Efficacy of pamidronate in children with chronic non-bacterial osteitis using whole body MRI as a marker of disease activity

Abstract

Background To study the response to pamidronate using whole body magnetic resonance imaging (WB-MRI) in children with chronic non-bacterial osteitis (CNO) in a tertiary health centre. Methods The medical records of children under the age of sixteen with a diagnosis of chronic non-bacterial osteitis between 2005 and 2018 were reviewed. All those who were treated with pamidronate were included and relevant data was collected. Response to therapy was determined based on the status of lesions on WB- MRI. Results Forty six patients were included in the study. Pre- and post-treatment WB-MRI was available in forty patients. Cumulative lesions pre-treatment were 150 and reduced to 45 (30%) post-treatment. Seventeen patients (42.5%) had a good response with complete resolution of all lesions and nine patients (22.5%) worsened during or following treatment with pamidronate. Vertebral disease had a good response and 82.3% of the lesions resolved completely. Conclusion Our study describes the experience with pamidronate in a tertiary health centre using WB-MRI as a marker of disease activity. Pamidronate was well tolerated in our cohort and treatment response was fairly good. Significance and innovation 1. Bisphosphonates can be used in the treatment of CNO when response to NSAIDs is suboptimal. 2. In the presence of spinal or mandibular lesions bisphosphonates were used as first line. 3. Treatment was escalated to a TNF blocker when response to bisphosphonates was suboptimal.

Chronic Nonbacterial Osteomyelitis in Children

“…The incidence of CNO varies across geographic areas, and this is thought to be due to increased awareness of the disease in the regions with higher incidence, rather than ethnic or environmental factors [ 4 ]. The median age at diagnosis in pediatric patients is 10 years, with most cases reported between 8 and 13 years [ 4 , 5 , 6 , 7 , 8 ]. In European cohorts, females seem more likely to be affected, with a female-to-male ratio of 2:1 [ 5 , 6 , 7 , 8 , 9 , 10 ], while in Latin American and Indian series a male prevalence is reported [ 11 , 12 ].…”

“…The median age at diagnosis in pediatric patients is 10 years, with most cases reported between 8 and 13 years [ 4 , 5 , 6 , 7 , 8 ]. In European cohorts, females seem more likely to be affected, with a female-to-male ratio of 2:1 [ 5 , 6 , 7 , 8 , 9 , 10 ], while in Latin American and Indian series a male prevalence is reported [ 11 , 12 ]. Diagnostic delay is common in pediatric CNO, with a mean interval of 12 months between symptom onset and diagnosis in most pediatric studies [ 4 , 6 , 8 , 13 ], possibly related to the rareness of the disease, the discrete findings on examination, and the absence of pathognomonic laboratory studies.…”

“…The percentage of patients presenting with systemic inflammation at CNO onset varies significantly. In particular, the proportion of increased inflammatory markers reported, such as C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), ranges between 19 and 90% in different studies [ 4 , 6 , 7 , 8 , 9 , 10 , 14 , 15 , 17 , 19 , 20 , 21 , 22 , 23 ]. It is interesting to note that ESR and CRP levels do not seem to be predictive of a particular course of the disease [ 4 , 5 ].…”

“…Non-steroidal anti-inflammatory drugs (NSAIDs) are frequently suggested as a first-line treatment in CNO patients, especially in children, known to respond better than adults to them [ 17 ]. Naproxen is the most prescribed NSAID, usually at a dose of 10 mg/kg (maximum 500 mg) twice daily [ 13 ], and is usually well tolerated [ 5 , 7 ]. It is suggested that it should be maintained for at least one month before evaluating the response [ 19 ].…”

“…The main benefits of treatment with BPs are related to their anti-inflammatory and pain-relief effects. Their mechanism in CNO is still not clear but is thought to be related to the decrease in osteoblast and osteocyte apoptosis, the reduction in bone resorption, and the increase in secondary bone mineralization [ 7 , 10 ]. The first retrospective studies concerning BPs’ use in CNO patients showed their efficacy in more than half of the children treated with pamidronate after failing NSAIDs [ 30 , 64 , 65 , 66 , 67 , 68 ].…”