Skip to main content

Advertisement

Log in

Sclerostin levels during growth in children

  • Original Article
  • Published:
Osteoporosis International Aims and scope Submit manuscript

Abstract

Summary

Serum sclerostin levels are associated with cortical porosity, suggesting that changes in sclerostin production during growth may play a role in defining cortical structure.

Introduction

Sclerostin, produced by osteocytes, is a potent inhibitor of Wnt signaling and bone formation. While sclerostin levels increase with age in adults and are higher in men compared to women, there is currently no information on changes in circulating sclerostin levels during growth in humans.

Methods

We measured serum sclerostin levels in 6- to 21-year-old girls (n = 62) and boys (n = 56) and related these to trabecular and cortical bone microarchitectural parameters using high-resolution peripheral quantitative computed tomography and to markers of bone turnover.

Results

Serum sclerostin levels were higher in boys as compared to girls and declined in both sexes following the onset of puberty. There was no consistent relationship between sclerostin levels and trabecular bone parameters in either sex. However, serum sclerostin levels were inversely associated with cortical volumetric bone mineral density and cortical thickness in girls and positively associated with the cortical porosity index in both girls and boys. Bone turnover markers were positively correlated with serum sclerostin levels in both sexes.

Conclusion

The gender difference in serum sclerostin levels appears to be established during puberty, and sclerostin levels tend to decline in late puberty in both girls and boys. Serum sclerostin levels are associated with cortical porosity, suggesting that changes in sclerostin production during growth may play a role in defining cortical structure.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Baron R, Rawadi G (2007) Targeting the Wnt/beta-catenin pathway to regulate bone formation in the adult skeleton. Endocrinology 148:2635–2643

    Article  PubMed  CAS  Google Scholar 

  2. Krishnan V, Bryant HU, MacDougald OA (2006) Regulation of bone mass by Wnt signaling. J Clin Invest 116:1202–1209

    Article  PubMed  CAS  Google Scholar 

  3. van Bezooijen RL, Roelen BAJ, Visser A, van der Wee-Pals L, de Wilt E, Karperien M, Hamersma H, Papapoulos SE, ten Dijke P, Lowik CWGM (2004) Sclerostin is an osteocyte-expressed negative regulator of bone formation, but not a classical BMP antagonist. J Exp Med 199:805–814

    Article  PubMed  Google Scholar 

  4. Semenov M, Tamai K, He X (2005) SOST is a ligand for LRP5/LRP6 and a Wnt signaling inhibitor. J Biol Chem 280:26770–26775

    Article  PubMed  CAS  Google Scholar 

  5. Poole KES, van Bezooijen RL, Loveridge N, Hamersma H, Papapoulos SE, Lowik CW, Reeve J (2005) Sclerostin is a delayed secreted product of osteocytes that inhibits bone formation. FASEB J 19:1842–1844

    PubMed  CAS  Google Scholar 

  6. van Bezooijen RL, ten Dijke P, Papapoulos SE, Lowik CW (2005) SOST/sclerostin, an osteocyte-derived negative regulator of bone formation. Cytokine Growth Factor Rev 16:319–327

    Article  PubMed  Google Scholar 

  7. Brunkow ME, Gardner JC, Van Ness J et al (2001) Bone dysplasia sclerosteosis results from loss of the SOST gene product, a novel cystine knot-containing protein. Am J Hum Genet 68:577–589

    Article  PubMed  CAS  Google Scholar 

  8. Balemans W, Ebeling M, Patel N et al (2001) Increase bone density in sclerosteosis is due to the deficiency of a novel secreted protein (SOST). Hum Mol Genet 10:537–543

    Article  PubMed  CAS  Google Scholar 

  9. Staehling-Hampton K, Proll S, Paeper BW et al (2002) A 52-kb deletion in the SOST-MEOX1 intergenic region on 17q12-q21 is associated with van Buchem disease in the Dutch population. Am J Med Genet 110:144–152

    Article  PubMed  Google Scholar 

  10. Balemans W, Patel N, Ebeling M et al (2002) Identification of a 52 kb deletion downstream of the SOST gene in patients with van Buchem disease. J Med Genet 39:91–97

    Article  PubMed  CAS  Google Scholar 

  11. Li X, Ominsky MS, Niu Q-T et al (2008) Targeted deletion of the sclerostin gene in mice results in increased bone formation and bone strength. J Bone Miner Res 23:860–869

    Article  PubMed  Google Scholar 

  12. Li X, Ominsky MS, Warmington KS et al (2009) Sclerostin antibody treatment increases bone formation, bone mass, and bone strength in a rat model of postmenopausal osteoporosis. J Bone Miner Res 24:578–588

    Article  PubMed  CAS  Google Scholar 

  13. Padhi D, Jang G, Stouch B, Fang L, Posvar E (2011) Single-dose, placebo-controlled, randomized study of AMG 785, a sclerostin monoclonal antibody. J Bone Miner Res 26:19–26

    Article  PubMed  CAS  Google Scholar 

  14. Glass DA II, Bialek P, Ahn JD et al (2005) Canonical Wnt signaling in differentiated osteoblasts controls osteoclast differentiation. Dev Cell 8:751–764

    Article  PubMed  CAS  Google Scholar 

  15. Modder UI, Hoey KA, Amin S, McCready LK, Achenbach SJ, Riggs BL, Melton LJI, Khosla S (2011) Relation of age, gender, and bone mass to circulating sclerostin levels in women and men. J Bone Miner Res 26:373–379

    Article  PubMed  CAS  Google Scholar 

  16. Bailey DA, Martin AD, McKay HA, Whiting S, Mirwald R (2000) Calcium accretion in girls and boys during puberty: a longitudinal analysis. J Bone Miner Res 15:2245–2250

    Article  PubMed  CAS  Google Scholar 

  17. Kirmani S, Christen D, van Lenthe GH et al (2009) Bone structure at the distal radius during adolescent growth. J Bone Miner Res 24:1033–1042

    Article  PubMed  Google Scholar 

  18. Khosla S, Melton LJ III, Dekutoski MB, Achenbach SJ, Oberg AL, Riggs BL (2003) Incidence of childhood distal forearm fractures over 30 years: a population-based study. JAMA 290:1479–1485

    Article  PubMed  CAS  Google Scholar 

  19. Landin LA (1983) Fracture patterns in children. Analysis of 8,682 fractures with special reference to incidence, etiology and secular changes in a Swedish urban population 1950–1979. Acta Orthop Scand Suppl 202:1–109

    PubMed  CAS  Google Scholar 

  20. Kramhoft M, Bodtker S (1988) Epidemiology of distal forearm fractures in Danish children. Acta Orthop Scand 59:557–559

    Article  PubMed  CAS  Google Scholar 

  21. Bailey DA, Wedge JH, McCulloch RG, Martin AD, Bernhardson SC (1989) Epidemiology of fractures of the distal end of the radius in children as associated with growth. J Bone Joint Surg 71-A:1225–1231

    Google Scholar 

  22. Tanner JM, Healy MJR, Goldstein H et al (2001) Assessment of skeletal maturity and prediction of adult height: TW3 method. Saunders, Philadelphia

    Google Scholar 

  23. Laib A, Hildebrand T, Hauselmann HJ, Ruegsegger P (1997) Ridge number density: a new parameter for in vivo bone structure analysis. Bone 21:541–546

    Article  PubMed  CAS  Google Scholar 

  24. Laib A, Hauselmann HJ, Ruegsegger P (1998) In vivo high resolution 3D-QCT of the human forearm. Technol Health Care 6:329–337

    PubMed  CAS  Google Scholar 

  25. Parfitt AM (1983) Stereologic basis of bone histomorphometry: Theory of quantitative microscopy and reconstruction of the third dimension. CRC Press, Boca Raton

    Google Scholar 

  26. Laib A, Ruegsegger P (1999) Calibration of trabecular bone structure measurements of in vivo three-dimensional peripheral quantitative computed tomography with 28-microm-resolution microcomputed tomography. Bone 24:35–39

    Article  PubMed  CAS  Google Scholar 

  27. MacNeil JA, Boyd SK (2007) Accuracy of high-resolution peripheral quantitative computed tomography for measurement of bone quality. Med Eng Phys 29:1096–1105

    Article  PubMed  Google Scholar 

  28. Terpos E, Christoulas D, Katodritou E et al (2009) High serum sclerostin correlates with advanced stage, increased bone resorption, reducted osteoblast function, and poor survival in newly-diagnosed patients with multiple myeloma. Blood 114:425, Abstract

    Article  Google Scholar 

  29. Modder UIL, Clowes JA, Hoey K, Peterson JM, McCready L, Oursler MJ, Riggs BL, Khosla S (2011) Regulation of circulating sclerostin levels by sex steroids in women and men. J Bone Miner Res 26:27–34

    Article  PubMed  CAS  Google Scholar 

  30. Gaudio A, Pennisi P, Bratengeier C, Torrisi V, Lindner B, Mangiafico RA, Pulvirenti I, Hawa G, Tringali G, Fiore CE (2010) Increased sclerostin serum levels associated with bone formation and resorption markers in patients with immoilization-induced bone loss. J Clin Endocrinol Metab 95:2248–2253

    Article  PubMed  CAS  Google Scholar 

  31. Khosla S, Amin S, Singh RJ, Atkinson EJ, Melton LJ, Riggs BL (2008) Comparison of sex steroid measurements in men by immunoassay versus mass spectroscopy and relationships with cortical and trabecular volumetric bone mineral density. Osteoporos Int 19:1465–1471

    Article  PubMed  CAS  Google Scholar 

  32. Drake MT, Srinivasan B, Modder UI, Peterson JM, McCready LK, Riggs BL, Dwyer D, Stolina M, Kostenuik P, Khosla S (2010) Effects of parathyroid hormone treatment on ciculating sclerostin levels in postmenopausal women. J Clin Endocrinol Metab 95:5056–5062

    Article  PubMed  CAS  Google Scholar 

  33. Burghardt AJ, Buie HR, Laib A, Majumdar S, Boyd SK (2010) Reproducibility of direct quantitative measures of cortical bone microarchitecture of the distal radius and tibia by HR-pQCT. Bone 47:519–528

    Article  PubMed  Google Scholar 

Download references

Funding

This work was supported by NIH grants AR027065 and UL1-RR24150 (Center for Translational Science Activities).

Conflicts of interest

None.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to S. Khosla.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kirmani, S., Amin, S., McCready, L.K. et al. Sclerostin levels during growth in children. Osteoporos Int 23, 1123–1130 (2012). https://doi.org/10.1007/s00198-011-1669-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00198-011-1669-z

Keywords

Navigation