Osteoporosis International

, Volume 24, Issue 4, pp 1333–1338 | Cite as

Low bone turnover and low bone density in a cohort of adults with Down syndrome

  • K. D. McKelvey
  • T. W. Fowler
  • N. S. Akel
  • J. A. Kelsay
  • D. Gaddy
  • G. R. Wenger
  • L. J. Suva
Original Article



Increased incidence of osteoporosis in Down syndrome has been reported, but etiology is not established. We report low bone turnover markers and bone mineral density (BMD) in a cohort of people with Down syndrome without consistent clinical risk factors. Our results should guide future studies and treatments for this common problem.


To better understand the etiology for osteoporosis in Down syndrome (DS), we measured bone density by dual-energy X-ray absorptiometry (DXA) and circulating biochemical markers of bone formation and resorption in a cohort of 30 community-dwelling DS adults.


Seventeen males and 13 females followed in the University of Arkansas Down Syndrome Clinic were evaluated by DXA to estimate BMD and underwent phlebotomy to measure serum procollagen type-1 intact N-terminal propeptide (P1NP) to evaluate bone formation, and serum C-terminal peptide of type-I collagen (CTx) to evaluate bone resorption.


Seven of 13 DS females and 12 of 17 DS males had low bone mass at one of measured sites (z ≤ −2.0). When data were grouped by age, males had apparent osteopenia earlier than females. The mean P1NP in the normal group was 19.2 ± 5.2 ng/ml vs. 2.2 ± 0.9 ng/ml in the DS group (P = 0.002). Serum CTx levels in the normal group were 0.4 ± 0.1 ng/ml vs. 0.3 ± 0.1 ng/ml (P = 0.369).


Low BMD in adults with DS is correlated with a significant decrease in bone formation markers, compared to controls without DS, and is independent of gender. These data suggest that diminished osteoblastic bone formation and inadequate accrual of bone mass, with no significant differences in bone resorption, are responsible for the low bone mass in DS. These observations question the use of antiresorptive therapy in this population and focus attention on increasing bone mass by other interventions.


Bone density Bone turnover Down syndrome Osteopenia Osteoporosis Trisomy 21 



This work was supported by the Rockefeller Chair in Clinical Genetics (KDM), the UAMS Translational Research Institute (TRI) clinical award (KDM), UAMS TRI UL1RR029884, and the Carl L. Nelson Endowed Chair in Orthopaedic Creativity (LJS).

Conflicts of interest



  1. 1.
    Gonzalez-Aguero A, Vicente-Rodriguez G, Moreno LA, Casajus JA (2011) Bone mass in male and female children and adolescents with Down syndrome. Osteoporos Int 22:2151–57PubMedCrossRefGoogle Scholar
  2. 2.
    Bittles AH, Glasson EJ (2004) Clinical, social, and ethical implications of changing life expectancy in Down syndrome. Dev Med Child Neurol 46:282–86PubMedCrossRefGoogle Scholar
  3. 3.
    Hawli Y, Nasrallah M, El-Hajj FG (2009) Endocrine and musculoskeletal abnormalities in patients with Down syndrome. Nat Rev Endocrinol 5:327–34PubMedCrossRefGoogle Scholar
  4. 4.
    Glasson EJ, Sullivan SG, Hussain R, Petterson BA, Montgomery PD, Bittles AH (2002) The changing survival profile of people with Down’s syndrome: implications for genetic counselling. Clin Genet 62:390–393PubMedCrossRefGoogle Scholar
  5. 5.
    van Allen MI, Fung J, Jurenka SB (1999) Health care concerns and guidelines for adults with Down syndrome. Am J Med Genet 89:100–110PubMedCrossRefGoogle Scholar
  6. 6.
    Kao CH, Chen CC, Wang SJ, Yeh SH (1992) Bone mineral density in children with Down’s syndrome detected by dual photon absorptiometry. Nucl Med Commun 13:773–75PubMedGoogle Scholar
  7. 7.
    Angelopoulou N, Matziari C, Tsimaras V, Sakadamis A, Souftas V, Mandroukas K (2000) Bone mineral density and muscle strength in young men with mental retardation (with and without Down syndrome). Calcif Tissue Int 66:176–80PubMedCrossRefGoogle Scholar
  8. 8.
    Angelopoulou N, Souftas V, Sakadamis A, Mandroukas K (1999) Bone mineral density in adults with Down’s syndrome. Eur Radiol 9:648–51PubMedCrossRefGoogle Scholar
  9. 9.
    Sepulveda D, Allison DB, Gomez JE, Kreibich K, Brown RA, Pierson RN Jr, Heymsfield SB (1995) Low spinal and pelvic bone mineral density among individuals with Down syndrome. Am J Ment Retard 100:109–14PubMedGoogle Scholar
  10. 10.
    Guijarro M, Valero C, Paule B, Gonzalez-Macias J, Riancho JA (2008) Bone mass in young adults with Down syndrome. J Intellect Disabil Res 52:182–89PubMedCrossRefGoogle Scholar
  11. 11.
    Baptista F, Varela A, Sardinha LB (2005) Bone mineral mass in males and females with and without Down syndrome. Osteoporos Int 16:380–388PubMedCrossRefGoogle Scholar
  12. 12.
    Suva LJ, Gaddy D, Perrien DS, Thomas RL, Findlay DM (2005) Regulation of bone mass by mechanical loading: microarchitecture and genetics. Curr Osteoporos Rep 3:46–51PubMedCrossRefGoogle Scholar
  13. 13.
    Blazek JD, Gaddy A, Meyer R, Roper RJ, Li J (2011) Disruption of bone development and homeostasis by trisomy in Ts65Dn Down syndrome mice. Bone 48:275–80PubMedCrossRefGoogle Scholar
  14. 14.
    Bull MJ (2011) Health supervision for children with Down syndrome. Pediatrics 128:393–406PubMedCrossRefGoogle Scholar
  15. 15.
    Sakadamis A, Angelopoulou N, Matziari C, Papameletiou V, Souftas V (2002) Bone mass, gonadal function and biochemical assessment in young men with trisomy 21. Eur J Obstet Gynecol Reprod Biol 100:208–12PubMedCrossRefGoogle Scholar
  16. 16.
    Hsiang YH, Berkovitz GD, Bland GL, Migeon CJ, Warren AC (1987) Gonadal function in patients with Down syndrome. Am J Med Genet 27:449–58PubMedCrossRefGoogle Scholar
  17. 17.
    Grimwood JS, Kumar A, Bickerstaff DR, Suvarna SK (2000) Histological assessment of vertebral bone in a Down’s syndrome adult with osteoporosis. Histopathology 36:279–80PubMedCrossRefGoogle Scholar
  18. 18.
    Monroe DG, McGee-Lawrence ME, Oursler MJ, Westendorf JJ (2012) Update on Wnt signaling in bone cell biology and bone disease. Gene 492:1–18PubMedCrossRefGoogle Scholar
  19. 19.
    Moester MJ, Papapoulos SE, Lowik CW, van Bezooijen RL (2010) Sclerostin: current knowledge and future perspectives. Calcif Tissue Int 87:99–107PubMedCrossRefGoogle Scholar
  20. 20.
    Mendonca GV, Pereira FD, Fernhall B (2011) Effects of combined aerobic and resistance exercise training in adults with and without Down syndrome. Arch Phys Med Rehabil 92:37–45PubMedCrossRefGoogle Scholar
  21. 21.
    Gupta S, Rao BK, Kumaran SD (2011) Effect of strength and balance training in children with Down’s syndrome: a randomized controlled trial. Clin Rehabil 25:425–32PubMedCrossRefGoogle Scholar
  22. 22.
    Cowley PM, Ploutz-Snyder LL, Baynard T, Heffernan KS, Jae SY, Hsu S, Lee M, Pitetti KH, Reiman MP, Fernhall B (2011) The effect of progressive resistance training on leg strength, aerobic capacity and functional tasks of daily living in persons with Down syndrome. Disabil Rehabil 33:2229–36PubMedCrossRefGoogle Scholar
  23. 23.
    Bachrach LK (2007) Consensus and controversy regarding osteoporosis in the pediatric population. Endocr Pract 13:513–20PubMedGoogle Scholar
  24. 24.
    Hui SL, Slemenda CW, Johnston CC Jr (1990) The contribution of bone loss to postmenopausal osteoporosis. Osteoporos Int 1:30–34PubMedCrossRefGoogle Scholar
  25. 25.
    Fergeson MA, Mulvihill JJ, Schaefer GB, Dehaai KA, Piatt J, Combs K, Bright BC, Neas BR (2009) Low adherence to national guidelines for thyroid screening in Down syndrome. Genet Med 11:548–51PubMedCrossRefGoogle Scholar
  26. 26.
    Ugazio AG, Maccario R, Notarangelo LD, Burgio GR (1990) Immunology of Down syndrome: a review. Am J Med Genet Suppl 7:204–12PubMedGoogle Scholar
  27. 27.
    Karlsson B, Gustafsson J, Hedov G, Ivarsson SA, Anneren G (1998) Thyroid dysfunction in Down’s syndrome: relation to age and thyroid autoimmunity. Arch Dis Child 79:242–45PubMedCrossRefGoogle Scholar
  28. 28.
    Seeman E (2002) Pathogenesis of bone fragility in women and men. Lancet 359:1841–50PubMedCrossRefGoogle Scholar

Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2012

Authors and Affiliations

  • K. D. McKelvey
    • 1
    • 2
  • T. W. Fowler
    • 3
    • 4
  • N. S. Akel
    • 3
  • J. A. Kelsay
    • 2
  • D. Gaddy
    • 3
    • 4
  • G. R. Wenger
    • 5
  • L. J. Suva
    • 3
    • 4
  1. 1.Department of Family MedicineUniversity of Arkansas for Medical SciencesLittle RockUSA
  2. 2.Department of Medical GeneticsUniversity of Arkansas for Medical SciencesLittle RockUSA
  3. 3.Department of Physiology and BiophysicsUniversity of Arkansas for Medical SciencesLittle RockUSA
  4. 4.Department of Orthopaedic Surgery, Center for Orthopaedic ResearchUniversity of Arkansas for Medical SciencesLittle RockUSA
  5. 5.Department of Pharmacology and ToxicologyUniversity of Arkansas for Medical SciencesLittle RockUSA

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