Comparison of different treatment approaches of pediatric chronic non-bacterial osteomyelitis
Chronic non-bacterial osteomyelitis (CNO) is a chronic inflammatory bone disease which usually manifests in children and adolescents. There are a few data about pathogenesis and treatment. The aim of the study to compare the efficacy of different treatment approaches in pediatric CNO cohort patient. Fifty two children (25 boys and 27 girls) with CNO with average age at the onset of the disease 8.4 years (5.4; 11.0), number of foci − 3.0 (2.0; 6.0, incl. multifocal cases in 80.8%). Non-steroid anti-inflammatory drugs (NSAID) was the first-line treatment for non-vertebral cases, as well as pamidronate (PAM) for vertebral involvement. Second-line treatment includes sulfasalazine (SSZ), methotrexate (MTX), PAM and tumor necrosis factor-α inhibitors (TNFα-inh). We evaluated the dynamics of pain, patient’s and physician’s (MDVAS) assessment with visual-analog scale (VAS) and ability to each medication to achieve remission of CNO activity. According to the NSAID, MTX, SSZ, PAM and TNFα-inh groups the following data were registered: patient’s VAS: − 14.2% (p = 0.05), − 50.0% (p = 0.04), − 23.1 (p = 0.89), − 83.3% (p = 0.0001), − 73.6% (p = 0.0007); painVAS: − 21.9% (p = 0.01), − 18.6% (p = 0.13), + 36.4 (p = 0.89), − 79.7% (p = 0.00016), − 74.1%, (p = 0.0015); MDVAS: − 13.8% (p = 0.13); − 56.4% (p = 0.09), + 30.8% (p = 0.89), − 74.7%, (p = 0.0001), − 82.1 (p = 0.0015) respectively. The ability of each treatment strategy to achieve the CNO remission was 52.6%, 44.4%, 57,1%, 88.8% and 73.3%, respectively (log-rank test, p = 0.001). The efficacy of treatment approaches for CNO depended on the severity of the disease. NSAID, methotrexate, and sulfasalazine were effective in forms without spine involvement, but pamidronate and TNF-a inhibitors were useful in vertebral forms of CNO. Pamidronate and TNF-a inhibitors more extensively suppressed CNO activity. The randomized controlled trials for assessment of the efficacy and safety of these medications is mandatory to confirm these results.
KeywordsChronic non-bacterial osteomyelitis Pamidronate TNFα-inhibitors
All authors were involved in drafting the article or revising it critically. All authors approved the final version to be submitted for publication. Dr. Kostik, Dr. Kopchak, and Dr. Mushkin had full access to all of the data in the study and took responsibility for the integrity of the data and the accuracy of the data analysis. Study conception and design: Kostik, Kopchak, Mushkin. Acquisition of data: Kostik, Kopchak, Chikova, Isupova. Analysis and interpretation of data: Kostik, Kopchak, Mushkin.
This work supported by the Russian Foundation for Basic Research (Grant No. 18-515-57001).
Compliance with ethical standards
Informed consent obtained from all parents/guardians of minors participating in the study according to the declaration of Helsinki.
The study was approved by the local Ethics Committee of St.-Petersburg State Pediatric University (protocol number 10/8 from 23.10.2017).
Conflict of interest
The authors declare that they have no conflict of interests.
- 2.Wipff J, Costantino F, Lemelle I, Pajot C, Duquesne A, Lorrot M, Faye A, Bader-Meunier B, Brochard K, Despert V, Jean S, Grall-Lerosey M, Marot Y, Nouar D, Pagnier A, Quartier P, Job-Deslandre C (2015) A large national cohort of French patients with chronic recurrent multifocal osteitis. Arthritis Rheumatol 67:1128–1137CrossRefGoogle Scholar
- 7.Hofmann SR, Schwarz T, Möller JC, Morbach H, Schnabel A, Rösen-Wolff A, Girschick HJ, Hedrich CM (2011) Chronic non-bacterial osteomyelitis is associated with impaired Sp1 signaling, reduced IL10 promoter phosphorylation and reduced myeloid IL-10 expression. Clin Immunol 141:317–327CrossRefGoogle Scholar
- 13.Sato H, Wada Y, Hasegawa E, Nozawa Y, Nakatsue T, Ito T, Kuroda T, Saeki T, Umezu H, Suzuki Y, Nakano M, Narita I (2017) Adult-onset chronic recurrent multifocal osteomyelitis with high intensity of muscles detected by magnetic resonance imaging, successfully controlled with tocilizumab. Intern Med 56:2353–2360CrossRefGoogle Scholar
- 17.Girschick H, Finetti M, Orlando F, Schalm S, Insalaco A, Ganser G, Nielsen S, Herlin T, Koné-Paut I, Martino S, Cattalini M, Anton J, Mohammed Al-Mayouf S, Hofer M, Quartier P, Boros C, Kuemmerle-Deschner J, Pires Marafon D, Alessio M, Schwarz T, Ruperto N, Martini A, Jansson A, Gattorno M (2018) The multifaceted presentation of chronic recurrent multifocal osteomyelitis: a series of 486 cases from the Eurofever international registry. Paediatric Rheumatology International Trials Organisation (PRINTO) and the Eurofever registry. Rheumatology 57(8):1504. https://doi.org/10.1093/rheumatology/key143 CrossRefGoogle Scholar
- 26.Santra G, Sarkar RN, Phaujdar S, Banerjee S, Siddhanta S (2010) Assessment of the efficacy of pamidronate in ankylosing spondylitis: an open prospective trial. Singap Med J 51:883–887Google Scholar
- 27.Miettunen P, Wei X, Kaura D, Reslan WA, Aguirre AN, Kellner JD (2009) Dramatic pain relief and resolution of bone inflammation following pamidronate in 9 pediatric patients with persistent chronic recurrent multifocal osteomyelitis (CRMO). Pediatr Rheumatol 7:2. https://doi.org/10.1186/1546-0096-7-2 CrossRefGoogle Scholar
- 28.Hofmann C, Wurm M, Schwarz T, Neubauer H, Beer M, Girschick H, Morbach H (2014) A standardized clinical and radiological follow-up of patients with chronic non-bacterial osteomyelitis treated with pamidronate. Clin Exp Rheumatol 32(4):604–609Google Scholar
- 29.Zhao Y, Wu EY, Oliver MS, Cooper AM, Basiaga ML, Vora SS, Lee TC, Fox E, Amarilyo G, Stern SM, Dvergsten JA, Haines KA, Rouster-Stevens KA, Onel KB, Cherian J, Hausmann JS, Miettunen P, Cellucci T, Nuruzzaman F, Taneja A, Barron KS, Hollander MC, Lapidus SK, Li SC, Ozen S, Girschick H, Laxer RM, Dedeoglu F, Hedrich CM, Ferguson PJ, Chronic Nonbacterial Osteomyelitis/Chronic Recurrent Multifocal Osteomyelitis Study Group and the Childhood Arthritis and Rheumatology Research Alliance Scleroderma, Vasculitis, Autoinflammatory and Rare Diseases Subcommittee (2017) Consensus treatment plans for chronic nonbacterial osteomyelitis refractory to nonsteroidal antiinflammatory drugs and/or with active spinal lesions. Arthritis Care Res (Hoboken). https://doi.org/10.1002/acr.23462 Google Scholar
- 33.Graepel P, Bentley P, Fritz H, Miyamoto M, Slater SR (1992) Reproduction toxicity studies with pamidronate. Arzneimittelforschung 42:654–667Google Scholar