Diagnostic and therapeutic practices in adult chronic nonbacterial osteomyelitis (CNO)

Abstract

Background Chronic nonbacterial osteomyelitis (CNO) is a rare, and impactful auto-inflammatory bone disease occurring in children and adults. Clinical care for CNO is challenging, as the condition lacks validated classification criteria and evidence-based therapies. This study aimed to map the current diagnostic and therapeutic practices for CNO in adults, as a first step towards a standardized disease definition and future consensus treatment plans. Methods A primary survey was spread among global rheumatological/bone networks and 57 experts as identified from literature (May 2022), covering terminology, diagnostic tools (clinical, radiological, biochemical) and treatment steps. A secondary survey (sent to primary survey responders in August 2022) further queried key diagnostic features, treatment motivations, disease activity and treatment response monitoring. Results 36 and 23 physicians completed the primary and secondary survey respectively. Diagnosis was mainly based on individual physician assessment, in which the combination of chronic relapsing-remitting bone pain with radiologically-proven osteitis/osteomyelitis, sclerosis, hyperostosis and increased isotope uptake on bone scintigraphy were reported indicative of CNO. Physicians appeared more likely to refer to the condition as synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome in the presence of joint and skin pathology. MRI was most frequently performed, and the preferred diagnostic test for 47%. X-rays were second-most frequently used, although considered least informative of all available tools. Typical imaging features reported were hyperostosis, osteitis, osteosclerosis, bone marrow edema, while degeneration, soft tissue calcification, and ankylosis were not regarded characteristic. Inflammation markers and bone markers were generally regarded unhelpful for diagnostic and monitoring purposes and physicians infrequently performed bone biopsies. Management strategies diverged, including indications for treatment, response monitoring and declaration of remission. Step-1 treatment consisted of non-steroidal anti-inflammatory drugs/COX-2 inhibitors (83%). Common step 2–3 treatments were pamidronate, methotrexate, and TNF-a-inhibition (anti-TNFα), the latter two regarded especially convenient to co-target extra-skeletal inflammation in SAPHO syndrome. Overall pamidronate and anti-TNFα and were considered the most effective treatments. Conclusions Following from our survey data, adult CNO is a broad and insufficiently characterized disease spectrum, including extra-osseous features. MRI is the favoured imaging diagnostic, and management strategies vary significantly. Overall, pamidronate and anti-TNFα are regarded most successful. The results lay out current practices for adult CNO, which may serve as backbone for a future consensus clinical guideline.

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

“… 2 Based on the results of a recent primary survey conducted among expert stake holders in the management of adult CNO, most of whom were rheumatologists, there was no consensus on the diagnostic imaging tools used in the diagnosis of adult CNO, and no standard diagnostic imaging features used to establish the diagnosis. 31 …”

Treatment and monitoring of SAPHO syndrome: a systematic review

“…Because approximately 50% of physicians managing adult CNO/CRMO distinguish between CNO/CRMO and SAPHO, some SAPHO patients in the literature may have been missed in the systematic review presented here. 47 Therapeutic approaches to CNO/CRMO are summarised and discussed elsewhere, and similarities exist in the treatment across the CNO/CRMO/SAPHO spectrum usually with NSAIDs considered first-line treatment options, and cDMARDs (eg, methotrexate or sulfasalazine), bisphosphonates and TNFi reserved for severe and/or treatment-refractory cases. 41 47 48 56 Similarly, opinions vary whether SAPHO and PAO constitute the same disease.…”

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

“…Chronic nonbacterial osteitis (CNO) is a rare bone disease with a heterogeneous clinical presentation, occurring in children and adults [ 1 – 3 ]. CNO has historically been indicated by various terms, including synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO)-syndrome and chronic recurrent multifocal osteomyelitis (CRMO).…”

“…CNO has historically been indicated by various terms, including synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO)-syndrome and chronic recurrent multifocal osteomyelitis (CRMO). The disease spectrum is centrally characterized by relapsing–remitting sterile bone inflammation, causing bone pain, stiffness, compromised joint mobility and bone deformation [ 3 , 4 ]. Despite ongoing efforts for timely diagnosis, patients with CNO still face an average diagnostic delay of 5 years during which they may be exposed to chronic pain [ 5 , 6 ].…”

“…After diagnosis, chronic pain remains the main contributor to overall disease burden, reflected in frequent work absence and decreased quality of life [ 6 – 8 ]. Clinical management of CNO therefore focuses on alleviating pain through targeting the osteitis with various anti-inflammatory and anti-resorptive treatments, all of which are off-label due to lack of supportive evidence [ 1 , 2 , 9 ].…”