligament imbalance must be addressed at all levels of deformity. Postoperatively, patients must be re-evaluated for continuation of orthoses and bracing.

New Insights into Adult and Paediatric Chronic Non-bacterial Osteomyelitis CNO.

PURPOSE OF REVIEW: To describe in detail the clinical synopsis and pathophysiology of chronic non-bacterial osteomyelitis and SAPHO syndrome. RECENT FINDINGS: Chronic non-bacterial osteomyelitis (CNO) has been identified as a disease entity for almost 50 years. This inflammatory bone disorder is characterized by osteolytic as well as hyperostotic/osteosclerotic lesions. It is chronic in nature, but it can present with episodic flairs and phases of remission, which have led to the denomination "chronic recurrent osteomyelitis", with its severe multifocal form "chronic recurrent multifocal osteomyelitis" (CRMO). For almost three decades, an infectious aetiology had been considered, since especially Propionibacterium acnes had been isolated from bone lesions of individual patients. However, this concept has been challenged since long-term antibiotic therapy did not alter the course of disease and modern microbiological techniques (including PCR) failed to confirm bone infection as an underlying cause. Over recent years, a profound dysregulation of cytokine expression profiles has been demonstrated in innate immune cells of CNO patients. A hallmark of monocytes from CNO patients is the failure to produce immune regulatory cytokines interleukin-10 (IL-10) and IL-19, which have been linked with genetic and epigenetic alterations. Subsequently, a significant upregulation of pro-inflammatory, NLRP3 inflammasome-dependent cytokines (IL-1ß and TNF-α), has been demonstrated. The current knowledge on CNO, the underlying molecular pathophysiology, and modern imaging strategies are summarized; differential diagnoses, treatment options, outcome measures, as well as quality of life studies are discussed.

Residual foreign body in the foot causing chronic osteomyelitis mimicking a pseudotumor: A case report.

Osteomyelitis from a retained foreign body should be included in the differential diagnosis of any osteolytic lesion of the foot. We report here a case of a 59-year-old man who presented with swelling over the dorsolateral aspect of the right foot. Plain x-ray showed an osteolytic lesion that mimicked a pseudotumor. Magnetic resonance imaging (MRI) showed multilocular fluid collection over the right cuboid with a hypointense lesion over the plantar fascia. The patient underwent surgery and a rubber fragment (1 cm × 0.8 cm) was removed from his foot that had been present for two years following a stabbing injury. The patient fully recovered without complication or disability.

Extensive maxillary osteomyelitis following tooth extraction in a patient with osteopetrosis.

Osteopetrosis (OP), also known as marble bone disease is an extremely rare inherited skeletal disorder, characterised by abnormal functioning of the osteoclasts that results in incremental bone deposition with lack of normal bone remodelling. This leads to the formation of hard and brittle bone can readily fracture. The compromised quality of marrow tissue with poor vascularity reduces bone healing and increases the risk of infections. The risk of jawbone osteomyelitis in patients with OP is high and invariably involves mandible. Involvement of maxilla is rare and has been sparingly reported in the literature. This paper highlights a case of extensive necrosis of maxilla and mid-face skeleton following tooth extraction in a patient with OP. Review of the English literature identifying 23 previously published reports of maxillary osteomyelitis in patients with OP is also presented. Demographic details, history of tooth extraction, extent of involvement, clinical presentation, imaging finding, treatment provided and the outcome have been discussed.

Genetic variants in FBLIM1 gene do not contribute to SAPHO syndrome and chronic recurrent multifocal osteomyelitis in typical patient groups.

BACKGROUND: Syndrome of synovitis acne pustulosis hyperostosis osteitis (SAPHO) and chronic recurrent multifocal osteomyelitis (CRMO) present two diseases of a dermatologic and rheumatologic spectrum that are variable in manifestation und therapeutic response. Genetic risk factors have long been assumed in both diseases, but no single reliable factor has been identified yet. Therefore, we aimed to clinically characterize a patient group with syndrome of synovitis acne pustulosis hyperostosis osteitis (SAPHO) (n = 47) and chronic recurrent multifocal osteomyelitis (CRMO)/ chronic non-bacterial osteomyelitis (CNO) (n = 9) and analyze a CRMO candidate gene. METHODS: Clinical data of all patients were collected and assessed for different combinations of clinical symptoms. SAPHO patients were grouped into categories according to the acronym; disease-contribution by pathogens was evaluated. We sequenced coding exons of FBLIM1. RESULTS: Palmoplantar pustular psoriasis (PPP) was the most common skin manifestation in CRMO/CNO and SAPHO patients; most SAPHO patients had sterno-costo-clavicular hyperostosis. The most common clinical category of the acronym was S_PHO (n = 26). Lack of pathogen detection from bone biopsies was more common than microbial isolation. We did not identify autosomal-recessive FBLIM1 variants. CONCLUSIONS: S_PHO is the most common combination of symptoms of its acronym. Genetic analyses of FBLIM1 did not provide evidence that this gene is relevant in our patient group. Our study indicates the need to elucidate SAPHO's and CRMO/CNO's pathogenesis.

Mid-term walking ability after Charcot foot reconstruction using the Ilizarov ring fixator.

BACKGROUND: Failed conservative treatment and complications are indications for foot reconstruction in Charcot arthropathy. External fixation using the Ilizarov principles offers a one-stage procedure for deformity correction and resection of osteomyelitic bone. The aim of this study was to determine whether external fixation with an Ilizarov ring fixator leads reliably to walking ability. MATERIALS AND METHODS: 29 patients treated with an Ilizarov ring fixator for Charcot arthropathy were retrospectively analyzed. Radiologic fusion at final follow up was assessed separately on conventional X-rays by two authors. The association between walking ability and the presence of osteomyelitis at the time of reconstruction, and the presence of fusion at final follow up was investigated using Fisher's exact test. RESULTS: Mean follow up was 35 months (range 5.3-107) months; mean time of external fixation was 113 days. Ten patients (34.5%) reached fusion, but 19 did not (65.5%). Two patients needed below knee amputation. 26 of the remaining 27 patients maintained walking ability, 23 of those without assistive devices. Walking ability was independent from the presence of osteomyelitis at the time of reconstruction and from the presence of fusion. CONCLUSION: Foot reconstruction with an Ilizarov ring fixator led to limb salvage in 93%. The vast majority (96.3%) of patients with successful limb salvage was ambulatory, independent from radiologic fusion, and presence of osteomyelitis at the time of reconstruction. These findings encourage limb salvage and deformity correction in this difficult-to-treat disease, even with underlying osteomyelitis.

Role of inflammatory markers in the healing time of diabetic foot osteomyelitis treated by surgery or antibiotics.

OBJECTIVE: To analyse the predictive role of inflammatory markers in the healing time of diabetic foot osteomyelitis treated by surgery or antibiotics. METHODS: An observational study of patients with diabetic foot ulcers (DFU) and clinically suspected osteomyelitis. The patients underwent surgical or antibiotic treatment for bone infection in a specialised diabetic foot unit. Blood samples were taken from each patient to analyse biomarkers. The main outcome was the number of weeks until healing occurred. RESULTS: A total of 116 patients took part in the study. The number of weeks until healing was similar for both groups (surgical n=96 and antiobiotic n=20, treatments). No association was observed among biomarkers as predictors of time-to-healing. CONCLUSION: There is not enough evidence to define the prognostic role of inflammatory markers in the healing time of DFUs complicated with diabetic foot osteomyelitis, regardless of the treatment administered.

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 10 years and 47% were female. Median delay in diagnosis was 12 months. 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.

Does an antibiotic nail made in a lubricated tube release antibiotic?

INTRODUCTION: The treatment of long-bone osteomyelitis has long been a difficult problem. Recently, antibiotic-impregnated intramedullary rods for the treatment of infected long-bone fractures have been gaining popularity but they are quite difficult to fabricate. Recently, a new technique that utilizes mineral oil to coat the inside of a chest tube mold prior to introduction of cement has been proven to ease fabrication. We hypothesized that the use of mineral oil would alter the elution characteristics of tobramycin from the intramedullary device. METHODS: Two groups of antibiotic nails were fabricated under sterile conditions. The control group utilized a chest tube mold. The study group utilized a chest tube that was coated with mineral oil prior to cement injection. Each intramedullary nail was placed in pooled human serum and incubated under physiologic conditions. The level of tobramycin in each sample was measured at timepoints 0, 1, 6, and 24 h. RESULTS: There was no significant difference when comparing control with the experimental group at any timepoint. Antibiotic nails eluted tobramycin at a rapid rate in the first 6 h of exposure to serum, regardless of their preparation with oil or without oil. The rate of elution fell precipitously between 6 and 24 h. CONCLUSION: We believe that although this study, as with any study, cannot perfectly recreate in vivo conditions, we have clearly shown that mineral oil has no significant effect on elution of tobramycin from antibiotic nails.

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.