Login Register Cart 0
Generic placeholder image

Current Pediatric Reviews

Editor-in-Chief

ISSN (Print): 1573-3963
ISSN (Online): 1875-6336

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Review Article

Chronic Non-bacterial Osteomyelitis (CNO) In Childhood: A Review

Author(s): Fiona Price-Kuehne and Kate Armon*

Volume 20, Issue 4, 2024

Published on: 27 December, 2022

Page: [405 - 411] Pages: 7

DOI: 10.2174/1573396319666221027123723

Price: $65

Abstract

Chronic non-bacterial osteomyelitis (CNO) is an autoinflammatory bone disorder mostly affecting children and adolescents. Although it is considered a rare disease, CNO is likely to be the single most common autoinflammatory bone disease in childhood, underdiagnosed and underreported due to a lack of awareness of the condition in both medics and patients and the absence of validated diagnostic criteria. The exact underlying pathogenesis of CNO remains unknown, making targeted treatment difficult. This issue is exacerbated by the lack of any randomised control trials, meaning that treatment strategies are based solely on retrospective reviews and case series.

This review summarises the current concepts in pathophysiology, the clinical features that help differentiate important differential diagnoses, and an approach to investigating and managing children with CNO. Ultimately, the timely and thorough investigation of children and young people with CNO is vitally important to exclude important mimics and initiate appropriate management that can prevent the complications of persistent inflammatory bone disease.

« Previous Next »
Graphical Abstract

[1]
Schnabel A, Range U, Hahn G, Berner R, Hedrich CM. Treatment response and longterm outcomes in children with chronic nonbacterial osteomyelitis. J Rheumatol 2017; 44(7): 1058-65.
[http://dx.doi.org/10.3899/jrheum.161255] [PMID: 28461645]
[2]
Ben-Chetrit E, Gattorno M, Gul A, et al. Consensus proposal for taxonomy and definition of the autoinflammatory diseases (AIDs): a Delphi study. Ann Rheum Dis 2018; 77(11): 1558-65.
[http://dx.doi.org/10.1136/annrheumdis-2017-212515] [PMID: 30100561]
[3]
McGonagle D, McDermott MF. A proposed classification of the immunological diseases. PLoS Med 2006; 3(8): e297.
[http://dx.doi.org/10.1371/journal.pmed.0030297] [PMID: 16942393]
[4]
Roderick MR, Shah R, Rogers V, Finn A, Ramanan AV. Chronic recurrent multifocal osteomyelitis (CRMO) – advancing the diagnosis. Pediatr Rheumatol Online J 2016; 14(1): 47.
[http://dx.doi.org/10.1186/s12969-016-0109-1] [PMID: 27576444]
[5]
Girshick H. Chronic nonbacterial osteomyelitis/Chronic recurrent multifocal osteomyelitis. In: Orphanet Encyclopedia. 2013.
[6]
Hofmann SR, Kapplusch F, Girschick HJ, et al. Chronic Recurrent Multifocal Osteomyelitis (CRMO): Presentation, Pathogenesis, and Treatment. Curr Osteoporos Rep 2017; 15(6): 542-54.
[http://dx.doi.org/10.1007/s11914-017-0405-9] [PMID: 29080202]
[7]
Suo C, Chia D, Toms A, Sanghrajka A, et al. OA33 Incidence of chronic recurrent multifocal osteomyelitis in the UK and Republic of Ireland: initial results from 13 months of surveillance study. Rheumatol Adv Pract 2022; 6
[http://dx.doi.org/10.1093/rap/rkac066.033]
[8]
Jansson AF, Grote V. Nonbacterial osteitis in children: data of a German Incidence Surveillance Study. Acta Paediatr 2011; 100(8): 1150-7.
[http://dx.doi.org/10.1111/j.1651-2227.2011.02205.x] [PMID: 21352353]
[9]
Zhao M, Wu D, Yu K, Shen M. Clinical and genetic features of chinese adult patients with chronic non-bacterial osteomyelitis: a single center report. Front Immunol 2022; 13: 860646.
[http://dx.doi.org/10.3389/fimmu.2022.860646] [PMID: 35422809]
[10]
Hofmann SR, Schnabel A, Rösen-Wolff A, Morbach H, Girschick HJ, Hedrich CM. Chronic nonbacterial osteomyelitis: Pathophysiological concepts and current treatment strategies. J Rheumatol 2016; 43(11): 1956-64.
[http://dx.doi.org/10.3899/jrheum.160256] [PMID: 27585682]
[11]
Broz P, Dixit VM. Inflammasomes: Mechanism of assembly, regulation and signalling. Nat Rev Immunol 2016; 16(7): 407-20.
[http://dx.doi.org/10.1038/nri.2016.58] [PMID: 27291964]
[12]
Brandt D, Sohr E, Pablik J, et al. CD14+ monocytes contribute to inflammation in chronic nonbacterial osteomyelitis (CNO) through in-creased NLRP3 inflammasome expression. Clin Immunol 2018; 196: 77-84.
[http://dx.doi.org/10.1016/j.clim.2018.04.011] [PMID: 29723617]
[13]
Kelley N, Jeltema D, Duan Y, He Y. The NLRP3 inflammasome: An overview of mechanisms of activation and regulation. Int J Mol Sci 2019; 20(13): 3328.
[http://dx.doi.org/10.3390/ijms20133328] [PMID: 31284572]
[14]
Hofmann SR, Kubasch AS, Ioannidis C, et al. Altered expression of IL-10 family cytokines in monocytes from CRMO patients result in enhanced IL-1β expression and release. Clin Immunol 2015; 161(2): 300-7.
[http://dx.doi.org/10.1016/j.clim.2015.09.013] [PMID: 26404542]
[15]
Hentunen TA, Choi SJ, Boyce BF, et al. A murine model of inflammatory bone disease. Bone 2000; 26(2): 183-8.
[http://dx.doi.org/10.1016/S8756-3282(99)00247-1] [PMID: 10678414]
[16]
Chitu V, Ferguson PJ, de Bruijn R, et al. Primed innate immunity leads to autoinflammatory disease in PSTPIP2-deficient cmo mice. Blood 2009; 114(12): 2497-505.
[http://dx.doi.org/10.1182/blood-2009-02-204925] [PMID: 19608749]
[17]
Chitu V, Nacu V, Charles JF, et al. PSTPIP2 deficiency in mice causes osteopenia and increased differentiation of multipotent myeloid precursors into osteoclasts. Blood 2012; 120(15): 3126-35.
[http://dx.doi.org/10.1182/blood-2012-04-425595] [PMID: 22923495]
[18]
Abe K, Fuchs H, Lisse T, Hans W, de Angelis MH. New ENU-induced semidominant mutation, Ali18, causes inflammatory arthritis, der-matitis, and osteoporosis in the mouse. Mamm Genome 2006; 17(9): 915-26.
[http://dx.doi.org/10.1007/s00335-006-0014-x] [PMID: 16964445]
[19]
Abe K, Cox A, Takamatsu N, et al. Gain-of-function mutations in a member of the Src family kinases cause autoinflammatory bone dis-ease in mice and humans. Proc Natl Acad Sci USA 2019; 116(24): 11872-7.
[http://dx.doi.org/10.1073/pnas.1819825116] [PMID: 31138708]
[20]
Jansson A, Renner ED, Ramser J, et al. Classification of non-bacterial osteitis: Retrospective study of clinical, immunological and genetic aspects in 89 patients. Rheumatology (Oxford) 2007; 46(1): 154-60.
[http://dx.doi.org/10.1093/rheumatology/kel190] [PMID: 16782988]
[21]
Lukens JR, Gurung P, Vogel P, et al. Dietary modulation of the microbiome affects autoinflammatory disease. Nature 2014; 516(7530): 246-9.
[http://dx.doi.org/10.1038/nature13788] [PMID: 25274309]
[22]
Kaut S, van den Wyngaert I, Christiaens D, Wouters C, Noppe N, Herregods N, et al. Chronic nonbacterial osteomyelitis in children: a multicentre Belgian cohort of 30 children. Pediatric Rheumatology 2022; 20(1)
[http://dx.doi.org/10.1186/s12969-022-00698-3]
[23]
O’Leary D, Killeen O, Wilson A. Chronic nonbacterial osteomyelitis is associated with HLA-B*27. Arthritis Rheumatol 2020; 72(10): 0083.
[24]
Taddio A, Ferrara G, Insalaco A, et al. Dealing with Chronic Non-Bacterial Osteomyelitis: a practical approach. Pediatr Rheumatol Online J 2017; 15(1): 87.
[http://dx.doi.org/10.1186/s12969-017-0216-7] [PMID: 29287595]
[25]
Ferguson PJ, Chen S, Tayeh MK, et al. Homozygous mutations in LPIN2 are responsible for the syndrome of chronic recurrent multifocal osteomyelitis and congenital dyserythropoietic anaemia (Majeed syndrome). Journal of Medical Genetics 2005; 42(7): 551 LP-7.
[26]
Aksentijevich I, Masters SL, Ferguson PJ, et al. An autoinflammatory disease with deficiency of the interleukin-1-receptor antagonist. N Engl J Med 2009; 360(23): 2426-37.
[http://dx.doi.org/10.1056/NEJMoa0807865] [PMID: 19494218]
[27]
Wise CA, Gillum JD, Seidman CE, et al. Mutations in CD2BP1 disrupt binding to PTP PEST and are responsible for PAPA syndrome, an autoinflammatory disorder. Hum Mol Genet 2002; 11(8): 961-9.
[http://dx.doi.org/10.1093/hmg/11.8.961] [PMID: 11971877]
[28]
Yeon HB, Lindor NM, Seidman JG, Seidman CE. Pyogenic arthritis, pyoderma gangrenosum, and acne syndrome maps to chromosome 15q. Am J Hum Genet 2000; 66(4): 1443-8.
[http://dx.doi.org/10.1086/302866] [PMID: 10729114]
[29]
Russo RAG, Brogan PA. Monogenic autoinflammatory diseases. Rheumatology (Oxford) 2014; 53(11): 1927-39.
[http://dx.doi.org/10.1093/rheumatology/keu170] [PMID: 24831056]
[30]
Morice A, Joly A, Ricquebourg M, et al. Cherubism as a systemic skeletal disease: evidence from an aggressive case. BMC Musculoskelet Disord 2020; 21(1): 564.
[http://dx.doi.org/10.1186/s12891-020-03580-z] [PMID: 32825821]
[31]
Skrabl-Baumgartner A, Singer P, Greimel T, Gorkiewicz G, Hermann J. Chronic non-bacterial osteomyelitis: a comparative study between children and adults. Pediatr Rheumatol Online J 2019; 17(1): 49.
[http://dx.doi.org/10.1186/s12969-019-0353-2] [PMID: 31337412]
[32]
Whyte MP. Hypophosphatasia - aetiology, nosology, pathogenesis, diagnosis and treatment. Nat Rev Endocrinol 2016; 12(4): 233-46.
[http://dx.doi.org/10.1038/nrendo.2016.14] [PMID: 26893260]
[33]
Girschick HJ, Mornet E, Beer M, Warmuth-Metz M, Schneider P. Chronic multifocal non-bacterial osteomyelitis in hypophosphatasia mimicking malignancy. BMC Pediatr 2007; 7(1): 3.
[http://dx.doi.org/10.1186/1471-2431-7-3] [PMID: 17241478]
[34]
Giedion A, Holthusen W, Masel LF, Vischer D. Subacute and chronic “symmetrical” osteomyelitis. Ann Radiol (Paris) 1972; 15(3): 329-42.
[PMID: 4403064]
[35]
Zhao Y, Wu EY, Oliver MS, et al. Consensus treatment plans for chronic nonbacterial osteomyelitis refractory to nonsteroidal anti-inflammatory drugs and/or with active spinal lesions. Arthritis Care Res (Hoboken) 2018; 70(8): 1228-37.
[http://dx.doi.org/10.1002/acr.23462] [PMID: 29112802]
[36]
Andreasen CM, Jurik AG, Deleuran BW, et al. Pamidronate in chronic non-bacterial osteomyelitis: a randomized, double-blinded, place-bo-controlled pilot trial. Scand J Rheumatol 2020; 49(4): 312-22.
[http://dx.doi.org/10.1080/03009742.2020.1724324] [PMID: 32484386]
[37]
Bhat CS, Roderick M, Sen ES, Finn A, Ramanan AV. Efficacy of pamidronate in children with chronic non-bacterial osteitis using whole body MRI as a marker of disease activity. Pediatr Rheumatol Online J 2019; 17(1): 35.
[http://dx.doi.org/10.1186/s12969-019-0340-7] [PMID: 31272461]
[38]
Ramanan AV, Hampson LV, Lythgoe H, et al. Defining consensus opinion to develop randomised controlled trials in rare diseases using Bayesian design: An example of a proposed trial of adalimumab versus pamidronate for children with CNO/CRMO. PLoS One 2019; 14(6): e0215739.
[http://dx.doi.org/10.1371/journal.pone.0215739] [PMID: 31166977]
[39]
Ramautar AIE, Andela CD, Hamdy NAT, Winter EM, Appelman-Dijkstra NM. Determinants of Quality of Life in Adult Patients with Chronic Non-Bacterial Osteomyelitis (CNO) of the Sternocostoclavicular Region (SCCH): A Dutch Single Center Study. J Clin Med 2022; 11(7): 1852.
[http://dx.doi.org/10.3390/jcm11071852] [PMID: 35407460]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy