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Relationship Between Aortic Mineral Elements and Osteodystrophy in Mice with Chronic Kidney Disease

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Abstract

In chronic kidney disease (CKD), osteodystrophy and arterial calcification often coexist. However, arterial alterations have not been addressed in CKD unaccompanied by evidence of calcification. We investigated the association of phosphate (P) and calcium (Ca) accumulation in calcification-free aortas with CKD-induced osteodystrophy. Aortic accumulation of magnesium (Mg), an inhibitor of calcification, was also examined. Male mice aged 26 weeks with CKD characterized by hyperparathyroidism and hyperphosphatemia (Nx, n = 8) and age-matched healthy male mice (shams, n = 8) were sampled for blood, and thoracic vertebrae and aortas were harvested. Bone structure and chemicals were analyzed by microcomputed tomography and infrared microspectroscopy, respectively, and aortic accumulation of P, Ca, and Mg was evaluated by plasma-atomic emission spectrometry. Volume fractions of cortical and trabecular bones were smaller in Nx than in sham animals (P < 0.05), attributed to cortical thinning and reduction in trabecular number, respectively. Bone chemicals were not different between the groups. No calcification was found in either group, but P, Ca, and Mg contents were higher in Nx than in shams (P < 0.05). The mass ratio of Ca/P was lower in Nx than in shams (P < 0.05), but that of Mg/Ca and Mg/P was not different between the groups. Aortic P and Ca contents were inversely correlated with the volume fraction of cortical bone (P < 0.05). In conclusion, the relationship of osteodystrophy with aortic P and Ca accumulation suggests the existence of a bone-vascular axis, even in calcification-free arteries in CKD. The preservation of ratios of Mg/Ca and Mg/P despite CKD development might contribute to calcification resistance.

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References

  1. Levin A, Bakris GL, Molitch M et al (2007) Prevalence of abnormal serum vitamin D, PTH, calcium, and phosphorus in patients with chronic kidney disease: results of the study to evaluate early kidney disease. Kidney Int 71:31–38

    Article  PubMed  CAS  Google Scholar 

  2. Isakova T, Wahl P, Vargas GS et al (2011) Fibroblast growth factor 23 is elevated before parathyroid hormone and phosphate in chronic kidney disease. Kidney Int 79:1370–1378

    Article  PubMed  CAS  Google Scholar 

  3. Kiattisunthorn K, Moe SM (2010) Chronic kidney disease-mineral bone disorder (CKD-MBD). IBMS BoneKEy 7:447–457

    Article  Google Scholar 

  4. Shanahan CM, Crouthamel MH, Kapustin A, Giachelli CM et al (2011) Arterial calcification in chronic kidney disease: key roles for calcium and phosphate. Circ Res 109:697–711

    Article  PubMed  CAS  Google Scholar 

  5. Chen NX, O'Neill KD, Duan D et al (2002) Phosphorus and uremic serum up-regulate osteopontin expression in vascular smooth muscle cells. Kidney Int 62:1724–1731

    Article  PubMed  CAS  Google Scholar 

  6. Mune S, Shibata M, Hatamura I et al (2009) Mechanism of phosphate-induced calcification in rat aortic tissue culture: possible involvement of Pit-1 and apoptosis. Clin Exp Nephrol 13:571–577

    Article  PubMed  CAS  Google Scholar 

  7. Yang H, Curinga G, Giachelli CM (2004) Elevated extracellular calcium levels induce smooth muscle cell matrix mineralization in vitro. Kidney Int 66:2293–2299

    Article  PubMed  CAS  Google Scholar 

  8. Panizo S, Cardus A, Encinas M et al (2009) RANKL increases vascular smooth muscle cell calcification through a RANK-BMP4-dependent pathway. Circ Res 104:1041–1048

    Article  PubMed  CAS  Google Scholar 

  9. London GM, Marty C, Marchais SJ et al (2004) Arterial calcifications and bone histomorphometry in end-stage renal disease. J Am Soc Nephrol 15:1943–1951

    Article  PubMed  Google Scholar 

  10. Adragao T, Herberth J, Monier-Faugere MC et al (2009) Low bone volume—a risk factor for coronary calcifications in hemodialysis patients. Clin J Am Soc Nephrol 4:450–455

    Article  PubMed  Google Scholar 

  11. Nikolov IG, Joki N, Nguyen-Khoa T et al (2010) Chronic kidney disease bone and mineral disorder (CKD-MBD) in apolipoprotein E-deficient mice with chronic renal failure. Bone 47:156–163

    Article  PubMed  CAS  Google Scholar 

  12. Moe SM, Chen NX, Seifert MF et al (2009) A rat model of chronic kidney disease-mineral bone disorder. Kidney Int 75:176–184

    Article  PubMed  CAS  Google Scholar 

  13. London GM (2009) Bone-vascular axis in chronic kidney disease: a reality? Clin J Am Soc Nephrol 4:254–257

    Article  PubMed  Google Scholar 

  14. Demer L, Tintut Y (2010) The bone-vascular axis in chronic kidney disease. Curr Opin Nephrol Hypertens 19:349–353

    Article  PubMed  Google Scholar 

  15. Ohashi K, Iwatani H, Kihara S et al (2007) Exacerbation of albuminuria and renal fibrosis in subtotal renal ablation model of adiponectin-knockout mice. Arterioscler Thromb Vasc Biol 27:1910–1917

    Article  PubMed  CAS  Google Scholar 

  16. Otsu N (1979) Threshold selection method from gray-level histograms. IEEE Trans Syst Man Cybern 9:62–66

    Article  Google Scholar 

  17. Doube M, Kłosowski MM, Arganda-Carreras I et al (2010) BoneJ: free and extensible bone image analysis in Image J. Bone 47:1076–1079

    Article  Google Scholar 

  18. Busa B, Miller LM, Rubin CT et al (2005) Rapid establishment of chemical and mechanical properties during lamellar bone formation. Calcif Tissue Int 77:386–394

    Article  PubMed  CAS  Google Scholar 

  19. Hengsberger S, Kulik A, Zysset P (2002) Nanoindentation discriminates the elastic properties of individual human bone lamellae under dry and physiological conditions. Bone 30:178–184

    Article  PubMed  CAS  Google Scholar 

  20. Dong A, Huang P, Caughey WS (1990) Protein secondary structures in water from second-derivative amide I infrared spectra. Biochemistry 29:3303–3308

    Article  PubMed  CAS  Google Scholar 

  21. Gadaleta SJ, Paschalis EP, Betts F et al (1996) Fourier transform infrared spectroscopy of the solution-mediated conversion of amorphous calcium phosphate to hydroxyapatite: new correlations between X-ray diffraction and infrared data. Calcif Tissue Int 58:9–16

    Article  PubMed  CAS  Google Scholar 

  22. Lund RJ, Davies MR, Brown AJ et al (2004) Successful treatment of an adynamic bone disorder with bone morphogenetic protein-7 in a renal ablation model. J Am Soc Nephrol 15:359–369

    Article  PubMed  CAS  Google Scholar 

  23. Phan O, Ivanovski O, Nguyen-Khoa T et al (2005) Sevelamer prevents uremia-enhanced atherosclerosis progression in apolipoprotein E-deficient mice. Circulation 112:2875–2882

    Article  PubMed  CAS  Google Scholar 

  24. Schober HC, Han ZH, Foldes AJ et al (1998) Mineralized bone loss at different sites in dialysis patients: implications for prevention. J Am Soc Nephrol 9:1225–1233

    PubMed  CAS  Google Scholar 

  25. Parfitt AM (2003) Renal bone disease: a new conceptual framework for the interpretation of bone histomorphometry. Curr Opin Nephrol Hypertens 12:387–403

    Article  PubMed  Google Scholar 

  26. Kazama JJ, Iwasaki Y, Yamato H et al (2003) Microfocus computed tomography analysis of early changes in bone microstructure in rats with chronic renal failure. Nephron Exp Nephrol 95:e152–e157

    Article  PubMed  Google Scholar 

  27. Dempster DW, Muller R, Zhou H et al (2007) Preserved three-dimensional cancellous bone structure in mild primary hyperparathyroidism. Bone 41:19–24

    Article  PubMed  CAS  Google Scholar 

  28. Lee MM, Chu EY, El-Abbadi MM et al (2010) Characterization of mandibular bone in a mouse model of chronic kidney disease. J Periodontol 81:300–309

    Article  PubMed  Google Scholar 

  29. Fukagawa M, Kazama JJ, Shigematsu T (2001) Skeletal resistance to PTH as a basic abnormality underlying uremic bone diseases. Am J Kidney Dis 38:S152–S155

    Article  PubMed  CAS  Google Scholar 

  30. Leonard MB (2009) A structural approach to skeletal fragility in chronic kidney disease. Semin Nephrol 29:133–143

    Article  PubMed  Google Scholar 

  31. Miller MA, Chin J, Miller SC et al (1998) Disparate effects of mild, moderate, and severe secondary hyperparathyroidism on cancellous and cortical bone in rats with chronic renal insufficiency. Bone 23:257–266

    Article  PubMed  CAS  Google Scholar 

  32. Oste L, Behets GJ, Dams G et al (2007) Role of dietary phosphorus and degree of uremia in the development of renal bone disease in rats. Ren Fail 29:1–12

    Article  PubMed  CAS  Google Scholar 

  33. Parfitt AM, Mathews CHE, Villanueva AR et al (1983) Relationship between surface, volume and thickness of iliac trabecular bone in ageing and in osteoporosis. J Clin Invest 72:1396–1409

    Article  PubMed  CAS  Google Scholar 

  34. Compston JE, Mellish RWE, Croucher PI et al (1989) Structural mechanisms of trabecular bone loss in man. Bone Miner 6:339–350

    Article  PubMed  CAS  Google Scholar 

  35. Iwasaki Y, Kazama JJ, Yamato H et al (2011) Changes in chemical composition of cortical bone associated with bone fragility in rat model with chronic kidney disease. Bone 48:1260–1267

    Article  PubMed  CAS  Google Scholar 

  36. Allen MR, Gineyts E, Leeming DJ et al (2008) Bisphosphonates alter trabecular bone collagen cross-linking and isomerization in beagle dog vertebra. Osteoporos Int 19:329–337

    Article  PubMed  CAS  Google Scholar 

  37. Isaksson H, Turunen MJ, Rieppo L et al (2010) Infrared spectroscopy indicates altered bone turnover and remodeling activity in renal osteodystrophy. J Bone Miner Res 25:1360–1366

    Article  PubMed  Google Scholar 

  38. Shobeiri N, Adams MA, Holden RM (2010) Vascular calcification in animal models of CKD: A review. Am J Nephrol 31:471–481

    Article  PubMed  Google Scholar 

  39. Spiegel DM (2011) Magnesium in chronic kidney disease: unanswered questions. Blood Purif 31:172–176

    Article  PubMed  CAS  Google Scholar 

  40. Luoma H, Nuuja T, Collan Y et al (1976) The effect of magnesium and fluoride on nephrocalcinosis and aortic calcification in rats given high sucrose diets with added phospnates. Calcif Tissue Res 20:291–302

    Article  PubMed  CAS  Google Scholar 

  41. Masuyama R (1995) The action of magnesium in reducing renal calcification in rats receiving high phosphorus supplemented diet. Nutr Res 15:1673–1682

    Article  CAS  Google Scholar 

  42. Turgut F, Kanbay M, Metin MR et al (2008) Magnesium supplementation helps to improve carotid intima media thickness in patients on hemodialysis. Int Urol Nephrol 40:1075–1082

    Article  PubMed  CAS  Google Scholar 

  43. Wei M, Esbaei K, Bargman J et al (2006) Relationship between serum magnesium, parathyroid hormone, and vascular calcification in patients on dialysis: a literature review. Perit Dial Int 26:366–373

    PubMed  CAS  Google Scholar 

  44. Kircelli F, Peter ME, Sevinc Ok E et al (2012) Magnesium reduces calcification in bovine vascular smooth muscle cells in a dose-dependent manner. Nephrol Dial Transplant 27:514–521

    Google Scholar 

  45. Villa-Bellosta R, Millan A, Sorribas V (2011) Role of calcium-phosphate deposition in vascular smooth muscle cell calcification. Am J Physiol Cell Physiol 300:C210–C220

    Article  PubMed  CAS  Google Scholar 

  46. Tohno S, Tohno Y, Minami T et al (2002) Elements of calcified sites in human thoracic aorta. Biol Trace Elem Res 86:23–30

    Article  PubMed  CAS  Google Scholar 

  47. Hak AE, Pols HA, van Hemert AM et al (2000) Progression of aortic calcification is associated with metacarpal bone loss during menopause: a populationbased longitudinal study. Arterioscler Thromb Vasc Biol 20:1926–1931

    Article  PubMed  CAS  Google Scholar 

  48. Tanko LB, Christiansen C, Cox DA et al (2005) Relationship between osteoporosis and cardiovascular disease in postmenopausal women. J Bone Mineral Res 20:1912–1920

    Article  Google Scholar 

  49. Barreto DV, Barreto Fde C, Carvalho AB et al (2008) Association of changes in bone remodeling and coronary calcification in hemodialysis patients: a prospective study. Am J Kidney Dis 52:1139–1150

    Article  PubMed  CAS  Google Scholar 

  50. London GM, Marchais SJ, Guérin AP et al (2008) Association of bone activity, calcium load, aortic stiffness, and calcifications in ESRD. J Am Soc Nephrol 19:1827–1835

    Article  PubMed  CAS  Google Scholar 

  51. Sebastian EM, Suva LJ, Friedman PA (2008) Differential effects of intermittent PTH(1–34) and PTH(7–34) on bone microarchitecture and aortic calcification in experimental renal failure. Bone 43:1022–1030

    Article  PubMed  CAS  Google Scholar 

  52. De Schutter TM, Neven E, Persy VP et al (2011) Vascular calcification is associated with cortical bone loss in chronic renal failure rats with and without ovariectomy: the calcification paradox. Am J Nephrol 34:356–366

    Article  PubMed  Google Scholar 

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Acknowledgments

Part of this work was supported by Grant-in-Aids for Scientific Research from the Japanese Government (21650112).

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The authors declare that they have no conflict of interest.

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Correspondence to Takeshi Matsumoto.

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Matsumoto, T., Fukushima, S., Kanasaki, T. et al. Relationship Between Aortic Mineral Elements and Osteodystrophy in Mice with Chronic Kidney Disease. Biol Trace Elem Res 150, 278–284 (2012). https://doi.org/10.1007/s12011-012-9466-x

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  • DOI: https://doi.org/10.1007/s12011-012-9466-x

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