Chapter 1 (Section 1) The Role Of Melatonin Of Abnormal Bone Density And Quality In Adolescent Idiopathic Scoliosis:Experimental Scoliosis In Bipedal C57BL/6J Mice

Objective.To clarify the effect of melatonin on the bone density and quality status in adolescent idiopathic scoliosis(AIS).we investigated radiological and histological changes in the C57BL/6J mice model.Methods.A total of 80 mice were randomly divided into four equal groups:20 quadrupedal mice served as controls(QP):20 bipedal mice(BP);the remaining 20 quadrupedal(QP+MLT)and 20 bipedal mice(BP+MLT)received daily intraperitoneal administration of melatonin(8 mg/kg body weight in 10%ethanol/saline)at 22:00.Bipedal mice will be amputated at 3 weeks old undder general anesthesia.The bipedal mice without a tail were able to walk with standing posture.whereas the quadrupedal mice did not walk with standing posture.The spines of all mice will be radiologically examined for the presence of scoliosis and micro-computed tomography(micro-CT)images will be used for the three-dimensional assessment of bone density and quality every 4 weeks.The following,parameters will be calculated:volumetric bone mineral density(vBMD).bone volume fraction(BV/TV).trabecular number(Tb.N).trabecular thickness(Tb.Th).trabecular separation(Tb.Sp).Before killing,blood samples were collected in the middle of dark cycle and melatonin levels were measured by radioimmunoassay.Histological specimens of the scanned lumbar vertebra were prepared,and a mid-sagittal section was stained with hematoxylin and eosin and tartrate-resistant acid phosphatase to evaluate the numbers of osteoclasts.Results.Scoliosis with rib humps developed in 16 of 20 bipedal mice and in six quadrupedal mice.In contrast,only 4 mice in the BP+MLT group and 1 in the QP+MLT group developed scoliosis.In BP and QP group,the serum melatonin was(6.4±4.7pg/ml and 4.9±3.]pg/ml,respectively);however,the normal level was restored in both BP + MLT and QP + MLT group(193.6±78.4pg/ml and 219.2±65.9pg/ml,respectively).Micro-CT data revealed that mean value of BMD in BP＋MLT groups were significantly higher at the vertebral body in mice compared with BP group(P<0.001).BV/TV.Tb.Th and Conn.Dn in the BP + MLT group were significantly higher than that in the BP group(P<0.001).while Tb.Sp in the BP+MLT group was significantly lower than that in BP(P<0.001).The number of osteoclasts was significantly decreased in the BP+MLT group,compared with BP group and QP group(P<0.001).Conclusion.Our results suggest that bipedal is critical in the development of scoliosis.Melatonin deficiency appears to play crucial role for the abnormal bone density and quality of scoliosis,and restoration of melatonin levels in bipedal mice prevents the development of scoliotic deformity,low bone density and abnormal bone quality.Chapter 1(section 2)Does disc wedging contribute to the flexibility of thoracic curve in adolescent idiopathic scoliosis?Objective.The appreciations of curve flexibility in AIS patients are important for determining structural curves,defining the safe range of correction,selecting the segment length for fusion,determining the appropriate surgical procedure,and predicting the results of surgical correction.However,the role of disc wedging in predicting spinal flexibility has not been well defined.The objective of this study was to investigate the effect of disc wedging on ccurve flexibility and gain insight into segmental mobility by comparing disc wedging in upright and side-bending radiographs in thoracic AIS.Methods.This study included a total of 126 consecutive AIS patients with main thoracic curve.According to thoracic curve flexibility index(TCFI),62 patients with TCFI<50%were assigned to group A(Stiff),and the other 64 patients with TCFI≥50%were assigned to group B(Flexible).Age.curve magnitude,disc wedging and disc wedging percentage were compared between the two groups,segmental flexibility indices(SFI)[(upright disc angle-bending disc angle)/(upright disc angle)]were computed and compared between periapical and remote levels.Correlations were estimated using Pearson correlation coefficients.After adjustment of covariates.logistic multivariate regression analysis of independent factors for TCFI was performed.Results.Significant differences with respect to the age and curve magnitude were observed between the two groups(6.42±2.45 vs.13.98±1.96,P<0.05 and 59.42°±0.19° vs.50.09°±5.95°.P<0.05).The wedging angle and wedging percentage on discs in group B were significantly higher than those in group A(26.96°± 5.67° vs.17.13°±8.23°.P<0.01 and 53.86%±9.45 vs.28.83%±10.16.P<0.01).There was a significant correlation between disc wedging percentage and TCFI(r=0.716.P<0.001).Multivariate regression analysis showed that the disc wedging percentage was the single greatest predictor of TCFI(β=0.676,P<0.001).And the disc wedging showed symmetric periapical distribution with significant decrease(all p values<0.01)for every cephalad(-)and caudad(+)level change.The apical level-1 and +1 wedged at 7.32°and 7.19°,respectively.We noted mean periapical SFIs of 41%(-1),43%(+1),58%(-2)and 80%(+2),which were significantly less(p<0.01)than for the group of remote SFIs 98%(-3).134%(+3),159%(-4)and 279%(+4).Conclusion.Disc wedging percentage,together with the Cobb angle,contribute to the spinal flexibility in thoracic adolescent idiopathic scoliosis.The average flexibility indices of the periapical discs are significantly less than that of the remote discs.These may offer useful information in the evaluation of curve progression and surgical planning.Chapter 1(section 3)Cosmetic and radiological outcomes after surgical treatment of Lenke 5C adolescent idiopathic scoliosis:a comparison of anterior versus posterior approachObjective.Improving cosmesis of AIS patients is an important of surgery.Anterior and posterior instrumentations are two established methods of correcting Lenke 5C AIS.Both methods have respective advantages and disadvantages.However,there was no report in the literatures focusing on detailed comparison of both the cosmetic and radiographic outcomes between the two methods.The objective of this study was to evaluate and compare the cosmetic and radiological outcomes of anterior versus posterior instrumentation in Lenke 5C AIS.Methods.Sixty female Lenke 5C patients who underwent surgery from 2006 to 2010 were included in this study.Thirty patients had anterior surgery(Group A),and thirty patients had posterior surgery(Group B).The mean duration of folloe-up was 26.34 months(range,23-44months).Cobb angles,apical vertebral translation(AVT).and apical vertebral rotation(AVR)were measured in the standard long-standing posteroanterior radiographs,waistline height index(WLHI).waistline depth index(WLDH).waistline area index(WLAI)-waist area index(WAI),and hump index(HI,α)were measured clinically and these 5 parameters combined into a composite cosmetic index(CCI).Cosmetic and radiological indices were compared between two groups pre-operatively and at last follow-up.Results.The mean age.major curve magnitude,number of levels involved in the major curve.AVT,AVR and CC]were comparable between two groups preoperative.No significant differences were observed regarding correction of CCI.Cobb angle,and AVT at last follow-up between both groups,and the fusion levels were similar between two groups(P>0.05),whereas AVR in Group A was superior to Group B at last follow-up(P<0.05).There were also no complications in either group which extended hospital stay or required an unplanned revision surgery,whereas operation time in Group A was significant longer than Group B(P<0.05).Conclusion.The present study showed that there was no significant difference in regards to cosmetic improvement and main curve correction between anterior and posterior surgery in the treatment of Lenke 5C AIS.And posterior instrumentation should be preferred because of the operational simplicity.Chapter 2(section 1)Vertebral Body and Intervertebral Disc Wedging:Which Contributes More to Thoracolumbar Kyphosis in Ankylosing Spondylitis Patients?Objective.Both vertebral body wedging and disc wedging are found in AS patients with thoracolumbar kyphosis.However,their relative contribution to thoracolumbar kyphosis is not fully understood.The objective of this study was to compare different contributions of vertebral and disc wedging to the thoracolumbar kyphosis in ankylosing spondylitis(AS)patients.Methods.This study included a total of 59 consecutive AS patients with thoracolumbar kyphosis.Based on global kyphosis(GK).26 patients with GK<70°were assigned to group A,and the other 33 patients with GK>70° were included in group B.Age,sex and disease duration were compared between the two groups.The wedging angle of each disc and vertebra comprising the thoracolumbar kyphosis was measured,and the proportion of the wedging angle to the GK was calculated accordingly.Inter-and intra-group comparisons were subsequently performed to investigate the different contributions of disc and vertebra to the GK.The correlation between the apical vertebral wedging angle and GK was calculated by Pearson correlation analysis.Results.With respect to the mean disease duration,significant difference was observed between the two(groups(P<0.01).The wedging angle and wedging percentage of discs were significantly higher than those of vertebrae in group A(34.8°±2.5°cs 26.7°±2.7°,P<0·01 and 56.6%vs 43.4%,P<0.01).whereas disc wedging and disc wedging percentage were significantly lower than vertebrae in group B(37.6°±7.0°vs 50.10±5.1°.P<0.01 and 42.7%vs 57.3%.P<0.01).The wedging of vertebrae was significantly higher in group B than in group A(50.1°±5.1°vs 26.7°±2.70°,P<0.01).Additionally,correlation analysis revealed a significant correlation between the apical vertebral wedging angle and GK(R=0.850.P=0.001).Conclusion.Various disc and vertebral wedging exist in thoracolumbar kyphosis secondary to AS.The discs wedging contributes more to the thoracolumbar kyphosis in patients with GK<70° than vertebral wedging,whereas vertebral wedging is more conducive to the thoracolumbar kyphosis in patients with GK≥ 70°,indicating different biomechanical pathogenesis in varied severity of thoracolumbar kyphosis secondary to AS.Chapter 2(section 2)Does the Length of the Aorta Change After Closing Wedge Osteotomy for Ankylosing Spondylitis Patients With Thoracolumbar Kyphosis?Objective.To investigate the change in aortic length in patients with thoracolumbar kyphosis secondary to AS after closing wedge osteotomy(CWO).Methods.From June 2013 to July 2015,twenty-four AS patients(22 males.2 females)with thoracolumbar kyphosis with a mean age of 38.1 years(range,23 to 54 yrs)were recruited in this study.All AS patients underwent one-level CWO surgery.Magnetic resonance imaging(MRI)examinations from the upper thoracic to the lower instrumented vertebra before and 2 weeks after surgery were performed.For each subject,the aortic diameter(AD)(at the osteotomized level)and length(AL)(the length between the superior endplate of the upper instrumented vertebra and the inferior endplate of L4)were measured on the MRI.Radiographic measurements included the global kyphosis,thoracic kyphosis(TK).lumbar lorcdosis(LL),local kyhosis(LK),angle of fusion levels(AFL),and anterior height of the osteotomized vertebra(AHOV).The height of these patients was also recorded.Results.The AL significantly increased by an average of 2.0 cm before and after surgery.Also,the AD at the osteotomized level decreased from 2.0± 0.2 cm to 1.6 ±0.3 cm(P<0.01).Significant changes in height.GK.LL.LK.AFL were observed(P<0.01).whereas theAHOV was comparable before and after surgery(P>0.05).Additionally.the correlation analysis revvealed a significant correlation between the aortic length and changes in GK(r=0.626.P＝0.021).LL(r=0.581.P = 0.015).LK(r=0.715.P=0.001),AFL(r=0.657.P=0.001)and height(r=0.613.P＝(0.001).Conclusion.The stretch of the aortic after CWO for the correction of thoracolumbar kyphosis was quantitatively verified by MRI investigation in this study.Spine surgeons should be aware of the potential vulnerability of aortic injury in AS patients undergoing CWO for the correction of thoracolumbar kyphosis.