FRI0383 PAMIDRONATE IN CHRONIC NON-BACTERIAL OSTEOMYELITIS: A RANDOMIZED, PLACEBO-CONTROLLED PILOT TRIAL

Abstract

Background Chronic non-bacterial osteitis (CNO) is an autoinflammatory disease often associated with seronegative spondyloarthritides. Osteitic bone lesions in adults are predominantly located in the anterior chest wall, the spine and pelvis. Case series suggest that the amino-bisphosphonate pamidronate may be effective in improving bone inflammation, pain, and disability. No randomized controlled trials have been conducted in CNO. Objectives In a randomized double-blinded, placebo-controlled trial we hypothesized that pamidronate reduces radiological signs of bone inflammation assessed by whole-body magnetic resonance imaging, improve pain, disability and reduces systemic markers of bone inflammation and bone turnover in blood. Methods Patients with an established diagnosis of CNO were assessed for eligibility. Inclusion criteria were 1. Mono- or multifocal bone inflammation (osteitis with or without sclerosis) 2. Jansson clinical score for CNO in children and adults ≥391 or malignancy and infection excluded by biopsy and 3. Symptoms duration > 6 weeks. Patients were randomized 1:1 to receive placebo or pamidronate 1 mg/kg, max 60 mg, given for three consecutive days at baseline, week 12 and week 24. Whole-body MRI was performed at baseline, week 12 and 36. CT scan of the anterior chest wall was performed at baseline and week 36. Changes in active and chronic radiological bone inflammation in the ACW and spine were systematically scored.2, 3 Patient-reported outcome were measured at baseline and week 1,4,12,24 and 36 using a visual analogue scale for pain and global health assessment, Health Assessment Questionnaire for physical functioning and, EuroQoL- 5 Dimension-3 Level and The Short Form (SF)-36 questionnaire for Quality of life. Biomarkers of bone turnover and inflammation in blood were measured at baseline and week 1,4,12,24 and 36. Results Analyses were performed in 12 patients with CNO, mean age 32 (range 20-63) years. From baseline to week 36 the radiological score of active bone inflammation decreased from 4,8(SD 2.2) to 2,5(SD 1.6) in the pamidronate group (p=0,01). This differed significantly from the placebo group in which no change from baseline was observed (p=0.04). We observed a decreasing trend in VAS pain from mean 38(SD 23)mm to 19(SD 18)mm and VAS global from 32(SD 22)mm to 13(SD 18)mm. Conclusion This study is the first randomized double-blinded, placebo-controlled trial in CNO. Treatment with pamidronate improved bone marrow oedema in the anterior chest wall assessed by whole-body magnetic resonance imaging. This pilot study points out methodological considerations in relation to study design and outcome measures in CNO.