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Pediatric Rheumatology
Published in: Pediatric Rheumatology 1/2017

Open Access 01-12-2017 | Research article

Bone metabolism and inflammatory characteristics in 14 cases of chronic nonbacterial osteomyelitis

Authors: Yurika Ata, Yutaka Inaba, Hyonmin Choe, Naomi Kobayashi, Jiro Machida, Naoyuki Nakamura, Tomoyuki Saito

Published in: Pediatric Rheumatology | Issue 1/2017

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Abstract

Background

Chronic nonbacterial osteomyelitis (CNO) is a multifocal autoinflammatory disease that often impairs daily life in children. This study aimed to investigate the bone metabolic and inflammatory characteristics of patients with CNO, and to assess the differences between responders and nonresponders to conservative treatment.

Methods

We investigated the clinical symptoms; laboratory data including inflammatory and bone metabolic biomarkers; and imaging findings from plain radiography, magnetic resonance imaging (MRI), fluorodeoxyglucose-positron emission tomography (FDG-PET), and dual-energy x-ray absorption (DEXA) in 14 patients with CNO. All patients underwent first-line treatment comprising systemic nonsteroidal anti-inflammatory drugs with or without bisphosphonate. According to the response to the first-line treatment, the patients were divided into the clinical remission/partial response group and the no response group. The differences in bone metabolic and inflammatory characteristics between the two groups were assessed.

Results

All patients had low bone mineral density assessed with DEXA. The bone metabolic biomarkers (bone-specific alkaline phosphatase and tartrate-resistant acid phosphatase 5b) were increased in boys of all ages and in young girls. Multiple inflammatory regions were detected in all patients by using FDG-PET including asymptomatic regions. The no response group had higher immunoglobulin G (IgG) and a greater number of bone inflammatory lesions detected on MRI than the clinical remission/partial response group.

Conclusion

Our data indicate the involvement of abnormal bone turnover, necessity of whole-body scanning, and association of higher serum IgG levels and greater numbers of inflammatory lesions with prolonged disease activity in patients with CNO.
Literature
1.
Voit AM, Arnoldi AP, Douis H, Bleisteiner F, Jansson MK, Reiser MF, Weckbach S, Jansson AF. Whole-body magnetic resonance imaging in chronic recurrent multifocal Osteomyelitis: clinical Longterm assessment may underestimate activity. Br J Rheumatol. 2015;42(8):1455–62.CrossRef
2.
von Kalle T, Heim N, Hospach T, Langendorfer M, Winkler P, Stuber T. Typical patterns of bone involvement in whole-body MRI of patients with chronic recurrent multifocal osteomyelitis (CRMO). RoFo. 2013;185(7):655–61.CrossRef
3.
El-Shanti HI, Ferguson PJ. Chronic recurrent multifocal osteomyelitis: a concise review and genetic update. Clin Orthop Relat Res. 2007;462:11–9.CrossRefPubMed
4.
Jansson A, Renner ED, Ramser J, Mayer A, Haban M, Meindl A, Grote V, Diebold J, Jansson V, Schneider K, et al. Classification of non-bacterial osteitis: retrospective study of clinical, immunological and genetic aspects in 89 patients. Rheumatology (Oxford, England). 2007;46(1):154–60.CrossRef
5.
Giedion A, Holthusen W, Masel LF, Vischer D. Subacute and chronic "symmetrical" osteomyelitis. Ann Radiol. 1972;15(3):329–42.PubMed
6.
Hedrich CM, Hahn G, Girschick HJ, Morbach H. A clinical and pathomechanistic profile of chronic nonbacterial osteomyelitis/chronic recurrent multifocal osteomyelitis and challenges facing the field. Expert Rev Clin Immunol. 2013;9(9):845–54.CrossRefPubMed
7.
Stern SM, Ferguson PJ. Autoinflammatory bone diseases. Rheum Dis Clin N Am. 2013;39(4):735–49.CrossRef
8.
Ferguson PJ, Laxer RM. New discoveries in CRMO: IL-1beta, the neutrophil, and the microbiome implicated in disease pathogenesis in Pstpip2-deficient mice. Semin Immunol. 2015;37(4):407–12.CrossRef
9.
Hedrich CM, Hofmann SR, Pablik J, Morbach H, Girschick HJ. Autoinflammatory bone disorders with special focus on chronic recurrent multifocal osteomyelitis (CRMO). Pediatr Rheumatol Online J. 2013;11(1):47.CrossRefPubMedPubMedCentral
10.
Falip C, Alison M, Boutry N, Job-Deslandre C, Cotten A, Azoulay R, Adamsbaum C. Chronic recurrent multifocal osteomyelitis (CRMO): a longitudinal case series review. Pediatr Radiol. 2013;43(3):355–75.CrossRefPubMed
11.
Beck C, Morbach H, Beer M, Stenzel M, Tappe D, Gattenlohner S, Hofmann U, Raab P, Girschick HJ. Chronic nonbacterial osteomyelitis in childhood: prospective follow-up during the first year of anti-inflammatory treatment. Arthritis Res Ther. 2010;12(2):R74.CrossRefPubMedPubMedCentral
12.
Salles M, Olive A, Perez-Andres R, Holgado S, Mateo L, Riera E, Tena X. The SAPHO syndrome: a clinical and imaging study. Clin Rheumatol. 2011;30(2):245–9.CrossRefPubMed
13.
Leclair N, Thormer G, Sorge I, Ritter L, Schuster V, Hirsch FW. Whole-body diffusion-weighted imaging in chronic recurrent multifocal Osteomyelitis in children. PLoS One. 2016;11(1):e0147523.CrossRefPubMedPubMedCentral
14.
Mandell GA, Contreras SJ, Conard K, Harcke HT, Maas KW. Bone scintigraphy in the detection of chronic recurrent multifocal osteomyelitis. J Nucl Med. 1998;39(10):1778–83.PubMed
15.
Girschick HJ, Raab P, Surbaum S, Trusen A, Kirschner S, Schneider P, Papadopoulos T, Muller-Hermelink HK, Lipsky PE. Chronic non-bacterial osteomyelitis in children. Ann Rheum Dis. 2005;64(2):279–85.CrossRefPubMedPubMedCentral
16.
Chong A, Ha JM, Hong R, Kwon SY. Variations in findings on (18) F-FDG PET/CT, Tc-99m HDP bone scan and WBC scan in chronic multifocal osteomyelitis. Int J Rheum Dis. 2014;17(3):344–5.CrossRefPubMed
17.
Miettunen PM, Wei X, Kaura D, Reslan WA, Aguirre AN, Kellner JD. Dramatic pain relief and resolution of bone inflammation following pamidronate in 9 pediatric patients with persistent chronic recurrent multifocal osteomyelitis (CRMO). Pediatr rheumatol Online J. 2009;7:2.CrossRefPubMedPubMedCentral
18.
Roderick M, Shah R, Finn A, Ramanan AV. Efficacy of pamidronate therapy in children with chronic non-bacterial osteitis: disease activity assessment by whole body magnetic resonance imaging. Rheumatology (Oxford, England). 2014;53(11):1973–6.CrossRef
19.
Huber AM, Lam PY, Duffy CM, Yeung RS, Ditchfield M, Laxer D, Cole WG, Kerr Graham H, Allen RC, Laxer RM. Chronic recurrent multifocal osteomyelitis: clinical outcomes after more than five years of follow-up. J Pediatr. 2002;141(2):198–203.CrossRefPubMed
20.
Borzutzky A, Stern S, Reiff A, Zurakowski D, Steinberg EA, Dedeoglu F, Sundel RP. Pediatric chronic nonbacterial osteomyelitis. Pediatrics. 2012;130(5):e1190–7.CrossRefPubMed
21.
Eleftheriou D, Gerschman T, Sebire N, Woo P, Pilkington CA, Brogan PA. Biologic therapy in refractory chronic non-bacterial osteomyelitis of childhood. Rheumatology (Oxford, England). 2010;49(8):1505–12.CrossRef
22.
Kaiser D, Bolt I, Hofer M, Relly C, Berthet G, Bolz D, Saurenmann T. Chronic nonbacterial osteomyelitis in children: a retrospective multicenter study. Pediatr Rheumatol Online J. 2015;13:25.CrossRefPubMedPubMedCentral
23.
Zhao Y, Chauvin NA, Jaramillo D, Burnham JM. Aggressive therapy reduces disease activity without skeletal damage progression in chronic nonbacterial Osteomyelitis. Br J Rheumatol. 2015;42(7):1245–51.CrossRef
24.
Wipff J, Costantino F, Lemelle I, Pajot C, Duquesne A, Lorrot M, Faye A, Bader-Meunier B, Brochard K, Despert V, et al. A large national cohort of French patients with chronic recurrent multifocal osteitis. Arthritis Rheumatol (Hoboken, NJ). 2015;67(4):1128–37.CrossRef
25.
Rauchenzauner M, Schmid A, Heinz-Erian P, Kapelari K, Falkensammer G, Griesmacher A, Finkenstedt G, Hogler W. Sex- and age-specific reference curves for serum markers of bone turnover in healthy children from 2 months to 18 years. J Clin Endocrinol Metab. 2007;92(2):443–9.CrossRefPubMed
26.
Hofmann SR, Roesen-Wolff A, Hahn G, Hedrich CM. Update: cytokine Dysregulation in chronic nonbacterial Osteomyelitis (CNO). Int J Rheum Dis. 2012;2012:310206.
27.
Ferrari J, Pilkington C. Chronic recurrent multifocal osteomyelitis: the prevalence of lower-limb and foot involvement. J Am Podiatr Med Assoc. 2014;104(6):583–7.CrossRefPubMed
28.
Johnsson A, Flato B, Knudsen PK, Lilleby V. Clinical outcome in a Norwegian cohort of patients with chronic recurrent multifocal osteomyelitis. Scand J Rheumatol. 2015;44(6):513–4.CrossRefPubMed
29.
Arnoldi AP, Schlett CL, Douis H, Geyer LL, Voit AM, Bleisteiner F, Jansson AF, Weckbach S. Whole-body MRI in patients with non-bacterial Osteitis: radiological findings and correlation with clinical data. Eur Radiol. 2017;27(6):2391–9.CrossRefPubMed
30.
Holden W, David J. Chronic recurrent multifocal osteomyelitis: two cases of sacral disease responsive to corticosteroids. Clin Infect Dis. 2005;40(4):616–9.CrossRefPubMed
31.
Wagner AD, Andresen J, Jendro MC, Hulsemann JL, Zeidler H. Sustained response to tumor necrosis factor alpha-blocking agents in two patients with SAPHO syndrome. Arthritis Rheum. 2002;46(7):1965–8.CrossRefPubMed
32.
Marangoni RG, Halpern AS. Chronic recurrent multifocal osteomyelitis primarily affecting the spine treated with anti-TNF therapy. Spine. 2010;35(7):E253–6.CrossRefPubMed
33.
Valls-Roc M, Sanmarti M, Salles M, Holgado S, Olive A. SAPHO syndrome and pamidronate revisited. Rheumatology (Oxford, England). 2005;44(1):137. author reply 137–138CrossRef
34.
Kerrison C, Davidson JE, Cleary AG, Beresford MW. Pamidronate in the treatment of childhood SAPHO syndrome. Rheumatology (Oxford, England). 2004;43(10):1246–51.CrossRef
35.
Amital H, Applbaum YH, Aamar S, Daniel N, Rubinow A. SAPHO syndrome treated with pamidronate: an open-label study of 10 patients. Rheumatology (Oxford, England). 2004;43(5):658–61.CrossRef
36.
Gleeson H, Wiltshire E, Briody J, Hall J, Chaitow J, Sillence D, Cowell C, Munns C. Childhood chronic recurrent multifocal osteomyelitis: pamidronate therapy decreases pain and improves vertebral shape. Br J Rheumatol. 2008;35(4):707–12.
37.
Bjorksten B, Boquist L. Histopathological aspects of chronic recurrent multifocal osteomyelitis. J Bone Joint Surg. 1980;62(3):376–80.CrossRef
38.
Corrado A, Santoro N, Cantatore FP. Extra-skeletal effects of bisphosphonates. Joint, Bone, Spine. 2007;74(1):32–8.CrossRefPubMed
39.
Hofmann SR, Kubasch AS, Range U, Laass MW, Morbach H, Girschick HJ, Hedrich CM. Serum biomarkers for the diagnosis and monitoring of chronic recurrent multifocal osteomyelitis (CRMO). Rheumatol Int. 2016;36(6):769–79.CrossRefPubMed
Metadata
Title
Bone metabolism and inflammatory characteristics in 14 cases of chronic nonbacterial osteomyelitis
Authors
Yurika Ata
Yutaka Inaba
Hyonmin Choe
Naomi Kobayashi
Jiro Machida
Naoyuki Nakamura
Tomoyuki Saito
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Pediatric Rheumatology / Issue 1/2017
Electronic ISSN: 1546-0096
DOI
https://doi.org/10.1186/s12969-017-0183-z

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