Ann M Neumeyer1, Natalia Cano Sokoloff2, Erin McDonnell3, Eric A Macklin4, Christopher J McDougle5, Madhusmita Misra6. 1. Lurie Center for Autism, Massachusetts General Hospital, Lexington, MA 02421, United States; Harvard Medical School, Boston, MA 02115, United States. Electronic address: aneumeyer@mgh.harvard.edu. 2. Lurie Center for Autism, Massachusetts General Hospital, Lexington, MA 02421, United States. 3. Biostatistics Center, Massachusetts General Hospital, Boston, MA 02114, United States. 4. Harvard Medical School, Boston, MA 02115, United States; Biostatistics Center, Massachusetts General Hospital, Boston, MA 02114, United States. 5. Lurie Center for Autism, Massachusetts General Hospital, Lexington, MA 02421, United States; Harvard Medical School, Boston, MA 02115, United States. 6. Harvard Medical School, Boston, MA 02115, United States; Pediatric Endocrine and Neuroendocrine Units, Massachusetts General Hospital, Boston, MA 02114, United States.
Abstract
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.
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:ASDparticipants 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. ASDparticipants 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, ASDparticipants 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. ASDparticipants 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, ASDparticipants 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 ASDparticipants 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.
Authors: Robyn P Thom; Christopher J Keary; Michelle L Palumbo; Caitlin T Ravichandran; Jennifer E Mullett; Eric P Hazen; Ann M Neumeyer; Christopher J McDougle Journal: Psychopharmacology (Berl) Date: 2019-05-28 Impact factor: 4.530
Authors: Ann M Neumeyer; Natalia Cano Sokoloff; Erin I McDonnell; Eric A Macklin; Christopher J McDougle; Tara M Holmes; Jane L Hubbard; Madhusmita Misra Journal: J Acad Nutr Diet Date: 2018-03-02 Impact factor: 4.910
Authors: Kelly Barnhill; Lucas Ramirez; Alan Gutierrez; Wendy Richardson; C Nathan Marti; Amy Potts; Rebeca Shearer; Claire Schutte; Laura Hewitson Journal: J Autism Dev Disord Date: 2017-11
Authors: Chadi A Calarge; James A Mills; Ekhard E Ziegler; Janet A Schlechte Journal: J Child Adolesc Psychopharmacol Date: 2017-11-07 Impact factor: 2.576
Authors: Meena Balasubramanian; Rebecca Jones; Elizabeth Milne; Charlotte Marshall; Paul Arundel; Kath Smith; Nicholas J Bishop Journal: Bone Rep Date: 2018-04-18