Skip to main content
SpringerLink
Log in

Bone kidney interactions

  • Published:
Reviews in Endocrine and Metabolic Disorders Aims and scope Submit manuscript

Abstract

The fact that bone disease and kidney disease co-exist is well known. Formally, this inter-relationship is called chronic kidney disease mineral bone disorder or CKD-MBD. Traditionally, it was thought that bone played a passive role in CKD-MBD - specifically that kidney disease caused disordered mineral metabolism which resulted in bone disease and ultimately fractures. More recently however our understanding of bone function in general and the role that bone plays in CKD-MBD in particular, has changed. This chapter will briefly review epidemiology of fractures in chronic kidney disease (CKD) and the roles that imaging and measuring markers of mineral metabolism can play in assessing fracture risk. We will then review more recent data consistent with the concept MBD occurs early in the course of CKD and, via the secretion of novel molecules and/or signalling pathways, the bone can influence other organ systems.

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. Nickolas TL, McMahon DJ, Shane E. Relationship between moderate to severe kidney disease and hip fracture in the United States. J Am Soc Nephrol. 2006;17:3223–32.

    Article  PubMed  Google Scholar 

  2. Dukas LC, Schacht E, Mazor Z, Stahelin HB. A new significant and independent risk factor for falls in elderly men and women: a low creatinine clearance of less than 65 ml/min. Osteoporos Int. 2005;16:332–8.

    Article  CAS  PubMed  Google Scholar 

  3. Ensrud KE, Lui LY, Taylor BC, Ishani A, Shlipak MG, Stone KL, et al. Renal function and risk of hip and vertebral fractures in older women. Arch Intern Med. 2007;167:133–9.

    Article  PubMed  Google Scholar 

  4. KDIGO clinical practice guideline for the diagnosis, evaluation, prevention, and treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD). Kidney Int Suppl. 2009;113:S1–130.

  5. Ketteler M, Elder GJ, Evenepoel P, Ix JH, Jamal SA, Lafage-Proust MH, et al. Revisiting KDIGO clinical practice guideline on chronic kidney disease-mineral and bone disorder: a commentary from a Kidney Disease: Improving Global Outcomes controversies conference. Kidney Int. 2015;87:502–28.

    Article  PubMed  Google Scholar 

  6. West SL, Lok CE, Langsetmo L, Cheung AM, Szabo E, Pearce D, et al. Bone mineral density predicts fractures in chronic kidney disease. J Bone Miner Res. 2015;30:913–9.

    Article  PubMed  Google Scholar 

  7. Yenchek RH, Ix JH, Shlipak MG, Bauer DC, Rianon NJ, Kritchevsky SB, et al. Bone mineral density and fracture risk in older individuals with CKD. Clin J Am Soc Nephrol. 2012;7:1130–6.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  8. Iimori S, Mori Y, Akita W, Kuyama T, Takada S, Asai T, et al. Diagnostic usefulness of bone mineral density and biochemical markers of bone turnover in predicting fracture in CKD stage 5D patients–a single-center cohort study. Nephrol Dial Transplant. 2012;27:345–51.

    Article  CAS  PubMed  Google Scholar 

  9. Akaberi S, Simonsen O, Lindergard B, Nyberg G. Can DXA predict fractures in renal transplant patients? Am J Transplant. 2008;8:2647–51.

    Article  CAS  PubMed  Google Scholar 

  10. Naylor KL, Leslie WD, Hodsman AB, Rush DN, Garg AX. FRAX predicts fracture risk in kidney transplant recipients. Transplantation. 2014;97:940–5.

    Article  CAS  PubMed  Google Scholar 

  11. Couttenye MM, D'Haese PC, Van Hoof VO, Lemoniatou E, Goodman W, Verpooten GA, et al. Low serum levels of alkaline phosphatase of bone origin: a good marker of adynamic bone disease in haemodialysis patients. Nephrol Dial Transplant. 1996;11:1065–72.

    Article  CAS  PubMed  Google Scholar 

  12. Bervoets AR, Spasovski GB, Behets GJ, Dams G, Polenakovic MH, Zafirovska K, et al. Useful biochemical markers for diagnosing renal osteodystrophy in predialysis end-stage renal failure patients. Am J Kidney Dis. 2003;41:997–1007.

    Article  CAS  PubMed  Google Scholar 

  13. Coen G, Ballanti P, Bonucci E, Calabria S, Centorrino M, Fassino V, et al. Bone markers in the diagnosis of low turnover osteodystrophy in haemodialysis patients. Nephrol Dial Transplant. 1998;13:2294–302.

    Article  CAS  PubMed  Google Scholar 

  14. Lehmann G, Ott U, Kaemmerer D, Schuetze J, Wolf G. Bone histomorphometry and biochemical markers of bone turnover in patients with chronic kidney disease Stages 3–5. Clin Nephrol. 2008;70:296–305.

    Article  CAS  PubMed  Google Scholar 

  15. Lehmann G, Stein G, Huller M, Schemer R, Ramakrishnan K, Goodman WG. Specific measurement of PTH (1–84) in various forms of renal osteodystrophy (ROD) as assessed by bone histomorphometry. Kidney Int. 2005;68:1206–14.

    Article  CAS  PubMed  Google Scholar 

  16. Herberth J, Branscum AJ, Mawad H, Cantor T, Monier-Faugere MC, Malluche HH. Intact PTH combined with the PTH ratio for diagnosis of bone turnover in dialysis patients: a diagnostic test study. Am J Kidney Dis. 2010;55:897–906.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  17. Iyer SNL, Nishiyama K, Dworakowski E, Cremers S, Zhang A, McMahon DJ, et al. Kidney transplantation with early corticosteroid withdrawal: paradoxical effects at the central and peripheral skeleton. J Am Soc Nephrol. 2014;25:1331–41.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  18. Nickolas TL, Stein EM, Dworakowski E, Nishiyama KK, Komandah-Kosseh M, Zhang CA, et al. Rapid cortical bone loss in patients with chronic kidney disease. J Bone Miner Res. 2013;28:1811–20.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  19. Nickolas TL, Cremers S, Zhang A, Thomas V, Stein E, Cohen A, et al. Discriminants of prevalent fractures in chronic kidney disease. J Am Soc Nephrol. 2011;22:1560–72.

    Article  PubMed Central  PubMed  Google Scholar 

  20. Perrin P, Caillard S, Javier RM, Braun L, Heibel F, Borni-Duval C, et al. Persistent hyperparathyroidism is a major risk factor for fractures in the five years after kidney transplantation. Am J Transplant. 2013;13:2653–63.

    Article  CAS  PubMed  Google Scholar 

  21. Slatopolsky E, Martin K, Hruska K. Parathyroid hormone metabolism and its potential as a uremic toxin. Am J Phys. 1980;239:F1–12.

    CAS  Google Scholar 

  22. Moe S, Drueke T, Cunningham J, Goodman W, Martin K, Olgaard K, et al. Definition, evaluation, and classification of renal osteodystrophy: a position statement from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int. 2006;69:1945–53.

    Article  CAS  PubMed  Google Scholar 

  23. Go AS, Chertow GM, Fan D, McCulloch CE, Hsu CY. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med. 2004;351:1296–305.

    Article  CAS  PubMed  Google Scholar 

  24. Raggi P, Giachelli C, Bellasi A. Interaction of vascular and bone disease in patients with normal renal function and patients undergoing dialysis. Nat Clin Pract Card. 2007;4:26–33.

    Article  CAS  Google Scholar 

  25. Evenepoel P, Meijers BK, de Jonge H, Naesens M, Bammens B, Claes K, et al. Recovery of hyperphosphatoninism and renal phosphorus wasting one year after successful renal transplantation. Clin J Am Soc Nephrol. 2008;3:1829–36.

    Article  PubMed Central  PubMed  Google Scholar 

  26. Rao M, Jain P, Ojo T, Surya G, Balakrishnan V. Fibroblast growth factor and mineral metabolism parameters among prevalent kidney transplant patients. Int J Nephrol. 2012;2012:490623.

  27. Pereira RC, Juppner H, Azucena-Serrano CE, Yadin O, Salusky IB, Wesseling-Perry K. Patterns of FGF-23, DMP1, and MEPE expression in patients with chronic kidney disease. Bone. 2009;45:1161–8.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  28. Gutierrez OM, Mannstadt M, Isakova T, Rauh-Hain JA, Tamez H, Shah A, et al. Fibroblast growth factor 23 and mortality among patients undergoing hemodialysis. N Engl J Med. 2008;359:584–92.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  29. Isakova T, Xie H, Yang W, Xie D, Anderson AH, Scialla J, et al. Fibroblast growth factor 23 and risks of mortality and end-stage renal disease in patients with chronic kidney disease. J Am Med Assoc. 2011;305:2432–9.

    Article  CAS  Google Scholar 

  30. Baia LC, Humalda JK, Vervloet MG, Navis G, Bakker SJ, de Borst MH, et al. Fibroblast growth factor 23 and cardiovascular mortality after kidney transplantation. Clin J Am Soc Nephrol. 2013;8:1968–78.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  31. Arnlov J, Carlsson AC, Sundstrom J, Ingelsson E, Larsson A, Lind L, et al. Serum FGF23 and risk of cardiovascular events in relation to mineral metabolism and cardiovascular pathology. Clin J Am Soc Nephrol. 2013;8:781–6.

    Article  PubMed Central  PubMed  Google Scholar 

  32. McClung MR, Grauer A, Boonen S, Bolognese MA, Brown JP, Diez-Perez A, et al. Romosozumab in postmenopausal women with low bone mineral density. N Engl J Med. 2014;370:412–20.

    Article  CAS  PubMed  Google Scholar 

  33. Mani A, Radhakrishnan J, Wang H, Mani A, Mani MA, Nelson-Williams C, et al. LRP6 mutation in a family with early coronary disease and metabolic risk factors. Science. 2007;315:1278–82.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  34. Brandenburg VM, Kramann R, Koos R, Kruger T, Schurgers L, Muhlenbruch G, et al. Relationship between sclerostin and cardiovascular calcification in hemodialysis patients: a cross-sectional study. BMC Nephrol. 2013;14:219.

    Article  PubMed Central  PubMed  Google Scholar 

  35. Cejka D, Marculescu R, Kozakowski N, Plischke M, Reiter T, Gessl A, et al. Renal elimination of sclerostin increases with declining kidney function. J Clin Endocrinol Metab. 2014;99:248–55.

    Article  CAS  PubMed  Google Scholar 

  36. Kramer I, Loots GG, Studer A, Keller H, Kneissel M. Parathyroid hormone (PTH)-induced bone gain is blunted in SOST overexpressing and deficient mice. J Bone Miner Res. 2010;25:178–89.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  37. Cejka D, Herberth J, Branscum AJ, Fardo DW, Monier-Faugere MC, Diarra D, et al. Sclerostin and dickkopf-1 in renal osteodystrophy. Clin J Am Soc Nephrol. 2011;6:877–82.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  38. Koos R, Brandenburg V, Mahnken AH, Schneider R, Dohmen G, Autschbach R, et al. Sclerostin as a potential novel biomarker for aortic valve calcification: an in-vivo and ex-vivo study. J Heart Valve Dis. 2013;22:317–25.

    PubMed  Google Scholar 

  39. Hampson G, Edwards S, Conroy S, Blake GM, Fogelman I, Frost ML. The relationship between inhibitors of the Wnt signalling pathway (Dickkopf-1(DKK1) and sclerostin), bone mineral density, vascular calcification and arterial stiffness in post-menopausal women. Bone. 2013;56:42–7.

    Article  CAS  PubMed  Google Scholar 

  40. Kanbay M, Siriopol D, Saglam M, Kurt YG, Gok M, Cetinkaya H, et al. Serum sclerostin and adverse outcomes in nondialyzed chronic kidney disease patients. J Clin Endocrinol Metab. 2014;99:E1854–61.

    Article  CAS  PubMed  Google Scholar 

  41. Drechsler C, Evenepoel P, Vervloet MG, Wanner C, Ketteler M, Marx N, et al. High levels of circulating sclerostin are associated with better cardiovascular survival in incident dialysis patients: results from the NECOSAD study. Nephrol Dial Transplant. 2015;30:288–93.

    Article  PubMed  Google Scholar 

  42. Moyses RM, Jamal SA, Graciolli FG, Dos Reis LM, Elias RM. Can we compare serum sclerostin results obtained with different assays in hemodialysis patients? Int Urol Nephrol. 2015;47:847–50.

    Article  CAS  PubMed  Google Scholar 

  43. Neve A, Corrado A, Cantatore FP. Osteocalcin: skeletal and extra-skeletal effects. J Cell Physiol. 2013;228:1149–53.

    Article  CAS  PubMed  Google Scholar 

  44. Gundberg CM, Nieman SD, Abrams S, Rosen H. Vitamin K status and bone health: an analysis of methods for determination of undercarboxylated osteocalcin. J Clin Endocrinol Metab. 1998;83:3258–66.

    CAS  PubMed  Google Scholar 

  45. Coen G, Mazzaferro S, Bonucci E, Taggi F, Ballanti P, Bianchi AR, et al. Bone GLA protein in predialysis chronic renal failure. Effects of 1,25(OH)2D3 administration in a long-term follow-up. Kidney Int. 1985;28:783–90.

    Article  CAS  PubMed  Google Scholar 

  46. Malluche HH, Faugere MC, Fanti P, Price PA. Plasma levels of bone Gla-protein reflect bone formation in patients on chronic maintenance dialysis. Kidney Int. 1984;26:869–74.

    Article  CAS  PubMed  Google Scholar 

  47. Lee NK, Sowa H, Hinoi E, Ferron M, Ahn JD, Confavreux C, et al. Endocrine regulation of energy metabolism by the skeleton. Cell. 2007;130:456–69.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  48. Booth SL, Centi A, Smith SR, Gundberg C. The role of osteocalcin in human glucose metabolism: marker or mediator? Nat Rev Endocrinol. 2013;9:43–55.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  49. Confavreux CB, Borel O, Lee F, Vaz G, Guyard M, Fadat C, et al. Osteoid osteoma is an osteocalcinoma affecting glucose metabolism. Osteoporos Int. 2012;23:1645–50.

    Article  CAS  PubMed  Google Scholar 

  50. Schafer AL, Sellmeyer DE, Schwartz AV, Rosen CJ, Vittinghoff E, Palermo L, et al. Change in undercarboxylated osteocalcin is associated with changes in body weight, fat mass, and adiponectin: parathyroid hormone (1–84) or alendronate therapy in postmenopausal women with osteoporosis (the PaTH study). J Clin Endocrinol Metab. 2011;96:E1982–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  51. Schwartz AV, Schafer AL, Grey A, Vittinghoff E, Palermo L, Lui LY, et al. Effects of antiresorptive therapies on glucose metabolism: results from the FIT, HORIZON-PFT, and FREEDOM trials. J Bone Miner Res. 2013;28:1348–54.

    Article  CAS  PubMed  Google Scholar 

  52. Bacchetta J, Boutroy S, Guebre-Egziabher F, Juillard L, Drai J, Pelletier S, et al. The relationship between adipokines, osteocalcin and bone quality in chronic kidney disease. Nephrol Dial Transplant. 2009;24:3120–5.

    Article  CAS  PubMed  Google Scholar 

  53. Holden RM, Morton AR, Garland JS, Pavlov A, Day AG, Booth SL. Vitamins K and D status in stages 3–5 chronic kidney disease. Clin J Am Soc Nephrol. 2010;5:590–7.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  54. Okuno S, Ishimura E, Tsuboniwa N, Norimine K, Yamakawa K, Yamakawa T, et al. Significant inverse relationship between serum undercarboxylated osteocalcin and glycemic control in maintenance hemodialysis patients. Osteoporos Int. 2013;24:605–12.

    Article  CAS  PubMed  Google Scholar 

Download references

Conflict of interest

Dr. Thomas L. Nickolas:

1. Columbia University has licensed patents for the use of Neutrophil-Gelatinase Associated Lipocalin for the diagnosis of acute kidney injury

2. Merck: Scientific advisory board.

Dr. Sophie A. Jamal:

Advisory Board Member

• Amgen

Speaker Fees

• Amgen

• Sanofi

• Shire

Consultancy

• Merck

Author information

Authors and Affiliations

  1. Department of Medicine, Nephrology, Columbia University Medical Center, 622 West 168th Street, PH4-124, New York, NY, 10032, USA

    Thomas L. Nickolas

  2. Department of Medicine, Endocrinology & Metabolism, University of Toronto & Women’s College Hospital, 790 Bay Street, 7th Floor, Toronto, ON, M5G 1N8, USA

    Sophie A. Jamal

Authors
  1. Thomas L. Nickolas
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sophie A. Jamal
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sophie A. Jamal.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Nickolas, T.L., Jamal, S.A. Bone kidney interactions. Rev Endocr Metab Disord 16, 157–163 (2015). https://doi.org/10.1007/s11154-015-9314-3

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11154-015-9314-3

Keywords

Search

Navigation