Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

Osteoporosis in patients with chronic kidney disease: Diagnosis, evaluation, and management

Paul D Miller, MD
Section Editor
Clifford J Rosen, MD
Deputy Editor
Jean E Mulder, MD


Changes in mineral metabolism and bone structure develop early in the course of chronic kidney disease (CKD) and worsen with progressive loss of kidney function. CKD-metabolic bone disease (MBD) includes abnormalities of calcium, phosphorus, parathyroid hormone (PTH), or vitamin D; abnormalities in bone turnover, mineralization, volume, linear growth, or strength; and/or vascular or other soft tissue calcification [1]. The more severe forms of CKD-MBD (renal osteodystrophy) occur in patients with advanced CKD. These include hyperparathyroid-mediated high-turnover bone disease or osteitis fibrosa cystica, adynamic bone disease, osteomalacia, and mixed uremic osteodystrophy.

Patients with CKD may have other bone diseases (osteoporosis, vitamin D deficiency) either before or after developing kidney disease. Osteoporosis is a common disease that is characterized by low bone mass with microarchitectural disruption and skeletal fragility, resulting in an increased risk of fracture, particularly at the spine, hip, wrist, humerus, and pelvis [2].

It is difficult to diagnose osteoporosis in the setting of CKD. This is particularly relevant for the aging population, where fragility fractures, reduced glomerular filtration rate (GFR), and low bone mineral density (BMD) are more prevalent. There are multiple reasons why this differentiation is important, not the least of which is that management of osteoporosis versus the spectrum of bone diseases in patients with CKD differ vastly.

This topic card will review the diagnosis, evaluation, and management of osteoporosis in patients with CKD. The pathogenesis, diagnosis, and management of other aspects or MBD in patients with CKD are reviewed elsewhere. (See "Overview of chronic kidney disease-mineral and bone disorder (CKD-MBD)" and "Bone biopsy and the diagnosis of renal osteodystrophy" and "Management of secondary hyperparathyroidism and mineral metabolism abnormalities in adult predialysis patients with chronic kidney disease" and "Management of secondary hyperparathyroidism and mineral metabolism abnormalities in dialysis patients".)


Magnitude of the problem — End-stage chronic kidney disease (CKD) is associated with an increased risk of fragility (low trauma) fractures [3,4]. In addition, the risk of fracture-related mortality increases with the severity of CKD [3,5]. In most [6-11], but not all [12], studies, more moderate degrees of renal insufficiency in men and women have also been associated with an increased fracture risk. As an example, in a case-cohort study of women ≥65 years, the risk of hip fracture was increased in women with an estimated glomerular filtration rate (eGFR) of 45 to 59 mL/minute (hazard ratio [HR] 1.57, 95% CI 0.89-2.76) and in those with an eGFR <45 mL/minute (HR 2.32, 95% CI 1.15-4.68) compared with women with an eGFR ≥60 mL/minute [7]. The risk of hip fracture remained, although was attenuated, after controlling for bone density [7,8].

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:

Subscribers log in here

Literature review current through: Oct 2017. | This topic last updated: Sep 28, 2016.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
  1. Moe S, Drüeke 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.
  2. Riggs BL, Melton LJ 3rd. The worldwide problem of osteoporosis: insights afforded by epidemiology. Bone 1995; 17:505S.
  3. Coco M, Rush H. Increased incidence of hip fractures in dialysis patients with low serum parathyroid hormone. Am J Kidney Dis 2000; 36:1115.
  4. 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.
  5. Nitsch D, Mylne A, Roderick PJ, et al. Chronic kidney disease and hip fracture-related mortality in older people in the UK. Nephrol Dial Transplant 2009; 24:1539.
  6. Jamal SA, West SL, Miller PD. Fracture risk assessment in patients with chronic kidney disease. Osteoporos Int 2012; 23:1191.
  7. Ensrud KE, Lui LY, Taylor BC, et al. Renal function and risk of hip and vertebral fractures in older women. Arch Intern Med 2007; 167:133.
  8. 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.
  9. Dukas L, Schacht E, Stähelin HB. In elderly men and women treated for osteoporosis a low creatinine clearance of <65 ml/min is a risk factor for falls and fractures. Osteoporos Int 2005; 16:1683.
  10. Fried LF, Biggs ML, Shlipak MG, et al. Association of kidney function with incident hip fracture in older adults. J Am Soc Nephrol 2007; 18:282.
  11. Dooley AC, Weiss NS, Kestenbaum B. Increased risk of hip fracture among men with CKD. Am J Kidney Dis 2008; 51:38.
  12. Jassal SK, von Muhlen D, Barrett-Connor E. Measures of renal function, BMD, bone loss, and osteoporotic fracture in older adults: the Rancho Bernardo study. J Bone Miner Res 2007; 22:203.
  13. Quarles LD. Skeletal secretion of FGF-23 regulates phosphate and vitamin D metabolism. Nat Rev Endocrinol 2012; 8:276.
  14. Hruska KA, Mathew S. The roles of the skeleton and phosphorus in the CKD mineral bone disorder. Adv Chronic Kidney Dis 2011; 18:98.
  15. Jüppner H. Phosphate and FGF-23. Kidney Int Suppl 2011; :S24.
  16. National Osteoporosis Foundation. Osteoporosis and chronic kidney disease updates, 2010 http://www.nof.org/sites/default/files/clinicalupdates/Issue20KidneyDisease/kidney.html (Accessed on September 25, 2012).
  17. Miller PD, Jamal S, West S. Bone mineral density in chronic kidney disease-use and misuse. Clin Rev Bone and Mineral Metab 2012; 10:163. http://www.springerlink.com/content/0364267gmnm85147/ (Accessed on September 25, 2012).
  18. Kanis JA, Hans D, Cooper C, et al. Interpretation and use of FRAX in clinical practice. Osteoporos Int 2011; 22:2395.
  19. Nickolas TL, Cremers S, Zhang A, et al. Discriminants of prevalent fractures in chronic kidney disease. J Am Soc Nephrol 2011; 22:1560.
  20. Nickolas TL, Stein E, Cohen A, et al. Bone mass and microarchitecture in CKD patients with fracture. J Am Soc Nephrol 2010; 21:1371.
  21. Jamal S, Cheung AM, West S, Lok C. Bone mineral density by DXA and HR pQCT can discriminate fracture status in men and women with stages 3 to 5 chronic kidney disease. Osteoporos Int 2012; 23:2805.
  22. 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.
  23. Ersoy FF, Passadakis SP, Tam P, et al. Bone mineral density and its correlation with clinical and laboratory factors in chronic peritoneal dialysis patients. J Bone Miner Metab 2006; 24:79.
  24. Jamal SA, Chase C, Goh YI, et al. Bone density and heel ultrasound testing do not identify patients with dialysis-dependent renal failure who have had fractures. Am J Kidney Dis 2002; 39:843.
  25. Parfitt AM, Drezner MK, Glorieux FH, et al. Bone histomorphometry: standardization of nomenclature, symbols, and units. Report of the ASBMR Histomorphometry Nomenclature Committee. J Bone Miner Res 1987; 2:595.
  26. 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.
  27. Wehrli FW, Leonard MB, Saha PK, Gomberg BR. Quantitative high-resolution magnetic resonance imaging reveals structural implications of renal osteodystrophy on trabecular and cortical bone. J Magn Reson Imaging 2004; 20:83.
  28. KDIGO Clinical Practice Guideline for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD). Chapter 3.1: Diagnosis of CKD-MBD: biochemical abnormalities. http://www.kdigo.org/guidelines/mbd/guide3.html#chap32 (Accessed on January 16, 2013).
  29. Gal-Moscovici A, Sprague SM. Osteoporosis and chronic kidney disease. Semin Dial 2007; 20:423.
  30. Miller PD. Diagnosis and treatment of osteoporosis in chronic renal disease. Semin Nephrol 2009; 29:144.
  31. World Health Organization. Assessment of fracture risk and its application to screening for postmenopausal osteoporosis. Geneva 1994. http://whqlibdoc.who.int/trs/WHO_TRS_843.pdf (Accessed on October 03, 2012).
  32. Johnell O, Kanis JA, Oden A, et al. Predictive value of BMD for hip and other fractures. J Bone Miner Res 2005; 20:1185.
  33. Coen G. Adynamic bone disease: an update and overview. J Nephrol 2005; 18:117.
  34. Barreto FC, Barreto DV, Moyses RM, et al. Osteoporosis in hemodialysis patients revisited by bone histomorphometry: a new insight into an old problem. Kidney Int 2006; 69:1852.
  35. Ferreira MA. Diagnosis of renal osteodystrophy: when and how to use biochemical markers and non-invasive methods; when bone biopsy is needed. Nephrol Dial Transplant 2000; 15 Suppl 5:8.
  36. Andress DL. Adynamic bone in patients with chronic kidney disease. Kidney Int 2008; 73:1345.
  37. Hruska KA, Mathew S, Lund RJ, et al. The pathogenesis of vascular calcification in the chronic kidney disease mineral bone disorder: the links between bone and the vasculature. Semin Nephrol 2009; 29:156.
  38. 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.
  39. Thompson B, Towler DA. Arterial calcification and bone physiology: role of the bone-vascular axis. Nat Rev Endocrinol 2012; 8:529.
  40. Tomiyama C, Carvalho AB, Higa A, et al. Coronary calcification is associated with lower bone formation rate in CKD patients not yet in dialysis treatment. J Bone Miner Res 2010; 25:499.
  41. Levin A, Bakris GL, Molitch M, et al. 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 2007; 71:31.
  42. Gal-Moscovici A, Popovtzer MM. New worldwide trends in presentation of renal osteodystrophy and its relationship to parathyroid hormone levels. Clin Nephrol 2005; 63:284.
  43. 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.
  44. Coen G, Bonucci E, Ballanti P, et al. PTH 1-84 and PTH "7-84" in the noninvasive diagnosis of renal bone disease. Am J Kidney Dis 2002; 40:348.
  45. Coen G, Ballanti P, Bonucci E, et al. Renal osteodystrophy in predialysis and hemodialysis patients: comparison of histologic patterns and diagnostic predictivity of intact PTH. Nephron 2002; 91:103.
  46. Miller PD. Unrecognized and unappreciated secondary causes of osteoporosis. Endocrinol Metab Clin North Am 2012; 41:613.
  47. Civitelli R, Armamento-Villareal R, Napoli N. Bone turnover markers: understanding their value in clinical trials and clinical practice. Osteoporos Int 2009; 20:843.
  48. Miller PD, Shane E. Management of transplantation renal bone disease: Interplay of bone mineral density and decisions regarding bisphosphonate use. In: Medical Management of Kidney Transplantation, Weir MR (Ed), Lippincott Williams & Wilkins, Philadelphia 2004. p.359.
  49. Baim S, Miller PD. Assessing the clinical utility of serum CTX in postmenopausal osteoporosis and its use in predicting risk of osteonecrosis of the jaw. J Bone Miner Res 2009; 24:561.
  50. Bauer D, Krege J, Lane N, et al. National Bone Health Alliance Bone Turnover Marker Project: current practices and the need for US harmonization, standardization, and common reference ranges. Osteoporos Int 2012; 23:2425.
  51. Vasikaran S, Eastell R, Bruyère O, et al. Markers of bone turnover for the prediction of fracture risk and monitoring of osteoporosis treatment: a need for international reference standards. Osteoporos Int 2011; 22:391.
  52. Leeming DJ, Alexandersen P, Karsdal MA, et al. An update on biomarkers of bone turnover and their utility in biomedical research and clinical practice. Eur J Clin Pharmacol 2006; 62:781.
  53. Garrett G, Sardiwal S, Lamb EJ, Goldsmith DJ. PTH--a particularly tricky hormone: why measure it at all in kidney patients? Clin J Am Soc Nephrol 2013; 8:299.
  54. Delanaye P, Souberbielle JC, Lafage-Proust MH, et al. Can we use circulating biomarkers to monitor bone turnover in CKD haemodialysis patients? Hypotheses and facts. Nephrol Dial Transplant 2014; 29:997.
  55. Miller PD. The role of bone biopsy in patients with chronic renal failure. Clin J Am Soc Nephrol 2008; 3 Suppl 3:S140.
  56. Miller PD. Renal bone diseases. In: Atlas of Metabolic Bone Diseases, 3rd, Orwoll E (Ed), Springer, New York 2008. p.135.
  57. Malluche HH, Mawad HW, Monier-Faugere MC. Renal osteodystrophy in the first decade of the new millennium: analysis of 630 bone biopsies in black and white patients. J Bone Miner Res 2011; 26:1368.
  58. Lang T, Streeper T, Cawthon P, et al. Sarcopenia: etiology, clinical consequences, intervention, and assessment. Osteoporos Int 2010; 21:543.
  59. Cruz-Jentoft AJ, Baeyens JP, Bauer JM, et al. Sarcopenia: European consensus on definition and diagnosis: Report of the European Working Group on Sarcopenia in Older People. Age Ageing 2010; 39:412.
  60. Murad MH, Elamin KB, Abu Elnour NO, et al. Clinical review: The effect of vitamin D on falls: a systematic review and meta-analysis. J Clin Endocrinol Metab 2011; 96:2997.
  61. West SL, Swan VJ, Jamal SA. Effects of calcium on cardiovascular events in patients with kidney disease and in a healthy population. Clin J Am Soc Nephrol 2010; 5 Suppl 1:S41.
  62. Jamal SA, Moe SM. Calcium builds strong bones, and more is better--correct? Well, maybe not. Clin J Am Soc Nephrol 2012; 7:1877.
  63. Rossouw JE, Anderson GL, Prentice RL, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial. JAMA 2002; 288:321.
  64. Anderson GL, Limacher M, Assaf AR, et al. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women's Health Initiative randomized controlled trial. JAMA 2004; 291:1701.
  65. 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.
  66. 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.
  67. Shih AW, Weir MA, Clemens KK, et al. Oral bisphosphonate use in the elderly is not associated with acute kidney injury. Kidney Int 2012; 82:903.
  68. KDIGO Clinical Practice Guideline for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD). Chapter 4.1: Treatment of CKD-MBD targeted at lowering high serum phosphorus and maintaining serum calcium. http://www.kdigo.org/guidelines/mbd/guide4.html#chap43 (Accessed on January 16, 2013).
  69. Jamal SA, West SL, Miller PD. Bone and kidney disease: diagnostic and therapeutic implications. Curr Rheumatol Rep 2012; 14:217.
  70. Block GA, Bone HG, Fang L, et al. A single-dose study of denosumab in patients with various degrees of renal impairment. J Bone Miner Res 2012; 27:1471.
  71. Miller PD. The kidney and bisphosphonates. Bone 2011; 49:77.
  72. Hartle JE, Tang X, Kirchner HL, et al. Bisphosphonate therapy, death, and cardiovascular events among female patients with CKD: a retrospective cohort study. Am J Kidney Dis 2012; 59:636.
  73. Miller PD. Fragility fractures in chronic kidney disease: an opinion-based approach. Cleve Clin J Med 2009; 76:715.
  74. Miller PD. Is there a role for bisphosphonates in chronic kidney disease? Semin Dial 2007; 20:186.
  75. Miller PD. A review of the efficacy and safety of denosumab in postmenopausal women with osteoporosis. Ther Adv Musculoskelet Dis 2011; 3:271.
  76. McCormick BB, Davis J, Burns KD. Severe hypocalcemia following denosumab injection in a hemodialysis patient. Am J Kidney Dis 2012; 60:626.
  77. Dalle Carbonare L, Zanatta M, Gasparetto A, Valenti MT. Safety and tolerability of zoledronic acid and other bisphosphonates in osteoporosis management. Drug Healthc Patient Saf 2010; 2:121.
  78. Recker RR, Lewiecki EM, Miller PD, Reiffel J. Safety of bisphosphonates in the treatment of osteoporosis. Am J Med 2009; 122:S22.
  79. Klawansky S, Komaroff E, Cavanaugh PF Jr, et al. Relationship between age, renal function and bone mineral density in the US population. Osteoporos Int 2003; 14:570.
  80. Coresh J, Selvin E, Stevens LA, et al. Prevalence of chronic kidney disease in the United States. JAMA 2007; 298:2038.
  81. Black DM, Delmas PD, Eastell R, et al. Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N Engl J Med 2007; 356:1809.
  82. Miller PD, Jamal SA, Evenepoel P, et al. Renal safety in patients treated with bisphosphonates for osteoporosis: a review. J Bone Miner Res 2013; 28:2049.
  83. US Food and Drug Administration. FDA Drug Safety Communication: New contraindication and updated warning on kidney impairment for Reclast (zoledronic acid). http://www.fda.gov/Drugs/DrugSafety/ucm270199.htm (Accessed on September 25, 2012).
  84. Miller PD, Ragi-Eis S, Mautalen C, et al. Effects of intravenous ibandronate injection on renal function in women with postmenopausal osteoporosis at high risk for renal disease--the DIVINE study. Bone 2011; 49:1317.
  85. Cummings SR, San Martin J, McClung MR, et al. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med 2009; 361:756.
  86. 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.
  87. Miller PD, Schwartz EN, Chen P, et al. Teriparatide in postmenopausal women with osteoporosis and mild or moderate renal impairment. Osteoporos Int 2007; 18:59.
  88. Palcu P, Dion N, Ste-Marie LG, et al. Teriparatide and bone turnover and formation in a hemodialysis patient with low-turnover bone disease: a case report. Am J Kidney Dis 2015; 65:933.
  89. Cejka D, Jäger-Lansky A, Kieweg H, et al. Sclerostin serum levels correlate positively with bone mineral density and microarchitecture in haemodialysis patients. Nephrol Dial Transplant 2012; 27:226.
  90. Cejka D, Herberth J, Branscum AJ, et al. Sclerostin and Dickkopf-1 in renal osteodystrophy. Clin J Am Soc Nephrol 2011; 6:877.
  91. Ishani A, Blackwell T, Jamal SA, et al. The effect of raloxifene treatment in postmenopausal women with CKD. J Am Soc Nephrol 2008; 19:1430.
  92. Hochberg MC, Greenspan S, Wasnich RD, et al. Changes in bone density and turnover explain the reductions in incidence of nonvertebral fractures that occur during treatment with antiresorptive agents. J Clin Endocrinol Metab 2002; 87:1586.
  93. Jacques RM, Boonen S, Cosman F, et al. Relationship of changes in total hip bone mineral density to vertebral and nonvertebral fracture risk in women with postmenopausal osteoporosis treated with once-yearly zoledronic acid 5 mg: the HORIZON-Pivotal Fracture Trial (PFT). J Bone Miner Res 2012; 27:1627.
  94. Eastell R, Hannon RA. Biomarkers of bone health and osteoporosis risk. Proc Nutr Soc 2008; 67:157.
  95. Miller PD. Bone strength and surrogate markers: the first, second, and third fiddle. J Bone Miner Res 2012; 27:1623.