Journal of Autism and Developmental Disorders

, Volume 47, Issue 11, pp 3608–3619 | Cite as

Bone Mineral Density in Boys Diagnosed with Autism Spectrum Disorder: A Case-Control Study

  • Kelly BarnhillEmail author
  • Lucas Ramirez
  • Alan Gutierrez
  • Wendy Richardson
  • C. Nathan Marti
  • Amy Potts
  • Rebeca Shearer
  • Claire Schutte
  • Laura Hewitson
Original Paper


This study compared bone mineral density (BMD) of the spine obtained by dual-energy X-ray absorptiometry (DEXA), nutritional status, biochemical markers, and gastrointestinal (GI) symptoms in 4–8 year old boys with Autism Spectrum Disorder (ASD) with a group of age-matched, healthy boys without ASD. Boys with ASD had significantly lower spine BMD compared to controls but this was not correlated with any biochemical markers, dietary intake of calcium and vitamin D, elimination diet status, or GI symptomology. Reduced BMD in 4–8 year old boys with ASD appears to involve factors other than nutrient intake and GI status, and requires further study.


Bone mineral density Autism spectrum disorder Nutrition Gastrointestinal symptoms Gluten-free/casein-free diet Vitamin D 



We are very grateful to all the families that participated in this research study. We would particularly like to thank Anissa Ryland, Morgan Devlin, Nichole Roatch, Tiffany Maudlin, Tony Phelan, Michael Rotko, Hannah Somerville, Meg Glausser, Sean Goetz, and all the support staff and clinicians at The Johnson Center for Child Health and Development, for assistance with implementing this study. Funding was provided by The Johnson Center for Child Health and Development.

Author contribution

KB and LH conceived the study, participated in its design and coordination, interpreted the data, and drafted the manuscript; LR, AG, RS and CS participated in the design of the study and performed the measurements; WR and AP participated in the design and coordination of the study and collected data; and CNM performed the statistical analysis, assisted in the interpretation of the data, and helped draft the manuscript. All authors read and approved the final manuscript.

Compliance with Ethical Standards

Conflict of interest

All of the authors declare that they have no conflicts of interest.

Ethical Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants, or participant’s representative (parent), included in the study and according to the above-mentioned principles.


  1. American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders. (5th edn.). Arlington, VA: American Psychiatric Association.CrossRefGoogle Scholar
  2. Baldwin, S. A., Bauer, D. J., Stice, E., & Rohde, P. (2011). Evaluating models for partially clustered designs. Psychological Methods, 16(2), 149–165. doi: 10.1037/a0023464.CrossRefPubMedPubMedCentralGoogle Scholar
  3. Barnhill, K., Gutierrez, A., Ghossainy, M., Marediya, Z., Marti, C. N., & Hewitson, L. (2017). Growth status of children with autism spectrum disorder: A case-control study. Journal of Human Nutrition and Dietetics, 30(1), 59–65. doi: 10.1111/jhn.12396.CrossRefPubMedGoogle Scholar
  4. Bates, D., Mächler, M., Bolker, B., & Walker, S. (2015). Fitting linear mixed-effects models using lme4. Journal of Statistical Software. doi: 10.18637/jss.v067.i01.Google Scholar
  5. Bausserman, M., & Michail, S. (2005). The use of Lactobacillus GG in irritable bowel syndrome in children: a double-blind randomized control trial. Journal of Pediatrics, 147(2), 197–201.CrossRefPubMedGoogle Scholar
  6. Bener, A., Khattab, A. O., & Al-Dabbagh, M. M. (2014). Is high prevalence of vitamin D deficiency evidence for autism disorder?: In a highly endogamous population. Journal of Pediatric Neuroscience, 9(3), 227–233. doi: 10.4103/1817-1745.147574.CrossRefGoogle Scholar
  7. Black, C., Kaye, J. A., & Jick, H. (2002). Relation of childhood gastrointestinal disorders to autism: Nested case-control study using data from the UK general practice research database. British Medical Journal, 325(7361), 419–421.CrossRefPubMedPubMedCentralGoogle Scholar
  8. Buie, T., Campbell, D. B., Fuchs, G. J., Furuta, G. T., Levy, J., Vandewater, J., et al. (2010a). Evaluation, diagnosis, and treatment of gastrointestinal disorders in individuals with ASDs: A consensus report. Pediatrics, 125(Suppl 1), S1–S18.Google Scholar
  9. Buie, T., Fuchs, G. J., Furuta, G. T., Kooros, K., Levy, J., Lewis, J. D., et al. (2010b). Recommendations for evaluation and treatment of common gastrointestinal problems in children with ASDs. Pediatrics, 125(Suppl 1), S19–S29. doi: 10.1542/peds.2009-1878D.Google Scholar
  10. Calarge, C. A., Burns, T. L., Schlechte, J. A., & Zemel, B. S. (2015). Longitudinal examination of the skeletal effects of selective serotonin reuptake inhibitors and risperidone in boys. Journal of Clinical Psychiatry, 76(5), 607–613. doi: 10.4088/JCP.14m09195.CrossRefPubMedGoogle Scholar
  11. Carter, D. R., Bouxsein, M. L., & Marcus, R. (1992). New approaches for interpreting projected bone densitometry data. Journal of Bone Mineral Research, 7(2), 137–145. doi: 10.1002/jbmr.5650070204.CrossRefPubMedGoogle Scholar
  12. Clark, J. H., Rhoden, D. K., & Turner, D. S. (1993). Symptomatic vitamin A and D deficiencies in an eight-year-old with autism. Journal of Parenteral and Enteral Nutrition, 17(3), 284–286. doi: 10.1177/0148607193017003284.CrossRefPubMedGoogle Scholar
  13. Core-Team, R. (2016). R: A language a nd environment for statistical computing. Accessed 14 July 2017.
  14. Davies, J. H., Evans, B. A., & Gregory, J. W. (2005). Bone mass acquisition in healthy children. Archives of Disease in Childhood, 90(4), 373–378. doi: 10.1136/adc.2004.053553.CrossRefPubMedPubMedCentralGoogle Scholar
  15. Dimenas, E., Carlsson, G., Glise, H., Israelsson, B., & Wiklund, I. (1996). Relevance of norm values as part of the documentation of quality of life instruments for use in upper gastrointestinal disease. Scandinavian Journal of Gastroenterology, 31(Suppl 221), 8–13.CrossRefGoogle Scholar
  16. Ekhlaspour, L., Baskaran, C., Campoverde, K. J., Sokoloff, N. C., Neumeyer, A. M., & Misra, M. (2016). Bone density in adolescents and young adults with autism spectrum disorders. Journal of Autism and Developmental Disorders. doi: 10.1007/s10803-016-2871-9.PubMedGoogle Scholar
  17. Evans, E. W., Must, A., Anderson, S. E., Curtin, C., Scampini, R., Maslin, M., et al. (2012). Dietary patterns and body mass index in children with autism and typically developing children. Research in Autism Spectrum Disorders, 6(1), 399–405. doi: 10.1016/j.rasd.2011.06.014.CrossRefPubMedPubMedCentralGoogle Scholar
  18. Golden, N. H., & Abrams, S. A.,& Committee on Nutrition. (2014). Optimizing bone health in children and adolescents. Pediatrics, 134(4), e1229–e1243. doi: 10.1542/peds.2014-2173.CrossRefGoogle Scholar
  19. Goodman, S. B., Jiranek, W., Petrow, E., & Yasko, A. W. (2007). The effects of medications on bone. Journal of the American Academy of Orthopedic Surgery, 15(8), 450–460.CrossRefGoogle Scholar
  20. Gotham, K., Risi, S., Pickles, A., & Lord, C. (2007). The autism diagnostic observation schedule: Revised algorithms for improved diagnostic validity. Journal of Autism and Developmental Disorders, 37(4), 613–627. doi: 10.1007/s10803-006-0280-1.CrossRefPubMedGoogle Scholar
  21. Hartman, C., Eliakim, R., & Shamir, R. (2009). Nutritional status and nutritional therapy in inflammatory bowel diseases. World Journal of Gastroenterology, 15(21), 2570–2578.CrossRefPubMedPubMedCentralGoogle Scholar
  22. Haubrock, J., Nothlings, U., Volatier, J. L., Dekkers, A., Ocke, M., Harttig, U., et al. (2011). Estimating usual food intake distributions by using the multiple source method in the EPIC-potsdam calibration study. Journal of Nutrition, 141(5), 914–920. doi: 10.3945/jn.109.120394.CrossRefPubMedGoogle Scholar
  23. Hediger, M. L., England, L. J., Molloy, C. A., Yu, K. F., Manning-Courtney, P., & Mills, J. L. (2008). Reduced bone cortical thickness in boys with autism or autism spectrum disorder. Journal of Autism and Developmental Disorders, 38(5), 848–856. doi: 10.1007/s10803-007-0453-6.CrossRefPubMedGoogle Scholar
  24. Herndon, A. C., DiGuiseppi, C., Johnson, S. L., Leiferman, J., & Reynolds, A. (2009). Does nutritional intake differ between children with autism spectrum disorders and children with typical development? Journal of Autism and Developmental Disorders, 39(2), 212–222. doi: 10.1007/s10803-008-0606-2.CrossRefPubMedGoogle Scholar
  25. Hyman, S. L., Stewart, P. A., Schmidt, B., Cain, U., Lemcke, N., Foley, J. T., et al. (2012). Nutrient intake from food in children with autism. Pediatrics, 130(Suppl 2), S145–S153. doi: 10.1542/peds.2012-0900L.Google Scholar
  26. Institute of Medicine (2005). Panel on macronutrients standing committee on the scientific evaluation of dietary reference intakes. Dietary reference intakes for energy, carbohydrate, fiber, fat, fatty acids, cholesterol, protein, and amino acids. Washington, D.C.: National Academies Press.Google Scholar
  27. Knivsberg, A. M., Reichelt, K. L., Hoien, T., & Nodland, M. (2002). A randomised, controlled study of dietary intervention in autistic syndromes. Nutritional Neuroscience, 5(4), 251–261. doi: 10.1080/10284150290028945.CrossRefPubMedGoogle Scholar
  28. Kushak, R. I., Buie, T. M., Murray, K. F., Newburg, D. S., Chen, C., Nestoridi, E., et al. (2016). Evaluation of intestinal function in children with autism and gastrointestinal symptoms. Journal of Pediatric Gastroenterology and Nutrition, 62(5), 687–691. doi: 10.1097/MPG.0000000000001174.CrossRefPubMedGoogle Scholar
  29. Lionetti, E., Miniello, V. L., Castellaneta, S. P., Magista, A. M., de Canio, A., Maurogiovanni, G., et al. (2006). Lactobacillus reuteri therapy to reduce side-effects during anti-Helicobacter pylori treatment in children: A randomized placebo controlled trial. Alimentary Pharmacology & Therapeutics, 24(10), 1461–1468. doi: 10.1111/j.1365-2036.2006.03145.x.[pii].CrossRefGoogle Scholar
  30. Lopes, L. H., Sdepanian, V. L., Szejnfeld, V. L., de Morais, M. B., & Fagundes-Neto, U. (2008). Risk factors for low bone mineral density in children and adolescents with inflammatory bowel disease. Digestive Diseases and Sciences, 53(10), 2746–2753. doi: 10.1007/s10620-008-0223-0.CrossRefPubMedGoogle Scholar
  31. Macdonald, M., Esposito, P., & Ulrich, D. (2011). The physical activity patterns of children with autism. BMC Research Notes, 4, 422. doi: 10.1186/1756-0500-4-422.CrossRefPubMedPubMedCentralGoogle Scholar
  32. Mahan, K. L., & Escott-Stump, S. (2008). Krause’s Food and Nutrition Therapy. (12th edn.). St Louis, MO: Saunders.Google Scholar
  33. Mari-Bauset, S., Llopis-González, A., Zazpe, I., Mari-Sanchís, A., & Suárez-Varela, M. M. (2015). Anthropometric measures of Spanish children with autism spectrum disorder. Research in Autism Spectrum Disorders, 9, 26–33.CrossRefGoogle Scholar
  34. Mari-Bauset, S., Zazpe, I., Mari-Sanchis, A., Llopis-González, A., & Suárez-Varela, M. M. (2012). Are there anthropometric differences between autistic and healthy children? Journal of Child Neurology, 28, 1226–1232.CrossRefGoogle Scholar
  35. Meguid, N. A., Kandeel, W. A., Wakeel, K. E., & El-Nofely, A. A. (2014). Anthropometric assessment of a middle eastern group of autistic children. World Journal of Pediatrics, 10(4), 318–323. doi: 10.1007/s12519-014-0510-0.CrossRefPubMedGoogle Scholar
  36. Millward, C., Ferriter, M., Calver, S., & Connell-Jones, G. (2004). Gluten- and casein-free diets for autistic spectrum disorder. The Cochrane Database of Systematic Reviews, 2:CD003498. doi: 10.1002/14651858.CD003498.pub2.Google Scholar
  37. Molloy, C. A., Kalkwarf, H. J., Manning-Courtney, P., Mills, J. L., & Hediger, M. L. (2010). Plasma 25(OH) D concentration in children with autism spectrum disorder. Developmental Medicine & Child Neurology, 52(10), 969–971. doi: 10.1111/j.1469-8749.2010.03704.x.CrossRefGoogle Scholar
  38. Neumeyer, A. M., Gates, A., Ferrone, C., Lee, H., & Misra, M. (2013). Bone density in peripubertal boys with autism spectrum disorders. Journal of Autism and Developmental Disorders, 43(7), 1623–1629. doi: 10.1007/s10803-012-1709-3.CrossRefPubMedPubMedCentralGoogle Scholar
  39. Neumeyer, A. M., Sokoloff, N. C., McDonnell, E., Macklin, E. A., McDougle, C. J., & Misra, M. (2017a). Bone accrual in males with autism spectrum disorder. Journal of Pediatrics, 181, 195–201. doi: 10.1016/j.jpeds.2016.10.080.CrossRefPubMedGoogle Scholar
  40. Neumeyer, A. M., Sokoloff, N. C., McDonnell, E., Macklin, E. A., McDougle, C. J., & Misra, M. (2017b). Bone microarchitecture in adolescent boys with autism spectrum disorder. Bone, 97, 139–146. doi: 10.1016/j.bone.2017.01.009.CrossRefPubMedGoogle Scholar
  41. Palacios, C. (2006). The role of nutrients in bone health, from A to Z. Critical Reviews in Food Science and Nutrition, 46, 621–628.CrossRefPubMedGoogle Scholar
  42. Porter, R. S., & Kaplan, J. L. (2011). The Merck Manual of Diagnosis and Therapy. (19th edn.). Whitehouse Station: Merck Research Laboratories.Google Scholar
  43. Roche, A. F., & Malina, R. M. (Eds.). (1983). Manual of Physical Status and Performance in Childhood: Physical Status (Vol. 1B). New York: Plenum Press.Google Scholar
  44. Roke, Y., van Harten, P. N., Buitelaar, J. K., Tenback, D. E., Quekel, L. G., de Rijke, Y. B., et al. (2012). Bone mineral density in male adolescents with autism spectrum disorders and disruptive behavior disorder with or without antipsychotic treatment. European Journal of Endocrinology, 167(6), 855–863. doi: 10.1530/EJE-12-0521.CrossRefPubMedGoogle Scholar
  45. Rutter, M., Le Couteur, A., & Lord, C. (2003). Autism diagnostic interview–revised (ADI–R) manual. Los Angeles: Western Psychological Services.Google Scholar
  46. Schaafsma, A., de Vries, P. J., & Saris, W. H. (2001). Delay of natural bone loss by higher intakes of specific minerals and vitamins. Critical Reviews in Food Science and Nutrition, 41(4), 225–249.CrossRefPubMedGoogle Scholar
  47. Schieve, L. A., Gonzalez, V., Boulet, S. L., Visser, S. N., Rice, C. E., Van Naarden Braun, K., et al. (2012). Concurrent medical conditions and health care use and needs among children with learning and behavioral developmental disabilities, National Health Interview Survey, 2006–2010. Research in Developmental Disabilities, 33(2), 467–476. doi: 10.1016/j.ridd.2011.10.008.CrossRefPubMedGoogle Scholar
  48. Schreck, K. A., Williams, K., & Smith, A. F. (2004). A comparison of eating behaviors between children with and without autism. Journal of Autism and Developmental Disorders, 34(4), 433–438.CrossRefPubMedGoogle Scholar
  49. Srinivasan, S., O’Rourke, J., Bersche Golas S., Neumeyer, A., & Misra, M. (2016). Calcium and vitamin D supplement prescribing practices among providers caring for children with autism spectrum disorders: Are we addressing bone health?. Autism Research and Treatment, 2016, 6763205. doi: 10.1155/2016/6763205.CrossRefPubMedPubMedCentralGoogle Scholar
  50. Stewart, P. A., Hyman, S. L., Schmidt, B. L., Macklin, E. A., Reynolds, A., Johnson, C. R., et al. (2015). Dietary supplementation in children with autism spectrum disorders: Common, insufficient, and excessive. Journal of the Academy of Nutrition and Dietetics, 115(8), 1237–1248. doi: 10.1016/j.jand.2015.03.026.CrossRefPubMedGoogle Scholar
  51. Svedlund, J., Sjodin, I., & Dotevall, G. (1988). GSRS—a clinical rating scale for gastrointestinal symptoms in patients with irritable bowel syndrome and peptic ulcer disease. Digests in Disability Science, 33(2), 129–134.CrossRefGoogle Scholar
  52. Thangarajah, D., Hyde, M. J., Konteti, V. K., Santhakumaran, S., Frost, G., & Fell, J. M. (2015). Systematic review: Body composition in children with inflammatory bowel disease. Alimentary Pharmacology & Therapeutics, 42(2), 142–157. doi: 10.1111/apt.13218.CrossRefGoogle Scholar
  53. Thomson, M., Fritscher-Ravens, A., Hall, S., Afzal, N., Ashwood, P., & Swain, C. P. (2004). Endoluminal gastroplication in children with significant gastro-oesophageal reflux disease. Gut, 53(12), 1745–1750, doi: 10.1136/gut.2004.041921.CrossRefPubMedPubMedCentralGoogle Scholar
  54. Valicenti-McDermott, M., McVicar, K., Rapin, I., Wershil, B. K., Cohen, H., & Shinnar, S. (2006). Frequency of gastrointestinal symptoms in children with autistic spectrum disorders and association with family history of autoimmune disease. Journal of Developmental and Behavioral Pediatrics, 27(2 Suppl), S128–S136.Google Scholar
  55. Weisshof, R., & Chermesh, I. (2015). Micronutrient deficiencies in inflammatory bowel disease. Current Opinion in Clinical Nutrition & Metabolic Care, 18(6), 576–581. doi: 10.1097/MCO.0000000000000226.CrossRefGoogle Scholar
  56. Williams, P. G., Dalrymple, N., & Neal, J. (2000). Eating habits of children with autism. Pediatric Nursing, 26(3), 259–264.PubMedGoogle Scholar
  57. Wong, H. H., & Smith, R. G. (2006). Patterns of complementary and alternative medical therapy use in children diagnosed with autism spectrum disorders. Journal of Autism and Developmental Disorders, 36(7), 901–909. doi: 10.1007/s10803-006-0131-0.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • Kelly Barnhill
    • 1
    Email author
  • Lucas Ramirez
    • 1
    • 3
  • Alan Gutierrez
    • 1
  • Wendy Richardson
    • 1
  • C. Nathan Marti
    • 2
  • Amy Potts
    • 1
    • 4
  • Rebeca Shearer
    • 1
  • Claire Schutte
    • 1
  • Laura Hewitson
    • 1
  1. 1.The Johnson Center for Child Health and DevelopmentAustinUSA
  2. 2.Abacist Analytics, LLCAustinUSA
  3. 3.Care Improvement Plus PractitionersXLHealthPleasant GroveUSA
  4. 4.Oklahoma City UniversityOklahomaUSA

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