leptin and Scoliosis

To compare the serum levels of leptin and soluble leptin receptor (sOB-R) with adolescent idiopathic scoliosis (AIS) girls and controls through meta-analysis. The MEDLINE via PubMed, Cochrane, Scopus, and EMBASE database, from the earliest available date of indexing between January 2010 and January 2019, were searched for comparative studies evaluating serum levels of leptin and sOB-R in AIS girls. Two authors performed the data extraction independently. Any discrepancies were resolved by a consensus. Six comparative studies were identified. There was no statistically significant difference in terms of leptin between AIS girls and control [p = 0.19, WMD = -2.06 (-5.14, 1.03) ng/mL]. However, the sOB-R level was significantly higher [p < 0.00001, WMD = 2.85 (1.81, 3.88) ng/mL] and the free leptin index was significantly lower [p = 0.0006, WMD = -0.12 (-0.19, -0.05)] in AIS girls than those of healthy control girls. The body mass index was significantly lower in AIS girls [p = 0.03, WMD = -1.53 (-2.95, -0.12) kg/m

Topics: Adolescent; Body Mass Index; Female; Humans; Leptin; Receptors, Leptin; Scoliosis

Adolescents with scoliosis consistently demonstrate lower body weight, lean muscle mass, and bone mineral density than healthy adolescent counterparts. Recent studies have focused on understanding how leptin and ghrelin signaling may play a role in adolescent idiopathic scoliosis (AIS). In our current study, we aim to evaluate the serum levels of leptin, soluble leptin receptor (sOB-R), and ghrelin in AIS patients through systematic review and meta-analysis.. We conducted our systematic review by searching the keywords in online databases including PubMed, Embase, Cochrane, Elsevier, Springer, and Web of Science from the time of database inception to January 2020. Inclusion criteria were studies that measure leptin, soluble leptin receptor (sOB-R), and ghrelin levels in AIS patients. Selection of studies, assessment of study quality, and data extraction were performed by two reviewers independently. Then, data was analyzed to calculate the mean difference and 95% confidence interval (CI).. Seven studies concerning leptin/sOB-R and three studies concerning ghrelin were qualified for meta-analysis (one study concerning both leptin and ghrelin). Serum leptin of patients with AIS were significantly lower when compared with healthy controls, with the weighted mean difference (WMD) of - 0.95 (95% CI - 1.43 to - 0.48, p < 0.0001) after reducing the heterogeneity using six studies for meta-analysis, while sOB-R and ghrelin level was significantly higher in AIS group when compared with control group, with the WMD of 2.64 (95% CI 1.60 to 3.67, p < 0.001) and 1.42 (95% CI 0.48 to 2.35, p = 0.003), respectively.. Our current meta-analysis showed that serum level of leptin in AIS patients was significantly lower when compared with control subjects, while serum sOB-R and ghrelin levels were significantly higher in AIS patients. More clinical studies are still required to further validate the predictive value of leptin or ghrelin for the curve progression for AIS patients.

Topics: Adolescent; Biomarkers; Disease Progression; Female; Ghrelin; Humans; Leptin; Male; Predictive Value of Tests; Receptors, Leptin; Scoliosis; Signal Transduction

The autonomic nervous system through its hypothalamic neuroendocrine control of puberty, skeletal growth and menarche contributes importantly to the pathogenesis of adolescent idiopathic scoliosis (AIS). Melatonin dysfunction detected in AIS subjects also involves the autonomic nervous system. The thoracospinal concept for the pathogenesis of right thoracic AIS in girls thought by some to result from dysfunction of the sympathetic nervous system (SNS), is supported by recent vascular and peripheral nerve studies. Lower body mass index (BMI).in girls with AIS is associated with decreased circulating leptin levels. Leptin, secreted by adipocytes, is a master hormone with many regulatory functions for growth and reproduction, including: 1) appetite repression, anorexigenic; 2) initiation of puberty in girls in a permissive action, and 3) in mice, longitudinal bone growth, chondrogenic and angiogenic, and in bone formation, antiosteogenic acting centrally through the SNS and possibly directly. In AIS girls, autonomic nervous system activity was reported to be higher than in controls. We suggest that in AIS susceptible girls, given adequate nutrition and energy stores, circulating leptin talks to the hypothalamus where dysfunction leads to an altered sensitivity to leptin resulting in increased SNS activity contributing with neuroendocrine mechanisms to: 1) earlier age at, and increased peak height velocity, 2) general skeletal overgrowth, 3) earlier skeletal maturation, 4) extra-spinal skeletal length asymmetries, including periapical ribs and ilia, 5) generalized osteopenia, and 6) lower BMI. The SNS-driven effects may also add adventitious changes to the spine including asymmetries complicating the neuroendocrine effects on adolescent spinal growth. In AIS pathogenesis, the leptin-SNS concept is complementary to our NOTOM escalator concept involving the somatic nervous system. Together these two concepts view AIS in girls as being initiated by a hypothalamic dysfunction of energy metabolism (bioenergetics) affecting skeletal growth in the trunk. Where, in susceptible girls, the postural mechanisms of the somatic nervous system fail to control the asymmetric spinal and/or rib growth changes in a rapidly enlarging adolescent spine; this failure becomes evident as mild back-shape shape asymmetry, or scoliosis. The environmentally-enhanced stature of normal subjects in the last 300 years, in girls susceptible to AIS, may have exaggerated any developmental dysha

Topics: Adolescent; Autonomic Nervous System; Body Mass Index; Female; Humans; Leptin; Melatonin; Posture; Risk Factors; Scoliosis; Spine; Sympathetic Nervous System; Thoracic Vertebrae

Adolescent idiopathic scoliosis (AIS) is a complex three-dimensional structural deformity of the spine with unknown etiology. Although leptin has been postulated as one of the etiologic factors in AIS, its effects on osteoblastic activity remain unknown. Herein, we conducted this study to investigate whether there are abnormal functional responses to leptin and abnormal expression of leptin receptor in AIS osteoblasts. In vitro assays were performed with osteoblasts isolated from 12 severe AIS girls and 6 non-AIS controls. The osteoblasts were exposed to different concentrations of leptin (0, 10, 100, 1000 ng/mL). The effects of leptin on cell proliferation, differentiation and mineralization were determined. Protein expressions of leptin receptor (LEP-R) under basal and osteogenic conditions were also evaluated by Western blot. Our results showed that leptin significantly stimulated osteoblasts from non-AIS subjects to proliferate, differentiate and mineralized. However, in the AIS group, the stimulatory effects of leptin on cell proliferation, differentiation, and mineralization were not observed. In addition, no statistically significant difference in the expression of leptin receptor under both basal and osteogenic conditions was found between AIS and control group. In conclusion, these findings might help to explain the low bone mass and deranged bone quality that is clinically associated with AIS girls.

Topics: Adolescent; Adult; Cell Differentiation; Cell Proliferation; Child; Child, Preschool; Female; Humans; Infant; Leptin; Male; Osteoblasts; Receptors, Leptin; Scoliosis; Spine; Young Adult

This was a case-control study.. This study aimed to investigate the body composition and its correlation with leptin and soluble leptin receptor (sOB-R) levels in girls with adolescent idiopathic scoliosis (AIS) and compared with healthy controls.. Patients with AIS are associated with lower body weight, taller stature, lower body mass index (BMI), and deranged bone quality. Despite the widely reported lower BMI and body weight in girls with AIS, the body composition of these patients was not thoroughly studied with sufficient sample size. Leptin is an important factor in regulating energy and bone metabolism, and has been postulated as one of the etiologic factors of AIS.. One hundred forty-eight AIS and 116 control girls aged 12 to 14 were recruited. Body composition was measured with bioelectrical impedance analysis. Caloric intake and physical activity level were assessed by food frequency and Baecke questionnaires respectively. Serum total leptin and sOB-R levels were measured with enzyme-linked immunosorbent assay, and free leptin index was calculated.. AIS girls had lower body weight and BMI, other anthropometric and sexual maturity parameters were comparable with controls. There were no difference in caloric intake and physical activity levels. After adjustment for physical activity level, AIS girls had lower skeletal muscle mass, lower body fat, and %body fat. Higher sOB-R and lower free leptin index were found in AIS girls after adjusted for age and body weight. Weaker correlations between serum total leptin, FLI, and body composition parameters were observed in AIS girls.. Results suggested that the lower body weight in AIS girls was contributed by both lower skeletal muscle mass and lower body fat. Altered leptin bioavailability also exists in AIS girls and could lead to lower body weight, lower BMI, and abnormal body composition that were manifested in AIS simultaneously.. 4.

Topics: Adipose Tissue; Adolescent; Biological Availability; Biomarkers; Body Composition; Case-Control Studies; Child; China; Female; Humans; Leptin; Muscle Strength; Muscle, Skeletal; Scoliosis

To investigate the underlying mechanisms of low metabolic activity of primary chondrocytes obtained from girls with adolescent idiopathic scoliosis (AIS); AIS is a spine-deforming disease that often occurs in girls. AIS is associated with a lower bone mass than that of healthy individuals and osteopenia. Leptin was shown to play an important role in bone growth. It can also regulate the function of chondrocytes. Changes in leptin and Ob-R levels in AIS patients have been reported in several studies. The underlying mechanisms between the dysfunction of peripheral leptin signaling and abnormal chondrocytes remain unclear; The following parameters were evaluated in AIS patients and the control groups: total serum leptin levels; Ob-R expression in the plasma membrane of primary chondrocytes; JAK2 and STAT3 phosphorylation status. Then, we inhibited the lysosome and proteasome and knocked down clathrin heavy chain (CHC) expression in primary chondrocytes isolated from girls with AIS and evaluated Ob-R expression. We investigated the effects of leptin combined with a lysosome inhibitor or CHC knockdown in primary chondrocytes obtained from AIS patients; Compared with the controls, AIS patients showed similar total serum leptin levels, reduced JAK2 and STAT3 phosphorylation, and decreased cartilage matrix synthesis in the facet joint. Lower metabolic activity and lower membrane expression of Ob-R were observed in primary chondrocytes from the AIS group than in the controls. Lysosome inhibition increased the total Ob-R content but had no effect on the membrane expression of Ob-R or leptin's effects on AIS primary chondrocytes. CHC knockdown upregulated the membrane Ob-R levels and enhanced leptin's effects on AIS primary chondrocytes; The underlying mechanism of chondrocytes that are hyposensitive to leptin in some girls with AIS is low plasma membrane Ob-R expression that results from an imbalance between the rate of receptor endocytosis and the insertion of newly synthesized receptors into the membrane.

Topics: Adolescent; Adult; Blotting, Western; Chondrocytes; Enzyme-Linked Immunosorbent Assay; Female; Fluorescent Antibody Technique; Humans; Leptin; Metabolic Diseases; Microscopy, Confocal; Real-Time Polymerase Chain Reaction; Receptors, Leptin; Scoliosis; Young Adult

An experimental study to investigate the role of enhanced central leptin activity in a bipedal mouse scoliosis model.. To investigate the influence of enhanced central leptin activity on the development of scoliosis in mice, and to support Burwell's hypothesis that central leptin dysfunction is involved in the etiopathogenesis of idiopathic scoliosis.. Significantly lower level of circulating leptin and higher level of soluble leptin receptor have been reported in adolescent idiopathic scoliosis compared with healthy adolescents, suggesting possible association between abnormal central leptin level and dysfunction.. Amputation of forelimbs and tail was performed on 50 male C3H/HeJ mice at the age of 3 weeks. Then, the mice were randomly divided into 2 groups: Group A consisted of 25 mice treated with injection into the hypothalamus with lentivirus vectors that overexpressed leptin; and Group B involved the remaining 25 mice receiving intracerebral injection with the control vectors. Radiographs were obtained at 20th week to determine the presence of spinal deformity. The incidence of scoliosis and curve magnitude were compared between groups.. The body weight was initially found to be slightly lower in mice of Group A when compared with Group B. Significantly higher peripheral serum leptin level was found in leptin-overexpressing mice than control mice. Scoliosis developed in 23 mice of Group A (92%), with an average Cobb angle of 30.2°, and in 13 of Group B (52%), with an average Cobb angle of 18.4°, respectively. A higher incidence (P = 0.002) and more severe curve (P <0.001) were observed in Group A.. In this bipedal mouse scoliosis model, enhanced central leptin activity might not only increase the risk of developing a scoliosis, but also contribute to the progression of scoliosis.. N/A.

Topics: Amputation, Surgical; Animals; Body Weight; Disease Models, Animal; Disease Progression; Leptin; Male; Mice; Mice, Inbred C3H; Receptors, Leptin; Risk; Scoliosis

Hyperleptinemia is implicated in obesity-associated lumbar disc degeneration. Nevertheless, the effect of leptin on the intracellular signaling of nucleus pulposus cells is not clear. The current study sought to delineate the possible involvement of the RhoA/ROCK pathway in leptin-mediated cytoskeleton reorganization in nucleus pulposus cells. Nucleus pulposus cells isolated from scoliosis patients were treated with 10 ng/mL of leptin. Fluorescent resonance energy transfer analysis was used to determine the activation of RhoA signaling in nucleus pulposus cells. The protein expression of LIMK1 and cofilin-2 were analyzed by western blot analysis. F-actin cytoskeletal reorganization was assessed by rhodamine-conjugated phalloidin immunoprecipitation. Leptin induced F-actin reorganization and stress fiber formation in nucleus pulposus cells, accompanied by localized RhoA activation and phosphorylation of LIMK1 and cofilin. The RhoA inhibitor C3 exoenzyme or the ROCK inhibitor Y-27632 potently attenuated the effects of leptin on F-actin reorganization and stress fiber formation. Both inhibitors also prevented leptin-induced phosphorylation of LIMK1 and cofilin-2. Our study demonstrated that leptin activated the RhoA/ROCK/LIMK/cofilin-2 cascade to induce cytoskeleton reorganization in nucleus pulposus cells. These findings may provide novel insights into the pathogenic mechanism of obesity-associated lumbar disc degeneration.

Topics: Actin Cytoskeleton; Adult; Cofilin 2; Female; Humans; Intervertebral Disc; Leptin; Lim Kinases; Male; rho-Associated Kinases; rhoA GTP-Binding Protein; Scoliosis; Signal Transduction

Adolescent idiopathic scoliosis (AIS) is associated with low bone mineral density (BMD). The underlying etiology and how it may relate to the development of osteopenia remains unknown. Leptin has been postulated as one of the etiologic factors of AIS because of its profound effects on bone metabolism and pubertal growth. Its modulator, soluble leptin receptor (sOB-R), may affect leptin bioavailability and signaling. This study aimed to investigate whether serum leptin and sOB-R levels may be associated with bone quality, and whether these relationships may differ between young adolescent girls with and without AIS.. This was a case-control study involving 94 newly diagnosed AIS girls (Cobb angle 12-48°) aged 12 to 14 years old and 87 age and gender-matched normal controls. Subjects with BMI>23.0 Kg/m(2) were excluded. Anthropometric measurements including body weight, height, arm span and sitting height were taken. Serum total leptin and sOB-R were assayed with ELISA. Non-dominant distal radius was scanned with High Resolution pQCT for assessing bone quality in terms of bone morphometry, volumetric BMD (vBMD) and trabecular bone micro-architecture.. Compared with normal controls, AIS girls had numerically higher sOB-R (p = 0.006), lower average vBMD (p = 0.048), lower cortical vBMD (p = 0.029), higher cortical bone perimeter (p = 0.014) and higher trabecular area (p = 0.027), but none remained statistically significant after the Hochberg-Benjamini procedure. Correlation analysis on serum leptin level indicated that distinctive correlations with trabecular bone parameters occurred only in AIS.. This study showed that bone quality in AIS girls was deranged as compared with controls. In addition, the distinct differences in correlation pattern between leptin and trabecular bone parameters indicated possible abnormalities in bone metabolism and dysfunction of the leptin signaling pathway in AIS.

Topics: Adolescent; Anthropometry; Body Mass Index; Bone and Bones; Bone Density; Case-Control Studies; Child; Female; Humans; Imaging, Three-Dimensional; Leptin; Receptors, Leptin; Scoliosis; Solubility; Tomography, X-Ray Computed

There is an increasing body of research suggesting that low body weight is associated with scoliosis, but this is based on case-control studies, which are prone to bias. No studies have investigated the components of body weight: fat and lean mass. We have therefore carried out the first population-based prospective study of the association between fat and lean mass at age 10 years assessed by dual-energy X-ray absorptiometry (DXA), with presence of scoliosis at age 15 years using the Avon Longitudinal Study of Parents and Children (ALSPAC). All children with scoliosis at age 10 years were excluded. Of 5299 children at age 15 years, 312 (5.9%) had scoliosis. Our results show a negative association between body mass index (BMI)/body weight at age 10 years and scoliosis at age 15 years, with a 20% reduced risk of scoliosis per SD increase in BMI (odds ratio [OR], 0.80; 95% confidence interval [CI], 0.70-0.92; p = 0.001). This association with BMI/body weight reflects associations with both fat mass and lean mass. After adjustment for age, gender, leg length, and fat mass per SD increase in lean mass, there was a 20% reduced risk of scoliosis (OR, 0.80; 95% CI, 0.65-0.97) and per SD increase in fat mass there was a 13% reduced risk of scoliosis (OR, 0.87; 95% CI, 0.74-1.03). In terms of adipocyte function, an inverse association was seen between leptin at age 10 years and scoliosis (OR for scoliosis per SD increase in leptin of 0.78; 95% CI, 0.63-0.99), and a positive association between adiponectin at age 10 years and scoliosis (OR for scoliosis per SD increase in adiponectin of 1.44; 95% CI, 0.99-2.10). This is the first study to address the association between the individual components of body weight and scoliosis in a prospective cohort study, and shows altered body composition that is present before the onset of clinically detected scoliosis.

Topics: Adiponectin; Adolescent; Age of Onset; Body Composition; Body Mass Index; Child; Cohort Studies; Female; Humans; Leptin; Longitudinal Studies; Male; Prospective Studies; Risk Factors; Scoliosis

This was a cross-sectional study.. The present study aimed to explore the differences in leptin bioavailability between adolescent idiopathic scoliosis (AIS) and healthy age-matched girls in a Chinese Han population.. AIS is a common spinal deformity mainly occurring in girls during the peripubertal period. The development of scoliosis is related to relative anterior spinal overgrowth. AIS girls also have associated lower body mass index (BMI) and lower bone mineral status. Leptin, together with soluble leptin receptor (sOB-R), was shown to play an important role in the regulation of bone and energy metabolism in children. It was hypothesized that leptin and sOB-R are abnormal and associated with deranged growth and anthropometric phenotypes in AIS girls.. Serum leptin and sOB-R were measured together with documentation of anthropometric parameters and clinical data in 95 AIS girls and 46 healthy matched controls (age 11-16 years). Serum leptin and sOB-R concentrations were measured by enzyme-linked immunosorbent assay and correlated with the different measured parameters.. AIS girls had significantly lower BMI and longer arm span than healthy controls. AIS girls were found to have significantly higher sOB-R levels and lower free leptin index (FLI) after adjusting for age and body weight in multivariate regression analysis. Significant correlation was found between sOB-R, FLI, and curve severity in AIS girls.. This is the first study demonstrating the presence of abnormal leptin bioavailability in AIS girls that might play an important role in the etiopathogenesis of AIS. Further investigation is required to provide a better understanding of the underlying mechanisms, with the aim to explore the potential clinical application as a biomarker for predicting curve initiation or progression in AIS.

Topics: Adolescent; Anthropometry; Body Height; Body Weight; Child; Cross-Sectional Studies; Female; Humans; Leptin; Receptors, Leptin; Scoliosis

Leptin has been suggested to play a role in the etiology of Adolescent Idiopathic Scoliosis (AIS), however, the leptin levels in AIS girls are still a discrepancy, and no in vitro study of leptin in AIS is reported. We took a series of case-control studies, trying to understand whether Leptin gene polymorphisms are involved in the etiology of the AIS or the change in leptin level is a secondary event, to assess the level of leptin receptor, and to evaluate the differences of response to leptin between AIS cases and controls. We screened all exons of Leptin gene in 45 cases and 45 controls and selected six tag SNPs to cover all the observed variations. Association analysis in 446 AIS patients and 550 healthy controls showed no association between the polymorphisms of Leptin gene and susceptibility/severity to AIS. Moreover, adipogenesis assay of bone mesenchymal stem cells (MSCs) suggested that the adipogenic ability of MSCs from AIS girls was lower than controls. After adjusting the differentiation rate, expressions of leptin and leptin receptor were similar between two groups. Meanwhile, osteogenesis assay of MSC showed the leptin level was similar after adjusting the differentiation rate, but the leptin receptor level was decreased in induced AIS osteoblasts. Immunocytochemistry and western blot analysis showed less leptin receptors expressed in AIS group. Furthermore, factorial designed studies with adipogenesis and osteogenesis revealed that the MSCs from patients have no response to leptin treatment. Our results suggested that Leptin gene variations are not associated with AIS and low serum leptin probably is a secondary outcome which may be related to the low capability of adipogenesis in AIS. The decreased leptin receptor levels may lead to the hyposensitivity to leptin. These findings implied that abnormal peripheral leptin signaling plays an important role in the pathological mechanism of AIS.

Topics: Adipose Tissue; Adolescent; Exons; Humans; Leptin; Polymorphism, Genetic; Receptors, Leptin; Scoliosis

Significantly lower circulating leptin level has been reported in adolescent idiopathic scoliosis (AIS) compared to healthy adolescents. It was hypothesized that leptin dysfunction might be involved in the etiopathogenesis of AIS. In this study, a scoliosis model of bipedal amputated mice with high central leptin activity was established to validate this hypothesis. Three days after bipedal amputation, the mice were randomly divided into two groups: then 8 mice were injected in the hypothalamus with lentivirus vectors which expressed leptin, whereas the remaining 8 were injected with lentivirus vectors expressing GFP (control vector). X-rays were obtained at 20th week to determine the development of spinal deformity. After that all mice were sacrificed, and blood samples were collected. Then peripheral leptin levels were measured by an ELISA kit. Comparisons for the incidence of scoliosis and the severity of the curves were performed between groups. The body weight was found to be slightly lower in the leptin-vector-treated C3H/HeJ mice when compared with control mice. Significantly higher peripheral serum leptin level was found in leptin-vector-treated mice than control mice. Scoliosis was observed in all leptin-vector-treated mice with an average Cobb angle of 28.2°, and in 4/8 of control with an average Cobb angle of 23.5°. The incidence of scoliosis was significantly higher in leptin-vector-treated mice than in control group, although no significant difference was found in terms of curve severity. The results of this study indicated that the high central leptin activity might not only increase the risk of developing a scoliosis in bipedal mice but also contribute to the progression of scoliosis. The high central leptin activity might play an important role in the etiopathogenesis of scoliosis.

Topics: Amputation, Surgical; Animals; Brain; Disease Models, Animal; Forelimb; Humans; Leptin; Mice; Mice, Inbred C3H; Scoliosis

a genetic association study was performed on 126 patients with adolescent idiopathic scoliosis and 197 healthy controls from independent Hungarian pedigrees.. to reveal implication of promoter polymorphisms of bone morphogenetic protein 4 (BMP4), interleukin-6 (IL6), leptin, matrix metalloproteinase-3 (MMP3), melatonin 1B receptor (MTNR1B) genes in adolescent idiopathic scoliosis (AIS). Combinatorial association of these candidate genes was also studied to detect additive effect of certain single-nucleotide polymorphism (SNP) patterns.. it was previously unraveled that IL6, MMP3, and MTNR1B genes could be considered as predisposition genes of AIS. Since BMP4 and leptin play a central role in bone formation and remodeling and are in direct interaction with melatonin, IL6, and MMP3, these also can be potential predisposition genes.. the genotyping was determined by polymerase chain reaction-restriction fragment length polymorphism.. at a single gene level, no significant differences were found for allele and genotype frequencies of the polymorphisms of these genes between cases or controls; therefore, the formerly detected association of IL6, MMP3, and MTNR1B with AIS was not confirmed in the Hungarian population by independent SNP analysis. However, significantly increased AIS risk was observed at particular combinations of genotypes of paired SNPs of the candidate genes.. the genetic effect of promoter polymorphisms of BMP4, IL6, leptin, MMP3, and MTNR1B can be synergistic for susceptibility to AIS. The combinatorial effect can modulate the final biological impact of many susceptibility polymorphisms; therefore, this should be considered at the comparison of results from case-control studies of different populations.

Topics: Adolescent; Bone Morphogenetic Protein 4; Female; Gene Frequency; Gene Regulatory Networks; Genetic Predisposition to Disease; Genotype; Humans; Interleukin-6; Leptin; Male; Matrix Metalloproteinase 3; Models, Genetic; Polymorphism, Single Nucleotide; Promoter Regions, Genetic; Receptor, Melatonin, MT2; Scoliosis; Young Adult

Lower body mass index (BMI) and lower circulating leptin levels have been reported in girls with AIS. In this paper we evaluate skeletal sizes and asymmetries by higher and lower BMI subsets about the means for each of three groups of girls age 11-18 years: 1) normals, 2) school screening referrals, and 3) preoperative girls. Higher and lower BMI subsets, likely to have separated subjects with higher from those with lower circulating leptin levels, identify: 1) girls with relatively earlier and later menarche; 2) trunk width size greater in the higher than in the lower BMI subset, of all three groups; 3) abnormal upper arm length (UAL) asymmetries (right minus left) in the lower BMI subset of the preoperative girls; and 4) in thoracic AIS of screened and preoperative girls, Cobb angle and apical vertebral rotation each significantly and positively correlate with UAL asymmetry in the lower BMI subset but not in the higher BMI subset. In preoperative girls, the lower BMI subset shows the combination of relatively reduced pelvic width and abnormal UAL asymmetry, suggesting that both are linked to lower circulating leptin levels. An earlier puberty with hormonal changes provides a plausible explanation for the larger trunk width at the shoulders and pelvis especially at the younger ages in the higher BMI subsets. At the shoulders, this widening is driven by the ribcage which, in human evolution was acquired with decoupling of head and trunk movements required for efficient bipedal gait. The UAL asymmetry patterns within the groups and BMI subsets are not explained by hormonal mechanisms. It is hypothesized that 1) normal trunk widening of the thoracic cage by hormones in human adolescence is supplemented via the sympathetic nervous system under leptin-hypothalamic control influenced by energy stores (metabolic fuel); and 2) hypothalamic dysfunction with altered hypothalamic sensitivity to leptin through a SNS-driven asymmetric effect may create skeletal length asymmetries in upper arms, ribs, ilia and vertebrae, and initiate AIS. Additional mechanisms acting in the spine and trunk may be required for AIS to progress including 1) somatic nervous system dysfunction, 2) biomechanical spinal growth modulation, and 3) osteopenia.

Topics: Adolescent; Anthropometry; Child; Female; Humans; Hypothalamus; Leptin; Menarche; Pilot Projects; Radiography; Reference Values; Risk Factors; Scoliosis; Sex Factors; Sexual Maturation; Skeleton; Sympathetic Nervous System; Thoracic Vertebrae

To investigate the correlation between the circulating leptin level and the anthropometric parameters and parameters related to pubertal growth, and to explore the role of leptin in the abnormal growth pattern in girls with adolescent idiopathic scoliosis (AIS).. One hundred and twenty AIS girls selected randomly from the out-patient and in-patient departments, divided into 2 groups: Group A1 (n = 73, aged 10 - 13) and Group A2 (n = 47, aged 14 - 17), and 80 14 - 17 year-old healthy girl students receiving physical examination underwent measurement of body height and weight. Body mass index (BMI) was calculated. Peripheral fasting blood samples were collected to detect the level of leptin. The anthropometric data, pubertal status, and circulating leptin level were compared between the AIS girls and the controls. The relationships between leptin and age, menstrual status, body weight, height, BMI and Risser sign were analyzed in the AIS girls.. Eighty-eight AIS girls (73%) and 14 healthy girls (18%) had a BMI score less than 18.0. The mean leptin level of Group A1 was 6.2 microg/L, significantly lower than of Group A2 (8.6 microg/L, P = 0.024). Compared with the healthy controls, the AIS girls had significantly greater corrected height (162.7 cm vs. 160.2 cm, P = 0.026), lower weight (44.3 kg vs. 53.6 kg, P = 0.01), lower BMI (17.5 kg/m(2) vs. 20.9 kg/m(2), P = 0.01), and lower circulating leptin (8.6 microg/L vs. 14.9 microg/L), even after the adjustment for age and menstrual status. An inverse correlation was observed between the leptin level and the age at menarche (AIS, r = -0.428, P < 0.001; controls, r = -0.280, P = 0.013). Whereas, positive correlations were found between leptin and age, menstrual status, body weight, height, BMI, and Risser sign (r = 0.234 - 0.506, P = 0.01 - < 0.001).. AIS girls have markedly decreased circulating leptin level. Circulating leptin level is associated with body weight, BMI, and other growth parameters, suggesting that leptin may play an important role in the lower body mass in AIS girls.

Topics: Adolescent; Body Height; Body Mass Index; Body Weight; Enzyme-Linked Immunosorbent Assay; Female; Humans; Leptin; Scoliosis

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.

Topics: Adolescent; Body Mass Index; Bone Density; Bone Diseases, Metabolic; Child; Female; Femur Neck; Humans; Leptin; Lumbar Vertebrae; Menarche; Menstruation; Prospective Studies; Scoliosis