title: Bone microarchitecture in adolescent boys with autism spectrum disorder.
abstract: 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.
  
  
  
  To assess ultradistal radius and distal tibia vBMD, bone microarchitecture and strength estimates in adolescent boys with ASD compared to TDC.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.affiliation: 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.
authors.forename: Ann M
authors.initials: AM
authors.lastname: Neumeyer
authors.affiliation: Lurie Center for Autism, Massachusetts General Hospital, Lexington, MA 02421, United States.
authors.forename: Natalia
authors.initials: N
authors.lastname: Cano Sokoloff
authors.affiliation: Biostatistics Center, Massachusetts General Hospital, Boston, MA 02114, United States.
authors.forename: Erin
authors.initials: E
authors.lastname: McDonnell
authors.affiliation: Harvard Medical School, Boston, MA 02115, United States; Biostatistics Center, Massachusetts General Hospital, Boston, MA 02114, United States.
authors.forename: Eric A
authors.initials: EA
authors.lastname: Macklin
authors.affiliation: Lurie Center for Autism, Massachusetts General Hospital, Lexington, MA 02421, United States; Harvard Medical School, Boston, MA 02115, United States.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: McDougle
authors.affiliation: Harvard Medical School, Boston, MA 02115, United States; Pediatric Endocrine and Neuroendocrine Units, Massachusetts General Hospital, Boston, MA 02114, United States.
authors.forename: Madhusmita
authors.initials: M
authors.lastname: Misra
mesh_terms: D000293:Adolescent; D000067877:Autism Spectrum Disorder / Q000473:pathology* / Q000503:physiopathology; D015415:Biomarkers / Q000378:metabolism; D015519:Bone Density; D001842:Bone and Bones / Q000473:pathology* / Q000503:physiopathology; D016022:Case-Control Studies; D002648:Child; D015444:Exercise; D006801:Humans; D008297:Male; D011884:Radius / Q000473:pathology / Q000503:physiopathology; D013977:Tibia / Q000473:pathology / Q000503:physiopathology
chemical_list: D015415:Biomarkers
keywords: Autism spectrum disorder; Bone microarchitecture; Bone mineral density