Abnormal skeletal growth and bone mineralization in the etiopathogenesis of adolescent idiopathic scoliosis.

摘要

The hypothesis in this thesis is that skeletal growth disturbance and low bone mineral status during peripubertal period may be related to the etiopathogenesis (onset and progress) of Adolescent idiopathic scoliosis (AIS).; Growth and bone mineral status of AIS were explored by different methods and at different levels.; By anthropometrical measurement with cross-section study, the abnormal growth patterns were found in AIS patients during peri-pubertal period. The scoliotic girls were further confirmed to be leaner, taller statures with longer upper and lower extremities after the onset of pubertal growth.; For the largest sample size of AIS scanned by DEXA and pQCT, significantly lower BMD at different sites was proven. The tBMD revealed that low bone mineral density already existed AIS in early stage AIS. The bone mass of AIS remained slower and persisted after age of 15 and breast stage five. The results indicated AIS with low bone mineral status.; To our knowledge, we are also the first group to scan the three-dimension structure of trabecular bone of AIS by MicroCT measurement. The pilot study showed that the 3D indices of trabecular bone of AIS were variable at different anatomical sites in AIS and at same site in different individual. Three dimensional structure analysis of AIS bone biopsy were however shown to correlate with BMD parameters especially with the tBMD indicating association between trabecular bone architecture and tBMD.; For the first time in literatures, this series of studies on osteopenic bone biopsy was studied with histomorphometry, electron microscopy and TUNEL methods. The histomorphometric study revealed disturbance of bone turnover in AIS. Electron microscopy showed osteocytes in trabecular bone degeneration in nucleus, cytoplasm and membrane. Abnormally osteoclasts were found. The result indicated that osteopenia found in AIS might be different from osteoporosis in postmenopausal woman and aging. TUNEL study indicated that membranous ossification might be reduced when compared with endochondral ossification. These abnormalities may have a significant effect on the development of abnormal bone mineral density and growth, which could also affect the etiopathogenesis of AIS.; In the Ph.D research, it is also the first study on non-collagen proteins expressions in the trabecular bone of AIS. The two small proteoglycans, i.e. decorin and biglycan, were preliminarily found in a low amount expression in iliac crest specimens from patients with AIS. The association between lower expression of two proteins and lower BMD were also observed. Further studies on the temporal and spatial patterns of expression of the non-collagen proteins in adolescent skeletal tissues would provide more insights into the possible disturbances in the molecular aspects of bone development. Overall, the results from this series of original study have provided evidence that intra-skeletal growth abnormality could play important role in the etiopathogenesis of AIS. (Abstract shortened by UMI.)