Bone turnover correlates with bone quantity but not bone microarchitecture in chronic hemodialysis

Abstract

Introduction

In chronic hemodialysis, high-turnover bone disease was associated with decreased bone mineral density (BMD), poor bone quality (chemical and structural), and increased fracture risk. Our aim was to correlate bone turnover markers (BTMs) with bone microarchitecture measured by trabecular bone score (TBS) before and after correction for BMD.

Materials and methods

We measured lumbar spine (LS), femoral neck, and 1/3 radius BMD and LS TBS by dual X-ray absorptiometry in 81 patients on permanent hemodialysis. Bone turnover was assessed using serum parathyroid hormone, osteocalcin, C-terminal crosslaps of type 1 collagen, procollagen 1 N-terminal propeptide (P1NP), and alkaline phosphatase (ALP). No patient had any partial or total parathyroidectomy and no previous or current treatment with anti-osteoporotic drugs.

Results

All BTMs correlated significantly with each other. Univariate regressions showed significant negative correlations between BTMs and BMD (best r = − 0.53, between P1NP and 1/3 radius Z-score) or BTMs and TBS (best r = − 0.27, p < 0.05 between ALP and TBS T-score). TBS correlated significantly with BMD at all three sites (best r = 0.5, between LS BMD and TBS T-score). Multivariate regression showed that TBS, crude or adjusted, correlated with LS BMD. No model retained any of the BTMs as independent variables due to the better prediction of BMD and multicollinearity.

Conclusion

We showed a progressively impaired bone microarchitecture with increasing bone turnover in chronic hemodialysis. However, this correlation is no longer present when controlling for bone mass. This suggests that impaired bone microarchitecture and increased fracture risk are dependent upon factors other than high bone turnover.

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

References

  1. 1.

    Alem AM, Sherrard DJ, Gillen DL, Weiss NS, Beresford SA, Heckbert SR, Wong C, Stehman-Breen C (2000) Increased risk of hip fracture among patients with end-stage renal disease. Kidney Int 58:369–396. https://doi.org/10.1046/j.1523-1755.2000.00178.x

    Article  Google Scholar 

  2. 2.

    Sidibé A, Auguste D, Desbiens L-C, Fortier C, Wang YP, Jean S, Moore L, Mac-Way F (2019) Fracture risk in dialysis and kidney transplanted patients: a systematic review. JBMR Plus 3:45–55. https://doi.org/10.1002/jbm4.10067

    Article  PubMed  Google Scholar 

  3. 3.

    Rodriguez-Garcia M, Gomez-Alonso C, Naves-Diaz M, Diaz-Lopez JB, Diaz-Corte C, Cannata-Andia JB, Asturias Study Group (2008) Vascular calcifications, vertebral fractures and mortality in haemodialysis patients. Nephrol Dial Transplant 24:239–246. https://doi.org/10.1093/ndt/gfn466

    Article  PubMed  PubMed Central  Google Scholar 

  4. 4.

    Fusaro M, Tripepi G, Noale M, Vajente N, Plebani M, Zaninotto M, Guglielmi G, Miotto D, Carbonare LD, D’Angelo A, Ciurlino D, Puggia R, Miozzo D, Giannini S, Gallieni M (2013) High prevalence of vertebral fractures assessed by quantitative morphometry in hemodialysis patients, strongly associated with vascular calcifications. Calcif Tissue Int 93:39–47. https://doi.org/10.1007/s00223-013-9722-x

    CAS  Article  PubMed  Google Scholar 

  5. 5.

    Danese MD, Kim J, Doan QV, Dylan M, Griffiths R, Chertow GM (2006) PTH and the risks for hip, vertebral, and pelvic fractures among patients on dialysis. Am J Kidney Dis 47:149–156. https://doi.org/10.1053/j.ajkd.2005.09.024

    Article  Google Scholar 

  6. 6.

    Kanis JA, Johnell O, Oden A, Johansson H, McCloskey E (2008) FRAXTM and the assessment of fracture probability in men and women from the UK. Osteoporos Int 19:385–397. https://doi.org/10.1007/s00198-007-0543-5

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  7. 7.

    Bucur RC, Panjwani DD, Turner L, Rader T, West SL, Jamal SA (2014) Low bone mineral density and fractures in stages 3–5 CKD: an updated systematic review and meta-analysis. Osteoporos Int 26:449–458. https://doi.org/10.1007/s00198-014-2813-3

    Article  PubMed  Google Scholar 

  8. 8.

    Zheng CM, Zheng JQ, Wu CC, Lu CL, Shyu JF, Yung-Ho H, Wu MY, Chiu IJ, Wang YH, Lin YF, Lu KC (2016) Bone loss in chronic kidney disease: quantity or quality? Bone 87:57–70

    Article  Google Scholar 

  9. 9.

    Leslie WD, Shevroja E, Johansson H, McCloskey EV, Harvey NC, Kanis JA, Hans D (2018) Risk-equivalent T-score adjustment for using lumbar spine trabecular bone score (TBS): the manitoba BMD registry. Osteoporos Int 29:751–758. https://doi.org/10.1007/s00198-018-4405-0

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  10. 10.

    Yavropoulou MP, Vaios V, Pikilidou M, Chryssogonidis I, Sachinidou M, Tournis S, Makris K, Kotsa K, Daniilidis M, Haritanti A, Liakopoulos V (2017) Bone quality assessment as measured by trabecular bone score in patients with end-stage renal disease on dialysis. J Clin Densitom 20:490–497. https://doi.org/10.1016/j.jocd.2016.11.002

    Article  PubMed  Google Scholar 

  11. 11.

    Dusceac R, Niculescu DA, Dobre R, Dragne MC, Tacu C, Peride I, David C, Checherita I, Poiana C (2018) Chronic hemodialysis is associated with lower trabecular bone score, independent of bone mineral density: a case-control study. Arch Osteoporos 13:125. https://doi.org/10.1007/s11657-018-0541-6

    Article  PubMed  Google Scholar 

  12. 12.

    Taal MW, Masud T, Green D, Cassidy MJD (1999) Risk factors for reduced bone density in haemodialysis patients. Nephrol Dial Transplant 14:1922–1928. https://doi.org/10.1093/ndt/14.8.1922

    CAS  Article  PubMed  Google Scholar 

  13. 13.

    Dusceac R, Niculescu DA, Ismail G, Poiană C (2015) Radius age-adjusted bone mineral density is correlated with parathyroid hormone serum levels in patients with end-stage renal disease. Acta Endocrinol (Copenh) 11:175–179. https://doi.org/10.4183/aeb.2015.175

    Article  Google Scholar 

  14. 14.

    Bergman A, Qureshi AR, Haarhaus M, Lindholm B, Barany P, Heimburger O, Stenvinkel P, Anderstam B (2017) Total and bone-specific alkaline phosphatase are associated with bone mineral density over time in end-stage renal disease patients starting dialysis. J Nephrol 30:255–262. https://doi.org/10.1007/s40620-016-0292-7

    CAS  Article  PubMed  Google Scholar 

  15. 15.

    Maruyama Y, Taniguchi M, Kazama JJ, Yokoyama K, Hosoya T, Yokoo T, Shigematsu T, Iseki K, Tsubakihara Y (2014) A higher serum alkaline phosphatase is associated with the incidence of hip fracture and mortality among patients receiving hemodialysis in Japan. Nephrol Dial Transplant 29:1532–1538. https://doi.org/10.1093/ndt/gfu055

    CAS  Article  PubMed  Google Scholar 

  16. 16.

    Wheater G, Elshahaly M, Tuck SP, Datta HK, van Laar JM (2013) The clinical utility of bone marker measurements in osteoporosis. J Transl Med 11:201

    Article  Google Scholar 

  17. 17.

    Aleksova J, Kurniawan S, Elder GJ (2018) The trabecular bone score is associated with bone mineral density, markers of bone turnover and prevalent fracture in patients with end stage kidney disease. Osteoporos Int 29:1447–1455. https://doi.org/10.1007/s00198-018-4468-y

    CAS  Article  PubMed  Google Scholar 

  18. 18.

    Jørgensen HS, Winther S, Bøttcher M, Hauge E-M, Rejnmark L, Svensson M, Ivarsen P (2017) Bone turnover markers are associated with bone density, but not with fracture in end stage kidney disease: a cross-sectional study. BMC Nephrol 18:284. https://doi.org/10.1186/s12882-017-0692-5

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  19. 19.

    Delanaye P, Warling X, Moonen M, Smelten N, Jouret F, Krzesinski JM, Maillard N, Pottel H, Cavalier E (2017) Variations of parathyroid hormone and bone biomarkers are concordant only after a long term follow-up in hemodialyzed patients. Sci Rep 7:12623. https://doi.org/10.1038/s41598-017-12808-3

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  20. 20.

    Evenepoel P, Claes K, Cavalier E, Meijers B, Stenvinkel P, Behets G, Jankowska M, D’Haese P, Bammens B (2019) A distinct bone phenotype in ADPKD patients with end-stage renal disease. Kidney Int 95:412–419. https://doi.org/10.1016/j.kint.2018.09.018

    CAS  Article  PubMed  Google Scholar 

  21. 21.

    Evenepoel P, Claes K, Meijers B, Laurent MR, Bammens B, Naesens M, Sprangers B, Pottel H, Cavalier E, Kuypers D (2019) Bone mineral density, bone turnover markers, and incident fractures in de novo kidney transplant recipients. Kidney Int 95:1461–1470. https://doi.org/10.1016/j.kint.2018.12.024

    Article  PubMed  Google Scholar 

  22. 22.

    Dolgos S, Hartmann A, Bønsnes S, Ueland T, Isaksen GA, Godang K, Pfeffer P, Bollerslev J (2008) Determinants of bone mass in end-stage renal failure patients at the time of kidney transplantation. Clin Transplant 22:462–468. https://doi.org/10.1111/j.1399-0012.2008.00810.x

    Article  PubMed  Google Scholar 

  23. 23.

    Nickolas TL, Stein EM, Dworakowski E, Nishiyama KK, Komandah-Kosseh M, Zhang CA, McMahon DJ, Liu XS, Boutroy S, Cremers S, Shane E (2013) Rapid cortical bone loss in patients with chronic kidney disease. J Bone Miner Res 28:1811–1820. https://doi.org/10.1002/jbmr.1916

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  24. 24.

    Huang G-S, Chu T-S, Lou M-F, Hwang S-L, Yang R-S (2009) Factors associated with low bone mass in the hemodialysis patients–a cross-sectional correlation study. BMC Musculoskelet Disord 10:60. https://doi.org/10.1186/1471-2474-10-60

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  25. 25.

    Dufour R, Winzenrieth R, Heraud A, Hans D, Mehsen N (2013) Generation and validation of a normative, age-specific reference curve for lumbar spine trabecular bone score (TBS) in French women. Osteoporos Int 24:2837–2846. https://doi.org/10.1007/s00198-013-2384-8

    CAS  Article  PubMed  Google Scholar 

  26. 26.

    Cheng P, Qi HM, Di WJ, Liu J, Yu J, Lv S, Shen YL, Zha JM, Cai JM, Lai B, Ding GX (2016) Establishment of TBS reference plots and correlation between TBS and BMD in healthy mainland Chinese women. Arch Osteoporos 11:1–6. https://doi.org/10.1007/s11657-015-0254-z

    Article  Google Scholar 

  27. 27.

    Brunerová L, Ronová P, Verešová J, Beranová P, Potoèková J, Kasalický P, Rychlík I (2016) Osteoporosis and impaired trabecular bone score in hemodialysis patients. Kidney Blood Press Res 41:345–354. https://doi.org/10.1159/000443439

    CAS  Article  PubMed  Google Scholar 

  28. 28.

    Borgen TT, Bjørnerem Å, Solberg LB, Andreasen C, Brunborg C, Stenbro M-B, Hübschle LM, Figved W, Apalset EM, Gjertsen J-E, Basso T, Lund I, Hansen AK, Stutzer J-M, Dahl C, Nordsletten L, Frihagen F, Eriksen EF (2019) Determinants of trabecular bone score and prevalent vertebral fractures in women with fragility fractures: a cross-sectional sub-study of NoFRACT. Osteoporos Int. https://doi.org/10.1007/s00198-019-05215-z

    Article  PubMed  PubMed Central  Google Scholar 

  29. 29.

    Iwasaki Y, Kazama JJ, Yamato H, Matsugaki A, Nakano T, Fukagawa M (2015) Altered material properties are responsible for bone fragility in rats with chronic kidney injury. Bone 81:247–254. https://doi.org/10.1016/j.bone.2015.07.015

    Article  PubMed  Google Scholar 

  30. 30.

    Heveran CM, Schurman CA, Acevedo C, Livingston EW, Howe D, Schaible EG, Hunt HB, Rauff A, Donnelly E, Carpenter RD, Levi M, Lau AG, Bateman TA, Alliston T, King KB, Ferguson VL (2019) Chronic kidney disease and aging differentially diminish bone material and microarchitecture in C57Bl/6 mice. Bone 127:91–103. https://doi.org/10.1016/j.bone.2019.04.019

    Article  PubMed  Google Scholar 

  31. 31.

    Malluche HH, Porter DS, Pienkowski D (2013) Evaluating bone quality in patients with chronic kidney disease. Nat Rev Nephrol 9:671–680

    Article  Google Scholar 

Download references

Author information

Affiliations

Authors

Contributions

Study design: RDu, DN, and CP; data collection: RDu, RDo, MS, CT, and CD; biochemical assays AC data analysis: RDu and DN; data interpretation: RDu, DN, and CP; drafting manuscript: RDu and DN; revising manuscript content: RDu, DN, RDo, AC, and CP; approving final version of manuscript: RDu, DN, RDo, MS, AC, CT, CD, and CP.

Corresponding author

Correspondence to Dan Alexandru Niculescu.

Ethics declarations

Conflict of interest

All authors have no conflicts of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

About this article

Verify currency and authenticity via CrossMark

Cite this article

Dusceac, R., Niculescu, D.A., Dobre, R. et al. Bone turnover correlates with bone quantity but not bone microarchitecture in chronic hemodialysis. J Bone Miner Metab 38, 597–604 (2020). https://doi.org/10.1007/s00774-020-01094-1

Download citation

Keywords

  • Trabecular bone score
  • Bone mineral density
  • Bone turnover
  • End-stage renal disease