A clinical and pathomechanistic profile of chronic nonbacterial osteomyelitis/chronic recurrent multifocal osteomyelitis and challenges facing the field

Abstract

Sporadic chronic nonbacterial osteomyelitis (CNO) is the most common auto-inflammatory bone disorder. The clinical picture is highly variable ranging from nonsymptomatic monofocal lesions to chronic recurrent multifocal disease. Symptoms include pain, local swelling and warmth in the absence or presence of fever. A subset of CNO patients exhibits additional symptoms of psoriatic skin involvement, palmoplantar pustulosis and inflammatory bowel disease. Novel insights into the pathogenesis of CNO link the failure to produce IL-10 and the resulting imbalance toward pro-inflammatory IL-6 and TNF-α with disease expression. Treatment is empiric and includes NSAIDs, corticosteroids, sulfasalazine, methotrexate, TNF inhibitors and bisphosphonates. Laboratory studies and clinical trials are warranted to: establish biomarkers that predict flares and clinical outcomes, identify patients that require additional treatment on top of NSAIDs, establish evidence-based treatment regimens, allow a risk–benefit assessment for the available therapeutic strategies, and identify novel therapeutic targets.

Keywords::

• chronic nonbacterial osteomyelitis
• chronic recurrent multifocal osteomyelitis
• inflammation
• IL-10
• TNF-α
• Sp-1
• chromatin
• TLR4
• treatment

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

The authors thank Christina Ioannidis for critically reading the manuscript.

Key issues

• • Regardless of recent advances, the precise pathomechanisms in chronic nonbacterial osteomyelitis (CNO)/chronic recurrent multifocal osetomyelitis (CRMO) remain unknown.

• • The failure to produce IL-10 is a hallmark of monocytes from CNO/CRMO patients and offers a putative pathomechanism that warrants future research.

• • Risk alleles and/or disease-causing mutations are highly likely but remain to be determined.

• • The role of associated IL-10 promoter polymorphisms with CNO/CRMO needs to be established.

• • Therapy is empiric, and broadly accepted treatment recommendations do not exist.

• • At this point, biomarkers or clinical scoring systems measuring disease activity, predicting flares and/or disease outcome are missing.

• • Predictors for the response or failure of NSAIDs and other treatment options need to be determined.