Skip to main content

Advertisement

SpringerLink
Log in

Higher serum sclerostin levels and insufficiency of vitamin D are strongly associated with vertebral fractures in hemodialysis patients: a case control study

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

Abstract

Summary

In hemodialysis patients, vertebral fractures were associated with elevated sclerostin levels, suggesting that sclerostin could reflect bone fragility in these patients.

Introduction

Fragility fractures are common in hemodialysis patients. The aims of our study were to determine the prevalence of vertebral fracture and analyze associations between sclerostin serum levels and vertebral fractures in hemodialysis patients.

Methods

Ninety-two hemodialysis patients and 100 controls matched for age and sex were studied. Bone mineral density was measured by ultrasonography at non-dominant heel. The markers of bone turnover included serum osteocalcin, C-terminal telopeptide, and sclerostin. All participants underwent radiography of the thoracic and lumbar spine to ascertain the presence of vertebral fractures.

Results

Bone ultrasound parameters at calcaneus were significantly lower in hemodialysis patients compared with controls; bone turnover markers and parathyroid hormone level were significantly higher, while serum of 25-OH-D3 was significantly lower in hemodialysis group. One or more moderate or severe vertebral fractures were found in 38 hemodialysis patients, whereas in control group, 10 patients had a vertebral fracture. In hemodialysis group, the comparison between patients with and without vertebral fractures showed that the patients with vertebral fractures had the serum sclerostin levels statistically higher than patients without vertebral, while serum levels of 25-OH-D3 was significantly lower in patients with vertebral fractures compared to the patients without vertebral fractures. Multivariate analysis disclosed that sclerostin levels were associated with an increased risk of vertebral fractures in hemodialysis patients after adjusting for multiple variables.

Conclusions

Our data shows high prevalence of vertebral fractures in hemodialysis patients and that it is associated with elevated sclerostin levels, reflecting bone fragility in these patients.

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

Similar content being viewed by others

References

  1. Trombetti A, Stoermann C, Chevalley T, Van Rietbergen B, Herrmann FR, Martin PY, Rizzoli R (2013) Alterations of bone microstructure and strength in end-stage renal failure. Osteoporos Int 24:1721–1732

    Article  CAS  PubMed  Google Scholar 

  2. Grzegorzewska AE, Mlot M (2007) Influence of age and sex on bone mineral density in dialysis patients. Adv Perit Dial 23:77–81

    PubMed  Google Scholar 

  3. Dooly AC, Weiss NS, Kestenbaum B (2008) Increased risk of hip fracture among men with CKD. Am J Kidney Dis 51:38–44

    Article  Google Scholar 

  4. Alem AM, Sherrard DJ, Gillen DL, Weiss NS, Beresford SA, Heckbert SR et al (2000) Increased risk of hip fracture among patients with end-stage renal disease. Kidney Int 58:396–399

    Article  CAS  PubMed  Google Scholar 

  5. Jadoul M, Albert JM, Akiba T, Akizawa T, Arab L, Bragg-Gresham JL et al (2006) Incidence and risk factors for hip or other bone fractures among hemodialysis patients in the dialysis outcomes and practice patterns study. Kidney Int 70(7):1358–1366

    Article  CAS  PubMed  Google Scholar 

  6. Fusaro M, Tripepi G, Noale M, Vajente N, Plebani M, Zaninotto M et al (2013) High prevalence of vertebral fractures assessed by quantitative morphometry in hemodialysis patients, strongly associated with vascular calcifications. Calcif Tissue Int 93(1):39–34

    Article  CAS  PubMed  Google Scholar 

  7. Maeno Y, Inaba M, Okuno S, Kohno K, Maekawa K, Yamakawa T et al (2009) Significant association of fracture of the lumbar spine with mortality in female hemodialysis patients: a prospective observational study. Calcif Tissue Int 85(4):310–316

    Article  CAS  PubMed  Google Scholar 

  8. Rodriguez-Garcia M, Gomez-Alonso C, Naves-Diaz M, Diaz-Lopez JB, Diaz-Corte C, Cannata-Andia JB (2009) Asturias study group vascular calcifications, vertebral fractures and mortality in haemodialysis patients. Nephrol Dial Transplant 24:239–246

    Article  PubMed  Google Scholar 

  9. Stehman-Breen CO, Sherrad DJ, Alem AM, Gillen DL, Heckbert SR, Wong CS et al (2000) Risk factors for hip fracture among patients with end-stage renal disease. Kidney Int 58:2200–2205

    Article  CAS  PubMed  Google Scholar 

  10. Iimori S, Mori Y, Akita W, Kuyama T, Takada S, Asai T et al (2012) Diagnostic usefulness of bone mineral density and biochemical markers of bone turn-over in predicting fracture in CKD stage 5D patients: a single-center cohort study. Nephrol Dial Transplant 27:345–351

    Article  CAS  PubMed  Google Scholar 

  11. Baron R, Rawadi G, Roman-Roman S (2006) Wnt signaling: a key regulator of bone mass. Curr Top Dev Biol 76:103–127

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  14. Arasu A, Cawthon PM, Lui LY, Do TP, Arora PS, Cauley JA et al (2012) Study of osteoporotic fractures research group serum sclerostin and risk of hip fracture in older Caucasian women. J Clin Endocrinol Metab 97(6):2027–2032

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Pelletier S, Confavreux CB, Haesebaert J, Guebre-Egziabher F, Bacchetta J, Carlier MC et al (2015) Serum sclerostin: the missing link in the bone-vessel cross-talk in hemodialysis patients? Osteoporos Int 26(8):2165–2174

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  17. Kauppila L, Polak J, Cupples L, Hannan M, Kiel D, Wilson P (1997) New indices to classify location, severity and progression of calcific lesions in the abdominal aorta: a 25-year follow-up study. Atherosclerosis 132:245–250

    Article  CAS  PubMed  Google Scholar 

  18. Fishbane S, Hazzan AD, Jhaveri KD, Ma L, Lacson E Jr (2016) Bone parameters and risk of hip and femur fractures in patients on hemodialysis. Clin J Am Soc Nephrol 29:09280915

  19. Wagner J, Jhaveri KD, Rosen L, Sunday S, Mathew AT, Fishbane S (2014) Increased bone fractures among elderly United States hemodialysis patients. Nephrol Dial Transplant 29(1):146–151

    Article  PubMed  Google Scholar 

  20. Fusaro M, Tripepi G, Noale M, Plebani M, Zaninotto M, Piccoli A et al (2015) Vertebral fractures and vascular calcifications study group. Prevalence of vertebral fractures, vascular calcifications, and mortality in warfarin treated hemodialysis patients. Curr Vasc Pharmacol 13(2):248–258

    Article  CAS  PubMed  Google Scholar 

  21. Fusaro M, Noale M, Viola V, Galli F, Tripepi G, Vajente N et al (2012) Vitamin K, vertebral fractures, vascular calcifications, and mortality: VItamin K Italian (VIKI) dialysis study. J Bone Miner Res 27(11):2271–2278

    Article  CAS  PubMed  Google Scholar 

  22. Bauer DC, Glüer CC, Genant HK, Stone K (1995) Quantitative ultrasound and vertebral fracture in postmenopausal women. J Bone Miner Res 10:353–358

    Article  CAS  PubMed  Google Scholar 

  23. Bauer DC, Glüer CC, Cauley JA, Vogt TM, Ensrud KE, Genant HK, Black DM (1997) Broadband ultrasound attenuation predicts fractures strongly and independently of densitometry in older women. A prospective study Study of Osteoporotic Fractures Research Group Arch Intern Med 157:629–634

    CAS  PubMed  Google Scholar 

  24. Bauer DC, Ewing SK, Cauley JA, Ensrud KE, Cummings SR, Orwoll ES (2007) Quantitative ultrasound predicts hip and non-spine fracture in men: the MrOS study. Osteoporos Int 18:771–777

    Article  CAS  PubMed  Google Scholar 

  25. Ambrus C, Almasi C, Berta K, Deak G, Marton A, Molnar MZ et al (2011) Vitamin D insufficiency and bone fractures in patients on maintenance hemodialysis. Int Urol Nephrol 43(2):475–482

    Article  CAS  PubMed  Google Scholar 

  26. Nickolas TL, Leonard MB, Shane E (2008) Chronic kidney disease and bone fracture: a growing concern. Kidney Int 74(6):721–731

    Article  PubMed  PubMed Central  Google Scholar 

  27. El Maghraoui A, Ouzzif Z, Mounach A, Rezqi A, Achemlal L, Bezza A et al (2012) Hypovitaminosis D and prevalent asymptomatic vertebral fractures in Moroccan postmenopausal women. BMC Womens Health 24:12–11

    Google Scholar 

  28. Pelletier S, Dubourg L, Carlier MC, Hadj-Aissa A, Fouque D (2013) The relation between renalvfunction and serum sclerostin in adult patients with CKD. Clin J Am Soc Nephrol 8:819–823

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Polyzos SA, Anastasilakis AD, Bratengeier C, Woloszczuk W, Papatheodorou A, Terpos E (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 23:1171–1176

    Article  CAS  PubMed  Google Scholar 

  30. Amrein K, Amrein S, Drexler C et al (2012) Sclerostin and its association with physical activity, age, gender, body composition, and bone mineral content in healthy adults. J Clin Endocrinol Metab 97:148–154

    Article  CAS  PubMed  Google Scholar 

  31. Modder UI, Hoey KA, Amin S et al (2011) Relation of age, gender, and bone mass to rcirculating sclerostin levels in women and men. J Bone Miner Res 26:373–379

    Article  CAS  PubMed  Google Scholar 

  32. Arasu A, Cawthon PM, Cummings SR et al (2012) Serum sclerostin and risk of hip fracture in older Caucasian women. J Clin Endocrinol Metab 97:2027–2032

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Ardawi MS, Rouzi AA, Al-Sibiani SA, Al-Senani NS, Qari MH, Mousa SA (2012) High serum sclerostin predicts the occurrence of osteoporotic fractures in postmenopausal women: the Center of Excellence for osteoporosis research study. J Bone Miner Res 27:2592–2602

    Article  CAS  PubMed  Google Scholar 

  34. Garnero P, Sornay-Rendu E, Munoz F, Borel O, Chapurlat RD (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):489–494

    Article  CAS  PubMed  Google Scholar 

  35. Szulc P, Bertholon C, Borel O, Marchand F, Chapurlat R (2013) Lower fracture risk in older men with higher sclerostin concentration: a prospective analysis from the MINOS study. J Bone Miner Res 28:855–864

    Article  CAS  PubMed  Google Scholar 

  36. Cejka D, Herberth J, Branscum AJ, Fardo DW, Monier-Faugere MC, Diarra D et al (2011) Sclerostin and Dickkopf-1 in renal osteodystrophy. Clin J Am Soc Nephrol 6(4):877–882

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Sabbagh YL, Graciolli FG, O’Brien S, Tang W, dos Reis LM, Ryan S, Phillips L, Boulanger J, Song W, Bracken C, Liu S, Ledbetter S, Dechow P, Canziani ME, Carvalho AB, Jorgetti V, Moyses RM (2012) Schiavi SC (2012) repression of osteocyte Wnt/β-catenin signaling is an early event in the progression of renal osteodystrophy. J Bone Miner Res 27(8):1757–1772

    Article  CAS  PubMed  Google Scholar 

  38. Morales-Santana S, Garcia-Fontana B, Garcia-Martin A, Rozas-Moreno P, Garcia-Salcedo JA, Reyes-Garcia R, Munoz-Torres M (2013) Atherosclerotic disease in type 2 diabetes is associated with an increase in sclerostin levels. Diabetes Care 36:1667–1674

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Winkler DG, Sutherland MK, Geoghegan JC, Yu C, Hayes T, Skonier JE, Shpektor D et al (2003) Osteocyte control of bone formation via sclerostin, a novel BMP antagonist. EMBO J 22(23):6267–6276

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Hampson G, Edwards S, Conroy S, Blake GM, Fogelman I, Frost ML (2013) The relationship between inhibitors of the Wnt signalling pathway (Dickkopf-1(DKK1) and sclerostin), bone mineral density, vascular calcification and arterial stiffness in postmenopausal women. Bone 56:42–47

    Article  CAS  PubMed  Google Scholar 

  41. Zhu D, Mackenzie NC, Millán JL, Farquharson C, MacRae VE (2011) The appearance and modulation of osteocyte marker expression during calcification of vascular smooth muscle cells. PLoS One 6(5):e19595

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Evenepoel P, D’Haese P, Brandenburg V (2015) Sclerostin and DKK1: new players in renal bone and vascular disease. Kidney Int 88(2):235–240 Review

    Article  CAS  PubMed  Google Scholar 

  43. Evrard S, Delanaye P, Kamel S, Cristol JP, Cavalier E (2015) SFBC/SN joined working group on vascular calcifications. Vascular calcification: from pathophysiology to biomarkers. Clin Chim Acta 438:401–414

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Clinical and Experimental Medicine, University of Messina, Pad. B, 2nd floor, A.O.U. Policlinico “G. Martino” Via C. Valeria, 98125, Messina, Italy

    M. Atteritano, E. Di Mauro, V. Canale, A. M. Bruzzese, C. A. Ricciardi, V. Cernaro, A. Lacquaniti, M. Buemi & D. Santoro

Authors
  1. M. Atteritano
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. E. Di Mauro
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. V. Canale
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. A. M. Bruzzese
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. C. A. Ricciardi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. V. Cernaro
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. A. Lacquaniti
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. M. Buemi
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. D. Santoro
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to M. Atteritano.

Ethics declarations

Conflicts of interest

None.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Atteritano, M., Di Mauro, E., Canale, V. et al. Higher serum sclerostin levels and insufficiency of vitamin D are strongly associated with vertebral fractures in hemodialysis patients: a case control study. Osteoporos Int 28, 577–584 (2017). https://doi.org/10.1007/s00198-016-3770-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00198-016-3770-9

Keywords

Search

Navigation