Skip to main content

Advertisement

SpringerLink
Log in

Sclerostin: a candidate biomarker of SCI-induced osteoporosis

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

Abstract

Summary

We assessed several circulating proteins as candidate biomarkers of bone status in men with chronic spinal cord injury. We report that sclerostin is significantly associated with bone mineral content and bone density at all skeletal sites tested. We found no association between bone and any other tested biomarker.

Introduction

Spinal cord injury results in severe osteoporosis. To date, no circulating biomarker of spinal cord injury (SCI)-induced osteoporosis has been identified. We recently reported that circulating sclerostin is associated with bone density in chronic SCI. In this study, we assessed several circulating proteins as candidate biomarkers of bone in men with chronic SCI.

Methods

We assessed the relationship between bone mineral content or bone density and the following circulating bone-related proteins: sclerostin, DKK-1, soluble receptor activator of nuclear factor kappa B ligand, osteoprotegerin, osteocalcin, and c-telopeptide in 39 men with chronic SCI and 10 men with no SCI.

Results

After adjusting for age, lower sclerostin levels were significantly associated with lower bone mineral content and bone density at all skeletal sites tested (p = 0.0002−0.03). No other circulating protein was associated with bone mineral content or bone mineral density (p = 0.18−0.99).

Conclusion

These findings suggest that circulating sclerostin reflects the severity of bone loss and is a candidate biomarker of osteoporosis severity in chronic SCI.

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

Access this article

Log in via an institution

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

References

  1. Szollar SM, Martin EM, Sartoris DJ, Parthemore JG, Deftos LJ (1998) Bone mineral density and indexes of bone metabolism in spinal cord injury. Am J Phys Med Rehabil 77(1):28–35

    Article  PubMed  CAS  Google Scholar 

  2. Morse LR et al (2009) Osteoporotic fractures and hospitalization risk in chronic spinal cord injury. Osteoporos Int 20(3):385–392

    Article  PubMed  CAS  Google Scholar 

  3. Morse LR et al (2009) VA-based survey of osteoporosis management in spinal cord injury. PM R 1(3):240–244

    Article  PubMed  Google Scholar 

  4. Morse LR et al (2009) Dual energy X-ray absorptiometry of the distal femur may be more reliable than the proximal tibia in spinal cord injury. Arch Phys Med Rehabil 90(5):827–831

    Article  PubMed  Google Scholar 

  5. Morse LR et al (2009) Barriers to providing dual energy X-ray absorptiometry services to individuals with spinal cord injury. Am J Phys Med Rehabil 88(1):57–60

    Article  PubMed  Google Scholar 

  6. Khosla S (2001) Minireview: the OPG/RANKL/RANK system. Endocrinology 142(12):5050–5055

    Article  PubMed  CAS  Google Scholar 

  7. Hauschka PV, Lian JB, Cole DE, Gundberg CM (1989) Osteocalcin and matrix Gla protein: vitamin K-dependent proteins in bone. Physiol Rev 69(3):990–1047

    PubMed  CAS  Google Scholar 

  8. Patterson-Buckendahl P (2011) Osteocalcin is a stress-responsive neuropeptide. Endocr Regul 45(2):99–110

    Article  PubMed  CAS  Google Scholar 

  9. Rosen HN et al (2000) Serum CTX: a new marker of bone resorption that shows treatment effect more often than other markers because of low coefficient of variability and large changes with bisphosphonate therapy. Calcif Tissue Int 66(2):100–103

    Article  PubMed  CAS  Google Scholar 

  10. Morse LR et al (2012) Association between sclerostin and bone density in chronic SCI. J Bone Miner Res Off J Am Soc Bone Miner Res 27(2):352–359

    Article  CAS  Google Scholar 

  11. Garshick E et al (2005) A prospective assessment of mortality in chronic spinal cord injury. Spinal Cord 43(7):408–416

    Article  PubMed  CAS  Google Scholar 

  12. Grandas NF et al (2005) Dyspnea during daily activities in chronic spinal cord injury. Arch Phys Med Rehabil 86(8):1631–1635

    Article  PubMed  Google Scholar 

  13. Kirshblum SC, Memmo P, Kim N, Campagnolo D, Millis S (2002) Comparison of the revised 2000 American Spinal Injury Association classification standards with the 1996 guidelines. Am J Phys Med Rehabil 81(7):502–505

    Article  PubMed  Google Scholar 

  14. Maimoun L et al (2002) Use of bone biochemical markers with dual-energy X-ray absorptiometry for early determination of bone loss in persons with spinal cord injury. Metabolism 51(8):958–963

    Article  PubMed  CAS  Google Scholar 

  15. Reiter AL, Volk A, Vollmar J, Fromm B, Gerner HJ (2007) Changes of basic bone turnover parameters in short-term and long-term patients with spinal cord injury. European Spine J: Off Publ Eur Spine Soc, Eur Spinal Deformity Soc, Eur Sect Cervical Spine Res Soc 16(6):771–776

    Article  Google Scholar 

  16. Modder UI et al (2011) Relation of age, gender, and bone mass to circulating sclerostin levels in women and men. J Bone Miner Res: Off J Am Soc Bone Miner Res 26(2):373–379

    Article  CAS  Google Scholar 

  17. Cejka D et al (2012) Sclerostin serum levels correlate positively with bone mineral density and microarchitecture in haemodialysis patients. Nephrol Dial Transplant Off Publ Eur Dial Transplant Assoc Eur Ren Assoc 27(1):226–230

    Article  CAS  Google Scholar 

  18. Drake MT et al (2010) Effects of parathyroid hormone treatment on circulating sclerostin levels in postmenopausal women. J Clin Endocrinol Metab 95(11):5056–5062

    Article  PubMed  CAS  Google Scholar 

  19. Agholme F, Isaksson H, Kuhstoss S, Aspenberg P (2011) The effects of Dickkopf-1 antibody on metaphyseal bone and implant fixation under different loading conditions. Bone 48(5):988–996

    Article  PubMed  CAS  Google Scholar 

  20. Li X et al (2008) Targeted deletion of the sclerostin gene in mice results in increased bone formation and bone strength. J Bone Miner Res 23(6):860–869

    Article  PubMed  Google Scholar 

  21. Lin C et al (2009) Sclerostin mediates bone response to mechanical unloading through antagonizing Wnt/beta-catenin signaling. J Bone Miner Res 24(10):1651–1661

    Article  PubMed  CAS  Google Scholar 

  22. MacDonald BT et al (2007) Bone mass is inversely proportional to Dkk1 levels in mice. Bone 41(3):331–339

    Article  PubMed  CAS  Google Scholar 

  23. Robling AG et al (2008) Mechanical stimulation of bone in vivo reduces osteocyte expression of Sost/sclerostin. J Biol Chem 283(9):5866–5875

    Article  PubMed  CAS  Google Scholar 

  24. Robling AG, Bellido T, Turner CH (2006) Mechanical stimulation in vivo reduces osteocyte expression of sclerostin. J Musculoskelet Neuronal Interact 6(4):354

    PubMed  CAS  Google Scholar 

  25. Li X et al (2005) Sclerostin binds to LRP5/6 and antagonizes canonical Wnt signaling. J Biol Chem 280(20):19883–19887

    Article  PubMed  CAS  Google Scholar 

  26. Mao B et al (2002) Kremen proteins are Dickkopf receptors that regulate Wnt/beta-catenin signalling. Nature 417(6889):664–667

    Article  PubMed  CAS  Google Scholar 

  27. Bonewald LF, Johnson ML (2008) Osteocytes, mechanosensing and Wnt signaling. Bone 42(4):606–615

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We thank Sam Davis, clinical research coordinator and technician, Boston VA Healthcare System, for assisting with bone density scans; Rachel Burns and Heather Colburn, research assistants, Boston VA Healthcare System, for collection of anthropometric data; and CW Wolff, research coordinator, Spaulding Rehabilitation Hospital, for editorial assistance.

Support

This study received support from: the National Institute of Child Health and Human Development [R21HD057030 and R21HD057030-02S1], the National Institute of Arthritis and Musculoskeletal and Skin Diseases [1R01AR059270], and the Office of Research and Development, Rehabilitation Research and Development [Merit Review Grant B6618R].

Conflicts of interest

None.

Author information

Authors and Affiliations

  1. Department of Physical Medicine and Rehabilitation, Harvard Medical School, Boston, MA, USA

    L. R. Morse & R. Zafonte

  2. Spaulding-Harvard SCI Model System, Spaulding Rehabilitation Hospital, Boston, MA, USA

    L. R. Morse, S. Sudhakar & R. Zafonte

  3. The Forsyth Institute, Cambridge, MA, USA

    L. R. Morse & R. A. Battaglino

  4. Spinal Cord Injury Service, VA Boston Healthcare System, Boston, MA, USA

    L. R. Morse

  5. Primary Care and Rehabilitation Sections, VA Boston Healthcare System and Boston University School of Medicine, Boston, MA, USA

    A. A. Lazzari

  6. Rehabilitation Medicine Service, VA Boston Healthcare System, Boston, MA, USA

    C. Tun

  7. Pulmonary and Critical Care Medicine Section, Medical Service, VA Boston Healthcare System, Boston, MA, USA

    E. Garshick

  8. Channing Laboratory, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    E. Garshick

  9. Department of Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, Boston, MA, USA

    R. A. Battaglino

  10. Skeletal Biology Department, The Forsyth Institute, 245 First St., Cambridge, MA, 02142, USA

    R. A. Battaglino

Authors
  1. L. R. Morse
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S. Sudhakar
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A. A. Lazzari
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. C. Tun
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. E. Garshick
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. R. Zafonte
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. R. A. Battaglino
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to R. A. Battaglino.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Morse, L.R., Sudhakar, S., Lazzari, A.A. et al. Sclerostin: a candidate biomarker of SCI-induced osteoporosis. Osteoporos Int 24, 961–968 (2013). https://doi.org/10.1007/s00198-012-2072-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00198-012-2072-0

Keywords

Search

Navigation