In children diagnosed with extended chronic nonbacterial osteomyelitis, early-onset pamidronate therapy reduced radiologic and clinical activity substantially over 2 years, although there were cases of continually active disease as well as relapses following remission during this period, according to a report published in The Journal of Rheumatology.
With a variable clinical course, treatment for this disease is often empiric, with nonsteroidal anti-inflammatory drugs used as first-line therapy, and amino-bisphosphonate pamidronate and/or tumor necrosis factor alpha inhibitors used as second-line therapies for those whose disease does not respond to first-line therapy. Investigators sought to determine whether pamidronate treatment in pediatric patients helped improve clinical and radiologic disease activity over 2 years.
A retrospective cohort study conducted at a single Danish center identified 51 patients (mean age at diagnosis, 10.7 years; 62.7% female; median time between first symptoms and diagnosis, 9 months; median follow-up time, 4 years; median erythrocyte sedimentation rate at diagnosis, 11 mm; HLA-B27 positivity, 14%) diagnosed from 2007 through 2015 with extended (n=32; 63%) or limited (n=19; 37%) chronic nonbacterial osteomyelitis according to the Bristol criteria. A total of 15 patients (29%) had inflammatory comorbidity at baseline.
Radiologic assessment at baseline was performed using whole-body and/or local magnetic resonance imaging (MRI), and/or bone scintigraphy. Extended disease was defined by multifocal or spinal inflammation not responsive to nonsteroidal anti-inflammatory drugs. In these individuals, clinical activity was evaluated annually, and whole-body MRI was performed at baseline and at 1 and 2 years in 88%, 84%, and 91% of cases, respectively. Those with extended disease were treated with a 2-year intravenous pamidronate regimen (0.5 mg/kg/d initially, followed by 1 mg/kg/d over 3 consecutive days every 3 months).
Radiologic remission required no bone lesions on follow-up MRI; clinical remission required patients to have no inflammatory signs or symptoms and normal erythrocyte sedimentation rate. On medication, clinical remission was defined as inactive disease for 6 months; off medication, remission required inactive disease for ≥12 months.
A median of 5 bone lesions were present at baseline in all children, with the tibia the most common location; 13 of 51 (25%) had spinal lesions, with the thoracic spine the most frequent site. Over the course of the first year, there were significant reductions in spinal bone lesions (P =.01) and lesions per patient, with the median decreasing from 6 to 2 in patients with extended disease (P =.01).
After the first year of pamidronate therapy, 12 of 32 (38%) of those with extended disease had clinical remission; 8 of these 12 (67%) eventually had relapse of disease. Radiologic results showed that 7 of 31 (23%) children from the extended group achieved remission, but 3 of 7 (43%) had relapse of disease after 24 months, and 10 of 31 (32%) had disease remission at 2 years. For those with limited disease, after 1 and 2 years, respectively, 10 of 19 (53%) and 10 of 16 (63%) patients were in clinical remission on and off medication, respectively.
Study limitations included a nonvalidated disease definition, treatment strategy according to institutional standards, retrospective design, and non-blinded assessments by pediatric radiologists.
“We found that pamidronate might contribute to clinical improvement and improvement of radiological outcome in [chronic nonbacterial osteomyelitis]. However, relapse is rather frequent,” noted the authors. They recommended that future research involve placebo-controlled designs that further develop outcome measures and evaluate treatment responses.
Andreasen CM, Jurik AG, Glerup M, et al. Response to early-onset pamidronate treatment in chronic non-bacterial osteomyelitis: a retrospective single center study [published online April 15, 2019]. J Rheumatol. doi:10.3899/jrheum.181254