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Osteoporosis International

, Volume 28, Issue 9, pp 2683–2689 | Cite as

Circulating levels of dickkopf-1, osteoprotegerin and sclerostin are higher in old compared with young men and women and positively associated with whole-body bone mineral density in older adults

  • J. Coulson
  • L. Bagley
  • Y. Barnouin
  • S. Bradburn
  • G. Butler-Browne
  • H. Gapeyeva
  • J.-Y. Hogrel
  • T. Maden-Wilkinson
  • A. B. Maier
  • C. Meskers
  • C. Murgatroyd
  • M. Narici
  • M. Pääsuke
  • L. Sassano
  • S. Sipilä
  • N. AL-Shanti
  • L. Stenroth
  • D. A. Jones
  • J. S. McPheeEmail author
Original Article

Abstract

Summary

Bone mineral density declines with increasing older age. We examined the levels of circulating factors known to regulate bone metabolism in healthy young and older adults. The circulating levels of dickkopf-1, osteocalcin, osteoprotegerin and sclerostin were positively associated with whole-body bone mineral density (WBMD) in older adults, despite the average WBMD being lower and circulating dickkopf-1, osteoprotegerin and sclerostin being higher in old than young.

Introduction

This study aims to investigate the relationship between whole-body bone mineral density (WBMD) and levels of circulating factors with known roles in bone remodelling during ‘healthy’ ageing.

Methods

WBMD and fasting plasma concentrations of dickkopf-1, fibroblast growth factor-23, osteocalcin, osteoprotegerin, osteopontin and sclerostin were measured in 272 older subjects (69 to 81 years; 52% female) and 171 younger subjects (18–30 years; 53% female).

Results

WBMD was lower in old than young. Circulating osteocalcin was lower in old compared with young, while dickkopf-1, osteoprotegerin and sclerostin were higher in old compared with young. These circulating factors were each positively associated with WBMD in the older adults and the relationships remained after adjustment for covariates (r values ranging from 0.174 to 0.254, all p < 0.01). In multivariate regression, the body mass index, circulating sclerostin and whole-body lean mass together accounted for 13.8% of the variation with WBMD in the older adults. In young adults, dickkopf-1 and body mass index together accounted for 7.7% of variation in WBMD.

Conclusion

Circulating levels of dickkopf-1, osteocalcin, osteoprotegerin and sclerostin are positively associated with WBMD in community-dwelling older adults, despite the average WBMD being lower and circulating dickkopf-1, osteoprotegerin and sclerostin being higher in old than young.

Keywords

DKK1 MYOAGE Osteoporosis Osteoprotegerin Sclerostin 

Notes

Acknowledgements

This project was supported by funding from European Union FP7 (‘MYOAGE’, #223576) and Medical Research Council (MR/K025252/1).

Compliance with ethical standards

Conflicts of interest

None.

References

  1. 1.
    Genant HK et al (1999) Interim report and recommendations of the World Health Organization task-force for osteoporosis. Osteoporos Int 10(4):259–264CrossRefPubMedGoogle Scholar
  2. 2.
    Hofbauer LC et al (1999) Estrogen stimulates gene expression and protein production of osteoprotegerin in human osteoblastic cells. Endocrinology 140(9):4367–4370CrossRefPubMedGoogle Scholar
  3. 3.
    Ferron M et al (2010) Insulin signaling in osteoblasts integrates bone remodeling and energy metabolism. Cell 142(2):296–308CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Kamiya N (2012) The role of BMPs in bone anabolism and their potential targets SOST and DKK1. Curr Mol Pharmacol 5(2):153–163CrossRefPubMedGoogle Scholar
  5. 5.
    Gaudio A et al (2010) Increased sclerostin serum levels associated with bone formation and resorption markers in patients with immobilization-induced bone loss. J Clin Endocrinol Metab 95(5):2248–2253CrossRefPubMedGoogle Scholar
  6. 6.
    Ke HZ et al (2012) Sclerostin and Dickkopf-1 as therapeutic targets in bone diseases. Endocr rev 33(5):747–783CrossRefPubMedGoogle Scholar
  7. 7.
    Takei Y, Minamizaki T, Yoshiko Y (2015) Functional diversity of fibroblast growth factors in bone formation. Int J Endocrinol 2015:729352CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Standal T, Borset M, Sundan A (2004) Role of osteopontin in adhesion, migration, cell survival and bone remodeling. Exp Oncol 26(3):179–184PubMedGoogle Scholar
  9. 9.
    McPhee JS et al (2013) Physiological and functional evaluation of healthy young and older men and women: design of the European MyoAge study. Biogerontology 14(3):325–337CrossRefPubMedGoogle Scholar
  10. 10.
    Monroe DG et al (2012) Update on Wnt signaling in bone cell biology and bone disease. Gene 492(1):1–18CrossRefPubMedGoogle Scholar
  11. 11.
    Brunetti G et al (2016) Impaired bone remodeling in children with osteogenesis imperfecta treated and untreated with bisphosphonates: the role of DKK1, RANKL, and TNF-alpha. Osteoporos Int 27(7):2355–2365CrossRefPubMedGoogle Scholar
  12. 12.
    Roforth MM et al (2014) Effects of age on bone mRNA levels of sclerostin and other genes relevant to bone metabolism in humans. Bone 59:1–6CrossRefPubMedGoogle Scholar
  13. 13.
    Butler JS et al (2011) The role of Dkk1 in bone mass regulation: correlating serum Dkk1 expression with bone mineral density. J Orthop res 29(3):414–418CrossRefPubMedGoogle Scholar
  14. 14.
    Szulc P et al (2013) Correlates of bone microarchitectural parameters and serum sclerostin levels in men: the STRAMBO study. J Bone Miner res 28(8):1760–1770CrossRefPubMedGoogle Scholar
  15. 15.
    Garnero P et al (2013) 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(2):489–494CrossRefPubMedGoogle Scholar
  16. 16.
    Polyzos SA et al (2012) 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):1171–1176CrossRefPubMedGoogle Scholar
  17. 17.
    Thorson S et al (2013) Sclerostin and bone strength in women in their 10th decade of life. J Bone Miner res 28(9):2008–2016CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Schett G et al (2003) Osteoprotegerin protects against generalized bone loss in tumor necrosis factor-transgenic mice. Arthritis Rheum 48(7):2042–2051CrossRefPubMedGoogle Scholar
  19. 19.
    Weitzmann MN (2013) The role of inflammatory cytokines, the RANKL/OPG axis, and the immunoskeletal interface in physiological bone turnover and osteoporosis. Scientifica (Cairo) 2013:125705Google Scholar
  20. 20.
    Jabbar S et al (2011) Osteoprotegerin, RANKL and bone turnover in postmenopausal osteoporosis. J Clin Pathol 64(4):354–357CrossRefPubMedGoogle Scholar
  21. 21.
    Oh KW et al (2005) Circulating osteoprotegerin and receptor activator of NF-kappaB ligand system are associated with bone metabolism in middle-aged males. Clin Endocrinol 62(1):92–98CrossRefGoogle Scholar
  22. 22.
    Rogers A et al (2002) Circulating estradiol and osteoprotegerin as determinants of bone turnover and bone density in postmenopausal women. J Clin Endocrinol Metab 87(10):4470–4475CrossRefPubMedGoogle Scholar
  23. 23.
    Liu JM et al (2005) Relationships between the changes of serum levels of OPG and RANKL with age, menopause, bone biochemical markers and bone mineral density in Chinese women aged 20–75. Calcif Tissue Int 76(1):1–6CrossRefPubMedGoogle Scholar
  24. 24.
    Samelson EJ et al (2008) Increased plasma osteoprotegerin concentrations are associated with indices of bone strength of the hip. J Clin Endocrinol Metab 93(5):1789–1795CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Stern A et al (2007) The sex-specific association of serum osteoprotegerin and receptor activator of nuclear factor kappaB legend with bone mineral density in older adults: the Rancho Bernardo study. Eur J Endocrinol 156(5):555–562CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Modder UI et al (2011) Regulation of circulating sclerostin levels by sex steroids in women and in men. J Bone Miner res 26(1):27–34CrossRefPubMedGoogle Scholar
  27. 27.
    Modder UI et al (2011) Relation of age, gender, and bone mass to circulating sclerostin levels in women and men. J Bone Miner res 26(2):373–379CrossRefPubMedGoogle Scholar
  28. 28.
    Mazziotti G et al (2006) Increased serum osteoprotegerin values in long-lived subjects: different effects of inflammation and bone metabolism. Eur J Endocrinol 154(3):373–377CrossRefPubMedGoogle Scholar
  29. 29.
    Moester MJ et al (2010) Sclerostin: current knowledge and future perspectives. Calcif Tissue Int 87(2):99–107CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Atalay S et al (2012) Diagnostic utility of osteocalcin, undercarboxylated osteocalcin, and alkaline phosphatase for osteoporosis in premenopausal and postmenopausal women. Ann lab med 32(1):23–30CrossRefPubMedGoogle Scholar
  31. 31.
    Mora S et al (2015) Sclerostin and DKK-1: two important regulators of bone metabolism in HIV-infected youths. Endocrine 49(3):783–790CrossRefPubMedGoogle Scholar
  32. 32.
    Fan B et al (2010) Does standardized BMD still remove differences between Hologic and GE-Lunar state-of-the-art DXA systems? Osteoporos Int 21(7):1227–1236CrossRefPubMedGoogle Scholar

Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2017

Authors and Affiliations

  • J. Coulson
    • 1
  • L. Bagley
    • 1
  • Y. Barnouin
    • 1
    • 2
  • S. Bradburn
    • 1
  • G. Butler-Browne
    • 3
  • H. Gapeyeva
    • 4
  • J.-Y. Hogrel
    • 3
  • T. Maden-Wilkinson
    • 5
  • A. B. Maier
    • 6
    • 7
  • C. Meskers
    • 8
  • C. Murgatroyd
    • 1
  • M. Narici
    • 9
  • M. Pääsuke
    • 4
  • L. Sassano
    • 10
  • S. Sipilä
    • 11
  • N. AL-Shanti
    • 1
  • L. Stenroth
    • 11
    • 12
  • D. A. Jones
    • 1
  • J. S. McPhee
    • 1
    Email author
  1. 1.School of Healthcare ScienceManchester Metropolitan UniversityManchesterUK
  2. 2.Baylor College of MedicineHoustonUSA
  3. 3.Institut de Myologie, GH Pitié-SalpêtrièreParisFrance
  4. 4.Institute of Sport Sciences and Physiotherapy, University of TartuTartuEstonia
  5. 5.School of Physical Activity and HealthSheffield Hallam UniversitySheffieldUK
  6. 6.Department of Human Movement Sciences, MOVE Research InstituteVrij UniversityAmsterdamThe Netherlands
  7. 7.Department of Medicine and Aged Care, The Royal Melbourne HospitalUniversity of MelbourneMelbourneAustralia
  8. 8.Rehabilitation MedicineVU University Medical CenterAmsterdamThe Netherlands
  9. 9.Graduate Entry Medicine and HealthUniversity of NottinghamNottinghamUK
  10. 10.Unilever DiscoverBedfordUK
  11. 11.Gerontology Research Center, Department of Health SciencesUniversity of JyväskyläJyväskyläFinland
  12. 12.Department of Applied PhysicsUniversity of Eastern FinlandKuopioFinland

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