Xusheng Qiu

Nanjing Medical University, Nan-ching, Jiangsu Sheng, China

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Publications (16)68.74 Total impact

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    ABSTRACT: To explore whether the suppressor of cytokine signaling-3 (SOCS3) gene polymorphisms are associated with the susceptibility and abnormal growth pattern of adolescent idiopathic scoliosis (AIS).
    07/2014;
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    ABSTRACT: To investigate the genotype of COL2A1 in a three-generation spondyloepiphyseal dysplasia congenita (SEDC) family. Five affected individuals from a Chinese SEDC family were enrolled in the study. All patients underwent thorough physical and radiographic examinations. DNA samples of the affected patients and the healthy controls were collected with the informed consent obtained from each participant. Two short tandem repeat polymorphic markers flanking COL2A1 gene region were detected to determine the haplotype of each patient. Subsequently, sequence analysis was performed in COL2A1 gene to identify potential genetic mutation. Haplotype analysis showed that the same disease-associated haplotype was segregated through the whole pedigree. A maximum LOD score of 1.5 was obtained with D12S85 and D12S368. DNA sequence analysis revealed a c.1636 G/A transition in exon 25 of the COL2A1 gene, which converted the codon GGT for glycine at position 546 to AGT, a codon for serine. The patients were all heterozygous for the mutation G546S, which was absent in either of the unaffected family members or of the normal individuals. This is the first familial report of G546S mutation in the COL2A1 gene that results in SEDC. Although great achievements have been made in the recognition of the mutation spectrum, more intensive studies are warranted to further identify correlations between genotype and phenotype.
    European Spine Journal 04/2014; · 2.47 Impact Factor
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    ABSTRACT: Adolescent idiopathic scoliosis (AIS) is a common rotational deformity of the spine that presents in children worldwide, yet its etiology is poorly understood. Recent genome-wide association studies (GWAS) have identified a few candidate risk loci. One locus near the chromosome 10q24.31 LBX1 gene (OMIM #604255) was originally identified by a GWAS of Japanese subjects and replicated in additional Asian populations. To extend this result, and to create larger AIS cohorts for the purpose of large-scale meta-analyses in multiple ethnicities, we formed a collaborative group called the International Consortium for Scoliosis Genetics (ICSG). Here, we report the first ICSG study, a meta-analysis of the LBX1 locus in six Asian and three non-Asian cohorts. We find significant evidence for association of this locus with AIS susceptibility in all nine cohorts. Results for seven cohorts containing both genders yielded P=1.22×10-43 for rs11190870, and P=2.94×10-48 for females in all nine cohorts. Comparing the regional haplotype structures for three populations, we refined the boundaries of association to a ∼25 kb block encompassing the LBX1 gene. The LBX1 protein, a homeobox transcription factor that is orthologous to the Drosophila ladybird late gene, is involved in proper migration of muscle precursor cells, specification of cardiac neural crest cells, and neuronal determination in developing neural tubes. Our results firmly establish the LBX1 region as the first major susceptibility locus for AIS in Asian and non-Hispanic white groups, and provide a platform for larger studies in additional ancestral groups.
    Journal of Medical Genetics 04/2014; · 5.70 Impact Factor
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    ABSTRACT: Adolescent idiopathic scoliosis (AIS) is the most common pediatric skeletal disease. We previously reported a locus on chromosome 10q24.31 associated with AIS susceptibility in Japanese using a genome-wide association study (GWAS) consisting of 1,033 cases and 1,473 controls. To identify additional AIS-associated loci, we expanded the study by adding X-chromosome SNPs in the GWAS and increasing the size of the replication cohorts. Through a stepwise association study including 1,819 cases and 25,939 controls, we identified a new susceptibility locus on chromosome 6q24.1 in Japanese (P = 2.25 × 10(-10); odds ratio (OR) = 1.28). The most significantly associated SNP, rs6570507, was in GPR126 (encoding G protein-coupled receptor 126). Its association was replicated in Han Chinese and European-ancestry populations (combined P = 1.27 × 10(-14); OR = 1.27). GPR126 was highly expressed in cartilage, and the knockdown of gpr126 in zebrafish caused delayed ossification of the developing spine. Our results should provide insights into the etiology and pathogenesis of AIS.
    Nature Genetics 05/2013; · 35.21 Impact Factor
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    ABSTRACT: Adolescent idiopathic scoliosis (AIS) is the most common spinal deformity, affecting around 2% of adolescents worldwide. Genetic factors play an important role in its etiology. Using a genome-wide association study (GWAS), we recently identified novel AIS susceptibility loci on chromosomes 10q24.31 and 6q24.1. To identify more AIS susceptibility loci relating to its severity and progression, we performed GWAS by limiting the case subjects to those with severe AIS. Through a two-stage association study using a total of ∼12,000 Japanese subjects, we identified a common variant, rs12946942 that showed a significant association with severe AIS in the recessive model (P = 4.00×10(-8), odds ratio [OR] = 2.05). Its association was replicated in a Chinese population (combined P = 6.43×10(-12), OR = 2.21). rs12946942 is on chromosome 17q24.3 near the genes SOX9 and KCNJ2, which when mutated cause scoliosis phenotypes. Our findings will offer new insight into the etiology and progression of AIS.
    PLoS ONE 01/2013; 8(9):e72802. · 3.53 Impact Factor
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    ABSTRACT: PURPOSE: To investigate whether rs11190870 near LBX1 correlates with the susceptibility or curve progression of adolescent idiopathic scoliosis (AIS) in a Han Chinese population. METHODS: A total of 949 AIS patients and 976 age-matched healthy controls were recruited. All the subjects were genotyped using the PCR-based invader assay. Case-control study and case-only study were performed to define the contribution of rs11190870 to predisposition and curve severity of AIS. Additionally, we further conducted a meta-analysis of the study findings together with those of previously reported studies. RESULTS: A significant association of rs11190870 with AIS was observed in the Han Chinese population (P = 1.8 × 10(-9); odd ratio = 1.51; 95 % confidence interval = 1.33-1.71), and AIS patients with TT genotype had a larger Cobb angle than those with TC or CC genotype (P = 0.005). The meta-analysis confirmed that the positive association of this SNP with AIS in the East Asian population. CONCLUSIONS: The SNP rs11190870 near LBX1 is associated with both susceptibility and curve progression of AIS.
    European Spine Journal 10/2012; · 2.47 Impact Factor
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    ABSTRACT: A prospective clinical magnetic resonance imaging study. To explore the differences in the position of the aorta relative to the spine in patients with single right thoracic adolescent idiopathic scoliosis (RT-AIS) in 2 different body positions (supine and prone). Pedicle screws are used widely in scoliosis surgery. With an increase in the incidence of vascular complications that result from misplaced pedicle screws, studies regarding the spatial relationship of the aorta and the vertebral body have also gradually increased and show that the aorta is positioned more posteriorly in patients with RT-AIS than in normal subjects. In these imaging studies, the patients received computed tomographic or magnetic resonance (MR) scans in the supine position. Recent studies of subjects without a spinal deformity found that the aorta moves from a posterolateral to an anteromedial position when the subject changes from a supine position to a prone position. However, no studies investigated aorta shifting with changing body position in patients with AIS. Twenty-six patients with single RT-AIS were recruited into this study. Each patient received an axial MR scan from T5 through L3 in both the supine and prone positions. In the Cartesian coordinate system, the left pedicle-aorta (LtP-Ao) angle, LtP-Ao distance, and vertebral rotation angle were measured from T5 through L3 in the axial plane MR images. We also simulated misplacement of the pedicle screw with commonly used length and 20° direction error, and the potential risk of aorta impingement was defined as the virtual pedicle screw crossing the aorta. The paired sample t test was used to compare these parameters between the 2 body positions. The mean LtP-Ao angle and mean LtP-Ao distance differed between the body positions at each level. At the T5-T10 levels, the patients in the prone position exhibited significantly smaller LtP-Ao angles (26.2° vs. 38.8°; P, 0.01) and distances (27.0 vs. 30.7 mm; P, 0.01) than those in the supine position. The vertebral rotation angle was larger in the prone position than in the supine position at periapical levels, although this difference did not reach statistical significance (P . 0.05). The percentage of potential risk of aorta impingement was significantly higher in the prone position than in the supine position at the T5-T10 levels (19.7% vs. 6.6%, respectively; P, 0.05). CONCLUSION.: The aorta shifts more anteromedially and more closely to the spine at the T5-T10 levels when patients with RT-AIS change from the supine to the prone position. Thus, in the prone position, the aorta is potentially at a higher risk for injury from anterior and lateral cortex penetration by the left pedicle screws. The spinal surgeon should be aware of these altered conditions to avoid injury to the aorta during pedicle screw insertion in patients with RT-AIS who are in the prone position.
    Spine 05/2012; 37(17):E1054-61. · 2.16 Impact Factor
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    ABSTRACT: To evaluate the safety and effectiveness of cervical disc arthroplasty (CDA) versus anterior cervical discectomy and fusion (ACDF) for single-level symptomatic cervical disc disease. We identified eligible randomized controlled trials (RCTs) in PubMed (April 2011), EMBASE (April 2011) and Cochrane Central Register of Controlled Trials (April 2011). Data were collected and extracted by two reviewers independently. The methodological quality and clinical relevance of the included studies were assessed. Data analysis was conducted with RevMan 5.0. Six RCTs involving 1,745 patients were included. The pooled analysis showed a higher prevalence of neurological and overall success [(P = 0.004, RR = 1.06, 95% CI = 1.02-1.10), (P = 0.0005, RR = 1.14, 95% CI = 1.06-1.22)], and a lower incidence of dysphagia and reoperation related to adjacent-segment degeneration [(P = 0.04, RR = 0.30, 95% CI = 0.09-0.97), (P = 0.03, RR = 0.46, 95% CI = 0.23-0.91)] with CDA compared to ACDF. However, there was no statistical difference in neck disability index (P = 0.92, SMD = 0.01, 95% CI = -0.25 to 0.27), neck and arm pain scores[(P = 0.33, SMD = -0.12, 95% CI = -0.37 to 0.13), (P = 0.54, SMD = 0.17, 95% CI = -0.36 to 0.70)], incidence of complications related to the implant or surgical procedure and reoperation related to primary surgery [(P = 0.32, RR = 0.76, 95% CI = 0.45-1.30), (P = 0.09, RR = 0.48, 95% CI = 0.20-1.12)]. Compared with ACDF, CDA carry a lower incidence of dysphagia complications and reoperation related to adjacent-segment degeneration, and a higher prevalence of neurological and overall success at 2 years postoperatively. As the poor quality of the included studies, it is still uncertain whether CDR is more effective and safer than ACDF treating single-level symptomatic cervical disc disease. Future large-scale RCTs with long-term follow-up are needed to provide clear evidence.
    Archives of Orthopaedic and Trauma Surgery 02/2012; 132(2):141-51. · 1.36 Impact Factor
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    ABSTRACT: Recently, several genome wide association studies suggested IL-17RC, CHL1, DSCAM and CNTNAP2 genes polymorphisms were associated with AIS. To confirm these associations, we performed this case-control study using data from 648 AIS patients and 573 healthy adolescent of Chinese Han population. A polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis was performed to detect the genotypes of polymorphic loci: rs708567 rs279545 in IL-17RC gene, and rs2055314, rs331894, rs2272524, rs2272522 in CHL1 gene, and rs2222973 in DSCAM gene, and rs2710102, rs11770843 in CNTNAP2 gene. Statistical analysis of genotype frequencies between AIS patients and controls were performed by χ2 test. Our results show that both the genotype frequency and allele frequency of loci rs708567 were significantly different between AIS patients and controls (P = 0.023, 0.028, respectively). As for polymorphic loci rs279545, rs2222973, rs279545, rs2055314, rs331894, rs2272524, rs2272522, no significant difference was found between AIS patients and controls either genotype or allele frequencies (p>0.05). Overall, our study found a significant association of IL-17RC gene polymorphisms with AIS in a Chinese Han population, indicating IL-17RC gene may be as a susceptibility gene for AIS; While CHL1, CNTNAP2 and DSCAM genes were not associated with AIS, suggesting that those genes may not be involved in the etiopathogenesis of AIS. However, association study of these genes with AIS in other races is needed to clarify the role of these genes in the etiology of AIS.
    Studies in health technology and informatics 01/2012; 176:47-51.
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    ABSTRACT: To investigate whether the predisposition genes previously reported to be associated with the occurrence or curve severity of adolescent idiopathic scoliosis (AIS) play a role in the effectiveness of brace treatment. A total of 312 AIS patients treated with bracing were enrolled in this study. The Cobb angle of the main curve was recorded at the beginning of brace treatment as well as at each follow-up. The patients were divided into two groups according to the outcome of brace treatment (success/failure). The failure of brace treatment was defined as a curve progression of more than 5° compared to the initial Cobb angle or surgical intervention because of curve progression. Single nucleotide polymorphism (SNP) sites in the genes for estrogen receptor α (ERα), estrogen receptor β (ERβ), tryptophan hydroxylase 1 (TPH-1), melatonin receptor 1B (MTNR1B) and matrillin-1 (MATN1), which were previously identified to be predisposition genes for AIS, were selected for genotyping by the PCR-RFLP method. Differences of genotype and allele distribution between the two groups were compared by the χ(2) test. A logistic regression analysis was used to figure out the independent predictors of the outcome of brace treatment. There were 90 cases (28.8%) in the failure group and 222 cases (71.2%) in the success group. Patients in the failure group were associated with the genotype GA (50.9 vs. 17.9% p < 0.001) and the G allele (27.1 vs. 12.0%, p < 0.001) at SNP rs9340799 of the ERα gene. Similarly, they were also associated with the genotype AT (33.3 vs. 13.0%, p = 0.002) and the A allele (16.7 vs. 9.6%, p = 0.033) at SNP rs10488682 of the TPH-1 gene. For MTNR1B, the difference of genotype distribution between the two groups was found to be statistically significant, while the difference of allele distribution between the two groups was found to be marginally statistically significant; for the MATN1 and ERβ genes, we found no significant differences of the genotype or allele distribution between the two groups. In the logistic regression analysis, ERα and TPH-1 were demonstrated to be independent factors predictive of bracing effectiveness. ERα and TPH-1 might be potential genetic markers that could predict the outcome of brace treatment. Patients with the G allele at the rs9340799 site of the ERα gene and the A allele at the rs10488682 site of the TPH-1 gene are prone to be resistant to brace treatment.
    European Spine Journal 06/2011; 20(10):1757-64. · 2.47 Impact Factor
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    ABSTRACT: Osteoarthritis (OA) is the most common form of arthritis and the precise etiology of this disease remains unclear. Genetic factors play a considerable role in pathogenesis of OA. Several OA-susceptibility genes have been identified. Recently, a new emerging role of pitx1 transcription factor in OA pathogenesis has been reported. Paired-like homeodomain transcription factor 1 (PITX1) has been implicated in hind limb development of mice and is essential to maintain cartilage function. Because of the different expression in the knee joint between OA and normal people, PITX1 may be involved in etiology and pathogenesis of OA. The present study is to evaluate the association of the PITX1 polymorphism (rs479632) with knee OA in a Chinese Han population. A case-control association study was conducted. The polymorphism was genotyped in 581 patients who had primary symptomatic knee OA with radiographic confirmation and in 570 matched controls. Allelic and genotypic frequencies were compared between patients and control subjects. No significant difference was detected in genotype or allele distribution between knee OA and control groups (all P > 0.05). The association was also negative even after stratification by sex. Furthermore, no association between the SNP genotype and the clinical variables age, sex, body mass index (BMI), and Kellgren/Lawrence (K/L) score was observed in OA patients. The present study suggests that the PITX1 polymorphism (rs479632) is not a risk factor for knee OA susceptibility in the Chinese Han population. Further studies are needed to give a global view of this polymorphism in pathogenesis of OA.
    Rheumatology International 05/2011; 31(5):629-33. · 2.21 Impact Factor
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    ABSTRACT: Developmental dysplasia of the hip (DDH) is a common skeletal disease, which is characterized by abnormal seating of the femoral head in the acetabulum. Genetic factors play a considerable role in the etiology of DDH. Asporin (ASPN) is an ECM protein which can bind to TGF-β1 and sequentially inhibit TGF-β/Smad signaling. A functional aspartic acid (D) repeat polymorphism of ASPN was first described as an osteoarthritis-associated polymorphism. As TGF-β is well known as an important regulator in the development of skeletal components, ASPN may also be involved in the etiology of DDH. Our objective is to evaluate whether the D repeat polymorphism of ASPN is associated with DDH in Han Chinese. The D repeat polymorphism was genotyped in 370 DDH patients and 445 control subjects, and the allelic association of the D repeat was examined. From D11 to D18, eight alleles were identified. D13 allele is the most common allele both in control and DDH groups, the frequencies are 67.3% and 58.1% respectively. In the DDH group, a significantly higher frequency of the D14 allele and significantly lower frequency of D13 was observed. The association of D14 and D13 was found in both females and males after stratification by gender. There was no significant difference in any other alleles we examined. Our results show an obvious association between the D repeat polymorphism of ASPN and DDH. It indicates that ASPN is an important regulator in the etiology of DDH.
    Arthritis research & therapy 02/2011; 13(1):R27. · 4.27 Impact Factor
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    ABSTRACT: Treatment of high congenital dislocation of the hip (CDH) remains controversial. We report the outcome of hip arthroplasty using a cementless threaded cup and a cementless straight stem in patients with high congenital hip dislocation. Between January 2001 and August 2004, 17 patients with high congenital hip dislocation were treated. During surgery, at least 25% of the cup was anchored in bone. By monitoring somatosensory-evoked potentials (SEPs) of the common peroneal nerve we were able to reduce the femoral head into position in the true acetabulum by releasing soft tissues. A bulk autogenous femoral head bone graft was implanted in 5 patients to achieve at least 75% bony coverage of the acertabular component. Follow-up ranged from 48 months to 91 months with an average of 69.7 months. The mean Harris hip score increased from 43 points preoperatively to 89 points at the time of final follow-up (P<0.001). Radiographic analysis showed bony union of the bone graft in all cases.
    Hip international: the journal of clinical and experimental research on hip pathology and therapy 01/2011; 21(1):71-5. · 0.34 Impact Factor
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    ABSTRACT: A genetic association study of the tissue inhibitor of metalloproteinase-2 (TIMP-2) gene with adolescent idiopathic scoliosis (AIS) in a Chinese population. To determine whether a promoter polymorphism of the TIMP-2 gene correlates with the occurrence and curve severity of AIS patients. Previous studies have suggested that genetic factors play an important role in the etiology of AIS. The relative anterior spinal column overgrowth due to abnormal endochondral ossification has been considered to be a significant factor in the etiopathogenesis of AIS. The specific role of matrix metalloproteases (MMPs) and their activity inhibitors, TIMPs, during endochondral ossification has been documented. The TIMP-2 is the major TIMP expressed during bone development and is located in one of the chromosomal regions linked to AIS. Therefore, the TIMP-2 gene is a potential candidate gene for AIS. This study included a total of 570 female AIS patients, who were divided into 2 groups according to curve patterns. Of them, 354 patients with right thoracic curve were in group A (326 cases with Lenke 1 type and 28 cases with Lenke 2 type), whereas 216 patients with a single lumbar curve were in group B (216 cases with Lenke 5 type). A total of 210 age-matched healthy girls were recruited as normal controls. One single-nucleotide polymorphism, -418G/C (rs8179090), in the promoter region was selected for the TIMP-2 gene. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism in each group. No significant differences of genotype and allele frequency distribution were found between AIS patients and normal controls either in group A or in group B. The frequency of C allele was significantly higher in patients with Cobb angle 40° or more than in those with Cobb angle less than 40° in group A (P < 0.05), while this difference was not noted in group B (P > 0.05). Among the patients who reached skeletal maturity without any interference of natural history, a significantly higher average maximum Cobb angle was found in patients with C allele than in those without C allele in group A (P < 0.05). However, in group B, the mean maximum Cobb angle was similar between patients with different genotypes in both cases with left-side curves and cases with right-side curves (P > 0.05). Furthermore, for the patients whose values of thoracic kyphosis were recorded, those with C allele had smaller average thoracic kyphosis than those without C allele in group A (P < 0.05). However, such significant difference was not observed in group B. The single-nucleotide polymorphism SNP-418G/C (rs8179090) in the promoter region of the TIMP-2 gene was not associated with the occurrence of AIS. However, it may predict curve severity of thoracic AIS. Hence, the TIMP-2 gene is a disease-modifier gene of thoracic AIS.
    Spine 01/2011; 37(1):41-7. · 2.16 Impact Factor
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    ABSTRACT: Developmental dysplasia of the hip is the most frequent inborn deformity of the locomotor apparatus. Genetic factors play a considerable role in pathogenesis of Developmental dysplasia of the hip. Recently, several DVWA SNPs were found to be consistent and most significantly associated in Japanese and Han Chinese knee OA studies. Its functions may be associated with cartilage. It may be involved in etiology and pathogenesis of Developmental dysplasia of the hip. Our objective is to evaluate whether the DVWA SNPs (rs7639618, rs9864422 and rs11718863) are associated with Developmental dysplasia of the hip in Han Chinese. Three SNPs rs7639618, rs9864422 and rs11718863 (in DVWA) were genotyped using a Taqman 5' allelic discrimination assay on an ABI 7500 real-time polymerase chain reaction (PCR) instrument in 368 children who suffered from Developmental dysplasia of the hip and 508 control subjects, and analyzed their associations. The genotype distribution and allele frequency were compared between Developmental dysplasia of the hip and healthy control. Neither genotype distributions nor allelic frequencies of the assayed single nucleotide polymorphisms were found to be significantly different between patients and controls. There was also no significant difference when the patients were stratified by sex or severity (all P > 0.05). Our results indicate that DVWA does not seem to be a risk factor for Developmental dysplasia of the hip etiology in Chinese Han population.
    Rheumatology International 03/2010; 31(7):883-7. · 2.21 Impact Factor
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    ABSTRACT: A prospective study was designed to investigate the circulating leptin level in girls with adolescent idiopathic scoliosis (AIS). To determine the circulating leptin levels in AIS girls, and to investigate its associations with body mass and bone mass. Abnormal growth pattern and osteopenia have been well documented in AIS patients throughout the peripubertal growth period. Leptin has been shown to regulate the growth of the whole body and bone particularly during childhood and adolescence. However, the circulating level of leptin, the relationships between leptin and lower body mass, and the relationships between leptin and lower bone mass in AIS patients remain unclear. One hundred twenty AIS girls and 80 healthy controls were recruited in this study. Measurements of anthropometry and circulating leptin were performed both in AIS and non-AIS girls. Evaluations of curve severity and measurements of bone mineral content/density (BMC/BMD) were performed only in AIS girls. The anthropometric data and circulating leptin levels were compared between older AIS girls and controls. The relationships between leptin and age, menstrual status, body weight, height, body mass index (BMI), Risser sign, curve magnitude, and BMC/BMD were analyzed in AIS girls. Compared with healthy controls, an abnormal growth pattern (higher corrected height, lower weight, and lower BMI), and a marked decrease of circulating leptin were found in AIS girls, even after the adjustment for age and menstrual status. Positive correlations were found between leptin and age, menstrual status, body weight, height, BMI, and Risser sign. No significant correlation was found between leptin and curve magnitude. There was no significant difference in age at menarche between menstruating AIS and non-AIS girls, though an inverse correlation was observed between leptin and the age at menarche. The relationship between leptin and BMC/BMD remained significantly positive after controlling for age and menstrual status, although it was not independent of body weight or BMI. A marked decrease of circulating leptin was observed in the current study. There was an association between leptin and body weight, BMI, other growth parameters, and BMC/BMD. This correlation suggests that leptin might play an important role in the lower body and bone mass in AIS girls.
    Spine 12/2007; 32(24):2703-10. · 2.16 Impact Factor