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

Abstract

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-1β and TNF-α), has been demonstrated. Summary 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.

Chronic nonbacterial osteomyelitis (CNO) and chronic recurrent multifocal osteomyelitis (CRMO)

“…However, this has not been proven experimentally yet. The presence of Cutibacterium acnes in a subset of bone biopsies causes a clinical dilemma as acute or chronic bacterial osteomyelitis may not cause significant elevation of systemic inflammatory parameters, especially when low virulent strains of bacteria are present [ 43 , 44 ].…”

“…Because of some clinical overlap between SAPHO and psoriasis treatment, the IL-17A neutralizing antibody secukinumab was successfully used in SAPHO patients [ 124 ]. Lastly, individual case reports suggest successful used of the PDE4-inhibitor apremilast and the JAK inhibitor tofacitinib in SAPHO [ 44 , [125] , [126] , [127] ].…”

“…Adult rheumatologists frequently use the acronym SAPHO talking about CNO. Technically, however, SAPHO should only be used for patients with cutaneous features, including acne and pustulosis [ [1] , [2] , [3] , [4] , [5] ].…”

TNAP as a New Player in Chronic Inflammatory Conditions and Metabolism

“…TNAP activity has recently been linked to new scientific fields, including inflammation and metabolism. In HPP, as a disease model for TNAP deficiency, inflammatory conditions, such as bone marrow edema/chronic non-bacterial osteomyelitis, myopathies, tendinitis, and increased predisposition for periodontitis, are very common in both children and adults [ 27 , 31 , 36 , 91 ]. Provided that TNAP deficiency contributes to inflammatory reactions, e.g., in bone and muscle in HPP patients, research groups from different fields teamed up to unravel the molecular mechanisms of TNAP activity that modulate inflammatory processes.…”

Literaturübersicht zur Therapie der CNO mit TNF-α-Inhibitoren

“…Aktuell wird die Notwendigkeit einer Therapieeskalierung bei therapierefraktären Fällen in einem Review von Hedrich et al eindrücklich dargelegt [10].…”