Chronic Nonbacterial Osteomyelitis (CNO): What a GI Doctor Should Know

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L Lim et al. The Journal of Pediatrics, Volume 283, 114636. Open Access! Chronic Nonbacterial Osteomyelitis: A Noninfectious Autoinflammatory Disorder of Bone

Prior to this review, I was familiar with the term chronic recurrent multifocal osteomyelitis (CRMO) but not CNO. CRMO is a severe form of CNO, usually characterized by symmetrical inflammatory bone lesions (DY Zhao et al. J Transl Autoimmun 2021; 4:100095. Chronic nonbacterial osteomyelitis (CNO) and chronic recurrent multifocal osteomyelitis (CRMO)).

In this useful review, it is noted that IBD was associated with ~9% of cases of chronic nonbacterial osteomyelitis (CNO).

    Key points:

    • “IBD identified before, during, or after CNO diagnosis, has been well-reported as an associated condition.34-37 A review of cases of CNO with IBD showed that the diagnosis of CNO preceded the diagnosis of IBD in over half of the reported cases.38“
    • “Children with CNO frequently experience a high burden of pain and impaired physical function. CNO can cause permanent deformities in any bone, but especially if there is spinal involvement and diagnosis and treatment are delayed”
    • “Bone biopsies should be performed if there is clinical suspicion of infection or malignancy, although tissue usually is not needed for diagnosis unless the clinical presentation is atypical”
    • “MRI is now the standard imaging test that usually starts with targeted examination of the affected area…A whole-body MRI (WB-MRI) should be considered for all patients with CNO at diagnosis when possible, as it may help support a diagnosis of CNO by detecting additional sites of bone inflammation that may be clinically inapparent, particularly vertebral lesions”
    • “Non-steroidal anti-inflammatory drugs (NSAIDs) are usually first-line treatment for children with CNO, except for those with vertebral lesions, who require systemic treatment… over half of children treated with NSAIDs experience a disease flare within the first 2 years,14 requiring either retreatment with NSAIDs or another systemic medication”
    • “In the presence of vertebral CNO lesions, or after failing NSAID monotherapy, three categories of systemic treatments are recommended by the Childhood Arthritis and Rheumatology Research Alliance (CARRA)56: 1) synthetic DMARDs, 2) bisphosphonates, or 3) tumor necrosis factor-inhibitor (TNFi) biologic agents with or without methotrexate (to prevent the development of antibodies to the drug)”
    • “In practice, TNFi tends to be used more if children also have comorbid conditions for which TNFi already is indicated such as inflammatory arthritis and sacroiliitis,7 IBD,4,72 and psoriasis.4,14,24 “

    My take: Being familiar with CNO is important for GI physicians as it can occur (rarely) in our patients with IBD. Another important caveat, which is not discussed in this review, is that CNO can occur paradoxically due to the use of TNFi treatment.

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    The London Eye. This view makes it look a lot like a bicycle wheel.

    Ten-Year Trends in Pediatric Pharmacology for Gastroesophageal Reflux and Pediatric Feeding Disorders

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    S Hirsch et al. J Pediatr 2025;283:114628. Ten-Year Trends in Pharmacologic Management of Gastroesophageal Reflux Disease and Pediatric Feeding Disorders in Young Children

    Methods: Single-center, retrospective cohort study of children less than 2 years (49,483) diagnosed with GERD or PFD (pediatric feeding disorder) between January 2014 and December 2023. Prescriptions were searched for proton pump inhibitors (PPI), H2-receptor antagonists (H2RA), cyproheptadine, erythromycin, metoclopramide, or prucalopride, and procedures were searched for intrapyloric botulinum injections.

    Key findings:

    • There was an increasing number of patients seen annually (6516 in 2014 vs 9109 in 2023)
    • The percent of patients receiving any prescription for GERD or PFD declined by almost 50%, from 36.5% in 2014 to 18.7% in 2023 (P < .001)
    • There was a particular decline in PPI prescriptions, with 25.3% of patients receiving PPI in 2014 and 7.1% receiving PPI in 2023 (P < .001)
    • There was also a decline in H2RA prescriptions, with 17.0% of patients receiving H2RA in 2014 and 11.1% receiving H2RA in 2023 (P < .0001).
    • In their discussion, the authors note that: “in contrast to the current findings, prior studies typically have shown increasing PPI prescriptions, with some of these studies demonstrating declining H2RA prescriptions (9-17)…. However, it is notable that 3 more recent international studies did demonstrate declining PPI prescriptions specifically in the final years of the study (18-20).”
    • “Multiple studies have failed to demonstrate efficacy of acid suppression in infants with nonspecific gastroesophageal reflux symptoms, and there is no evidence that acid suppression affects feeding behaviors.(21-23)”
    • “In addition, there has been growing concern about PPI side effects, which include increased infections, decreased bone density, and increased allergy development
      including eosinophilic esophagitis, with numerous recent studies on these risks.(24-26)”

    My take: I’ve been a big fan of the aerodigestive research from the pediatric GI group in Boston. This is another useful study showing less use of acid suppression, especially PPIs in young children and infants. This likely indicates better alignment of clinical practice with consensus recommendations that advise against acid suppression as first-line management in this population.

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    Medications and the Risk of Microscopic Colitis

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    H Khalili et al. Annals of Internal Medicine 2025; https://doi.org/10.7326/ANNALS-25-0026. Medications and Risk for Microscopic Colitis: A Nationwide Study of Older Adults in Sweden

    Methods: The authors used Total Population Register, which includes information on the age and sex of all residents in Sweden. Then the cohort of older adults in Sweden was linked to the ESPRESSO study), which contains data on GI-related biopsies from all 28 pathology departments in Sweden from January 1965 until April 2017.

    Key findings:

    • Estimated 12-month risk differences were close to null under angiotensin-converting enzyme versus calcium-channel blocker (CCB) initiation, angiotensin-receptor blocker versus CCB initiation, nonsteroidal anti-inflammatory drug initiation versus noninitiation, proton-pump inhibitor initiation versus noninitiation, and statin initiation versus noninitiation. 
    • There was a slight increase risk of microscopic colitis in patients receiving SSRIs compared to mirtazapine. The estimated 12-month risk difference was 0.04% (95% CI, 0.03% to 0.05%) for selective serotonin receptor inhibitors (SSRIs) versus mirtazapine.
    • Several medications were also associated with increased risk for receiving a colonoscopy with a normal colorectal mucosa biopsy result.

    My take: Microscopic colitis is a very infrequent problem in the pediatric population. With the exception of SSRIs, this study in older adults did not find a significant relationship between purported “trigger” medications and the development of microscopic colitis. In addition, the low persistent associations with SSRI initiation may be due to surveillance bias.

    Impact of Mediterranean Diet on Constipation

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    Y Wang et al. Gastroenterol 2025; (Epub). Dietary Patterns and Incident Chronic Constipation in Three Prospective Cohorts of Middle- and Older-aged Adults

    Methods: In three large cohorts, the Nurses’ Health Study (NHS), NHSII, and the Health Professional Follow-up Study (HPFS) (combined >95,000 participants), the authors identified chronic constipation based on repeatedly-measured self-reported constipation symptoms for ≥12 weeks in the past year.

    Key Findings:

    • The top quintiles of alternate Mediterranean diet (aMED) and plant-based dietary index (PDI) were associated with 16% (9-22%) and 20% (14-27%) reduced risk for constipation. Vegetable and nut intake, which are enriched in aMED and PDI, were associated with decreased constipation risks.
    • A Western diet in the top quintile was associated with a 22% (11-33%) increased risk for constipation

    My take: The results from this study are not surprising, but nice to see more data on the effects of diet on constipation. While this data focused on adults, it is clear that dietary patterns have a big role in the frequency of constipation in children too.

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    Will You Be Able to Find a Caregiver When You Need One?

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    PMG Santos et al. NEJM 2025; 393: 105-107. Who Will Care for America? Immigration Policy and the Coming Health Workforce Crisis

    This article outlines the role of undocumented immigrants in our health care system with a focus on home health aides. Given the increase in the numbers of Americans older than 65 yrs, 56 million in 2020 and projected to be 80 million in 2030, current immigration policies will worsen the severe health care worker shortages.

    An excerpt:

    Immigrants are a vital part of the U.S. health care system: at least one in five U.S. health care workers is foreign-born, including 29% of physicians, 17% of nurses, and 24% of direct care workers…Data suggest that most (if not all) foreign-born physicians and nurses are naturalized U.S. citizens or lawfully permanent residents. In contrast, of the 37% of foreign-born direct care workers who are noncitizens, nearly half may be undocumented.4 This divergence is at least partly attributable to policies that streamline pathways to legal permanent residency or citizenship for some but not all immigrants…

    As federal policies threaten to further destabilize the direct care workforce, nonimmigrants are unlikely to fill the resulting void. Direct care workers assist with household chores as well as bathing, dressing, and toileting — thereby enabling frail, older adults and those with disabilities to live safely at home….The physically demanding nature of direct care work, combined with low pay and high susceptibility to exploitation, makes these roles unattractive to U.S.-born and highly skilled foreign-born workers…

    This is not the first time that immigrants have helped fill critical health care roles that were unattractive to U.S.-born workers…the Exchange Visitor Program in 1948, allowing Filipino nurses to obtain temporary work visas. Later, the Immigration and Nationality Act of 1965 allowed Filipino nurses to stay in the United States permanently…

    Federal officials could effectuate immigration reform in a way that secures our borders while addressing labor shortages. Instead, current policies threaten to further shrink this essential workforce, maligning and driving out hard-working immigrants at the expense of an aging America…compromising care for older adults and the health care system at large…

    The recent deportation of immigrant health care workers is our canary in the coal mine: policymakers must act swiftly, or risk endangering the health of us all.

    My take: I doubt the consequences of mass deportation have been carefully considered amid the heated rhetoric. There is saying, often attributed to Otto von Bismarck: “Only a fool learns from his own mistakes. A wise man learns from the mistakes of others.” As such, it appears that we are destined to learn from mistakes rather than avoiding them.

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    Seven Sisters Hike: Seaford to Eastbourne, UK

    Esophageal and Gastric Outcomes of Bleach Ingestion in Children

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    P Quitadamo et al. J Pediatr Gastroenterol Nutr. 2025;81:11–17. The effects of liquid bleach ingestion on children’s esophageal and gastric mucosa

    Background:  It has been recently reported that household bleach ingestion cause no or low-grade esophagitis in adults.13

    Methods: This prospective observational study was carried out between January 2017 and December 2023. One hundred children with a mean age of 58.7 months were included and divide into three groups. Group 1, children who had ingested household chlorine-based bleach; Group 2, children who had ingested household peroxidase-based bleach; Group 3, children who had ingested artisanal or industrial bleaches.

    Key findings:

    • Eighty-nine/100 (89%) children had ingested household bleaches (both chlorine- or peroxidase-based) while 11/100 (11%) had ingested homemade or industrial bleaches
    • 73/100 (73%) patients were symptomatic. The most commonly reported symptoms were vomiting and drooling
    • 13/100 (13%) were intentional with self-injurious or suicidal purposes
    • Among the 71 children who performed EGD, no children reported severe esophageal lesions
    • Zargar’s score 2a in 2/71 (2.8%). Both patients who reported moderate esophageal mucosal lesions (Zargar’s grade 2a) had ingested a homemade NaOCl-based (sodium hypochlorite) bleach with unknown dilution
    • Gastric injury was reported in 6/71 (8.5%) patients, including hemorrhagic gastritis in one child. Among these children, five had ingested an artisanal or industrial bleach, and two had ingested a peroxidase-based bleach

    My take (borrowed from authors): “Endoscopy is generally unnecessary in case of household bleach ingestion …[but] should be performed in children who ingest homemade or industrial bleaches.” Children having ingested commercially available household bleaches did not report significant mucosal lesions. The authors also advocated endoscopy in those with large volume ingestions (>100 mL) if symptomatic.

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    Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition

    Health Disinformation Risks from AI Chatbots

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    MD Modi et al. Annals of Internal Medicine; 2025. https://doi.org/10.7326/ANNALS-24-0393. Abstract: Assessing the System-Instruction Vulnerabilities of Large Language Models to Malicious Conversion Into Health Disinformation Chatbots

    Methods: This study assessed the effectiveness of safeguards in foundational LLMs against malicious instruction into health disinformation chatbots. Five foundational LLMs—OpenAI’s GPT-4o, Google’s Gemini 1.5 Pro, Anthropic’s Claude 3.5 Sonnet, Meta’s Llama 3.2-90B Vision, and xAI’s Grok Beta—were evaluated via their application programming interfaces (APIs). Each API received system-level instructions to produce incorrect responses to health queries, delivered in a formal, authoritative, convincing, and scientific tone.

    Key findings:

    • Of the 100 health queries posed across the 5 customized LLM API chatbots, 88 (88%) responses were health disinformation

    Examples of how AI systems can be used to create disinformation:

    My take: This study shows how easy it is to get AI systems to provide misleading information in a convincing fashion. It might be interesting to include one of these systems to provide answers for the board game Balderdash.

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    Unpacking Health Care Corporatization in the U.S.

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    ECF Brown. NEJM 2025; 393; 1-3. Defining Health Care “Corporatization”

    This blog has had many posts detailing the many flaws in the U.S. health care system. While the U.S. expends more per capita than any other country, our life expectancy is 4 years less than similar countries in Europe and Canada.

    This article in the NEJM is the first of a series examining the ‘corporatization’ of health care and potential ways to improve health care delivery.

    Excerpts:

    The percentage of hospitals owned by companies controlling three or more hospitals increased from 11.6% in the 1980s to 56.1% today…and now nine megahospital chains own more than 50 hospitals each.

    In the early 1980s, three quarters of U.S. physicians owned their practice, whereas in 2023 a similar proportion of physicians was employed by hospitals or corporate entities, including private equity funds.

    Insurance conglomerates, such as UnitedHealthcare and CVS–Aetna, now control physicians, home care, pharmacies, and pharmacy benefit managers (PBMs). Horizontal hospital consolidation has been pursued for the promise of economies of scale and market power…

    The term “corporatization” now refers to the general trend throughout the health care industry toward higher levels of integrated control by consolidated profit-seeking enterprises… First is the elevation of profit generation as the primary goal of the health care enterprise…the primary duty of the corporation is to maximize shareholder profits. Shareholder primacy subordinates the interests of other stakeholders, such as patients, the health care workforce, or the community…

    Even nonprofit hospitals can become corporatized as they grow in size and organizational scale…powerful nonprofit health systems may come to prioritize revenue over patient and community welfare, evidenced by inflated prices, insurance network exclusions, medical debt–collection actions against patients, facility closures in low-income areas, and cuts to staffing levels and pay.

    The second key element of corporatization is consolidation… Conglomerates’ market dominance, diversification across platforms, and change in locus of control insulate them from reputational or market discipline…

    Corporatization has produced a system that is incredibly profitable for investors but increasingly unaffordable, inaccessible, and uncaring for everyone else — in other words, it has created a Gilded Age of medicine.5 …Corporate control over medical practices and the drive for profit have undermined many clinicians’ professionalism, autonomy, trust, and morale…

    Traditional health policy interventions such as antitrust enforcement, tax subsidies and exemptions, prohibitions on the corporate practice of medicine, and payment reforms have not stopped the rise of the corporation in health care, owing to lax enforcement, political capture, and sophisticated regulatory workarounds…

    Confronting corporatization may require a fundamental reorientation of the industrial organization of the health system… Future health policy efforts must confront the fundamental question of whom our health care system is meant to serve: corporate giants or the members of our society as a whole.

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    Navigating FDA-Approved International Infant Formulas

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    A Porto et al. J Pediatr Gastroenterol Nutr. 2025;81:5–10. New international infant formulas in the United States: Understanding the Food and Drug Administration-enforcement discretion

    Background: In February 2022, the United States experienced a significant infant formula shortage, due to a major product recall by the country’s largest infant formula manufacturer, compounded by global supply chain issues and import restrictions.1, 2 In response, the Food and Drug Administration (FDA) launched Operation Fly Formula in mid-2022, which allowed international infant formula manufacturers to market, import and distribute their formulas in the United States…Currently, a total of five companies, who produce 14 international formulas, have opted to work with the FDA in transitioning to the US market.5 Many of these international formulas are significantly cheaper than the domestic alternatives, which have contributed to their rising popularity.

    Key points:

    • 8 of 14 formulas are stage formulas with Stage 1 for 0-6 months, and Stage 2 for >6 months. “Stage 1 formulas tend to contain less iron, which may provide an insufficient amount of iron for infants >6 months.11 Also, infants <6 months should not consume Stage 2 formula since it does not contain carnitine, believed to be an essential nutrient in this age group.12“
    • Of the 14 formulas, all the labels were in English and contained all the FDA nutrient requirement
    • “Two of the imported formulas [Aptamil brands] contained less than 1 mg/100 calories of formula of iron, the minimum amount to be considered iron fortified by the FDA, and did include a label which highlighted that additional iron may be necessary”
    • “All the foreign formulas contained prebiotics… The FDA, however, reports that probiotics can be dangerous for preterm infants and put them at risk for potentially fatal infection caused by the bacteria or yeast contained in the probiotic.6 Therefore, pediatricians should be aware that international formulas should not be used for preterm infants.”
    • MIXING INSTRUCTIONS: “Eleven out of the fourteen international formulas use a different scoop to water ratio from what is typically standard of American formulas…coops from international formulas may also be a different size compared to their US counterparts. Given the variation in different mixing ratios and scoop sizes, there is a risk of formula being mixed incorrectly”
    • “Consider that the family may be purchasing from a 3rd party vendor and ask for the specific website that they are purchasing from. Formulas should not be purchased at 3rd party vendor websites due to them being unregulated, and safety concerns with improper shipping or storage”
    • “If the label is not in English, it is highly likely that the formula has been purchased through a 3rd party vendor. Recommend counseling on safety concerns as listed above. Many of the foreign infant formulas use different mixing ratios so it is important that parents read the label to confirm mixing ratios”

    My take: The availability of FDA-approved international formulas has been helpful especially with recent shortages. This article makes several important points to assure their proper use, especially regarding mixing instructions and using Stage formulas for appropriate age.

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