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Bone histomorphometric changes in children with rheumatic disorders on chronic glucocorticoids
Jennifer Harrington1,2, Douglas Holmyard3, Earl Silverman4,5
1Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, Canada. jennifer.harrington@sickkids.ca.
Insights
Children with rheumatic diseases on glucocorticoids show impaired bone micro-architecture and mineralization. These bone deficits correlate with glucocorticoid dose, impacting fracture risk in pediatric patients.
Area of Science:
- Pediatric Rheumatology
- Bone Biology
- Skeletal Health
Background:
- Rheumatic diseases increase fracture risk in children.
- Bone micro-architecture in pediatric rheumatic diseases is not well understood.
- Glucocorticoids used for rheumatic diseases can negatively impact bone health.
Purpose of the Study:
- To characterize bone micro-architecture in children with rheumatic diseases on chronic glucocorticoids.
- To investigate associations between bone micro-architecture and clinical/radiological factors.
- To assess bone mineralization in this pediatric cohort.
Main Methods:
- Trans-iliac bone biopsies were performed on children with rheumatic diseases and vertebral fractures.
- Histomorphometric analysis evaluated trabecular bone structure and osteoid parameters.
- Quantitative backscattered electron imaging (qBSE) assessed bone mineralization.
Main Results:
- Children showed decreased trabecular thickness, osteoid thickness, and osteoblast surface, with increased trabecular separation compared to norms.
- Trabecular deficits correlated with glucocorticoid dose, height, and BMI Z-scores.
- Bone mineralization was heterogeneous and hypermineralized, linked to cumulative glucocorticoid exposure.
Conclusions:
- Children with rheumatic diseases and vertebral fractures exhibit abnormal bone micro-architecture and mineralization.
- These bone abnormalities are associated with chronic glucocorticoid use.
- Findings highlight the detrimental effects of glucocorticoids on pediatric bone health in rheumatic diseases.
Background:
Rheumatic diseases are associated with an increased fracture risk. The tissue level characteristics of the bone involvement in children have not been well elucidated. Our objectives were to describe the bone micro-architectural characteristics in children with rheumatic diseases on chronic glucocorticoids, and to determine associations between micro-architectural findings with clinical and radiological variables.
Methods:
Children on chronic glucocorticoids for an underlying rheumatic disease were referred for evaluation of bone fragility given the presence of vertebral compression fractures. A trans-iliac bone biopsy was performed as part of the clinical assessment. Histomorphometric analysis and quantitative backscattered electron imaging (qBSE) of the biopsy samples were undertaken.
Results:
Data of 15 children (14.0 ± 3.2 years) with a duration of glucocorticoid exposure of 6.2 ± 4.1 years and average prednisone dose of 14.1 ± 6.2 mg/m2/day were assessed. Histomorphometric analyses demonstrated significant decrease in trabecular thickness (p = 0.01), osteoid thickness (p < 0.01), osteoblast surface (p = 0.02) and increase in trabecular separation (p = 0.04) compared to published age-matched normative data. Severity of the trabecular deficit was correlated to glucocorticoid dose, height and body mass index Z score, but not bone mineral density or measures of disease activity. Using qBSE to measure bone mineralization, the subjects were shown to have a heterogeneous and hypermineralized profile, with higher cumulative glucocorticoid dose being associated with greater mineralization (p < 0.01).
Conclusions:
In children with rheumatic diseases presenting with vertebral fractures, there is evidence of abnormal bone matrix mineralization and impairments of bone micro-architecture that correlate to glucocorticoid dose.
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