September 2026 Research Update

This month added a clearer picture that NSAIDs alone may not fully control chronic nonbacterial osteomyelitis (CNO) for many children, and that moving on to stronger medicines is common in routine care. In a small series, most patients had multifocal bone involvement and only a few had a complete response to NSAIDs, while second-line medicines such as methotrexate and TNF inhibitors were used often. The follow-up information was limited, but the report included children who reached clinical remission by 1 year. [1]

In this Latvian hospital experience, 2 of 13 children had a complete response on NSAIDs, while methotrexate and TNF inhibitors were frequently used alone or together. A smaller group also received bisphosphonates, including in the setting of spine or other axial involvement. Among the 8 children with 1-year follow-up data, 5 were reported to have clinical remission and 3 still had symptoms. [1]

For families, this mainly helps set expectations about what care can look like over time rather than pointing to a single best treatment. It shows that in one real-world pediatric center, needing medicines beyond NSAIDs was common, and some children did reach remission within a year, although outcomes were only available for part of the group. Because this was a small, single-center review without a comparison group, it is best read as a description of care patterns and possible outcomes, not proof that one approach works better than another. [1]

These studies highlighted that blood markers of inflammation can look very different across children at diagnosis, and very high values may signal a heavier disease burden. In one cohort, children with markedly elevated inflammation tests had more bone lesions on whole-body MRI and a distribution that included areas like the pelvis and sacroiliac joints more often. At the same time, their treatments and remission rates were reported as similar to children without such high markers, suggesting that high lab values did not automatically mean worse short-term outcomes in that dataset. [2]

In this 51-patient pediatric cohort, 16 children (31.4%) had markedly elevated acute-phase reactants (CRP 30 mg/L or higher and/or ESR 60 mm/h or higher). This group had a higher number of bone lesions on whole-body MRI and a moderate correlation was reported between CRP level and total lesion count. The authors also noted that children with markedly elevated markers had lower scores when applying the 2025 classification criteria, meaning very high inflammation could make classification less straightforward even when imaging shows extensive disease. [2]

For patients and caregivers, this helps clarify what very high inflammation blood tests might mean at the start of CNO: in one center, they often went along with more spots of bone inflammation seen on imaging. It also raises a practical research point that some classification scoring systems may not fit everyone equally well, especially when inflammation tests are unusually high. This evidence may matter now for understanding why doctors sometimes order broader imaging or think carefully about related conditions, but it does not by itself show that any specific treatment works better for this subgroup. [2]

This month included early, exploratory work suggesting that CRMO involves specific immune changes, alongside a few individual patient reports using newer immune-targeting medicines. The lab-focused human study found signs of chronically activated neutrophils and reduced PSTPIP2 protein in children with CRMO, and these changes looked closer to normal in patients receiving anti-TNF treatment. Separately, case reports described clinical improvement with guselkumab (an IL-23 inhibitor) and tofacitinib (a JAK inhibitor), while a small case-based literature review noted that imaging did not always improve in JAK inhibitor cases even when symptoms did. [3] [4] [5]

In a case-control study of children with CRMO, neutrophils showed ongoing activation and lower PSTPIP2 protein levels than controls, and the neutrophil activation measure correlated with MRI disease burden. The study reported that children on anti-TNF therapy had normalization of neutrophil activation and PSTPIP2 downregulation, while IL-1beta and CXCL8 were not elevated in this dataset. A small transcriptomic analysis pointed to NF-kappaB and chemokine signaling pathways, with several gene signals tracking with disease burden. [3]

A case report of a 59-year-old man with mandibular involvement described symptom improvement and improved bone scan findings within 3 months of guselkumab after other therapies had failed. In the same paper's review of five additional reported cases using IL-17/IL-23 inhibitors or JAK inhibitors for mandibular disease, all cases noted clinical improvement, but two JAK inhibitor cases had radiologic progression. This pattern highlights that pain and imaging may not always move together in the limited case literature. [4]

A separate single-patient report described a 16-year-old with multifocal CNO and acne who did not respond to NSAIDs and then became symptom-free after starting tofacitinib. Imaging also improved, with a substantial reduction in MRI signals by 8 weeks and continued regression by 6 months, and the report did not discuss side effects, so it gives no information about safety. Because this is one person, it is an early signal rather than a reliable estimate of how often this might happen. [5]

For patients, this group of studies mainly adds understanding of what may be happening in the immune system and points to possible future treatment directions, but it is not strong enough to change care on its own. The neutrophil and PSTPIP2 findings help explain why CRMO is considered an inflammatory condition and give researchers concrete signals that might be tracked in future studies. The medication reports are limited to individual cases and a small case-based review, so they can show what is possible but cannot predict who will benefit or how safe these approaches are across many patients. [3] [4] [5]