Journal of Autism and Developmental Disorders

, Volume 46, Issue 11, pp 3387–3391 | Cite as

Bone Density in Adolescents and Young Adults with Autism Spectrum Disorders

  • Laya EkhlaspourEmail author
  • Charumathi Baskaran
  • Karen Joanie Campoverde
  • Natalia Cano Sokoloff
  • Ann M. Neumeyer
  • Madhusmita Misra
Original Paper


Patients with autism spectrum disorder (ASD) are at increased risk for fracture, and peri-pubertal boys with ASD have lower bone mineral density (BMD) than controls. Data are lacking regarding BMD in older adolescents with ASD. We compared BMD using dual-energy X-ray absorptiometry in 9 adolescents/young adults with ASD against 9 typically developing matched controls. Patients with ASD and controls were excluded if they had other underlying conditions that may affect bone. Compared to controls, patients with ASD had (i) lower femoral neck and hip BMD Z-scores, and (ii) lower spine, femoral neck and hip height adjusted BMD Z-scores even after controlling for BMI. Understanding the underlying pathophysiology will be key to developing therapies to improve BMD and reduce fracture risk.


Autism spectrum disorder Bone mineral density Adolescent Dual energy X-ray absorptiometry Body mass index 


Author Contributions

MM and AMN conceived the study and interpreted the data. LE, CB, KJC and NCS collected the data and interpreted the data. LE and KJC performed the statistical analysis. LE and CB drafted the manuscript. All authors read and approved the final manuscript.

Supplementary material

10803_2016_2871_MOESM1_ESM.docx (11 kb)
Supplementary material 1 (DOCX 11 kb)


  1. American Psychiatric Association. (2013). Diagnostic and statistical manual disorders (5th ed.). VA: American Psychiatric Association.CrossRefGoogle Scholar
  2. Babayigit, A., Dirik, E., Bober, E., & Cakmakci, H. (2006). Adverse effects of antiepileptic drugs on bone mineral density. Pediatric Neurology, 35(3), 177–181. doi: 10.1016/j.pediatrneurol.2006.03.004.CrossRefPubMedGoogle Scholar
  3. Beniczky, S. A., Viken, J., Jensen, L. T., & Andersen, N. B. (2012). Bone mineral density in adult patients treated with various antiepileptic drugs. Seizure, 21(6), 471–472. doi: 10.1016/j.seizure.2012.04.002.CrossRefPubMedGoogle Scholar
  4. 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
  5. Chou, I. J., Lin, K. L., Wang, H. S., & Wang, C. J. (2007). Evaluation of bone mineral density in children receiving carbamazepine or valproate monotherapy. Acta Paediatrica Taiwanica, 48(6), 317–322.PubMedGoogle Scholar
  6. 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
  7. Deere, K., Sayers, A., Rittweger, J., & Tobias, J. H. (2012). A cross-sectional study of the relationship between cortical bone and high-impact activity in young adult males and females. Journal of Clinical Endocrinology and Metabolism, 97(10), 3734–3743. doi: 10.1210/jc.2012-1752.CrossRefPubMedPubMedCentralGoogle Scholar
  8. Emin, O., Fatih, M., Emre, D., & Nedim, S. (2011). Lack of bone metabolism side effects after 3 years of nasal topical steroids in children with allergic rhinitis. Journal of Bone and Mineral Metabolism, 29(5), 582–587. doi: 10.1007/s00774-010-0255-3.CrossRefPubMedGoogle Scholar
  9. Estrada, K., Styrkarsdottir, U., Evangelou, E., Hsu, Y. H., Duncan, E. L., Ntzani, E. E., et al. (2012). Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture. Nature Genetics, 44(5), 491–501. doi: 10.1038/ng.2249.CrossRefPubMedPubMedCentralGoogle Scholar
  10. Freedberg, D. E., Haynes, K., Denburg, M. R., Zemel, B. S., Leonard, M. B., Abrams, J. A., et al. (2015). Use of proton pump inhibitors is associated with fractures in young adults: A population-based study. Osteoporosis International, 26(10), 2501–2507. doi: 10.1007/s00198-015-3168-0.CrossRefPubMedPubMedCentralGoogle Scholar
  11. Ginty, F., Rennie, K. L., Mills, L., Stear, S., Jones, S., & Prentice, A. (2005). Positive, site-specific associations between bone mineral status, fitness, and time spent at high-impact activities in 16- to 18-year-old boys. Bone, 36(1), 101–110. doi: 10.1016/j.bone.2004.10.001.CrossRefPubMedGoogle Scholar
  12. 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
  13. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  14. Kanis, J. A., Johnell, O., De Laet, C., Johansson, H., Oden, A., Delmas, P., et al. (2004). A meta-analysis of previous fracture and subsequent fracture risk. Bone, 35(2), 375–382. doi: 10.1016/j.bone.2004.03.024.CrossRefPubMedGoogle Scholar
  15. Lehtonen-Veromaa, M. K., Mottonen, T. T., Nuotio, I. O., Irjala, K. M., Leino, A. E., & Viikari, J. S. (2002). Vitamin D and attainment of peak bone mass among peripubertal Finnish girls: A 3-y prospective study. American Journal of Clinical Nutrition, 76(6), 1446–1453.PubMedGoogle Scholar
  16. 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
  17. Neumeyer, A. M., O’Rourke, J. A., Massa, A., Lee, H., Lawson, E. A., McDougle, C. J., et al. (2015). Brief report: Bone fractures in children and adults with autism spectrum disorders. Journal of Autism and Developmental Disorders, 45(3), 881–887. doi: 10.1007/s10803-014-2228-1.CrossRefPubMedPubMedCentralGoogle Scholar
  18. Nishiyama, K. K., Macdonald, H. M., Moore, S. A., Fung, T., Boyd, S. K., & McKay, H. A. (2012). Cortical porosity is higher in boys compared with girls at the distal radius and distal tibia during pubertal growth: An HR-pQCT study. Journal of Bone and Mineral Research, 27(2), 273–282. doi: 10.1002/jbmr.552.CrossRefPubMedGoogle Scholar
  19. Pan, C. Y. (2008). Objectively measured physical activity between children with autism spectrum disorders and children without disabilities during inclusive recess settings in Taiwan. Journal of Autism and Developmental Disorders, 38(7), 1292–1301. doi: 10.1007/s10803-007-0518-6.CrossRefPubMedGoogle Scholar
  20. Rieger-Wettengl, G., Tutlewski, B., Stabrey, A., Rauch, F., Herkenrath, P., Schauseil-Zipf, U., et al. (2001). Analysis of the musculoskeletal system in children and adolescents receiving anticonvulsant monotherapy with valproic acid or carbamazepine. Pediatrics, 108(6), E107.CrossRefPubMedGoogle Scholar
  21. Riggs, B. L., & Melton, L. J, 3rd. (1986). Involutional osteoporosis. New England Journal of Medicine, 314(26), 1676–1686. doi: 10.1056/NEJM198606263142605.CrossRefPubMedGoogle Scholar
  22. 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
  23. Schoenau, E. (2005). From mechanostat theory to development of the “functional muscle-bone-unit”. Journal of Musculoskeletal and Neuronal Interactions, 5(3), 232–238.PubMedGoogle Scholar
  24. Serin, H. M., Koc, Z. P., Temelli, B., & Esen, I. (2015). The bone mineral content alterations in pediatric patients medicated with levetiracetam, valproic acid, and carbamazepine. Epilepsy & Behavior, 51, 221–224. doi: 10.1016/j.yebeh.2015.06.025.CrossRefGoogle Scholar
  25. Sheth, R. D., Binkley, N., & Hermann, B. P. (2008). Progressive bone deficit in epilepsy. Neurology, 70(3), 170–176. doi: 10.1212/01.wnl.0000284595.45880.93.CrossRefPubMedGoogle Scholar
  26. Tan, V. P., Macdonald, H. M., Kim, S., Nettlefold, L., Gabel, L., Ashe, M. C., et al. (2014). Influence of physical activity on bone strength in children and adolescents: A systematic review and narrative synthesis. Journal of Bone and Mineral Research, 29(10), 2161–2181. doi: 10.1002/jbmr.2254.CrossRefPubMedGoogle Scholar
  27. Tekgul, H., Serdaroglu, G., Huseyinov, A., & Gokben, S. (2006). Bone mineral status in pediatric outpatients on antiepileptic drug monotherapy. Journal of Child Neurology, 21(5), 411–414.PubMedGoogle Scholar
  28. Theintz, G., Buchs, B., Rizzoli, R., Slosman, D., Clavien, H., Sizonenko, P. C., et al. (1992). Longitudinal monitoring of bone mass accumulation in healthy adolescents: Evidence for a marked reduction after 16 years of age at the levels of lumbar spine and femoral neck in female subjects. Journal of Clinical Endocrinology and Metabolism, 75(4), 1060–1065. doi: 10.1210/jcem.75.4.1400871.PubMedGoogle Scholar
  29. Warden, S. J., Burr, D. B., & Brukner, P. D. (2006). Stress fractures: Pathophysiology, epidemiology, and risk factors. Curr Osteoporos Rep, 4(3), 103–109.CrossRefPubMedGoogle Scholar
  30. Wren, T. A., Kalkwarf, H. J., Zemel, B. S., Lappe, J. M., Oberfield, S., & Shepherd, J. A. (2014). Longitudinal tracking of dual-energy X-ray absorptiometry bone measures over 6 years in children and adolescents: Persistence of low bone mass to maturity. The Journal of Pediatrics, 164(6), 1280–1285. doi: 10.1016/j.jpeds.2013.12.040.CrossRefPubMedPubMedCentralGoogle Scholar
  31. Yaghini, O., Tonekaboni, S. H., Amir Shahkarami, S. M., Ahmad Abadi, F., Shariat, F., & Abdollah Gorji, F. (2015). Bone mineral density in ambulatory children with epilepsy. Indian Journal of Pediatrics, 82(3), 225–229. doi: 10.1007/s12098-014-1518-0.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.Pediatric Endocrine UnitMassachusetts General Hospital for Children and Harvard Medical SchoolBostonUSA
  2. 2.Neuroendocrine UnitMassachusetts General HospitalBostonUSA
  3. 3.Lurie Center for AutismMassachusetts General Hospital and Harvard Medical SchoolLexingtonUSA

Personalised recommendations