Deficient bone formation in idiopathic juvenile osteoporosis: a histomorphometric study of cancellous iliac bone.
Idiopathic juvenile osteoporosis (IJO), a rare cause of osteoporosis in children, is characterized by the occurrence of vertebral and metaphyseal fractures. Little is known about the histopathogenesis of IJO. We analyzed by quantitative histomorphometry iliac crest biopsies from 9 IJO patients (age, 10.0-12.3 years; 7 girls) after tetracycline labeling. Results were compared with identically processed samples from 12 age-matched children without metabolic bone disease and 11 patients with osteogenesis imperfecta type I. Compared with healthy controls, cancellous bone volume (BV) was markedly decreased in IJO patients (mean [SD]: 10.0% [3.1%] vs. 24.4% [3.8%]), because of a 34% reduction in trabecular thickness (Tb.Th) and a 37% lower trabecular number (Tb.N; p < 0.0001 each; unpaired t-test). Bone formation rate (BFR) per bone surface was decreased to 38% of the level in controls (p = 0.0006). This was partly caused by decreased recruitment of remodeling units, as shown by a trend toward lower activation frequency (54% of the control value; p = 0.08). Importantly, osteoblast team performance also was impaired, as evidenced by a decreased wall thickness (W.Th; 70% of the control value; p < 0.0001). Reconstruction of the formative sites revealed that osteoblast team performance was abnormally low even before mineralization started at a given site. No evidence was found for increased bone resorption. Compared with children with osteogenesis imperfecta (OI), IJO patients had a similarly decreased cancellous BV but a much lower bone turnover. These results suggest a pathogenetic model for IJO, in which impaired osteoblast team performance decreases the ability of cancellous bone to adapt to the increasing mechanical needs during growth. This will finally result in load failure at sites where cancellous bone is essential for stability.
Rauch
F
F
Genetics Unit, Shriners Hospital, McGill University, Montréal, Québec, Canada.
Travers
R
R
Norman
M E
ME
Taylor
A
A
Parfitt
A M
AM
Glorieux
F H
FH
D017668:Age of Onset; D016723:Bone Remodeling; D016022:Case-Control Studies; D002648:Child; D006801:Humans; D007085:Ilium / Q000503:physiopathology*; D010013:Osteogenesis Imperfecta / Q000503:physiopathology; D010024:Osteoporosis / Q000473:pathology / Q000503:physiopathology*