Clinical characteristics and outcomes of chronic nonbacterial osteomyelitis in children: a multicenter case series

Abstract

Objective The aim of this study was to evaluate demographic, clinical, laboratory, imaging, histopathology characteristics, and treatment responses of children with Chronic nonbacterial osteomyelitis (CNO). Methods Retrospective multi-center case series study of pediatric patients diagnosed with CNO treated at five tertiary centers in south China. Results Totally there were 18 patients diagnosed as CNO between 2014 and 2020. The median age of onset was 9.2 years (range 3.7–13.1) and 55.6% were female. Median delay in diagnosis was 10.9 months (range 1.0–72.0). The most frequent presenting symptoms were bone pain (100%) and fever (44.4%). Most patients had more than one lesion (median of 5, range 1–7). Most frequently affected bones were tibiofibula (88.9%) and femur (77.8%). The MRI characteristics mainly presented as bone edema and hyperintensity in bone marrow. Bone biopsy was conducted in 11 patients (61.1%) with inflammatory cells infiltration manifested as chronic osteomyelitis, and none showed bacterial infection or tumor. In treatment, non-steroid anti-inflamatory drugs (NSAIDs) is used as the first-line drug followed by steriods, methotexate (MTX), salazosulfadimidine (SASP), Bisphosphonates and TNF-α inhibitor. Two refractory cases received combination therapy with Bisphosphonates and TNF-α inhibitor, and achieved good therapeutic effect. Conclusions The present study described a multicenter series of CNO from south China and highlighted the clinical features, laboratory tests, imaging characteristics and treatment outcomes. Increasing awareness of this disease is important to decrease time to diagnosis, improve access to treatment, and reduce complications.

A Successful Bisphosphonates Monotherapy in Spinal Form of Paediatric Chronic Recurrent Multifocal Osteomyelitis (CRMO)—Case Report

“…In cases of more severe CRMO, instead of first-line medicaments, NSAIDs or, in combination with them, a wide range of second-line treatment options is available, including disease-modifying anti-rheumatic drugs (DMARDs), glucocorticoids and bisphosphonates [ 25 , 26 ]. Pamidronate, classified as a nitrogen-containing bisphosphonate, inhibits farnesyl diphosphate synthase in osteoclasts by mimicking its substrate.…”

“…Early reports suggest that the bisphosphonates offer promising efficacy in controlling CRMO, as well as safety of use [ 16 , 28 ], though results of recent studies indicated a burden of adverse events (AEs) in pamidronate therapy. In some patients, bisphosphonates were found to worsen bone pain [ 25 ], as well as lead to nausea, headache, fever and phlebitis [ 29 ], which ultimately decrease patients’ compliance [ 30 ]. The presented patient’s therapy was well tolerated and led to no significant AEs.…”

“…As for therapeutic safety, its efficacy was also ambiguously discussed in recent studies. Some reports state that more than 2/3 patients treated with bisphosphonates achieved remission of CRMO symptoms and the progression of their disorder was inhibited, both in spinal and peripheral lesions [ 25 , 26 , 29 , 30 , 31 , 32 , 33 , 34 ]. It was also suggested that pamidronate leads to a rapid improvement in patient’s condition [ 26 ], which is in accordance with the observations of this study—within 1.5 years the reported patient returned to regular height range (50.-75. centile) from the threshold of 10. centile.…”

Case report: Child chronic nonbacterial osteomyelitis with rapid progressive scoliosis-an association with disease?

“…Early reports of spinal involvement in CNO/CRMO were considered rare in the literature, but in the last 20 years there has been a gradual increase with an incidence of approximately 10%-38% (3,(10)(11)(12)(13). We reviewed the vertebral involvement of CNO/ CRMO patients in the literature since 2000 (Table 1).…”

Update on treatment responses and outcome measure development in chronic nonbacterial osteomyelitis

“…The data shown for bisphosphonates in Table 1[37 ▪▪ ,38 ▪ ,39,40,41 ▪ ,42 ▪ ,43 ▪ ,44,45,46,47 ▪▪ ] and TNFi in Table 2[37 ▪▪ ,38 ▪ ,39,40,41 ▪ ,42 ▪ ,43 ▪ ,44,45,47 ▪▪ ,48 ▪ ] demonstrates the difficulty of comparing retrospective outcome studies. The dosing regimens were different, and some studies used clinical outcomes measures while others reported imaging outcomes.…”