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Osteoprotegerin and uremic osteoporosis in chronic hemodialysis patients

  • Nephrology - Original Paper
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Abstract

Introduction

Osteoprotegerin (OPG) is a powerful inhibitor of osteoclast activity, and it plays an important role in bone metabolism. In hemodialysis (HD) patients, the relationship between OPG and bone mineral density (BMD) is important, but remains unclear yet. The study objective was to assess the OPG role related to uremic osteoporosis in HD patients.

Methods

This cross-sectional study has been realized on a cohort of 63 chronic HD patients. Inclusion criteria: elderly prevalent HD patients with an age over 55 years old. Exclusion criteria: previous bone disease or previous renal transplant; neoplasia; parathyroidectomy, hormone replacement therapy. The data regarding demographical and clinical characteristics, including treatments for mineral and cardiovascular complications, were recorded. Serum OPG and mineral markers levels were measured. BMD was assessed by calcaneus quantitative ultrasound; it measured broadband ultrasound attenuation, speed of sound (SOS) and stiffness index (STI).

Results

The high OPG levels were associated with higher bone mineral density (OPG–SOS P = 0.003; R = 0.37; OPG–STI P = 0.03; R = 0.28). Malnutrition, anemia and advanced age correlated with bone demineralization. Males had higher bone density parameters than females. In patients treated with vitamin D (P = 0.005), the BMD was increased comparing to patients without these treatments.

Conclusions

OPG levels had directly correlated with bone mineral density parameters. Our study further confirms the critical role of OPG in the pathogenesis of uremic osteoporosis in ESRD. Whether the increased circulant OPG protect against bone loss in patients undergoing HD remains to be established.

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References

  1. Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Work Group (2009) KDIGO clinical practice guideline for the diagnosis, evaluation, prevention, and treatment of chronic kidney disease–mineral and bone disorder (CKD–MBD). Kidney Int Suppl 113:S1–S130

    Google Scholar 

  2. National Institutes of Health (2001) Consensus development panel on osteoporosis prevention D, therapy. Osteoporosis prevention, diagnosis, and therapy. JAMA 285:785–795

    Article  Google Scholar 

  3. National Osteoporosis Foundation. Clinician’s Guide to Prevention and Treatment of Osteoporosis (2014). http://nof.org/files/nof/public/content/file/2791/upload/919.pdf (Accessed on 16 Oct 2016)

  4. Kanis JA on behalf of the World Health Organization Scientific Group (2008) Assessment of osteoporosis at the primary health-care. In: Technical Report. UK: WHO Collaborative Centre, University of Sheffield

  5. West SL, Patel P, Jamal SA (2015) How to predict and treat increased fracture risk in chronic kidney disease. J Intern Med 278(1):19–28

    Article  CAS  PubMed  Google Scholar 

  6. Yenchek RH, Ix JH, Shlipak MG, Bauer DC, Rianon NJ, Kritchevsky SB, Fried LF (2012) Bone mineral density and fracture risk in older individuals with CKD. Clin J Am Soc Nephrol 7(7):1130–1136

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Ureña P, Bernard-Poenaru O, Ostertag A et al (2003) Bone mineral density, biochemical markers and skeletal fractures in haemodialysis patients. Nephrol Dial Transplant 18:2325–2331

    Article  PubMed  Google Scholar 

  8. Iimori S, Mori Y, Akita W, Kuyama T, Takada S, Asai T, Kuwahara M, Sasaki S, Tsukamoto Y (2011) 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 27:345–351

    Article  PubMed  Google Scholar 

  9. Khaw KT, Reeve J, Luben R et al (2004) Prediction of total and hip fracture risk in men and women by quantitative ultrasound of the calcaneus: EPIC-Norfolk prospective population study. Lancet 363:197

    Article  PubMed  Google Scholar 

  10. Hodson J, Marsh J (2003) Quantitative ultrasound and risk factor enquiry as predictors of postmenopausal osteoporosis: comparative study in primary care. BMJ 326:1250

    Article  PubMed  PubMed Central  Google Scholar 

  11. Glüer CC, Barkmann R, Blenk T, Stewart A, Kolta S, Finigan J, Graeff C, Gablentz J, Eastell R, Reid DM, Roux C, Felsenberg D (2007) Quantitative ultrasound predicts incident vertebral and hip fractures at least as strongly as DXA: the OPUS study. J Bone Miner Res 22(Suppl 1):1075

    Google Scholar 

  12. Hans D, Durosier C, Kans JA, Johansson H, Schott-Pethelaz AM, Krieg MA (2008) Assessment of the 10- year probability of osteoporotic hip fracture combining clinical risk factors and heel bone ultrasound: the EPISEM prospective cohort of 12,958 elderly women. J Bone Miner Res 23(7):1045–1051

    Article  PubMed  Google Scholar 

  13. Bondor C, Kacso Potra A, Moldovan D et al (2015) Relationship of adiponectin to markers of oxidative stress in type 2 diabetic patients: influence of incipient diabetes-associated kidney disease. Int Urol Nephrol 47(7):1173–1180

    Article  CAS  PubMed  Google Scholar 

  14. Min H, Morony S, Sarosi I et al (2000) Osteoprotegerin reverses osteoporosis by inhibiting endosteal osteoclasts and prevents vascular calcification by blocking a process resembling osteoclastogenesis. J Exp Med 192:463–474

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Doumouchtsis KK, Kostakis AI, Doumouchtsis SK et al (2008) Associations between osteoprotegerin and femoral neck BMD in hemodialysis patients. J Bone Miner Metab 26:66–72

    Article  CAS  PubMed  Google Scholar 

  16. Lewiecki EM (2009) Denosumab in postmenopausal osteoporosis: what the clinician needs to know. Ther Adv Musculoskelet Dis 1(1):13–26

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Cummings SR, San Martin J, McClung MR et al (2009) Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med 361:756

    Article  CAS  PubMed  Google Scholar 

  18. Ersoy FF (2007) Osteoporosis in the elderly with chronic kidney disease. Int Urol Nephrol 39(1):321–331

    Article  PubMed  Google Scholar 

  19. McCloskey EV, Kanis JA, Odén A, Harvey NC, Bauer D, González-Macias J, Johansson H (2015) Predictive ability of heel quantitative ultrasound for incident fractures: an individual-level meta-analysis. Osteoporos Int 26(7):1979–1987

    Article  CAS  PubMed  Google Scholar 

  20. Barreto FC, Barreto DV, Moyses RM et al (2006) Osteoporosis in hemodialysis patients revisited by bone histomorphometry: a new insight into an old problem. Kidney Int 69(10):1852–1857

    Article  CAS  PubMed  Google Scholar 

  21. Kuo CW, Ho SY, Chang TH et al (2010) Quantitative ultrasound of the calcaneus in hemodialysis patients. Ultrasound Med Biol 36(4):589–594

    Article  PubMed  Google Scholar 

  22. Arici M, Erturk H, Altun B et al (2000) Bone mineral density in haemodialysis patients: a comparative study of dual-energy X-ray absorptiometry and quantitative ultrasound. Nephrol Dial Transplant 15:1847–1851

    Article  CAS  PubMed  Google Scholar 

  23. Krieg MA, Barkmann R, Gonnelli S, Stewart A, Bauer DC, Barquero LR, Kaufman JJ, Lorenc R, Miller PD, Olszynski WP, Poiana C, Scott AM, Lewiecki EM, Hans D (2008) Quantitative ultrasound in the management of osteoporosis: the 2007 ISCD Official Positions. J Clin Densitom 11(1):163–187

    Article  PubMed  Google Scholar 

  24. Guglielmi G, Adams J, Link TM (2009) Quantitative ultrasound in the assessment of skeletal status. Eur Radiol 19(8):1837–1848

    Article  PubMed  Google Scholar 

  25. Moayyeri A, Kaptoge S, Dalzell N et al (2009) Is QUS or DXA better for predicting the 10-year absolute risk of fracture? J Bone Miner Res 24(7):1319–1325

    Article  PubMed  Google Scholar 

  26. West SL, Lok CE, Langsetmo L, Cheung AM, Szabo E, Pearce D, Jamal SA (2015) Bone mineral density predicts fractures in chronic kidney disease. J Bone Miner Res 30(5):913–919

    Article  PubMed  Google Scholar 

  27. Bauer DC, Ewing SK, Cauley JA, Ensrud KE, Cummings SR, Orwoll ES (2007) osteoporotic fractures in men (MrOS) research group. Quantitative ultrasound predicts hip and non-spine fracture in men: the MrOS study. Osteoporos Int 18(6):771–777

    Article  CAS  PubMed  Google Scholar 

  28. Bucur RC, Panjwani DD, Turner L, Rader T, West SL, Jamal SA (2015) Low bone mineral density and fractures in stages 3–5 CKD: an updated systematic review and meta-analysis. Osteoporos Int 26:449–458

    Article  CAS  PubMed  Google Scholar 

  29. Demir P, Erdenen F, Aral H et al (2016) Serum osteoprotegerin levels related with cardiovascular risk factors in chronic kidney disease. J Clin Lab Anal 30(6):811–817

    Article  CAS  PubMed  Google Scholar 

  30. Bernardi S, Fabris B, Thomas M et al (2014) Osteoprotegerin increases in metabolic syndrome and promotes adipose tissue proinflammatory changes. Mol Cell Endocrinol 394(1):13–20

    Article  CAS  PubMed  Google Scholar 

  31. Nakashima A, Yorioka N, Doi S et al (2006) Osteoprotegerin and bone mineral density in hemodialysis patients. Osteoporosis Int 17(6):841–846

    Article  CAS  Google Scholar 

  32. Avila-Diaz M, Prado C, Ventura M et al (2010) Vitamin D receptor gene, biochemical bone markers and bone mineral density in Mexican women on dialysis. Nephrol Dial Transplant 25(7):2259–2265

    Article  Google Scholar 

  33. Wu WT, Lee RP, Wang CH et al (2010) The association of serum osteoprotegerin and osteoporosis in postmenopausal hemodialysis patients: a pilot study. J Women’s Health 19(4):785–790

    Article  Google Scholar 

  34. Yilmaz MI, Siriopol D, Saglam M, et al (2016) Osteoprotegerin in chronic kidney disease: associations with vascular damage and cardiovascular events. Calcif Tissue Int 99(2):121–130

    Article  CAS  PubMed  Google Scholar 

  35. Lee JE, Kim HJ, Moon SJ et al (2013) Serum osteoprotegerin is associated with vascular stiffness and the onset of new cardiovascular events in hemodialysis patients. Korean J Intern Med 28(6):668–677

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Moldovan D, Moldovan I, Rusu C et al (2011) Vascular calcifications and renal osteodystrophy in chronic hemodialysis patients: what is the relationship between them? Internat Urol Nephrol 43(4):1179–1186

    Article  CAS  Google Scholar 

  37. Nascimento MM, Hayashi SY, Riella MC, Lindholm B (2014) Elevated levels of plasma osteoprotegerin are associated with all-cause mortality risk and atherosclerosis in patients with stages 3 to 5 chronic kidney disease. Braz J Med Biol Res 47(11):995–1002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Jamal SA, Ljunggren O, Stehman-Breen C et al (2011) Effects of denosumab on fracture and bone mineral density by level of kidney function. J Bone Miner Res 26(8):1829–1835

    Article  CAS  PubMed  Google Scholar 

  39. Block GA, Bone HG, Fang L et al (2012) A single-dose study of denosumab in patients with various degrees of renal impairment. J Bone Miner Res 27(7):1471–1479

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Schipper LG, Fleuren HW, van den Bergh JP, Meinardi JR, Veldman BA, Kramers C (2015) Treatment of osteoporosis in renal insufficiency. Clin Rheumatol 34(8):1341–1345

    Article  PubMed  Google Scholar 

  41. Hayashi T, Joki N, Tanaka Y, Iwasaki M, Kubo S, Asakawa T, Hase H (2015) The FRAX as a predictor of mortality in Japanese incident hemodialysis patients: an observational, follow-up study. J Bone Mineral Metab 33(6):674–683

    Article  Google Scholar 

  42. Castillo RF, de la Rosa RJ (2009) Relation between body mass index and bone mineral density among haemodialysis patients with chronic kidney disease. J Ren Care 35(Suppl 1):57–64

    Article  PubMed  Google Scholar 

  43. Pluskiewicz W, Zwiec J, Gumprecht J et al (2007) Quantitative ultrasound of phalanges of adults with end-stage renal disease or who have undergone renal transplantation. Ultrasound Med Biol 33(9):1353–1361

    Article  CAS  PubMed  Google Scholar 

  44. Jamal SA, Nickolas TL (2015) Bone imaging and fracture risk assessment in kidney disease. Curr Osteoporos Rep 3(3):166–172

    Article  Google Scholar 

  45. Kazama JJ, Matsuo K, Iwasaki Y, Fukagawa M (2015) Chronic kidney disease and bone metabolism. J Bone Miner Metab 33(3):245–252

    Article  CAS  PubMed  Google Scholar 

  46. Pérez-Sáez MJ, Prieto-Alhambra D, Barrios C, Crespo M, Redondo D, Nogués X, Pascual J (2015) Increased hip fracture and mortality in chronic kidney disease individuals: the importance of competing risks. Bone 73:154–159

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Nephrology, University of Medicine and Pharmacy “Iuliu Hatieganu”, Cluj-Napoca, Romania

    Diana Moldovan, Crina Rusu, Alina Potra, Mirela Gherman-Caprioara & Ina Maria Kacso

  2. Military Hospital Cluj-Napoca, Cluj-Napoca, Romania

    Ioan Moldovan

  3. Nefromed Dialysis Center Cluj-Napoca, Cluj-Napoca, Romania

    Ioan Mihai Patiu

  4. Nephrology and Dialysis Clinic, Emergency County Hospital, „Mihai Manasia”, 3-5 Clinicilor Street, Cluj-Napoca, Romania

    Diana Moldovan

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  1. Diana Moldovan
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  2. Crina Rusu
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Correspondence to Diana Moldovan.

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Moldovan, D., Rusu, C., Potra, A. et al. Osteoprotegerin and uremic osteoporosis in chronic hemodialysis patients. Int Urol Nephrol 49, 895–901 (2017). https://doi.org/10.1007/s11255-017-1529-7

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  • DOI: https://doi.org/10.1007/s11255-017-1529-7

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