The Effect Of Different Doses Of Melatonin On The Incidence Of Scoliosis In Bipedal Mice And The Management Of Spinal Deformities

Chapter One The effect of melatonin on the pathogeneses of scoliosis Section 1 The effect of different doses of melatonin on the incidence of scoliosis in bipedal C57BL/6J mice modelObjective. The lack of endogenous melatonin is one of the most important mechanism for adolescent idiopathic scoliosis. Melatonin-deficient bipedal C57BL/6J mice was reported to high incidence of scoliosis, meanwhile intraperitoneal injection of melatonin was demonstrated to prevent the development of scoliosis. However, there is a paucity of knowledge concerning the correlation between the effect of intraperitoneal injection of melatonin and its dose. Therefore, the current study aimed to investigate the effect of different doses of melatonin injection on the incidence of scoliosis in female C57BL/6J mice.Methods.105 female 3-week-old C57BL/6J mice were selected. Amputation of forelimbs and tail was performed on 75 of the mice. All the quadrupedal mice were randomly divided into 2 Groups:Group A,15 quadrupedal mice treated with saline water; Group B,15 quadrupedal mice treated with melatonin 8 mg/kg BW/day. The bipedal mice were devided into 5 groups:Group C,15 bipedal mice treated with saline water; Group D to Group G, each group consisted of 15 bipedal mice treated with melatonin with 4 mg/kg BW/day,8mg/kg BW/day,16 mg/kg BW/day and 32 mg/kg BW/day, respectively. Radiographs were obtained at 20th week after amputation surgery to determine the presence of spinal deformity. One-way analysis of variance was used to compare the incidences of scoliosis among different groups.Results. For quadrupedal mice, scoliosis developed in 2 mice of Group A(13.3%). There were 19(25.3%) mice presented scoliosis in all the bipedal mice, of which 14(93.3%) mice were in Group C,3(20%) mice were in Group E and the remain 2 mice were in Group D and Group F, respectively. A remarkable higher incidence of scoliosis were observed in Group C. However, there was no significant difference concerning the incidences among Group D to Group G, which were divided according to the dose of melatonin supplementation (P>0.05).Conclusions. Melatonin deficiency in C57BL/6J bipedal played an crucial role for the development of scoliosis, and intraperitoneal injection with melatonin could marvelously decrease the incidence of scoliosis in this model. However, this effect is not affected by the dose of injected melatonin.Chapter two Study on the management of spinal deformitiesSection 1 Clavicle chest cage angle difference:is it a radiographic and clinical predictor of postoperative shoulder imbalance in Lenke 1 adolescent idiopathic scoliosis?Objective. Clavicle chest cage angle difference (CCAD) is a novel predictor of postoperative radiographic shoulder imbalance in adolescent idiopathic scoliosis (AIS). However, radiographic shoulder balance does not always correspond to cosmetic shoulder balance. This study was to evaluate the effect of preoperative CCAD on postoperative radiographic shoulder imbalance, cosmetic shoulder balance, patient's satisfaction and surgeon's fulfillment in Lenke I AIS.Methods.. Forty-four Lenke I AIS patients treated with posterior spinal fusion with a minimum 2-year follow-up were analyzed. Shoulder height difference (SHD) and CCAD were measured on anteroposterior (AP) standing radiographs. The inner shoulder height (SHi) and the outer shoulder height (SHo) were measured using the patients' photographs. The patients' satisfaction and the surgeons' fulfillment were evaluated using a questionnaire. A receiver operative characteristic curve analysis was performed to explore the threshold values of preoperative CCAD in the prediction of the final follow-up radiographic shoulder imbalance, patients'satisfaction and surgeons' fulfillment.Results. At the final follow-up, the preoperative CCAD was significantly greater in patients with unbalanced shoulders (SHD^ 1 cm). For cosmetic shoulder balance at the final follow-up, there was no significant difference in preoperative CCAD between Group li (SHi?1 cm, n=14) and Group 2i (SHi<1 cm, n=30), and the preoperative CCAD was also similar between Group lo (SHo?1lcm, n=17) and Group 2o (SHo<lcm, n=27). For patients'satisfaction and surgeons'fulfillment, the preoperative CCAD was significantly greater in patients with unsatisfied outcomes. The threshold value of preoperative CCAD to predict the final follow-up radiographic shoulder imbalance, patients'satisfaction and surgeons'fulfillment was 5.5°.Conclusions. CCAD is a good radiographic predictor for postoperative radiographic shoulder imbalance in Lenke I AIS patients. Moreover, it is also associated with the patients'satisfaction and surgeons'fulfillment postoperatively. However, CCAD cannot predict postoperative cosmetic shoulder balance.Section 2 Thoracic kyphosis increases at mid-term follow-up after anterior spinal fusion for thoracic adolescent idiopathic scoliosis:is it due to posterior spinal growth?Objective To investigate whether the change of thoracic kyphosis(TK) after anterior spinal fusion is due to the posterior spinal growth.Methods 40 Lenke 1 adolescent idiopathic scoliosis patients treated with anterior spinal fusion were enrolled in the study. According to their Risser sign before surgery, patients were divided into 3 groups:group A, Risser O; group B, Risser 1-3; group C, Risser 4-5. The following sagittal parameters were measured on the anterior-posterior and lateral radiographs preoperatively,3 months postoperatively and at final follow-up, which included:the Cobb angle of the thoracic curve and lumbar curve, thoracic kyphosis, the anterior and posterior height of the vertebral body from T5 to T12 (VBHa and VBHp, respectively), the height of the pedicles (PH) and the distance from the inferior edge of the higher pedicle to the superior edge of the lower pedicle (IPH).Results There were 7,14,19 patients in group A, B and C, respectively. The average TK was changed from 10.4°±12.2° preoperatively to 15.1°±8.6° three months after surgery, and to 18.1°±6.5° at final follow-up. Compared with the data 3 months after surgery, the TK of group A and group B were changed by 8.3° and 2.2° at final follow-up, respectively. The values of SVBHp/SVBHa and (SIPH+SPH)/SVBHa of group A and the value of (SIPH+SPH)/SVBHa of group B significantly increased from 3 months postoperation to the final follow-up. However, the values of SVBHp/SVBHa and (SIPH+SPH)/SVBHa of group C were not significantly changed during the follow-up period.Conclusion After anterior spinal fusion, the TK of low Risser sign Lenke 1AIS patients significantly increased during the postoperative follow-up period, which was due to the continued growth of the posterior spine.Section 3 The influence of anterior or posterior selective thoracolumbar/lumbar fusion on sagittal spinal alignment in Lenke5 AIS:a comparison analysisObjective To compare and analyze the change of the sagittal spine alignment of Lenke type 5 adolescent idiopathic scoliosis (AIS) treated with anterior or posterior approach selective thoracolumbar/lumbar (TL/L) fusion postoperatively and investigate the influence of different surgical approaches on sagittal spine profile.Methods 49 Lenke5 AIS patients who received TL/L spine fusion in one institution from January 2005 to December 2010 with a minimum of 2 years follow-up were retrospectively evaluated.23 patients underwent anterior spinal instrumentation and fusion (group A), and other 26 patients were treated with posterior spinal fusion (group B). Pre-and postop radiological parameters were measured and quantified as follows: curve magnitude of primary thoracolumbar/lumbar and secondary thoracic curve, thoracic kyphosis (TK), lumbar lordosis (LL), proximal junctional angle (PJA).Results Preoperatively, thoracic and thoracolumbar/lumbar curve and other demographic data were all comparable between group A and group B, and the sagittal parameters were also matched between the two groups. The fusion levels were similar in group A and group B, and primary TL/L and secondary thoracic curves were corrected with a similar effect in both groups postoperatively and at the last follow-up. There was a proliferation for TK, while for LL, lordosis decreased 6.6 degrees and 1 degree in group A and group B, respectively. For PJA, there was a increase in group A (0.2 degrees) and group B (2.9 degrees). No significant differences were found in all postop parameters between both groups (P>0.05). Duration of follow-up was 2.8± 0.9 years and 2.3 ± 0.5 years in group A and group B respectively. There was a small magnitude increase for TK, LL and PJA in both groups at 1 year postop and the final follow-up compared with those postop. However, the TK of group B significantly greater than group A.Conclusion When Lenke5 AIS patients were treated with selection TL/L instrumentation and fusion, in the sagittal plane, anterior and posterior surgery can improve TK and LL, but the TK was better improved by posterior surgery. Therefore, posterior surgery was a better method for sagittal reconstruction of Lenke5 AIS patients. Section 3 Does Halo gravity traction affect the bone mineral density of patientswith severe kyphoscoliosis?Objective. HGT is one of the most commonly-used peri-operative technique for the treatment of severe kyphoscoliosis. However, there is a paucity of knowledge concerning the impact of HGT on the BMD of these patients. This study was to explore the influence of Halo gravity traction (HGT) on the bone mineral density (BMD) of patients with severe kyphoscoliosis.Methods. Patients with severe kyphoscoliosis treated by preoperative HGT for at least 2 months were included. The pre-HGT and post-HGT BMD was assessed by dual energy X-ray absorptiometry at lumbar spine (LS, L2-L4) and femur neck (FN) of the non-dominant side. The reduction rates of BMD were calculated. The weight and duration of traction, as well as baseline characteristics including body mass index (BMI), magnitude of the major coronal curve and global kyphosis (GK), were recorded for each patient. A paired t test was used to compare the difference between pre-HGT BMD and post-HGT BMD. Chi-square test was used to the compare the incidence of osteoporosis before and after the completion of HGT. Factors related to the change ofBMD were analyzed by student t test, one-way analysis of variance or Pearson correlation test.Results. Twenty patients were recruited with a mean age of 16.3 ± 7.6 years. The average traction duration was 77.9 ± 13.0 days while the mean traction weight was 39.9% ±11.1% of total body weight. Remarkable decrease of BMD was observed at LS of 17 (85%) patients and at FN of 18 (90%) patients compared with the initial values. After HGT,75% of patients were found to have osteoporosis, the incidence of which was significant higher than that before HGT (35%). The correlation analysis revealed BMD reduction was significantly correlated with the traction duration.Conclusions. The procedure of HGT prior to surgical intervention can have obvious impact on the BMD. The BMD reduction is associated with traction duration, suggesting that long traction duration may bring more bone mineral loss.