Polymorphism in vitamin D receptor is associated with bone mineral density in patients with adolescent idiopathic scoliosis

Low bone mass and osteopenia have been reported in the axial and peripheral skeleton of adolescent idiopathic scoliosis (AIS) patients. Furthermore, several recent studies have shown that gene polymorphisms are related to osteoporosis. However, no study has yet linked polymorphisms in the vitamin D receptor (VDR) gene and bone mass in AIS. Accordingly, the authors examined the association between bone mass and VDR gene polymorphisms in 198 girls diagnosed with AIS. The VDR BsmI (rs1544410), FokI (rs2228670) and Cdx2 (rs11568820) polymorphisms and bone mineral density at the lumbar spine (LSBMD) and femoral neck (FNBMD) were analyzed and compared to their levels in healthy controls. Mean LSBMD and FNBMD in AIS patients were lower than in age- and sex-matched healthy controls (P = 0.0022 and P = 0.0013, respectively). A comparison of genotype frequencies in AIS patients and controls revealed a significant difference for the BsmI polymorphism only (P = 0.0054). Furthermore, a significant association was found between the VDR BsmI polymorphism and LSBMD. In particular, LSBMD in AIS patients with the AA genotype was found to be significantly lower than in patients with the GA (P < 0.05) or GG (P < 0.01) genotypes. However, no significant association was found between LSBMD or FNBMD and the VDR FokI or Cdx2 polymorphisms. These results suggest that the VDR BsmI polymorphism is associated with LSBMD in girls with AIS.     

Decreased osteogenic differentiation of mesenchymal stem cells and reduced bone mineral density in patients with adolescent idiopathic scoliosis

Generalized low bone mass and osteopenia in both axial and peripheral skeletons have been reported in adolescent idiopathic scoliosis (AIS). However, the mechanism and causes of bone loss in AIS have not been identified. Therefore, this study examined the relationship between the osteogenic and adipogenic differentiation abilities of mesenchymal stem cells (MSCs) and bone mass in 19 patients with AIS and compared these with those of 16 age- and gender-matched patients with lower leg fracture. Mean lumbar spinal bone mineral density (LSBMD) in AIS patients was found to be lower than in controls (P = 0.037) and the osteogenic differentiation abilities and alkaline phosphatase activities of MSCs from patients were also found to be lower than those of controls (P = 0.0073 and P = 0.001, respectively), but the abilities of the MSCs of patients and controls to undergo adipogenic differentiation were similar. The osteogenic differentiation ability was found to be positively correlated with alkaline phosphatase activity in the AIS group. However, the osteogenic and adipogenic abilities were not found to be correlated with LSBMD in either patients or controls. These findings suggest that the decreased osteogenic differentiation ability of MSCs might be one of the possible mechanisms leading to low bone mass in AIS. However, we did not determine definite mechanisms of low bone mass in AIS. Therefore, further study with large scale will be needed to identify the mechanism involved.     

The association of disproportionate skeletal growth and abnormal radius dimension ratio with curve severity in adolescent idiopathic scoliosis

Abnormal anthropometric measurements during the peripubertal growth spurt have been documented in adolescent idiopathic scoliosis (AIS). Magnetic resonance (MR) imaging studies of the spine have suggested a disproportionate endochondral and membranous ossification in AIS. The present study aimed at investigating whether disproportional ossification and skeletal growth occurred in the peripheral bone of AIS patients using the radius as the target bone. Skeletally mature AIS girls with different severity (n = 290) and age-matched control healthy girls (n = 80) were recruited. The anthropometric parameters were recorded. The midshaft of non-dominant radius was scanned with peripheral quantitative computed tomography (pQCT) and the radius diameter was calculated from the cross-sectional area. Radius dimension ratio was derived from the ratio of radius diameter to radius length. The anthropometric parameters were compared between AIS and control with adjustment for age. The radius dimension ratio was further correlated with curve severity in AIS girls using Pearson’s correlation test. The analysis showed that the arm span and radius length were slightly longer in AIS girls. The BMI of AIS girls was significantly lower than the controls. The radius dimension ratio in severe AIS girls was significantly lower than the controls and the ratio of AIS girls correlated with the curve severity (r = −0.120; p = 0.039). The abnormal radius dimension ratio supported the presence of systemic growth abnormalities in AIS. Disproportional endochondral-membranous ossification could explain for the observation. The observation of the association of radius dimension ratio with curve severity provides an important potentially clinically measurable parameter for further longitudinal studies on the prognostication of curve progression in AIS.     

Association of osteopenia with curve severity in adolescent idiopathic scoliosis: a study of 919 girls

Generalized osteopenia and spinal deformity occur concomitantly in adolescent idiopathic scoliosis (AIS) during the peripubertal period. No large-scale study has been performed to reveal the link between scoliotic deformity and bone-mineral status in AIS. In a cross-sectional study, the extent of scoliotic-curve severity in relation to bone-mineral status was examined for 619 AIS girls and compared with those of 300 healthy non-AIS counterparts aged 11–16 years. Curve severity was categorized into a moderate (10–39°) and a severe group (40°) based on Cobb angle. Anthropometric parameters, bone mineral-density (BMD) and bone mineral-content (BMC) of lumbar spine, proximal femur and distal tibia were determined by dual-energy X-ray absorptiometry and peripheral QCT. Differences in anthropometric parameters and bone mass among control and the AIS-moderate and AIS-severe groups were tested by one-way ANOVA. Association between Cobb angle and bone mass was determined by univariate and multivariate analyses. Mean Cobb angle of the moderate and severe groups were 25±6.3° and 50.2±11.3°, respectively. Arm span and leg length among the moderate and severe AIS subjects were almost all longer than for the controls from age 13 years. Age-adjusted arm span and leg length were significantly correlated with curve severity ( p <0.015). Starting from age 13 years, most axial and peripheral BMD and BMC of the moderate or severe AIS group was significantly lower than for the controls ( p <0.029). Age-adjusted Cobb angle was inversely correlated with BMD and BMC of the distal tibia and lumbar spine among AIS subjects ( p 0.042). The proportion of osteopenic AIS girls in the severe group was significantly higher than that in the moderate group ( p 0.033). Multivariate analysis indicated that Cobb angle was inversely and independently associated with axial and peripheral BMD and BMC ( p 0.042). To conclude, curve severity was an inverse and independent associated factor on bone mineral mass of AIS during peripuberty. The study implied that prevention of osteopenia could be as important as controlling spinal progression in the management of AIS.     

Elevated soluble receptor activator of nuclear factor-κB ligand and reduced bone mineral density in patients with adolescent idiopathic scoliosis

Generalized low bone mass and osteopenia in both axial and peripheral skeleton in adolescent idiopathic scoliosis (AIS) have been reported in literature. However, the exact mechanisms and causes of the bone loss in AIS are not identified yet. Therefore, this study examined the relationship between serum concentration of soluble receptor activator of nuclear factor-κB ligand (RANKL), serum level of osteoprotegerin (OPG) and bone mass in 72 patients with AIS and compared to those of 64 age- and gender-matched healthy controls. The mean lumbar spinal bone mineral density (LSBMD) and femoral neck BMD (FNBMD) in patients with AIS were decreased compared with that in control individuals, respectively (P = 0.0029 and P = 0.0192, respectively). The mean RANKL and RANKL to OPG ratio in patients with AIS were increased compared with that in control subjects, respectively (P = 0.0004 and P = 0.0032, respectively). The RANKL and RANKL to OPG ratios were negatively correlated to the LSBMD and serum OPG levels in both groups. Serum OPG levels were positively correlated to the LSBMD and FNBMD in both groups. These findings mean that the imbalance and the disturbed interaction of RANKL and OPG may be an important cause and pathogenesis in reduced BMD in AIS.     

Daily Physical Education in the School Curriculum in Prepubertal Girls during 1 Year is Followed by an Increase in Bone Mineral Accrual and Bone Width—Data from the Prospective Controlled Malmö Pediatric Osteoporosis Prevention Study

The aim of this study was to evaluate a general school-based 1-year exercise intervention program in a population-based cohort of girls at Tanner stage I. Fifty-three girls aged 7–9 years were included. The school curriculum-based exercise intervention program included 40 minutes/school day. Fifty healthy age-matched girls assigned to the general school curriculum of 60 minutes physical activity/week served as controls. Bone mineral content (BMC, g) and areal bone mineral density (aBMD, g/cm²) were measured with dual X-ray absorptiometry (DXA) of the total body (TB), lumbar spine (L2–L4 vertebrae), third lumbar vertebra (L3), femoral neck (FN), and leg. Volumetric bone mineral density (g/cm³) and bone width were calculated at L3 and FN. Total lean body mass and total fat mass were estimated from the TB scan. No differences at baseline were found in age, anthropometrics, or bone parameters when the groups were compared. The annual gain in BMC was 4.7 percentage points higher in the lumbar spine and 9.5 percentage points higher in L3 in cases than in controls (both P < 0.001). The annual gain in aBMD was 2.8 percentage points higher in the lumbar spine and 3.1 percentage points higher in L3 in cases than in controls (both P < 0.001). The annual gain in bone width was 2.9 percentage points higher in L3 in cases than in controls (P < 0.001). A general school-based exercise program in girls aged 7–9 years enhances the accrual of BMC and aBMD and increases bone width.     

Defining the bone morphometry,micro-architecture and volumetric density profile in osteopenic vs non-osteopenic adolescent idiopathic scoliosis

Purpose

Osteopenia has been widely reported in about 30 % of girls with adolescent idiopathic scoliosis (AIS). However, the bone quality profile of the 70 % non-osteopenic AIS defined by areal bone mineral density (BMD) with conventional dual-energy X-ray absorptiometry (DXA) has not been adequately studied. Our purpose was to verify whether abnormal volumetric BMD (vBMD) and bone structure (morphometry and micro-architecture) also existed in the non-osteopenic AIS when compared with matched controls using both DXA and high-resolution peripheral computed tomography (HR-pQCT).

Methods

This was a case–control cross-sectional study. 257 AIS girls with a mean age of 12.7 (SD = 0.8) years old and 187 age- and gender-matched normal controls with an average age of 12.9 (SD = 0.5) years old were included. Areal BMD (aBMD) and bone quality were measured with standard DXA and HR-pQCT, respectively. The parameters of HR-pQCT could be categorized as bone morphometry, vBMD and bone micro-architecture. The results were compared between the osteopenic AIS and osteopenic control, and between the non-osteopenic AIS and non-osteopenic control.

Results

In addition to the lower aBMD and vBMD, osteopenic AIS showed significantly greater cortical perimeter and trabecular area than the osteopenic control even after adjustments of age (P < 0.05). Non-osteopenic AIS also showed significantly lower aBMD together with lower cortical area, thickness and vBMD than the non-osteopenic control (P < 0.05). After adjustments of age, cortical area and vBMD, and trabecular number and separation continued to show statistical significance (P < 0.05). Both the osteopenic and non-osteopenic AIS subgroups revealed significant abnormal bone quality parameters from that in the control group after adjustments of age and aBMD with multi-linear regression analysis (P < 0.05).

Conclusions

The present study specifically defined the abnormal profile of bone quality in the osteopenic and non-osteopenic AIS for the first time. Both the osteopenic and non-osteopenic AIS were likely to have relatively lower bone mineral status and abnormal bone morphometry, micro-architecture and volumetric density profile compared with their normal matched controls. The observed abnormalities were suggestive of decreased endocortical bone apposition or active endocortical resorption that could affect the mechanical bone strength in AIS. The underlying pathomechanism might be attributed to abnormal bone modeling/remodeling that could be associated with the etiopathogenesis of AIS.

     

A 3-Year Longitudinal Study of the Effect of Physical Activity on the Accrual of Bone Mineral Density in Healthy Adolescent Males

It has previously been suggested that physical activity predominantly influences the accumulation of bone density before puberty. The purpose of the present study was to examine the effect of physical activity on the accumulation of bone mass in male athletes between 16 and 19 years of age. The cohort studied consisted of 12 badminton players (aged 16.1 ± 0.5), 20 ice hockey players (aged 16.1 ± 0.5), and 24 age-matched controls (aged 16.1 ± 0.6). The bone mineral density (BMD, g/cm²) of the total body, spine, dominant and nondominant humerus, head and femoral neck was measured twice with a 3-year interval by dual energy X-ray absorptiometry (DXA). In addition, at the femoral neck, volumetric bone mineral density (vBMD, mg/cm³) was estimated. At baseline, the athletes as a whole group had significantly higher BMD at the total body (P = 0.03), dominant (P = 0.006) and nondominant humerus (P = 0.009) and femoral neck (P = 0.007) compared to the controls. At the 3-year followup, the athletes had significantly higher BMD at all sites (total body; P = 0.003, spine; P = 0.02, dominant humerus; P = 0.001, nondominant humerus; P = <0.001, femoral neck; P = 0.001) except for the head (P = 0.91) compared with controls. The athletes also had higher vBMD at the femoral neck compared with the controls (P = 0.01). Furthermore, to be an athlete was found to be independently associated with a higher increase in nondominant humerus BMD ( = 0.24; P < 0.05) and femoral neck BMD ( = 0.30; P < 0.05) compared with the controls, during the study period. In summary, these results suggests that it is possible to achieve continuous gains in bone mass in sites exposed to osteogenic stimulation after puberty in males by engaging in weight-bearing physical activity.     

Bone mineral density in girls and boys at different pubertal stages: relation with gonadal steroids, bone formation markers, and growth parameters

Puberty has a key role in bone development. During puberty, several nutritional and hormonal factors play a major role in this process. The aim of this study was to determine the changes in areal bone mineral density (BMD), gonadal steroids, bone formation markers, and growth parameters in healthy Turkish pubertal girls and boys at different pubertal stages. In additional, we aimed to detect the relationship between BMD, sex steroids, and growth parameters, and to reveal the most important determinant of BMD in the pubertal period. BMD of the lumbar spine and total body was performed by dual-energy X-ray absorptiometry (Lunar DPX series) in 174 healthy pubertal children (91 girls, 83 boys), aged 11–15 years. Height and weight were measured. Pubertal stages were assesed. Bone formation markers and gonadal steroids were measured. BMD values significantly increased until stage IV in girls. In boys, BMD values also increased during puberty (P < 0.05), but it was significantly higher in stage IV compared with that in other pubertal stages (P < 0.01). Testosterone levels increased until stage IV in both sexes, particularly in boys. Estrogen levels significantly increased during puberty in girls, whereas it was significantly higher at stage IV in boys (P < 0.001). Bone-specific alkaline phosphatase (BAP) level was higher in early and midpuberty, and decreased in late puberty in girls (P < 0.001). BAP level was higher in stage IV in boys. Osteocalcin level was shown not to change significantly in pubertal stages. There was a modest correlation between BMD values and estrogen and testosterone levels in boys. In girls, there was a correlation between BMD values and estrogen levels only (P < 0.05). Weight was significantly associated with BMD in both sexes (P < 0.05). Estrogen had a significant influence on BMD in boys and girls. In conclusion, bone mass increased throughout puberty in both sexes. Peak bone mass was not achieved in girls, but was obtained at stage IV in boys. Bone formation markers were good predictors of bone mass in girls, but not in boys. Estrogen level made the greatest contribution to bone mineral acquisition in boys and girls. The achievement of peak bone mass was sustained by estrogen in boys. The major independent determinant of BMD in both sexes was weight.     

Bone gained from physical activity and lost through detraining: a longitudinal study in young males

The aim of this study was to investigate the effect of training and detraining on bone mineral density of both weight-bearing and non-weight-bearing bone in a cohort of young males who participated in ice hockey training. Forty-three healthy adolescent ice hockey players (16.7±0.6 years) training for a mean of 9.7±2.4 h/week and 25 control subjects (16.8±0.3 years) training for 2.1±2.7 h/week, were included in this longitudinal study. Bone mineral density (BMD, g/cm²) of the arms, the dominant and non-dominant humerus, dominant and non-dominant femur, and the right femoral neck, total hip, and bone area of the femur, humerus and hip were measured at baseline and again after 30 and 70 months using dual-energy X-ray absorptiometry. From baseline to the first follow-up, athletes gained significantly more BMD in the femoral neck (0.07 versus 0.03 g/cm²) and arms (0.09 versus 0.06 g/cm²) compared with the controls (P=0.04 for both). Between the first and the second follow-up, 21 ice hockey players stopped their active sports career. These men lost significantly more BMD at the femoral neck (–0.02 versus –0.10 g/cm², P<0.001), total hip (–0.05 versus –0.09, P=0.04), dominant (0.02 versus –0.03 g/cm², P=0.009) and non-dominant humerus (0.03 versus –0.01 g/cm², P=0.03) than the still active ice hockey players (n=22). At the second follow-up examination, at 22 years of age, the former ice hockey players still had significantly higher BMD at the non-dominant humerus than the controls (P<0.01). During the total study period, the still active athletes (n=22) gained significantly more BMD compared with the controls at the femoral neck (0.09 g/cm²; P=0.008), total hip (0.05 g/cm², P=0.04) and arms (0.07 g/cm²; P=0.01). No differences were seen in bone areas when comparing the different groups. In conclusion, training associated with ice hockey is related to continuous accumulation of BMD after puberty in males. Reduced activity is followed by BMD loss within 3 years of cessation of sports career at predominantly weight-bearing sites. The effects are confined to bone density and not bone size.