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Specific Bone and Mineral Disorders in Patients with Chronic Kidney Disease

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Abstract

Bone lesions, collectively known as renal osteodystrophy (ROD), are a common complication of chronic kidney disease (CKD). Besides osteitis fibrosa and mixed lesions, other bone and mineral disorders such as adynamic bone disease, osteomalacia, osteoporosis, dialysis-related amyloidosis, and calcific uremic arteriolopathy are increasingly recognized in patients with CKD. Although bone lesions usually begin early in the course of CKD and are progressive, symptoms and signs such as bone pain and fractures may not occur until the patient is already on maintenance dialysis. More importantly, these disorders are associated with increased risk of cardiovascular disease and mortality in patients with CKD. The term ROD does not reflect the full spectrum of bone pathology or clinical manifestations of bone and mineral disorders in patients with CKD. Accordingly, the National Kidney Foundation and, more recently the Kidney Disease: Improving Global Outcomes, now consider ROD to represent only one measure of the skeletal component of the broader syndrome of chronic kidney disease-mineral and bone disorders in which abnormalities in bone and mineral metabolism or extraskeletal calcification are observed. In this review, we will discuss, in detail, the epidemiology, pathogenesis, histopathology, clinical manifestation, diagnosis, and treatment of these disorders.

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References

  1. Andress DL. Adynamic bone in patients with chronic kidney disease. Kidney Int. 2008;73:1345–54.

    Article  PubMed  CAS  Google Scholar 

  2. Sherrard DJ, Hercz G, Pei Y, et al. The spectrum of bone disease in end-stage renal failure–an evolving disorder. Kidney Int. 1993;43:436–42.

    Article  PubMed  CAS  Google Scholar 

  3. Hercz G, Pei Y, Greenwood C, et al. Aplastic osteodystrophy without aluminum: the role of “suppressed” parathyroid function. Kidney Int. 1993;44:860–6.

    Article  PubMed  CAS  Google Scholar 

  4. Kurz P, Monier-Faugere MC, Bognar B, et al. Evidence for abnormal calcium homeostasis in patients with adynamic bone disease. Kidney Int. 1994;46:855–61.

    Article  PubMed  CAS  Google Scholar 

  5. London GM, Marty C, Marchais SJ, et al. Arterial calcifications and bone histomorphometry in end-stage renal disease. J Am Soc Nephrol. 2004;15:1943–51.

    Article  PubMed  Google Scholar 

  6. 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:S1–130.

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

    PubMed  CAS  Google Scholar 

  8. Moore C, Yee J, Malluche H, et al. Relationship between bone histology and markers of bone and mineral metabolism in African-American hemodialysis patients. Clin J Am Soc Nephrol. 2009;4:1484–93.

    Article  PubMed  Google Scholar 

  9. Brandenburg VM, Floege J. Adynamic bone disease–bone and beyond. NDT Plus. 2008;1:135–47.

    Article  Google Scholar 

  10. K/DOQI clinical practice guidelines for bone metabolism and disease in chronic kidney disease. Am J Kidney Dis 2003;42:S1–201.

    Google Scholar 

  11. Changsirikulchai S, Domrongkitchaiporn S, Sirikulchayanonta V, et al. Renal osteodystrophy in Ramathibodi Hospital: histomorphometry and clinical correlation. J Med Assoc Thai. 2000;83:1223–32.

    PubMed  CAS  Google Scholar 

  12. Cunningham J, Sprague SM, Cannata-Andia J, et al. Osteoporosis in chronic kidney disease. Am J Kidney Dis. 2004;43:566–71.

    Article  PubMed  Google Scholar 

  13. Martin KJ, Olgaard K, Coburn JW, et al. Diagnosis, assessment, and treatment of bone turnover abnormalities in renal osteodystrophy. Am J Kidney Dis. 2004;43:558–65.

    Article  PubMed  Google Scholar 

  14. Rocha LA, Higa A, Barreto FC, et al. Variant of adynamic bone disease in hemodialysis patients: fact or fiction? Am J Kidney Dis. 2006;48:430–6.

    Article  PubMed  Google Scholar 

  15. Spasovski GB, Bervoets AR, Behets GJ, et al. Spectrum of renal bone disease in end-stage renal failure patients not yet on dialysis. Nephrol Dial Transplant. 2003;18:1159–66.

    Article  PubMed  CAS  Google Scholar 

  16. D’Haese PC, Spasovski GB, Sikole A, et al. A multicenter study on the effects of lanthanum carbonate (Fosrenol) and calcium carbonate on renal bone disease in dialysis patients. Kidney Int. 2003;63:S73–8.

    Article  Google Scholar 

  17. Ferreira A, Frazao JM, Monier-Faugere MC, et al. Effects of sevelamer hydrochloride and calcium carbonate on renal osteodystrophy in hemodialysis patients. J Am Soc Nephrol. 2008;19:405–12.

    Article  PubMed  CAS  Google Scholar 

  18. Moe SM, Drueke TB. A bridge to improving healthcare outcomes and quality of life. Am J Kidney Dis. 2004;43:552–7.

    Article  PubMed  Google Scholar 

  19. Cannata-Andia JB. Hypokinetic azotemic osteodystrophy. Kidney Int. 1998;54:1000–16.

    Article  PubMed  CAS  Google Scholar 

  20. Saidak Z, Brazier M, Kamel S, et al. Agonists and allosteric modulators of the calcium-sensing receptor and their therapeutic applications. Mol Pharmacol [Review]. 2009;76:1131–44.

    Article  CAS  Google Scholar 

  21. Barreto FC, Barreto DV, Moyses RM, et al. K/DOQI-recommended intact PTH levels do not prevent low-turnover bone disease in hemodialysis patients. Kidney Int. 2008;73:771–7.

    Article  PubMed  CAS  Google Scholar 

  22. Monier-Faugere MC, Geng Z, Mawad H, et al. Improved assessment of bone turnover by the PTH-(1–84)/large C-PTH fragments ratio in ESRD patients. Kidney Int. 2001;60:1460–8.

    Article  PubMed  CAS  Google Scholar 

  23. Qunibi W, Kalantar-Zadeh K. Target levels for serum phosphorus and parathyroid hormone. Semin Dialysis. 2011;24:29–33.

    Article  Google Scholar 

  24. Slatopolsky E. The interaction of parathyroid hormone and aluminum in renal osteodystrophy. Kidney Int. 1987;31:842–54.

    Article  PubMed  CAS  Google Scholar 

  25. Iwasaki-Ishizuka Y, Yamato H, Nii-Kono T, et al. Downregulation of parathyroid hormone receptor gene expression and osteoblastic dysfunction associated with skeletal resistance to parathyroid hormone in a rat model of renal failure with low turnover bone. Nephrol Dial Transplant. 2005;20:1904–11.

    Article  PubMed  CAS  Google Scholar 

  26. Massry SG, Stein R, Garty J, et al. Skeletal resistance to the calcemic action of parathyroid hormone in uremia: role of 1, 25 (OH)2 D3. Kidney Int. 1976;9:467–74.

    Article  PubMed  CAS  Google Scholar 

  27. Picton ML, Moore PR, Mawer EB, et al. Down-regulation of human osteoblast PTH/PTHrP receptor mRNA in end-stage renal failure. Kidney Int. 2000;58:1440–9.

    Article  PubMed  CAS  Google Scholar 

  28. Heaf J. Adynamic bone disease and malnutrition-inflammation-cachexia syndrome. Kidney Int 2007;71:1326; author reply 7.

    Google Scholar 

  29. Kalantar-Zadeh K, Shah A, Duong U, et al. Kidney bone disease and mortality in CKD: revisiting the role of vitamin D, calcimimetics, alkaline phosphatase, and minerals. Kidney Int. 2010;78:S10–21.

    Article  CAS  Google Scholar 

  30. Fouque D, Kalantar-Zadeh K, Kopple J, et al. A proposed nomenclature and diagnostic criteria for protein-energy wasting in acute and chronic kidney disease. Kidney International [Congresses Research Support, Non-U.S. Gov’t]. 2008;73:391–8.

    CAS  Google Scholar 

  31. Sanchez-Gonzalez MC, Lopez-Barea F, Bajo MA, et al. Serum albumin levels, an additional factor implicated in hyperparathyroidism outcome in peritoneal dialysis: a prospective study with paired bone biopsies. Adv Perit Dial. 2006;22:198–202.

    PubMed  CAS  Google Scholar 

  32. Carlstedt E, Ridefelt P, Lind L, et al. Interleukin-6 induced suppression of bovine parathyroid hormone secretion. Biosci Rep. 1999;19:35–42.

    Article  PubMed  CAS  Google Scholar 

  33. Amerling R, Harbord NB, Pullman J, et al. Bisphosphonate use in chronic kidney disease: association with adynamic bone disease in a bone histology series. Blood Purif. 2010;29:293–9.

    Article  PubMed  CAS  Google Scholar 

  34. Goodman WG, Ramirez JA, Belin TR, et al. Development of adynamic bone in patients with secondary hyperparathyroidism after intermittent calcitriol therapy. Kidney Int. 1994;46:1160–6.

    Article  PubMed  CAS  Google Scholar 

  35. Hamdy NA, Kanis JA, Beneton MN, et al. Effect of alfacalcidol on natural course of renal bone disease in mild to moderate renal failure. BMJ. 1995;310:358–63.

    Article  PubMed  CAS  Google Scholar 

  36. Balint E, Marshall CF, Sprague SM. Effect of the vitamin D analogues paricalcitol and calcitriol on bone mineral in vitro. Am J Kidney Dis. 2000;36:789–96.

    Article  PubMed  CAS  Google Scholar 

  37. Malluche HH, Mawad H, Monier-Faugere MC. Effects of treatment of renal osteodystrophy on bone histology. Clin J Am Soc Nephrol. 2008;3(Suppl 3):S157–63.

    Article  PubMed  Google Scholar 

  38. Spasovski GB. Bone biopsy as a diagnostic tool in the assessment of renal osteodystrophy. Int J Artif Organs. 2004;27:918–23.

    PubMed  CAS  Google Scholar 

  39. Moe S, Drueke T, Cunningham J, 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  PubMed  CAS  Google Scholar 

  40. Herberth J, Monier-Faugere MC, Mawad HW, et al. The five most commonly used intact parathyroid hormone assays are useful for screening but not for diagnosing bone turnover abnormalities in CKD-5 patients. Clin Nephrol. 2009;72:5–14.

    PubMed  CAS  Google Scholar 

  41. Gupta A, Kallenbach LR, Zasuwa G, et al. Race is a major determinant of secondary hyperparathyroidism in uremic patients. J Am Soc Nephrol. 2000;11:330–4.

    PubMed  CAS  Google Scholar 

  42. Herberth J, Branscum AJ, Mawad H, et al. 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  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  44. Lindberg JS, Moe SM. Osteoporosis in end-state renal disease. Semin Nephrol. 1999;19:115–22.

    PubMed  CAS  Google Scholar 

  45. Danese MD, Kim J, Doan QV, et al. PTH and the risks for hip, vertebral, and pelvic fractures among patients on dialysis. Am J Kidney Dis. 2006;47:149–56.

    Article  PubMed  Google Scholar 

  46. Coco M, Rush H. Increased incidence of hip fractures in dialysis patients with low serum parathyroid hormone. Am J Kidney Dis. 2000;36:1115–21.

    Article  PubMed  CAS  Google Scholar 

  47. Yajima A, Ogawa Y, Ikehara A, et al. Development of low-turnover bone diseases after parathyroidectomy and autotransplantation. Int J Urol. 2001;8:S76–9.

    Article  PubMed  CAS  Google Scholar 

  48. Alem AM, Sherrard DJ, Gillen DL, et al. Increased risk of hip fracture among patients with end-stage renal disease. Kidney Int. 2000;58:396–9.

    Article  PubMed  CAS  Google Scholar 

  49. Rudser KD, de Boer IH, Dooley A, et al. Fracture risk after parathyroidectomy among chronic hemodialysis patients. J Am Soc Nephrol. 2007;18:2401–7.

    Article  PubMed  Google Scholar 

  50. Haris A, Sherrard DJ, Hercz G. Reversal of adynamic bone disease by lowering of dialysate calcium. Kidney Int. 2006;70:931–7.

    Article  PubMed  CAS  Google Scholar 

  51. London GM, Marchais SJ, Guerin AP, et al. Association of bone activity, calcium load, aortic stiffness, and calcifications in ESRD. J Am Soc Nephrol. 2008;19:1827–35.

    Article  PubMed  CAS  Google Scholar 

  52. Asci G, Ok E, Savas R, et al. The link between bone and coronary calcifications in CKD-5 patients on haemodialysis. Nephrol Dial Transplant. 2011;26:1010–5.

    Article  PubMed  Google Scholar 

  53. Barreto DV, Barreto FC, Carvalho AB, et al. Coronary calcification in hemodialysis patients: the contribution of traditional and uremia-related risk factors. Kidney Int. 2005;67:1576–82.

    Article  PubMed  Google Scholar 

  54. Mawad HW, Sawaya BP, Sarin R, et al. Calcific uremic arteriolopathy in association with low turnover uremic bone disease. Clin Nephrol. 1999;52:160–6.

    PubMed  CAS  Google Scholar 

  55. Jean G, Lataillade D, Genet L, et al. Association between very low PTH Levels and poor survival rates in haemodialysis patients: results from the French ARNOS cohort. Nephron Clin Pract. 2010;118:c211–6.

    Article  PubMed  CAS  Google Scholar 

  56. Kalantar-Zadeh K, Kuwae N, Regidor DL, et al. Survival predictability of time-varying indicators of bone disease in maintenance hemodialysis patients. Kidney Int. 2006;70:771–80.

    Article  PubMed  CAS  Google Scholar 

  57. Ganesh SK, Stack AG, Levin NW, et al. Association of elevated serum PO(4), Ca x PO(4) product, and parathyroid hormone with cardiac mortality risk in chronic hemodialysis patients. J Am Soc Nephrol. 2001;12:2131–8.

    PubMed  CAS  Google Scholar 

  58. Block GA, Klassen PS, Lazarus JM, et al. Mineral metabolism, mortality, and morbidity in maintenance hemodialysis. J Am Soc Nephrol. 2004;15:2208–18.

    Article  PubMed  CAS  Google Scholar 

  59. Nakai S, Akiba T, Kazama J, et al. Effects of serum calcium, phosphorous, and intact parathyroid hormone levels on survival in chronic hemodialysis patients in Japan. Ther Apher Dial. 2008;12:49–54.

    Article  PubMed  CAS  Google Scholar 

  60. Kovesdy CP, Ahmadzadeh S, Anderson JE, et al. Secondary hyperparathyroidism is associated with higher mortality in men with moderate to severe chronic kidney disease. Kidney Int. 2008;73:1296–302.

    Article  PubMed  CAS  Google Scholar 

  61. Dukkipati R, Kovesdy CP, Colman S, et al. Association of relatively low serum parathyroid hormone with malnutrition-inflammation complex and survival in maintenance hemodialysis patients. J Ren Nutr. 2010;20:243–54.

    Article  PubMed  CAS  Google Scholar 

  62. Tangri N, Wagner M, Griffith JL, et al. Effect of bone mineral guideline target achievement on mortality in incident dialysis patients: an analysis of the United Kingdom Renal Registry. Am J Kidney Dis. 2011;57:415–21.

    Article  PubMed  Google Scholar 

  63. Kuizon BD, Goodman WG, Juppner H, et al. Diminished linear growth during intermittent calcitriol therapy in children undergoing CCPD. Kidney Int. 1998;53:205–11.

    Article  PubMed  CAS  Google Scholar 

  64. van Driel M, Koedam M, Buurman CJ, et al. Evidence that both 1alpha, 25-dihydroxyvitamin D3 and 24-hydroxylated D3 enhance human osteoblast differentiation and mineralization. J Cell Biochem. 2006;99:922–35.

    Article  PubMed  CAS  Google Scholar 

  65. Baldock PA, Thomas GP, Hodge JM, et al. Vitamin D action and regulation of bone remodeling: suppression of osteoclastogenesis by the mature osteoblast. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research [Comparative StudyResearch Support, Non-U.S. Gov’t]. 2006;21:1618–26.

    CAS  Google Scholar 

  66. Fretz JA, Zella LA, Kim S, et al. 1, 25-Dihydroxyvitamin D3 induces expression of the Wnt signaling co-regulator LRP5 via regulatory elements located significantly downstream of the gene’s transcriptional start site. J Steroid Biochem Mol Biol [Research Support, N.I.H., Extramural]. 2007;103:440–5.

    CAS  Google Scholar 

  67. Panda DK, Miao D, Bolivar I, et al. Inactivation of the 25-hydroxyvitamin D 1alpha-hydroxylase and vitamin D receptor demonstrates independent and interdependent effects of calcium and vitamin D on skeletal and mineral homeostasis. The Journal of biological chemistry [Research Support, Non-U.S. Gov’t]. 2004;279:16754–66.

    CAS  Google Scholar 

  68. Teng M, Wolf M, Lowrie E, et al. Survival of patients undergoing hemodialysis with paricalcitol or calcitriol therapy. N Engl J Med. 2003;349:446–56.

    Article  PubMed  CAS  Google Scholar 

  69. Teng M, Wolf M, Ofsthun MN, et al. Activated injectable vitamin D and hemodialysis survival: a historical cohort study. J Am Soc Nephrol. 2005;16:1115–25.

    Article  PubMed  CAS  Google Scholar 

  70. Mathew S, Lund RJ, Chaudhary LR, et al. Vitamin D receptor activators can protect against vascular calcification. J Am Soc Nephrol. 2008;19:1509–19.

    Article  PubMed  CAS  Google Scholar 

  71. Chertow GM, Burke SK, Raggi P. Sevelamer attenuates the progression of coronary and aortic calcification in hemodialysis patients. Kidney Int. 2002;62:245–52.

    Article  PubMed  CAS  Google Scholar 

  72. Raggi P, James G, Burke SK, et al. Decrease in thoracic vertebral bone attenuation with calcium-based phosphate binders in hemodialysis. J Bone Miner Res. 2005;20:764–72.

    Article  PubMed  CAS  Google Scholar 

  73. Jamal SA, Hodsman AB. Reducing the risk of re-fracture in the dialysis population: is it time to consider therapy with PTH analogues? Semin Dial. 2011;24:12–5.

    Article  PubMed  Google Scholar 

  74. Fujimori A, Yorifuji M, Sakai M, et al. Low-calcium dialysate improves mineral metabolism in hemodialysis patients. Clin Nephrol. 2007;67:20–4.

    PubMed  CAS  Google Scholar 

  75. Lezaic V, Pejanovic S, Kostic S, et al. Effects of lowering dialysate calcium concentration on mineral metabolism and parathyroid hormone secretion: a multicentric study. Ther Apher Dial. 2007;11:121–30.

    Article  PubMed  CAS  Google Scholar 

  76. Spasovski G, Gelev S, Masin-Spasovska J, et al. Improvement of bone and mineral parameters related to adynamic bone disease by diminishing dialysate calcium. Bone. 2007;41:698–703.

    Article  PubMed  CAS  Google Scholar 

  77. Cejka D, Kodras K, Bader T, et al. Treatment of Hemodialysis-Associated Adynamic Bone Disease with Teriparatide (PTH(1–34)): A Pilot Study. Kidney Blood Press Res. 2010;33:221–6.

    Article  PubMed  CAS  Google Scholar 

  78. Silver J, Bushinsky D. Harnessing the parathyroids to create stronger bones. Curr Opin Nephrol Hypertens. 2004;13:471–6.

    Article  PubMed  CAS  Google Scholar 

  79. Goodman WG, Hladik GA, Turner SA, et al. The Calcimimetic agent AMG 073 lowers plasma parathyroid hormone levels in hemodialysis patients with secondary hyperparathyroidism. J Am Soc Nephrol. 2002;13:1017–24.

    PubMed  CAS  Google Scholar 

  80. Ishii H, Wada M, Furuya Y, et al. Daily intermittent decreases in serum levels of parathyroid hormone have an anabolic-like action on the bones of uremic rats with low-turnover bone and osteomalacia. Bone. 2000;26:175–82.

    Article  PubMed  CAS  Google Scholar 

  81. Gowen M, Stroup GB, Dodds RA, et al. Antagonizing the parathyroid calcium receptor stimulates parathyroid hormone secretion and bone formation in osteopenic rats. J Clin Invest. 2000;105:1595–604.

    Article  PubMed  CAS  Google Scholar 

  82. Jaffe JA, Liftman C, Glickman JD. Frequency of elevated serum aluminum levels in adult dialysis patients. Am J Kidney Dis. 2005;46:316–9.

    Article  PubMed  Google Scholar 

  83. Araujo SM, Ambrosoni P, Lobao RR, et al. The renal osteodystrophy pattern in Brazil and Uruguay: an overview. Kidney Int. 2003;63:S54–6.

    Article  Google Scholar 

  84. Jorgetti V, Lopez BD, Caorsi H, et al. Different patterns of renal osteodystrophy in Iberoamerica. Am J Med Sci. 2000;320:76–80.

    Article  PubMed  CAS  Google Scholar 

  85. Hruska KA, Teitelbaum SL. Renal osteodystrophy. N Engl J Med. 1995;333:166–74.

    Article  PubMed  CAS  Google Scholar 

  86. Felsenfeld AJ, Gutman RA, Llach F, et al. Osteomalacia in chronic renal failure: a syndrome previously reported only with maintenance dialysis. Am J Nephrol. 1982;2:147–54.

    Article  PubMed  CAS  Google Scholar 

  87. Nebeker HG, Coburn JW. Aluminum and renal osteodystrophy. Annu Rev Med. 1986;37:79–95.

    Article  PubMed  CAS  Google Scholar 

  88. Andress DL, Kopp JB, Maloney NA, et al. Early deposition of aluminum in bone in diabetic patients on hemodialysis. N Engl J Med. 1987;316:292–6.

    Article  PubMed  CAS  Google Scholar 

  89. Pei Y, Hercz G, Greenwood C, et al. Renal osteodystrophy in diabetic patients. Kidney Int. 1993;44:159–64.

    Article  PubMed  CAS  Google Scholar 

  90. Vincenti F, Arnaud SB, Recker R, et al. Parathyroid and bone response of the diabetic patient to uremia. Kidney Int. 1984;25:677–82.

    Article  PubMed  CAS  Google Scholar 

  91. Ott SM. Histomorphometric measurements of bone turnover, mineralization, and volume. Clin J Am Soc Nephrol. 2008;3(Suppl 3):S151–6.

    Article  PubMed  Google Scholar 

  92. Kausz AT, Antonsen JE, Hercz G, et al. Screening plasma aluminum levels in relation to aluminum bone disease among asymptomatic dialysis patients. Am J Kidney Dis. 1999;34:688–93.

    Article  PubMed  CAS  Google Scholar 

  93. D’Haese PC, Couttenye MM, Goodman WG, et al. Use of the low-dose desferrioxamine test to diagnose and differentiate between patients with aluminium-related bone disease, increased risk for aluminium toxicity, or aluminium overload. Nephrol Dial Transplant. 1995;10:1874–84.

    PubMed  Google Scholar 

  94. Netter P, Kessler M, Burnel D, et al. Aluminum in the joint tissues of chronic renal failure patients treated with regular hemodialysis and aluminum compounds. J Rheumatol. 1984;11:66–70.

    PubMed  CAS  Google Scholar 

  95. Baker LR, Muir JW, Sharman VL, et al. Controlled trial of calcitriol in hemodialysis patients. Clin Nephrol. 1986;26:185–91.

    PubMed  CAS  Google Scholar 

  96. Felsenfeld AJ, Rodriguez M, Coleman M, et al. Desferrioxamine therapy in hemodialysis patients with aluminum-associated bone disease. Kidney Int. 1989;35:1371–8.

    Article  PubMed  CAS  Google Scholar 

  97. Malluche HH, Smith AJ, Abreo K, et al. The use of deferoxamine in the management of aluminium accumulation in bone in patients with renal failure. N Engl J Med. 1984;311:140–4.

    Article  PubMed  CAS  Google Scholar 

  98. McCarthy JT, Milliner DS, Johnson WJ. Clinical experience with desferrioxamine in dialysis patients with aluminium toxicity. Q J Med. 1990;74:257–76.

    PubMed  CAS  Google Scholar 

  99. Nickolas TL, Leonard MB, Shane E. Chronic kidney disease and bone fracture: a growing concern. Kidney Int. 2008;74:721–31.

    Article  PubMed  Google Scholar 

  100. NIH Consensus Development Panel on Osteoporosis Prevention, Diagnosis, and Therapy. Osteoporosis prevention, diagnosis, and therapy. JAMA. 2001;285(6):785–95.

    Article  Google Scholar 

  101. Jadoul M, Albert JM, Akiba T, et al. Incidence and risk factors for hip or other bone fractures among hemodialysis patients in the dialysis outcomes and practice patterns study. Kidney Int. 2006;70:1358–66.

    Article  PubMed  CAS  Google Scholar 

  102. Taal MW, Roe S, Masud T, et al. Total hip bone mass predicts survival in chronic hemodialysis patients. Kidney Int. 2003;63:1116–20.

    Article  PubMed  Google Scholar 

  103. Seeman E. Pathogenesis of bone fragility in women and men. Lancet. 2002;359:1841–50.

    Article  PubMed  Google Scholar 

  104. Huang GS, Chu TS, Lou MF, et al. Factors associated with low bone mass in the hemodialysis patients–a cross-sectional correlation study. BMC Musculoskelet Disord. 2009;10:60.

    Article  PubMed  CAS  Google Scholar 

  105. Lindergard B, Johnell O, Nilsson BE, et al. Studies of bone morphology, bone densitometry and laboratory data in patients on maintenance hemodialysis treatment. Nephron. 1985;39:122–9.

    Article  PubMed  CAS  Google Scholar 

  106. Assessment of fracture risk and its application to screening for postmenopausal osteoporosis. Report of a WHO Study Group. World Health Organ Tech Rep Ser 1994;843:1–129.

    Google Scholar 

  107. Yamaguchi T, Kanno E, Tsubota J, et al. Retrospective study on the usefulness of radius and lumbar bone density in the separation of hemodialysis patients with fractures from those without fractures. Bone. 1996;19:549–55.

    Article  PubMed  CAS  Google Scholar 

  108. Jamal SA, Hayden JA, Beyene J. Low bone mineral density and fractures in long-term hemodialysis patients: a meta-analysis. Am J Kidney Dis. 2007;49:674–81.

    Article  PubMed  Google Scholar 

  109. Desmet C, Beguin C, Swine C, et al. Falls in hemodialysis patients: prospective study of incidence, risk factors, and complications. Am J Kidney Dis. 2005;45:148–53.

    Article  PubMed  Google Scholar 

  110. Park JC, Kovesdy CP, Duong U, et al. Association of serum alkaline phosphatase and bone mineral density in maintenance hemodialysis patients. Hemodial Int. 2010;14:182–92.

    Article  PubMed  Google Scholar 

  111. Miller PD. The kidney and bisphosphonates. Bone 2011.

  112. Hodsman AB. Fragility fractures in dialysis and transplant patients. Is it osteoporosis, and how should it be treated? Perit Dial Int. 2001;21(Suppl 3):S247–55.

    PubMed  Google Scholar 

  113. Miller PD, Roux C, Boonen S, et al. Safety and efficacy of risedronate in patients with age-related reduced renal function as estimated by the Cockcroft and Gault method: a pooled analysis of nine clinical trials. J Bone Miner Res. 2005;20:2105–15.

    Article  PubMed  CAS  Google Scholar 

  114. Jamal SA, Bauer DC, Ensrud KE, et al. Alendronate treatment in women with normal to severely impaired renal function: an analysis of the fracture intervention trial. J Bone Miner Res. 2007;22:503–8.

    Article  PubMed  CAS  Google Scholar 

  115. Lu KC, Yeung LK, Lin SH, et al. Acute effect of pamidronate on PTH secretion in postmenopausal hemodialysis patients with secondary hyperparathyroidism. Am J Kidney Dis. 2003;42:1221–7.

    Article  PubMed  CAS  Google Scholar 

  116. Miller PD. Fragility fractures in chronic kidney disease: an opinion-based approach. Cleve Clin J Med. 2009;76:715–23.

    Article  PubMed  Google Scholar 

  117. Westenfeld R, Ketteler M, Brandenburg VM. Anti-RANKL therapy–implications for the bone-vascular-axis in CKD? Denosumab in post-menopausal women with low bone mineral density. Nephrol Dial Transplant. 2006;21:2075–7.

    Article  PubMed  CAS  Google Scholar 

  118. Jamal SA, Ljunggren O, Stehman-Breen C, et al. Effects of denosumab on fracture and bone mineral density by level of kidney function. J Bone Miner Res. 2011;26:1829–35.

    Article  PubMed  CAS  Google Scholar 

  119. Danesh F, Ho LT. Dialysis-related amyloidosis: history and clinical manifestations. Semin Dial. 2001;14:80–5.

    Article  PubMed  CAS  Google Scholar 

  120. Drueke TB, Massy ZA. Beta2-microglobulin. Semin Dial. 2009;22:378–80.

    Article  PubMed  Google Scholar 

  121. Yamamoto S, Kazama JJ, Narita I, et al. Recent progress in understanding dialysis-related amyloidosis. Bone. 2009;45(Suppl 1):S39–42.

    Article  PubMed  CAS  Google Scholar 

  122. Warren DJ, Otieno LS. Carpal tunnel syndrome in patients on intermittent haemodialysis. Postgrad Med J. 1975;51:450–2.

    Article  PubMed  CAS  Google Scholar 

  123. Kenzora JE. Dialysis carpal tunnel syndrome. Orthopedics. 1978;1:195–203.

    PubMed  CAS  Google Scholar 

  124. Gejyo F, Yamada T, Odani S, et al. A new form of amyloid protein associated with chronic hemodialysis was identified as beta 2-microglobulin. Biochem Biophys Res Commun. 1985;129:701–6.

    Article  PubMed  CAS  Google Scholar 

  125. Schwalbe S, Holzhauer M, Schaeffer J, et al. Beta 2-microglobulin associated amyloidosis: a vanishing complication of long-term hemodialysis? Kidney Int. 1997;52:1077–83.

    Article  PubMed  CAS  Google Scholar 

  126. Jadoul M, Garbar C, Noel H, et al. Histological prevalence of beta 2-microglobulin amyloidosis in hemodialysis: a prospective post-mortem study. Kidney Int. 1997;51:1928–32.

    Article  PubMed  CAS  Google Scholar 

  127. Otsubo S, Kimata N, Okutsu I, et al. Characteristics of dialysis-related amyloidosis in patients on haemodialysis therapy for more than 30 years. Nephrol Dial Transplant. 2009;24:1593–8.

    Article  PubMed  Google Scholar 

  128. Winchester JF, Salsberg JA, Levin NW. Beta-2 microglobulin in ESRD: an in-depth review. Adv Ren Replace Ther. 2003;10:279–309.

    Article  PubMed  Google Scholar 

  129. Copley JB, Lindberg JS. Nontransplant therapy for dialysis-related amyloidosis. Semin Dial. 2001;14:94–8.

    Article  PubMed  CAS  Google Scholar 

  130. Gejyo F, Homma N, Suzuki Y, et al. Serum levels of beta 2-microglobulin as a new form of amyloid protein in patients undergoing long-term hemodialysis. N Engl J Med. 1986;314:585–6.

    Article  PubMed  CAS  Google Scholar 

  131. Moe SM, Hack BK, Cummings SA, et al. Role of IL-1 beta and prostaglandins in beta 2-microglobulin-induced bone mineral dissolution. Kidney Int. 1995;47:587–91.

    Article  PubMed  CAS  Google Scholar 

  132. Koch KM. Dialysis-related amyloidosis. Kidney Int. 1992;41:1416–29.

    Article  PubMed  CAS  Google Scholar 

  133. Saito A, Gejyo F. Current clinical aspects of dialysis-related amyloidosis in chronic dialysis patients. Ther Apher Dial. 2006;10:316–20.

    Article  PubMed  CAS  Google Scholar 

  134. Zumrutdal A, Sezer S, Demircan S, et al. Cardiac troponin I and beta 2 microglobulin as risk factors for early-onset atherosclerosis in patients on haemodialysis. Nephrology (Carlton). 2005;10:453–8.

    Article  CAS  Google Scholar 

  135. Cheung AK, Rocco MV, Yan G, et al. Serum beta-2 microglobulin levels predict mortality in dialysis patients: results of the HEMO study. J Am Soc Nephrol. 2006;17:546–55.

    Article  PubMed  CAS  Google Scholar 

  136. DiRaimondo CR, Casey TT, DiRaimondo CV, et al. Pathologic fractures associated with idiopathic amyloidosis of bone in chronic hemodialysis patients. Nephron. 1986;43:22–7.

    Article  PubMed  CAS  Google Scholar 

  137. Bindi P, Chanard J. Destructive spondyloarthropathy in dialysis patients: an overview. Nephron. 1990;55:104–9.

    Article  PubMed  CAS  Google Scholar 

  138. Kuntz D, Naveau B, Bardin T, et al. Destructive spondylarthropathy in hemodialyzed patients. A new syndrome. Arthritis Rheum. 1984;27:369–75.

    Article  PubMed  CAS  Google Scholar 

  139. Saijo Y, Utsugi M, Yoshioka E, et al. Relationship of beta2-microglobulin to arterial stiffness in Japanese subjects. Hypertens Res. 2005;28:505–11.

    Article  PubMed  CAS  Google Scholar 

  140. Wilson AM, Kimura E, Harada RK, et al. Beta2-microglobulin as a biomarker in peripheral arterial disease: proteomic profiling and clinical studies. Circulation. 2007;116:1396–403.

    Article  PubMed  CAS  Google Scholar 

  141. McCarthy JT, Williams AW, Johnson WJ. Serum beta 2-microglobulin concentration in dialysis patients: importance of intrinsic renal function. J Lab Clin Med. 1994;123:495–505.

    PubMed  CAS  Google Scholar 

  142. Locatelli F, Mastrangelo F, Redaelli B, et al. Effects of different membranes and dialysis technologies on patient treatment tolerance and nutritional parameters. The Italian Cooperative Dialysis Study Group. Kidney Int. 1996;50:1293–302.

    Article  PubMed  CAS  Google Scholar 

  143. Koda Y, Nishi S, Miyazaki S, et al. Switch from conventional to high-flux membrane reduces the risk of carpal tunnel syndrome and mortality of hemodialysis patients. Kidney Int. 1997;52:1096–101.

    Article  PubMed  CAS  Google Scholar 

  144. Locatelli F, Marcelli D, Conte F, et al. Comparison of mortality in ESRD patients on convective and diffusive extracorporeal treatments. The Registro Lombardo Dialisi E Trapianto. Kidney Int. 1999;55:286–93.

    Article  PubMed  CAS  Google Scholar 

  145. Ward RA, Greene T, Hartmann B, et al. Resistance to intercompartmental mass transfer limits beta2-microglobulin removal by post-dilution hemodiafiltration. Kidney Int. 2006;69:1431–7.

    PubMed  CAS  Google Scholar 

  146. Eloot S, Van Biesen W, Dhondt A, et al. Impact of hemodialysis duration on the removal of uremic retention solutes. Kidney Int. 2008;73:765–70.

    Article  PubMed  CAS  Google Scholar 

  147. Skroeder NR, Jacobson SH, Holmquist B, et al. Beta 2-microglobulin generation and removal in long slow and short fast hemodialysis. Am J Kidney Dis. 1993;21:519–26.

    PubMed  CAS  Google Scholar 

  148. Raj DS, Ouwendyk M, Francoeur R, et al. Beta(2)-microglobulin kinetics in nocturnal haemodialysis. Nephrol Dial Transplant. 2000;15:58–64.

    Article  PubMed  CAS  Google Scholar 

  149. Stamopoulos D, Bouziotis P, Benaki D, et al. Nanobiotechnology for the prevention of dialysis-related amyloidosis. Ther Apher Dial. 2009;13:34–41.

    Article  PubMed  CAS  Google Scholar 

  150. Campistol JM. Dialysis-related amyloidosis after renal transplantation. Semin Dial. 2001;14:99–102.

    Article  PubMed  CAS  Google Scholar 

  151. Mourad G, Argiles A. Renal transplantation relieves the symptoms but does not reverse beta 2-microglobulin amyloidosis. J Am Soc Nephrol. 1996;7:798–804.

    PubMed  CAS  Google Scholar 

  152. Bleibel W, Hazar B, Herman R. A case report comparing various radiological tests in the diagnosis of calcific uremic arteriolopathy. Am J Kidney Dis. 2006;48:659–61.

    Article  PubMed  Google Scholar 

  153. Qunibi WY. Consequences of hyperphosphatemia in patients with end-stage renal disease (ESRD). Kidney Int. 2004;66:S8–12.

    Article  Google Scholar 

  154. Fine A, Zacharias J. Calciphylaxis is usually non-ulcerating: risk factors, outcome and therapy. Kidney Int. 2002;61:2210–7.

    Article  PubMed  Google Scholar 

  155. Brandenburg VM, Cozzolino M, Ketteler M. Calciphylaxis: a still unmet challenge. J Nephrol. 2011;24:142–8.

    Article  PubMed  Google Scholar 

  156. Nigwekar SU, Wolf M, Sterns RH, et al. Calciphylaxis from nonuremic causes: a systematic review. Clin J Am Soc Nephrol. 2008;3:1139–43.

    Article  PubMed  Google Scholar 

  157. Au S, Crawford RI. Three-dimensional analysis of a calciphylaxis plaque: clues to pathogenesis. J Am Acad Dermatol. 2002;47:53–7.

    Article  PubMed  Google Scholar 

  158. Angelis M, Wong LL, Myers SA, et al. Calciphylaxis in patients on hemodialysis: a prevalence study. Surgery. 1997;122:1083–9. discussion 9–90.

    Article  PubMed  CAS  Google Scholar 

  159. Mason D, Best SD. Calcific uremic arteriolopathy: contemporary pharmacotherapy. Adv Chronic Kidney Dis. 2010;17:428–38.

    Article  PubMed  Google Scholar 

  160. Budisavljevic MN, Cheek D, Ploth DW. Calciphylaxis in chronic renal failure. J Am Soc Nephrol. 1996;7:978–82.

    PubMed  CAS  Google Scholar 

  161. Mazhar AR, Johnson RJ, Gillen D, et al. Risk factors and mortality associated with calciphylaxis in end-stage renal disease. Kidney Int. 2001;60:324–32.

    Article  PubMed  CAS  Google Scholar 

  162. Rogers NM, Teubner DJ, Coates PT. Calcific uremic arteriolopathy: advances in pathogenesis and treatment. Semin Dial. 2007;20:150–7.

    Article  PubMed  Google Scholar 

  163. Fine A, Fontaine B. Calciphylaxis: the beginning of the end? Perit Dial Int. 2008;28:268–70.

    PubMed  Google Scholar 

  164. Selye H, Gabbiani G, Strebel R. Sensitization to calciphylaxis by endogenous parathyroid hormone. Endocrinology. 1962;71:554–8.

    Article  PubMed  CAS  Google Scholar 

  165. Janigan DT, Hirsch DJ, Klassen GA, et al. Calcified subcutaneous arterioles with infarcts of the subcutis and skin (“calciphylaxis”) in chronic renal failure. Am J Kidney Dis. 2000;35:588–97.

    Article  PubMed  CAS  Google Scholar 

  166. Sowers KM, Hayden MR. Calcific uremic arteriolopathy: pathophysiology, reactive oxygen species and therapeutic approaches. Oxid Med Cell Longev. 2010;3:109–21.

    Article  PubMed  Google Scholar 

  167. Moe SM. Calcific uremic arteriolopathy: A new look at an old disorder. NephSAP. 2004;3:77–83.

    Google Scholar 

  168. Hayden MR, Goldsmith DJ. Sodium thiosulfate: new hope for the treatment of calciphylaxis. Semin Dial. 2010;23:258–62.

    Article  PubMed  Google Scholar 

  169. Krueger T, Westenfeld R, Schurgers L, et al. Coagulation meets calcification: the vitamin K system. Int J Artif Organs. 2009;32:67–74.

    PubMed  CAS  Google Scholar 

  170. Franks AG Jr. Skin manifestations of internal disease. Med Clin North Am. 2009;93:1265–82.

    Article  PubMed  CAS  Google Scholar 

  171. Weenig RH, Sewell LD, Davis MD, et al. Calciphylaxis: natural history, risk factor analysis, and outcome. J Am Acad Dermatol. 2007;56:569–79.

    Article  PubMed  Google Scholar 

  172. Rogers NM, Coates PT. Calcific uraemic arteriolopathy: an update. Curr Opin Nephrol Hypertens. 2008;17:629–34.

    Article  PubMed  Google Scholar 

  173. Rogers NM, Chang SH, Tuebner DJ, et al. Hyperbaric oxygen as effective adjuvant therapy in the treatment of distal calcific uraemic arteriolopathy. NDT Plus. 2008;4:244–9.

    Article  CAS  Google Scholar 

  174. Naik BJ, Lynch DJ, Slavcheva EG, et al. Calciphylaxis: medical and surgical management of chronic extensive wounds in a renal dialysis population. Plast Reconstr Surg. 2004;113:304–12.

    Article  PubMed  Google Scholar 

  175. Girotto JA, Harmon JW, Ratner LE, et al. Parathyroidectomy promotes wound healing and prolongs survival in patients with calciphylaxis from secondary hyperparathyroidism. Surgery. 2001;130:645–50, discussion 50–1.

    Article  PubMed  CAS  Google Scholar 

  176. Hafner J, Keusch G, Wahl C, et al. Uremic small-artery disease with medial calcification and intimal hyperplasia (so-called calciphylaxis): a complication of chronic renal failure and benefit from parathyroidectomy. J Am Acad Dermatol. 1995;33:954–62.

    Article  PubMed  CAS  Google Scholar 

  177. Schlieper G, Brandenburg V, Ketteler M, et al. Sodium thiosulfate in the treatment of calcific uremic arteriolopathy. Nat Rev Nephrol. 2009;5:539–43.

    Article  PubMed  CAS  Google Scholar 

  178. Cicone JS, Petronis JB, Embert CD, et al. Successful treatment of calciphylaxis with intravenous sodium thiosulfate. Am J Kidney Dis. 2004;43:1104–8.

    Article  PubMed  Google Scholar 

  179. Adams JE. Dialysis bone disease. Semin Dial. 2002;15(4):277–89.

    Article  PubMed  Google Scholar 

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Correspondence to Wajeh Qunibi.

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Morrow, B., Qunibi, W. Specific Bone and Mineral Disorders in Patients with Chronic Kidney Disease. Clinic Rev Bone Miner Metab 10, 184–208 (2012). https://doi.org/10.1007/s12018-011-9114-6

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