270(81.8%) subjects completed 2-year supplementation when changes in left femoral neck aBMD, trabecular vBMD, Trabecular BV/TV, Trabecular Number and Trabecular Separation indicated significant bone health improvement with Ca+Vit-D supplementation(p less then 0.05). At 6-year(mean age=19.2 years), no between-group difference on bone parameters was noted except increase in Cortical Thickness being greater only in Group3 than in Group1. After 4-year supplement discontinuation, the treatment effect from the initial 2-year supplementation mostly dissipated indicating the need of continued supplementation in AIS girls to sustain therapeutic improvement on bone health as subjects approach towards Peak Bone Mass.Adolescent Idiopathic Scoliosis (AIS) occurs during pubertal rapid growth period and is closely associated with low bone mass. The underlying mechanisms for systemic low bone mass in AIS remains unclear. Wnt signalling pathway is one of the important pathways regulating bone metabolism and influencing bone strength, its family member Wnt16 associates with lower bone mineral density (BMD) in late adulthood, and plays key regulatory role in determining cortical bone quality in adult ****. Our randomized control trial have reported vitamin D (VitD) supplementation significantly improved bone mass and reduced the risk of curve progression in AIS. A case-control study and animal study were employed to answer if WNT16 is associated with the abnormal bone quality in AIS and if the effect of VitD supplementation is associated with Wnt16, respectively. A cohort of 161 AIS and control female subjects were recruited for measurement of anthropometric parameters, bone qualities, and circulating Wnt16 level. In animal study, WT and Wnt16 gKO **** were both subjected to special VitD diet from week 4 and terminated at week 7 and 10 for samples harvesting. AIS showed significantly lower BMD, circulating WNT16 level, and elevated serum level of type I procollagen N-terminal propeptide. Wnt16 gKO **** demonstrated lower cortical bone density compared with WT **** from week 7 of age and Wnt16 gKO were less prone to cortical bone loss induced by high dosage VitD diet. Further study on the biological role of WNT16 and crosstalk with VitD metabolism on bone qualities is warranted which might shed light on prognostic gene of osteopenia and new perspectives for potential target to prevent curve progression.Idiopathic scoliosis in man is believed to be related to the unique human sagittal profile. Patients with a thoracic scoliosis have a longer, more proximal, posteriorly inclined segment of the spine as compared to lumbar scoliosis and controls, whereas patients with a lumbar scoliosis have a more caudal, shorter and steeper posteriorly inclined segment. In 22q11.2 deletion syndrome, half of the patients develop a scoliosis that is very similar to idiopathic scoliosis and may serve as a model for the general population. In our center, all patients with 22q11.2 deletion syndrome older than 6 years receive standardized radiographic spine imaging every 2 years to screen for scoliosis. In this prospective proof-of-principle study the goal was to determine whether there are differences in sagittal alignment between patients that develop scoliosis vs. controls before the onset of scoliosis, and obtain data to perform a power calculation for future studies. To capture the sagittal shape of the spine into one risk factor for development for scoliosis, we combined relative length and magnitude of dorsal inclination into a new parameter the posterior inclined triangle surface (PITS). We included 31 patients with initially straight spines, five developed a thoracic scoliosis and seven developed a (thoraco)lumbar scoliosis after a mean follow-up of 3.4 years. The PITS was considerably higher in the group that developed scoliosis as compared to the controls (59 vs 43). Based on this pilot study, we have identified a potential overall sagittal profile risk parameter for the development of idiopathic scoliosis.AIS is three-dimensional spinal deformity with unclear etiopathogenesis. LBX1 is so far the only multi-centers validated AIS predisposing gene. The imbalance of posterior paraspinal muscles is an important factor in AIS etiopathogenesis. It is poorly understood how LBX1 contributes to the abnormal paraspinal muscles and onset/progression of AIS. https://www.selleckchem.com/products/dcz0415.html We aimed to evaluate the expression of LBX1 in paraspinal muscles at the concave and convex side in AIS, and whether alternation of LBX1 expression could affect myoblastsactivities and potentially influence muscle-bone interaction via myokines expression. Paraspinal muscles from AIS and age- and curvature-matched congenital scoliosis (CS) patients were collected for fiber types analysis. Biopsies were also subjected to qPCR to validate expression of myogenic markers, selected myokines and LBX1. Human skeletal muscle myoblast (HSMM) was used for LBX1 loss-of-function study in vitro. Muscle fiber types analysis showed type I and type IIX/IIAX fibers proportion were significantly different between AIS concave and convex but not in two sides of CS. LBX1, myogenic markers and one myokine were significantly imbalanced in AIS but not in CS. Loss-of-function study showed knockdown of LBX1 could inhibit myogenic markers expression and myokines as well. This study provides new insight into the association between imbalanced paraspinal muscle and potential muscle-bone crosstalk in AIS patients and the biological function of predisposing gene LBX1. Further investigation with appropriate animal models is warranted to explore if asymmetric expression of LBX1 could result in distinct muscle phenotypes and bone qualities thus affect the progression of spine curvature in AIS.The etiology of the adolescent idiopathic scoliosis (AIS) remains unknown. Variations in the sagittal profile of the spine between the early stage scoliotic and non-scoliotic pediatric patients have been shown. However, no quantitative study has shown the link between the sagittal profile and 3D deformity of the spine. 126 right thoracic scoliosis with spinal and 3D reconstructions were included. A 2D finite element model was developed for each of the sagittal curve types without any deformity in the frontal or axial planes. Physiological loadings were determined from the literature and were applied in the finite element model. The 3D deformation patterns of the models were compared to the 3D spinal patterns of the AIS with the same sagittal type. A significant correlation was found between the 3D deformity of the scoliotic curves and the numerical finite element simulation of the corresponding sagittal profile as determined by pattern correlation, p less then 0.001. The sagittal curve deformation patterns corresponded to the spinal deformities in the patients with the same sagittal curvature.
270(81.8%) subjects completed 2-year supplementation when changes in left femoral neck aBMD, trabecular vBMD, Trabecular BV/TV, Trabecular Number and Trabecular Separation indicated significant bone health improvement with Ca+Vit-D supplementation(p less then 0.05). At 6-year(mean age=19.2 years), no between-group difference on bone parameters was noted except increase in Cortical Thickness being greater only in Group3 than in Group1. After 4-year supplement discontinuation, the treatment effect from the initial 2-year supplementation mostly dissipated indicating the need of continued supplementation in AIS girls to sustain therapeutic improvement on bone health as subjects approach towards Peak Bone Mass.Adolescent Idiopathic Scoliosis (AIS) occurs during pubertal rapid growth period and is closely associated with low bone mass. The underlying mechanisms for systemic low bone mass in AIS remains unclear. Wnt signalling pathway is one of the important pathways regulating bone metabolism and influencing bone strength, its family member Wnt16 associates with lower bone mineral density (BMD) in late adulthood, and plays key regulatory role in determining cortical bone quality in adult mice. Our randomized control trial have reported vitamin D (VitD) supplementation significantly improved bone mass and reduced the risk of curve progression in AIS. A case-control study and animal study were employed to answer if WNT16 is associated with the abnormal bone quality in AIS and if the effect of VitD supplementation is associated with Wnt16, respectively. A cohort of 161 AIS and control female subjects were recruited for measurement of anthropometric parameters, bone qualities, and circulating Wnt16 level. In animal study, WT and Wnt16 gKO mice were both subjected to special VitD diet from week 4 and terminated at week 7 and 10 for samples harvesting. AIS showed significantly lower BMD, circulating WNT16 level, and elevated serum level of type I procollagen N-terminal propeptide. Wnt16 gKO mice demonstrated lower cortical bone density compared with WT mice from week 7 of age and Wnt16 gKO were less prone to cortical bone loss induced by high dosage VitD diet. Further study on the biological role of WNT16 and crosstalk with VitD metabolism on bone qualities is warranted which might shed light on prognostic gene of osteopenia and new perspectives for potential target to prevent curve progression.Idiopathic scoliosis in man is believed to be related to the unique human sagittal profile. Patients with a thoracic scoliosis have a longer, more proximal, posteriorly inclined segment of the spine as compared to lumbar scoliosis and controls, whereas patients with a lumbar scoliosis have a more caudal, shorter and steeper posteriorly inclined segment. In 22q11.2 deletion syndrome, half of the patients develop a scoliosis that is very similar to idiopathic scoliosis and may serve as a model for the general population. In our center, all patients with 22q11.2 deletion syndrome older than 6 years receive standardized radiographic spine imaging every 2 years to screen for scoliosis. In this prospective proof-of-principle study the goal was to determine whether there are differences in sagittal alignment between patients that develop scoliosis vs. controls before the onset of scoliosis, and obtain data to perform a power calculation for future studies. To capture the sagittal shape of the spine into one risk factor for development for scoliosis, we combined relative length and magnitude of dorsal inclination into a new parameter the posterior inclined triangle surface (PITS). We included 31 patients with initially straight spines, five developed a thoracic scoliosis and seven developed a (thoraco)lumbar scoliosis after a mean follow-up of 3.4 years. The PITS was considerably higher in the group that developed scoliosis as compared to the controls (59 vs 43). Based on this pilot study, we have identified a potential overall sagittal profile risk parameter for the development of idiopathic scoliosis.AIS is three-dimensional spinal deformity with unclear etiopathogenesis. LBX1 is so far the only multi-centers validated AIS predisposing gene. The imbalance of posterior paraspinal muscles is an important factor in AIS etiopathogenesis. It is poorly understood how LBX1 contributes to the abnormal paraspinal muscles and onset/progression of AIS. https://www.selleckchem.com/products/dcz0415.html We aimed to evaluate the expression of LBX1 in paraspinal muscles at the concave and convex side in AIS, and whether alternation of LBX1 expression could affect myoblastsactivities and potentially influence muscle-bone interaction via myokines expression. Paraspinal muscles from AIS and age- and curvature-matched congenital scoliosis (CS) patients were collected for fiber types analysis. Biopsies were also subjected to qPCR to validate expression of myogenic markers, selected myokines and LBX1. Human skeletal muscle myoblast (HSMM) was used for LBX1 loss-of-function study in vitro. Muscle fiber types analysis showed type I and type IIX/IIAX fibers proportion were significantly different between AIS concave and convex but not in two sides of CS. LBX1, myogenic markers and one myokine were significantly imbalanced in AIS but not in CS. Loss-of-function study showed knockdown of LBX1 could inhibit myogenic markers expression and myokines as well. This study provides new insight into the association between imbalanced paraspinal muscle and potential muscle-bone crosstalk in AIS patients and the biological function of predisposing gene LBX1. Further investigation with appropriate animal models is warranted to explore if asymmetric expression of LBX1 could result in distinct muscle phenotypes and bone qualities thus affect the progression of spine curvature in AIS.The etiology of the adolescent idiopathic scoliosis (AIS) remains unknown. Variations in the sagittal profile of the spine between the early stage scoliotic and non-scoliotic pediatric patients have been shown. However, no quantitative study has shown the link between the sagittal profile and 3D deformity of the spine. 126 right thoracic scoliosis with spinal and 3D reconstructions were included. A 2D finite element model was developed for each of the sagittal curve types without any deformity in the frontal or axial planes. Physiological loadings were determined from the literature and were applied in the finite element model. The 3D deformation patterns of the models were compared to the 3D spinal patterns of the AIS with the same sagittal type. A significant correlation was found between the 3D deformity of the scoliotic curves and the numerical finite element simulation of the corresponding sagittal profile as determined by pattern correlation, p less then 0.001. The sagittal curve deformation patterns corresponded to the spinal deformities in the patients with the same sagittal curvature.
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