Skip to main content

Advertisement

Log in

Association of serum sclerostin with bone mineral density, bone turnover, steroid and parathyroid hormones, and fracture risk in postmenopausal women: the OFELY study

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

Abstract

Summary

Sclerostin is a key regulator of bone formation. In a population of 572 postmenopausal women (mean age, 67 years) followed prospectively for a median of 6 years, there was no significant association between baseline levels of serum sclerostin and incidence of all fractures which occurred in 64 subjects.

Introduction

Sclerostin, an osteocyte soluble factor, is a major negative regulator of osteoblastic activity. Circulating sclerostin levels were reported to increase with age and to be modestly associated with bone mineral density (BMD) and bone turnover, but there are no data on the association with fracture risk.

Methods

We investigated 572 postmenopausal women (mean age, 67 ± 8.5 years) from the OFELY population-based cohort. The associations of serum sclerostin measured with a new two-site ELISA and spine and hip BMD by DXA, serum β-isomerized C-terminal crosslinking of type I collagen (CTX), intact N-terminal propeptide of type I collagen (PINP), intact PTH, 25-hydroxyvitamin D [25(OH)D], estradiol, testosterone, and fracture risk were analyzed. At the time of sclerostin measurements, 98 postmenopausal women had prevalent fractures. After a median of 6 years (interquartile range, 5–7 years) follow-up, 64 postmenopausal sustained an incident fracture.

Results

Serum sclerostin correlated positively with spine (r = 0.35, p < 0.0001) and total hip (r = 0.25, <0.0001) BMD. Conversely, serum sclerostin was weakly negatively associated with the bone markers PINP (r = −0.10, p = 0.014) and CTX (r = −0.13, p = 0.0026) and with intact PTH (r = −0.13, p = 0.0064). There was no significant association of serum sclerostin with 25(OH)D, estradiol, free estradiol index, or testosterone. Serum sclerostin considered as a continuous variable or in quartiles was not significantly associated with the risk of prevalent or incident fracture.

Conclusion

Serum sclerostin is weakly correlated with BMD, bone turnover, and PTH in postmenopausal women. It was not significantly associated with the risk of all fractures, although the number of incident fractures recorded may not allow detecting a modest association.

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.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Enisa Shevroja, Jean-Yves Reginster, … Nicholas C. Harvey

References

  1. Bonewald LF (2011) The amazing osteocytes. J Bone Miner Res 26:229–238

    Article  PubMed  CAS  Google Scholar 

  2. van Bezooijen RL, Roelen BA, Visser A, van der Wee-Pals L, de Wilt E, Karperien M, Hamersma H, Papapoulos SE, ten Dijke P, Löwik 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 

  3. Li X, Zhang Y, Kang H, Liu W, Liu P, Zhang J, Harris SE, Wu D (2005) Sclerostin binds to LRP5/6 and antagonizes canonical Wnt signaling. J Biol Chem 280:19883–19887

    Article  PubMed  CAS  Google Scholar 

  4. Poole KE, van Bezooijen RL, Loverridge N et al (2005) Sclerostin is a delayed product of osteocytes that inhibits bone formation. FASEB J 19:1842–1844

    PubMed  CAS  Google Scholar 

  5. Bellido T, Ali AA, Gubrij I, Plotkin LI, Fu Q, O’Brien CA, Manolagas SC, Jilka RL (2005) Chronic elevation of parathyroid hormone in mice reduces expression of sclerostin by osteocytes: a novel mechanism for hormonal control of osteoblastogenesis. Endocrinology 146:4577–4583

    Article  PubMed  CAS  Google Scholar 

  6. Keller H, Kneissel M (2005) SOST is a target gene for PTH in bone. Bone 37:148–158

    Article  PubMed  CAS  Google Scholar 

  7. Silvestrini G, Ballanti P, Leopizzi M, Sebastiani M, Berni S, Vito M, Bonucci E (2007) Effects of intermittent parathyroid hormone (PTH) administration on SOST mRNA and protein in rat bone. J Mol Histol 38:261–269

    Article  PubMed  CAS  Google Scholar 

  8. Kramer I, Loots GG, Studer A, Keller H, Kneissel M (2009) Parathyroid hormone (PTH) induced bone gain is blunted in SOST overexpressing and deficient mice. J Bone Miner Res 25:178–189

    Article  Google Scholar 

  9. Li X, Ominsky MS, Warmington KS, Morony S, Gong J, Cao J, Gao Y, Shalhoub V, Tipton B, Haldankar R, Chen Q, Winters A, Boone T, Geng Z, Niu QT, Ke HZ, Kostenuik PJ, Simonet WS, Lacey DL, Paszty C (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 

  10. Ominsky MS, Vlasseros F, Jolette J, Smith SY, Stouch B, Doellgast G, Gong J, Gao Y, Cao J, Graham K, Tipton B, Cai J, Deshpande R, Zhou L, Hale MD, Lightwood DJ, Henry AJ, Popplewell AG, Moore AR, Robinson MK, Lacey DL, Simonet WS, Paszty C (2010) Two doses of sclerostin antibody in cynomolgus monkeys increases bone formation, bone mineral density, and bone strength. J Bone Miner Res 25:948–59

    Article  PubMed  CAS  Google Scholar 

  11. Padhi D, Graham J, Stouch B, Liang F, 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 

  12. Mc Nulty M, Singh RJ, Li X, Bergstralh EJ, Kumar R (2011) Determination of serum and plasma sclerostin concentrations by enzyme-linked immunoassays. Clin Endocrinol Metab 96:E1159–E1162

    Article  Google Scholar 

  13. Costa AG, Cremers S, Rubin MR, McMahon DJ, Sliney J Jr, Lazaret-Castro M, Silverberg SJ, Bilezikian JP (2011) Circulating sclerostin in disorders of parathyroid gland function. J Clin Endocrinol Metab 96:3804–10

    Article  PubMed  CAS  Google Scholar 

  14. Kirmani S, Moedder UK, Hoey K, Peterson J, McCready L, Shreyasee Amin SL, Melton J, Riggs JB, Ralph Muller R, Khosla S (2010) Gender differences in circulating sclerostin levels are established during puberty and correlate with cortical porosity. J Bone Miner Res 21(Suppl 1):S54

    Google Scholar 

  15. Mirza FS, Padhi ID, Raisz LG, Lorenzo JA (2010) Serum sclerostin levels negatively correlate with parathyroid hormone levels and free estrogen index in postmenopausal women. J Clin Endocrinol Metab 95:1991–7

    Article  PubMed  Google Scholar 

  16. Mödder UI, Hoey KA, Amin S, McCready LK, Achenbach SJ, Lawrence Riggs B, Joseph Melton L 3rd, 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  Google Scholar 

  17. Mödder UI, Clowes JA, Hoey K, Peterson JM, McCready L, Oursler MJ, Riggs BL, Khosla S (2010) Regulation of circulating sclerostin levels by sex steroids in women and in men. J Bone Miner Res 26:27–34

    Article  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  19. olyzos SA, Anastasolakis AD, Bratengeier C, Woloszczuk W, Papatheodorou A, Terpos E (2011) Serum sclerostin levels positively correlate with lumbar spinal bone mineral density in postmenopausal women-the six-month effect of risedronate and teriparatide. Osteoporos Int 23(3):1171–1176

    Article  PubMed  Google Scholar 

  20. Ardawi MS, Al-Kadi HA, Rouzzi AA, Qari MH (2011) Determinants of serum sclerostin in healthy pre and postmenopausal women. J Bone Miner Res 26:2812–2822

    Article  PubMed  CAS  Google Scholar 

  21. Eastell R, Hannon R, Gossiel F. (2010). Regulators of bone formation in postmenopausal osteoporosis: effect of bisphosphonate treatment. J Bone Miner Res 26(Suppl 1): S31

  22. Gossiel F, Lane N, Eastell R (2011). The effect of glucocorticoid therapy on regulators of bone formation in postmenopausal women treated with PTH. J Bone Miner Res 26(Suppl 1): S80

  23. Arlot ME, Sornay-Rendu E, Garnero P, Vey-Marty B, Delmas PD (1997) Apparent pre- and postmenopausal bone loss evaluated by DXA at different skeletal sites in women: the OFELY cohort. J Bone Miner Res 12:683–690

    Article  PubMed  CAS  Google Scholar 

  24. Garnero P, Sornay-Rendu E, Chapuy MC, Delmas PD (1996) Increased bone turnover in late postmenopausal women is a major determinant of osteoporosis. J Bone Miner Res 11:337–349

    Article  PubMed  CAS  Google Scholar 

  25. Genant HK, Wu CY, Van Kuijk C, Nevitt MC (1993) Vertebral fracture assessment using a semiquantitative technique. J Bone Miner Res 8:1137–1148

    Article  PubMed  CAS  Google Scholar 

  26. Keller H, Kneissel M (2005) SOST is a target gene for PTH in bone. Bone 37:148–158

    Article  PubMed  CAS  Google Scholar 

  27. Leupin O, Kramer I, Collette NM, Loots GG, Natt F, Kneissel M, Keller (2007) Control of the SOST enhancer by PTH using MEF2 transcription factors. J Bone Miner Res 22:1957–1967

    Article  PubMed  CAS  Google Scholar 

  28. Yu EW, Kumbhani R, Siwila-Sackman E, Leder BZ (2011) Acute decline in serum sclerostin in response to PTH infusion in healthy men. J Clin Endocrin Metab 96:E1848–E1851

    Article  CAS  Google Scholar 

  29. Santosh SNH, Joseph F, Hamilton A, Durham B, Robinson A, Tang J, Voras JP, Fraser D (2011) Circulating sclerostin demonstrates a circadian rhythm in young healthy men. J Bone Miner Res 26(Suppl 1): SU389

  30. Arasu A, Xawthon PM Do T, Arora PS, Lui L-Y, Cauley JA, Ebsrud KE, Cummings SR. (2011) Sclerostin and risk of hip fracture in older women. J Bone Miner Res 26:S143

    Google Scholar 

Download references

Acknowledgments

We thank Teco Medical for providing ELISA for serum sclerostin.

Conflicts of interest

None.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to P. Garnero.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Garnero, P., Sornay-Rendu, E., Munoz, F. et al. Association of serum sclerostin with bone mineral density, bone turnover, steroid and parathyroid hormones, and fracture risk in postmenopausal women: the OFELY study. Osteoporos Int 24, 489–494 (2013). https://doi.org/10.1007/s00198-012-1978-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00198-012-1978-x

Keywords

Navigation