Nutrition and Bone Density in Boys with Autism Spectrum Disorder.

BACKGROUND: Boys with autism spectrum disorder (ASD) have lower bone mineral density (BMD) than typically developing controls. Differences in diet and exercise may contribute to low BMD. OBJECTIVE: Our aim was to examine macro- and micronutrient intakes and self-reported physical activity in boys with ASD compared to TDC and the relationship of these variables with BMD. DESIGN/METHODS: We conducted a cross-sectional study of 49 boys (25 ASD, 24 typically developing controls) assessed for 3-day food records and physical activity records, and BMD of the whole body less head, hip, and spine using dual-energy x-ray absorptiometry. Fasting levels of 25(OH) vitamin D and calcium were obtained. PARTICIPANTS: Participants were adolescent boys, aged 8 to 17 years, recruited from a clinic population (ASD) or community advertisements (ASD and typically developing controls) matched for age. RESULTS: ASD participants were approximately 9 months younger than typically developing control participants on average. Body mass index and serum vitamin D and calcium levels were similar. Boys with ASD consumed 16% fewer calories, with a larger percentage obtained from carbohydrates, and 37% less animal protein and 20% less fat than typically developing controls. A lower proportion of ASD participants were categorized as "very physically active" (27% vs 79%; P<0.001). BMD z scores were 0.7 to 1.2 standard deviations lower in ASD than typically developing controls at all locations. Higher animal protein, calcium, and phosphorus intakes were associated positively with bone density measures in boys with ASD. CONCLUSIONS: Compared to typically developing controls, boys with ASD had lower protein, calcium, and phosphorus intakes, activity levels, and BMD z scores at the lumbar spine, femoral neck, total hip, and whole body less head. Protein, calcium, and phosphorus intakes were associated positively with BMD.

Bone microarchitecture in adolescent boys with autism spectrum disorder.

BACKGROUND: Boys with autism spectrum disorder (ASD) have lower areal bone mineral density (aBMD) than typically developing controls (TDC). Studies of volumetric BMD (vBMD) and bone microarchitecture provide information about fracture risk beyond that provided by aBMD but are currently lacking in ASD. OBJECTIVES: To assess ultradistal radius and distal tibia vBMD, bone microarchitecture and strength estimates in adolescent boys with ASD compared to TDC. DESIGN/METHODS: Cross-sectional study of 34 boys (16 ASD, 18 TDC) that assessed (i) aBMD at the whole body (WB), WB less head (WBLH), hip and spine using dual X-ray absorptiometry (DXA), (ii) vBMD and bone microarchitecture at the ultradistal radius and distal tibia using high-resolution peripheral quantitative CT (HRpQCT), and (iii) bone strength estimates (stiffness and failure load) using micro-finite element analysis (FEA). We controlled for age in all groupwise comparisons of HRpQCT and FEA measures. Activity questionnaires, food records, physical exam, and fasting levels of 25(OH) vitamin D and bone markers (C-terminal collagen crosslinks and N-terminal telopeptide (CTX and NTX) for bone resorption, N-terminal propeptide of Type 1 procollagen (P1NP) for bone formation) were obtained. RESULTS: ASD participants were slightly younger than TDC participants (13.6 vs. 14.2years, p=0.44). Tanner stage, height Z-scores and fasting serum bone marker levels did not differ between groups. ASD participants had higher BMI Z-scores, percent body fat, IGF-1 Z-scores, and lower lean mass and aBMD Z-scores than TDC at the WB, WBLH, and femoral neck (P<0.1). At the radius, ASD participants had lower trabecular thickness (0.063 vs. 0.070mm, p=0.004), compressive stiffness (56.7 vs. 69.7kN/mm, p=0.030) and failure load (3.0 vs. 3.7kN, p=0.031) than TDC. ASD participants also had 61% smaller cortical area (6.6 vs. 16.4mm2, p=0.051) and thickness (0.08 vs. 0.22mm, p=0.054) compared to TDC. At the tibia, ASD participants had lower compressive stiffness (183 vs. 210kN/mm, p=0.048) and failure load (9.4 vs. 10.8kN, p=0.043) and 23% smaller cortical area (60.3 vs. 81.5mm2, p=0.078) compared to TDC. A lower proportion of ASD participants were categorized as "very physically active" (20% vs. 72%, p=0.005). Differences in physical activity, calcium intake and IGF-1 responsiveness may contribute to group differences in stiffness and failure load. CONCLUSION: Bone microarchitectural parameters are impaired in ASD, with reductions in bone strength estimates (stiffness and failure load) at the ultradistal radius and distal tibia. This may result from lower physical activity and calcium intake, and decreased IGF-1 responsiveness.

Bone Accrual in Males with Autism Spectrum Disorder.

OBJECTIVE: To test the hypothesis that bone accrual over a 4-year period is reduced in boys with autism spectrum disorder (ASD) compared with typically developing controls. STUDY DESIGN: Twenty-five boys with ASD and 24 controls were assessed for bone outcomes. Fourteen boys with ASD and 11 controls were assessed both at baseline and after 4 years. The mean subject age was 11.0 ± 1.6 years at study initiation and 14.9 ± 1.6 years at follow-up. Bone mineral density (BMD) was measured at the spine, hip, and whole body using dual-energy X-ray absorptiometry and normalized for age, race, and sex (BMD z-scores). Height adjustments were performed as well. We assessed medical history, physical activity using questionnaires, vitamin D and calcium intake using food records, and serum calcium, phosphorus, 25(OH)-vitamin D, and pubertal hormone levels. RESULTS: Boys with ASD had lower spine, hip, and whole body BMD z-scores compared with controls. In those subjects assessed both at baseline and after 4 years, bone accrual rates did not differ between the 2 groups; however, spine and hip BMD z-scores remained lower in the boys with ASD than in controls at follow-up. Notably, the ASD group was less physically active at both time points. CONCLUSION: Although pubertal bone accrual was similar to that in controls, BMD in children with ASD remained low over a 4-year follow-up period, suggesting that low BMD is a consequence of prepubertal factors, such as low physical activity. Studies are needed to investigate the causes and consequences of decreased BMD, to assess BMD in females and adults with ASD, and to evaluate therapeutic interventions.

Exercise, Training, and the Hypothalamic-Pituitary-Gonadal Axis in Men and Women.

The hypothalamic-pituitary-gonadal (HPG) axis is essential for adequate responses to exercise and training both acutely and chronically. Both testosterone and estrogen play leading roles in neuromuscular adaptation to exercise in males and females. The purpose of this chapter is to illustrate the physiological and pathological changes that occur in the HPG axis secondary to exercise and training. In males, testosterone increases with acute bouts of exercise, but long-term effects are less clear, with evidence of lower testosterone in endurance athletes. Restricted energy availability may negatively affect hormone levels in male endurance athletes, but data regarding low energy availability and its impact on the HPG axis are limited in male athletes. Conversely, in females there is significant evidence that decreased energy availability inhibits the HPG axis, leading to menstrual irregularities and lower bone density. Hormonal changes secondary to acute bouts of exercise are more challenging to interpret in females due to menstrual variability, which traditionally has not been taken into account in many studies. However, some evidence supports an increase in testosterone and estradiol with acute exercise. More work is needed to elucidate the relationships among energy availability, basal hormonal fluctuations, and exercise, and their collective effects on the HPG axis.

Diets High in Fiber and Vegetable Protein Are Associated with Low Lumbar Bone Mineral Density in Young Athletes with Oligoamenorrhea.

BACKGROUND: Associations of bone mineral density (BMD) with specific food components, including dietary fiber and isoflavones (that have a negative association with serum estrogen), are unclear and need to be determined, particularly in populations more likely to consume large amounts of these nutrients (such as young athletes). OBJECTIVE: To determine dietary intake of specific food components in athletes with oligoamenorrhea (OA) compared to athletes with eumenorrhea (EA) and nonathletes (NA), and associations of the dietary intake of these nutrients with lumbar spine BMD. DESIGN AND SUBJECTS: This cross-sectional study evaluated 68 OA, 24 EA, and 26 NA individuals aged 14 to 23 years. Measurements included 4-day food records, a dual x-ray absorptiometry scan evaluating lumbar spine BMD and body composition, and hormone levels. Multivariate analysis was used to estimate associations of nutrients with lumbar spine BMD. RESULTS: Compared with EA and NA, OA had higher intake of fiber, phytic acid, and vegetable protein (all P values <0.0001). Intake of isoflavones, genistein, and daidzein was higher in OA than NA (P=0.003 and P=0.0002, respectively). OA had lower consumption of energy from saturated fatty acids than NA (P=0.002). After controlling for confounders such as body weight, menstrual status (indicative of estrogen status), calcium intake, and serum vitamin D (known BMD determinants), lumbar spine BMD z scores were inversely associated with dietary fiber (ß=-.30; P=0.01), vegetable protein (ß= -.28; P=0.02), phytic acid (ß=-.27; P=0.02), genistein (ß=-.25; P=0.01), and daidzein (ß=-.24; P=0.01), and positively associated with percent energy from fatty acids (ß=.32; P=0.0006). CONCLUSIONS: Compared with EA and NA, OA had a higher dietary intake of fiber, vegetable protein, and phytic acid, which were inversely associated with lumbar spine BMD z scores. Further studies are needed to assess dietary recommendations for OA to optimize bone accrual.

Altered trabecular bone morphology in adolescent and young adult athletes with menstrual dysfunction.

CONTEXT: Young amenorrheic athletes (AA) have lower bone mineral density (BMD) and an increased prevalence of fracture compared with eumenorrheic athletes (EA) and non-athletes. Trabecular morphology is a determinant of skeletal strength and may contribute to fracture risk. OBJECTIVES: To determine the variation in trabecular morphology among AA, EA, and non-athletes and to determine the association of trabecular morphology with fracture among AA. DESIGN AND SETTING: A cross-sectional study performed at an academic clinical research center. PARTICIPANTS: 161 girls and young women aged 14-26 years (97 AA, 32 EA, and 32 non-athletes). MAIN OUTCOME MEASURE: We measured volumetric BMD (vBMD) and skeletal microarchitecture using high-resolution peripheral quantitative computed tomography. We evaluated trabecular morphology (plate-like vs. rod-like), orientation, and connectivity by individual trabecula segmentation. RESULTS: At the non-weight-bearing distal radius, the groups did not differ for trabecular vBMD. However, plate-like trabecular bone volume fraction (pBV/TV) was lower in AA vs. EA (p=0.03), as were plate number (p=0.03) and connectivity (p=0.03). At the weight-bearing distal tibia, trabecular vBMD was higher in athletes vs. non-athletes (p=0.05 for AA and p=0.009 for EA vs. non-athletes, respectively). pBV/TV was higher in athletes vs. non-athletes (p=0.04 AA and p=0.005 EA vs. non-athletes), as were axially-aligned trabeculae, plate number, and connectivity. Among AA, those with a history of recurrent stress fracture had lower pBV/TV, axially-aligned trabeculae, plate number, plate thickness, and connectivity at the distal radius. CONCLUSIONS: Trabecular morphology and alignment differ among AA, EA, and non-athletes. These differences may be associated with increased fracture risk.

Bone parameters in relation to attitudes and feelings associated with disordered eating in oligo-amenorrheic athletes, eumenorrheic athletes, and nonathletes.

OBJECTIVES: Disordered eating may negatively impact bone in athletes. However, it is not known whether this effect is independent of the associated amenorrhea and relative hypercortisolemia. We aimed to compare attitudes, feelings, and cognitions associated with disordered eating using the Three-Factor Eating Questionnaire (TFEQ) and Eating Disorder Inventory-2 (EDI-2) in normal-weight oligomenorrheic athletes (OA), eumenorrheic athletes (EA), and nonathletes, and determine the associations with bone independent of confounders. METHOD: 109 OA, 39 EA, and 36 nonathletes (14-25 years) completed the TFEQ and EDI-2. Dual-energy X-ray absorptiometry was used to assess spine bone mineral density (BMD), and high-resolution pQCT to assess radius microarchitecture. We measured integrated cortisol (q 20', 11 PM-7 AM), bone formation (procollagen Type 1 N-terminal propeptide, P1NP), and resorption (C-telopeptide, CTX) markers in a subset. RESULTS: OA had lower spine BMD Z-scores than EA. Cognitive eating restraint (CER), drive for thinness (DT), ineffectiveness, and interoceptive awareness (IA) were higher in OA than EA (p < 0.05); CER was higher in OA versus nonathletes (p = 0.03). Pulsatile cortisol was positively associated with DT, ineffectiveness, and IA (p < 0.03). CER was inversely associated with BMD Z-scores and P1NP, and ineffectiveness with radius cross-sectional area even after controlling for age, BMI, amenorrhea duration, and cortisol (p < 0.03). DISCUSSION: Higher CER in athletes independently predicts lower BMD.

Regional fat depots and their relationship to bone density and microarchitecture in young oligo-amenorrheic athletes.

CONTEXT: Various fat depots have differential effects on bone. Visceral adipose tissue (VAT) is deleterious to bone, whereas subcutaneous adipose tissue (SAT) has positive effects. Also, marrow adipose tissue (MAT), a relatively newly recognized fat depot is inversely associated with bone mineral density (BMD). Bone mass in athletes depends on many factors including gonadal steroids and muscle mass. Exercise increases muscle mass and BMD, whereas, estrogen deficiency decreases BMD. Thus, the beneficial effects of weight-bearing exercise on areal and volumetric BMD (aBMD and vBMD) in regularly menstruating (eumenorrheic) athletes (EA) are attenuated in oligo-amenorrheic athletes (OA). Of note, data regarding VAT, SAT, MAT and regional muscle mass in OA compared with EA and non-athletes (C), and their impact on bone are lacking. METHODS: We used (i) MRI to assess VAT and SAT at the L4 vertebra level, and cross-sectional muscle area (CSA) of the mid-thigh, (ii) 1H-MRS to assess MAT at L4, the proximal femoral metaphysis and mid-diaphysis, (iii) DXA to assess spine and hip aBMD, and (iv) HRpQCT to assess vBMD at the distal radius (non-weight-bearing bone) and tibia (weight-bearing bone) in 41 young women (20 OA, 10 EA and 11 C 18-25 years). All athletes engaged in weight-bearing sports for ≥ 4 h/week or ran ≥ 20 miles/week. MAIN OUTCOME MEASURES: VAT, SAT and MAT at L4; CSA of the mid-thigh; MAT at the proximal femoral metaphysis and mid-diaphysis; aBMD, vBMD and bone microarchitecture. RESULTS: Groups had comparable age, menarchal age, BMI, VAT, VAT/SAT and spine BMD Z-scores. EA had higher femoral neck BMD Z-scores than OA and C. Fat mass was lowest in OA. SAT was lowest in OA (p = 0.048); L4 MAT was higher in OA than EA (p = 0.03). We found inverse associations of (i) VAT/SAT with spine BMD Z-scores (r = -0.42, p = 0.01), (ii) L4 MAT with spine and hip BMD Z-scores (r = -0.44, p = 0.01; r = -0.36, p = 0.02), and vBMD of the radius and tibia (r = -0.49, p = 0.002; r = -0.41, p = 0.01), and (iii) diaphyseal and metaphyseal MAT with vBMD of the radius (r ≤ -0.42, p ≤ 0.01) and tibia (r ≤ -0.34, p ≤ 0.04). In a multivariate model including VAT/SAT, L4 MAT and thigh CSA, spine and hip BMD Z-scores were predicted inversely by L4 MAT and positively by thigh CSA, and total and cortical radius and total tibial vBMD were predicted inversely by L4 MAT. VAT/SAT did not predict radius or tibia total vBMD in this model, but inversely predicted spine BMD Z-scores. When L4 MAT was replaced with diaphyseal or metaphyseal MAT in the model, diaphyseal and metaphyseal MAT did not predict aBMD Z-scores, but diaphyseal MAT inversely predicted total vBMD of the radius and tibia. These results did not change after adding percent body fat to the model. CONCLUSIONS: VAT/SAT is an inverse predictor of lumbar spine aBMD Z-scores, while L4 MAT is an independent inverse predictor of aBMD Z-scores at the spine and hip and vBMD measures at the distal tibia and radius in athletes and non-athletes. Diaphyseal MAT independently predicts vBMD measures of the distal tibia and radius.

Fractures in Relation to Menstrual Status and Bone Parameters in Young Athletes.

INTRODUCTION: This study was aimed to compare fracture prevalence in oligoamenorrheic athletes (AA), eumenorrheic athletes (EA), and nonathletes (NA) and determine relationships with bone density, structure, and strength estimates. METHODS: One hundred seventy-five females (100 AA, 35 EA, and 40 NA) 14-25 yr old were studied. Lifetime fracture history was obtained through participant interviews. Areal bone mineral density (BMD) was assessed by DXA at the spine, hip, and whole body (WB). Bone structure was assessed by HRpQCT at the radius and tibia, and strength by finite element analysis. RESULTS: AA, EA, and NA did not differ in age, sexual maturity, or height. AA had lower BMI, and older menarchal age than EA and NA (P ≤ 0.001). Bone mineral density Z-scores were lower in AA versus EA at the total hip, femoral neck, spine, and whole body (P ≤ 0.001). Lifetime fracture risk was higher in AA than EA and NA (47%, 25.7%, 12.5%; P ≤ 0.001), largely driven by stress fractures in AA versus EA and NA (32% vs 5.9% vs 0%). In AA, those who fractured had lower lumbar and WB BMD Z-scores, volumetric BMD (vBMD) of outer trabecular region in radius and tibia, and trabecular thickness of the radius (P ≤ 0.05). In AA, those who had two or more stress fractures had lower lumbar and WB BMD Z-scores, total cross-sectional area, trabecular vBMD, stiffness, and failure load at radius; and lower stiffness and failure load at tibia versus those with fewer than two stress fractures (P ≤ 0.05). CONCLUSION: Weight-bearing athletic activity increases BMD but may increase stress fracture risk in those with menstrual dysfunction. Bone microarchitecture and strength differences are more pronounced in AA with multiple stress fractures. This is the first study to examine fractures in relation to bone structure in adolescent female athletes.

Update on body composition and bone density in children with Prader-Willi syndrome.

AIM: To compare body composition in children with Prader-Willi syndrome (PWS) not naïve to growth hormone (GH) with obese and lean controls. METHODS: Participants included 12 children with PWS, 12 children with obesity (body fat percentage >95th percentile for age and sex) and 12 lean children (body fat percentage <85th percentile for age and sex) matched by age and height. Fat mass, lean mass, bone mineral content (BMC), bone mineral density (BMD) and BMD z-score for total body, hips and lumbar spine were obtained through dual X-ray absorptiometry. RESULTS: PWS had higher fat percentage in the legs (p = 0.04) but similar leg fat mass (p = 1.00) compared to obese. PWS exhibited lower lean mass in the body (p = 0.04) and legs (p = 0.02) than obese, but similar to lean (p = 1.00 and p = 0.89, respectively). PWS had lower hip BMC (p < 0.01), BMD (p < 0.01) and BMD z-score (p < 0.01) compared to obese but similar to lean. No other differences were found between PWS and obese (p > 0.05 for all). CONCLUSIONS: Children with PWS not naïve to GH present differences in fat and lean mass distribution compared to obese controls. BMC and BMD appear unaffected by PWS, except at the hips.