Bone histomorphometric changes in children with rheumatic disorders on chronic glucocorticoids.
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.
Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, Canada. jennifer.harrington@sickkids.ca.|Division of Endocrinology, Hospital for Sick Children, 555 University Avenue, Toronto, ON, M5G1X8, Canada. jennifer.harrington@sickkids.ca.
Jennifer
J
Harrington
Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Canada.
Douglas
D
Holmyard
Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, Canada.|Division of Rheumatology, Hospital for Sick Children, Toronto, Canada.
Earl
E
Silverman
Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, Canada.
Etienne
E
Sochett
Samuel Lunenfeld Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Canada.
Marc
M
Grynpas
D015502:Absorptiometry, Photon / Q000379:methods; D000293:Adolescent; D001706:Biopsy / Q000379:methods; D015519:Bone Density / Q000187:drug effects; D001842:Bone and Bones / Q000187:drug effects / Q000473:pathology; D002170:Canada; D002648:Child; D004305:Dose-Response Relationship, Drug; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D000069451:Long Term Adverse Effects / Q000209:etiology / Q000473:pathology / Q000517:prevention & control; D008297:Male; D010024:Osteoporosis / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D012216:Rheumatic Diseases / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D012720:Severity of Illness Index; D016103:Spinal Fractures / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D013223:Statistics as Topic
D005938:Glucocorticoids
Bone histomorphometry; Bone mineralization; Glucocorticoids; Juvenile idiopathic arthritis; Osteoporosis; Systemic lupus erythematosis