Long-term fracture risk following renal transplantation: a population-based study


Abnormal bone metabolism is a recognized complication of end-stage renal disease, but fracture risk following renal transplantation has not been well quantified. We followed the 86 Olmsted County, Minnesota, residents who underwent initial renal transplantation in 1965–1995 for 911 person-years (median, 10.6 years per subject) in a retrospective cohort study. Fractures, and possible risk factors, were assessed through review of each subject’s complete community medical records. Altogether, 117 fractures were observed during follow-up extending to 33 years. The cumulative incidence of any fracture at 15 years was 60% versus 20% expected (P<0.001). There was a significantly increased risk of fractures generally [standardized incidence ratio (SIR), 4.8; 95% CI, 3.6–6.4] and vertebral (SIR, 23.1; 95% CI, 12.3–39.6) and foot fractures (SIR, 8.4; 95% CI, 5.1–12.9) especially. Age at first transplantation, renal failure due to diabetes, pancreas transplantation, peripheral neuropathy, peripheral vascular disease and blindness were all associated with overall fracture risk. In a multivariate analysis, however, only age and diabetic nephropathy were independent predictors of fracture risk generally, while higher activity status was protective. Diabetes was the only independent predictor of lower limb fractures, whereas age and osteoporosis history predicted vertebral fractures. Cumulative corticosteroid dosage was not associated with increased fracture risk in this analysis. Despite the fact that our patients had few risk factors for preexisting bone disease attendant to postmenopausal osteoporosis, prior corticosteroid use or renal osteodystrophy, these data indicate that renal transplantation is associated with a significant increase in fracture risk among unselected patients in the community. Diabetic patients, particularly, experience excess lower limb fractures. Patients and their care providers should be aware of this elevated fracture risk, which continues long-term.

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  1. 1.

    US Renal Data System (2000) USRDS 2000 Annual Data Report. National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Md.

  2. 2.

    Pascual M, Theruvath T, Kawai T, Tolkoff-Rubin N, Cosimi AB (2002) Strategies to improve long-term outcomes after renal transplantation. N Engl J Med 346:580–590

    Article  PubMed  Google Scholar 

  3. 3.

    Hariharan S, Johnson CP, Bresnahan BA, Taranto SE, McIntosh MJ, Stablein D (2000) Improved graft survival after renal transplantation in the United States, 1988 to 1996. N Engl J Med 342:605–612

    CAS  PubMed  Google Scholar 

  4. 4.

    Gonzalez EA, Martin KJ (2001) Renal osteodystrophy. Rev Endocr Metab Disord 2:187–193

    Article  CAS  PubMed  Google Scholar 

  5. 5.

    Elder G (2002) Pathophysiology and recent advances in the management of renal osteodystrophy. J Bone Miner Res 17:2094–2105

    CAS  PubMed  Google Scholar 

  6. 6.

    Julian BA, Laskow DA, Dubovsky J, Dubovsky EV, Curtis JJ, Quarles LD (1991) Rapid loss of vertebral mineral density after renal transplantation. N Engl J Med 325:544–550

    CAS  PubMed  Google Scholar 

  7. 7.

    Kwan JT, Almond MK, Evans K, Cunningham J (1992) Changes in total body bone mineral content and regional bone mineral density in renal patients following renal transplantation. Miner Electrolyte Metab 18:166–168

    Google Scholar 

  8. 8.

    Almond MK, Kwan JTC, Evans K, Cunningham J (1994) Loss of regional bone mineral density in the first 12 months following renal transplantation. Nephron 66:52–57

    CAS  PubMed  Google Scholar 

  9. 9.

    Horber FF, Casez JP, Steiger U, Czerniak A, Montandon A, Jaeger P (1994) Changes in bone mass early after kidney transplantation. J Bone Miner Res 9:1–9

    CAS  PubMed  Google Scholar 

  10. 10.

    Grotz WH, Mundinger FA, Rasenack J et al. (1995) Bone loss after kidney transplantation: a longitudinal study in 115 graft recipients. Nephrol Dial Transplant 10:2096–100

    CAS  PubMed  Google Scholar 

  11. 11.

    Torregrosa J-V, Campistol J-M, Montesinos M et al. (1995) Factors involved in the loss of bone mineral density after renal transplantation. Transplant Proc 27:2224–2225

    CAS  PubMed  Google Scholar 

  12. 12.

    Aroldi A, Tarantino A, Montagnino G, Cesana B, Cocucci C, Ponticelli C (1997) Effects of three immunosuppressive regimens on vertebral bone density in renal transplant recipients: a prospective study. Transplantation 63:380–386

    CAS  PubMed  Google Scholar 

  13. 13.

    Kušec V, Šmalcelj R, Cvijetiae S, Rožman B, Škreb F (2000) Determinants of reduced bone density and increased bone turnover after kidney transplantation: cross-sectional study. Croat Med J 41:396–400

    PubMed  Google Scholar 

  14. 14.

    Giannini S, D’Angelo A, Carraro G et al. (2001) Alendronate prevents further bone loss in renal transplant recipients. J Bone Miner Res 16:2111–2117

    CAS  PubMed  Google Scholar 

  15. 15.

    Kovač D, Lindič J, Kandus A, Bren FA (2003) Quantitative ultrasound of the calcaneus and dual X-ray absorptiometry of the lumbar spine in assessment and follow-up of skeletal status in patients after kidney transplantation. Osteoporos Int 14:166–170

    PubMed  Google Scholar 

  16. 16.

    Abbott KC, Oglesby RJ, Hypolite IO et al. (2001) Hospitalizations for fractures after renal transplantation in the United States. Ann Epidemiol 1:450–457

    Article  Google Scholar 

  17. 17.

    Patel S, Kwan JT, McCloskey E et al. (2001) Prevalence and causes of low bone density and fractures in kidney transplant patients. J Bone Miner Res 16:1863–1870

    CAS  PubMed  Google Scholar 

  18. 18.

    Wolpaw T, Deal CL, Fleming-Brooks S, Bartucci MR, Schulak JA, Hricik DE (1994) Factors influencing vertebral bone density after renal transplantation. Transplantation 58:1186–1189

    CAS  PubMed  Google Scholar 

  19. 19.

    Bagni B, Gilli P, Cavallini A et al. (1994) Continuing loss of vertebral mineral density in renal transplant recipients. Eur J Nucl Med 21:108–112

    CAS  PubMed  Google Scholar 

  20. 20.

    Grotz WH, Mundinger FA, Gugel B, Exner V, Kirste G, Schollmeyer PJ (1994) Bone fracture and osteodensitometry with dual energy X-ray absorptiometry in kidney transplant recipients. Transplantation 58:912–915

    CAS  PubMed  Google Scholar 

  21. 21.

    Behnke B, Altrogge H, Delling G, Kruse H-P, Müller-Wiefel DE (1996) Bone mineral density in pediatric patients after renal transplantation. Clin Nephrol 46:24–29

    CAS  PubMed  Google Scholar 

  22. 22.

    Pichette V, Bonnardeaux A, Prudhomme L, Gagné M, Cardinal J, Ouimet D (1996) Long-term bone loss in kidney transplant recipients: a cross-sectional and longitudinal study. Am J Kidney Dis 28:105–114

    CAS  PubMed  Google Scholar 

  23. 23.

    Cueto-Manzano AM, Konel S, Hutchison AJ et al. (1999) Bone loss in long-term renal transplantation: histopathology and densitometry analysis. Kidney Int 55:2021–2029

    Article  CAS  PubMed  Google Scholar 

  24. 24.

    Parker CR, Freemont AJ, Blackwell PJ, Grainge MJ, Hosking DJ (1999) Cross-sectional analysis of renal transplantation osteoporosis. J Bone Miner Res 14:1943–1951

    CAS  PubMed  Google Scholar 

  25. 25.

    Caglar M, Adeera L (1999) Factors affecting bone mineral density in renal transplant patients. Ann Nucl Med 13:141–145

    CAS  PubMed  Google Scholar 

  26. 26.

    Cayco AV, Wysolmerski J, Simpson C et al. (2000) Posttransplant bone disease: evidence for a high bone resorption state. Transplantation 70:1722–1728

    CAS  PubMed  Google Scholar 

  27. 27.

    Carlini RG, Rojas E, Weisinger JR et al. (2000) Bone disease in patients with long-term renal transplantation and normal renal function. Am J Kidney Dis 36:160–166

    CAS  PubMed  Google Scholar 

  28. 28.

    Kovač D, Lindič J, Kandus A, Bren AF (2001) Bone mineral density in kidney transplant recipients. Transplant Proc 33:3668–3669

    Article  PubMed  Google Scholar 

  29. 29.

    Giannini S, D’Angelo A, Carraro G et al. (2001) Persistently increased bone turnover and low bone density in long-term survivors to kidney transplantation. Clin Nephrol 56:353–363

    CAS  PubMed  Google Scholar 

  30. 30.

    Tannirandorn P, Epstein S (2000) Drug-induced bone loss. Osteoporos Int 11:637–659

    Article  PubMed  Google Scholar 

  31. 31.

    Shane E, Epstein S (2001) Transplantation osteoporosis. Transplant Rev 15:11–32

    Google Scholar 

  32. 32.

    Melton LJ III, Riggs BL (2003) Epidemiology, classification and history of osteoporosis. In: Hochberg M, Silman A, Smolen J, Weinblatt M, Weisman M (eds) Rheumatology, 3rd edn. Volume 2. Mosby, Edinburg

  33. 33.

    Elmstedt E, Svahn T (1981) Skeletal complications following renal transplantation. Acta Orthop Scand 52:279–286

    CAS  PubMed  Google Scholar 

  34. 34.

    Takeo Y, Tominaga K, Tsuji H, Yoh K, Nakano K (1989) Spontaneous fracture and osteoporosis following renal transplantation. J Jpn Orthop Assoc 63:507–513

    CAS  Google Scholar 

  35. 35.

    Bruce DS, Newell KA, Josephson MA et al. (1996) Long-term outcome of kidney-pancreas transplant recipients with good graft function at one year. Transplantation 62:451–456

    CAS  PubMed  Google Scholar 

  36. 36.

    Smets YFC, van der Pijl J, de Fijter JW, Ringers J, Lemkes HHPJ, Hamdy NAT (1998) Low bone mass and high incidence of fractures after successful simultaneous pancreas-kidney transplantation. Nephrol Dial Transplant 13:1250–1255

    Article  CAS  PubMed  Google Scholar 

  37. 37.

    Chiu MY, Sprague SM, Bruce DS, Woodle ES, Thistlethwaite JR Jr, Josephson MA (1998) Analysis of fracture prevalence in kidney-pancreas allograft recipients. J Am Soc Nephrol 9:677–683

    CAS  PubMed  Google Scholar 

  38. 38.

    Nisbeth U, Lindh E, Ljunghall S, Backman U, Fellström B (1999) Increased fracture rate in diabetes mellitus and females after renal transplantation. Transplantation 67:1218–1222

    CAS  PubMed  Google Scholar 

  39. 39.

    O’Shaughnessy EA, Dahl DC, Smith CL, Kasiske BL (2002) Risk factors for fractures in kidney transplantation. Transplantation 74:362–366

    PubMed  Google Scholar 

  40. 40.

    Griffiths HJ, Ennis JT, Bailey G (1974) Skeletal changes following renal transplantation. Radiology 113:621–626

    CAS  PubMed  Google Scholar 

  41. 41.

    Nielsen HE, Melsen F, Christensen MS (1979) Spontaneous fractures following renal transplantation. Clinical and biochemical aspects, bone mineral content and bone morphometry. Miner Electrolyte Metab 2:323–330

    Google Scholar 

  42. 42.

    Ramsey-Goldman R, Dunn JE, Dunlop DD et al. (1999) Increased risk of fracture in patients receiving solid organ transplants. J Bone Miner Res 14:456–463

    CAS  PubMed  Google Scholar 

  43. 43.

    Ball AM, Gillen DL, Sherrard D et al. (2002) Risk of hip fracture among dialysis and renal transplant recipients. JAMA 288:3014–3018

    Article  PubMed  Google Scholar 

  44. 44.

    Melton LJ III (1996) History of the Rochester Epidemiology Project. Mayo Clin Proc 71:266–274

    PubMed  Google Scholar 

  45. 45.

    Frohnert PP, Sterioff S (1990) Twenty-five years of renal transplantation at Mayo Clinic. Dial Transplant 19:646–655

    Google Scholar 

  46. 46.

    Cooper C, Atkinson, EJ, O’Fallon WM, Melton LJ III (1992) Incidence of clinically diagnosed vertebral fractures: a population-based study in Rochester, Minnesota, 1985–1989. J Bone Miner Res 7:221–227

    CAS  PubMed  Google Scholar 

  47. 47.

    Melton LJ III (1997) The threat to medical records research. N Engl J Med 337:1466–1470

    Article  PubMed  Google Scholar 

  48. 48.

    Melton LJ III, Sampson JM, Morrey BF, Ilstrup DM (1981) Epidemiologic features of pelvic fractures. Clin Orthop 155:43–47

    PubMed  Google Scholar 

  49. 49.

    Rose SH, Melton LJ III, Morrey BF, Ilstrup DM, Riggs BL (1982) Epidemiologic features of humerus fractures. Clin Orthop 168:24–30

    PubMed  Google Scholar 

  50. 50.

    Melton LJ III, Atkinson EJ, Madhok R (1996) Downturn in hip fracture incidence. Public Health Rep 111:146–150

    PubMed  Google Scholar 

  51. 51.

    Melton LJ III, Amadio PC, Crowson CS, O’Fallon WM (1998) Long-term trends in the incidence of distal forearm fractures. Osteoporos Int 8:341–348

    Article  PubMed  Google Scholar 

  52. 52.

    Melton LJ III, Crowson CS, O’Fallon WM (1999) Fracture incidence in Olmsted County, Minnesota: comparison of urban with rural rates and changes in urban rates over time. Osteoporos Int 9:29–37

    Article  PubMed  Google Scholar 

  53. 53.

    Cox DR (1953) Some simple approximate tests for Poisson variates. Biometrika 40:354–60

    Google Scholar 

  54. 54.

    Kaplan EL, Meier P (1958) Non-parametric estimation from incomplete observations. J Am Stat Assoc 53:457–481

    Google Scholar 

  55. 55.

    Kalbfleisch JD, Prentice RL (1980) The statistical analysis of failure time data. Wiley, New York, pp 1–321

  56. 56.

    Cox DR (1972) Regression models and life-tables (with discussion). J R Statist Soc B 34:187–220

    Google Scholar 

  57. 57.

    Alem AM, Sherrard DJ, Gillen DL, et al (2000) Increased risk of hip fracture among patients with end-stage renal disease. Kidney Int 58:396–399

    Article  CAS  PubMed  Google Scholar 

  58. 58.

    Tzamaloukas AH (1990) Diagnosis and management of bone disorders in chronic renal failure and dialyzed patients. Med Clin N Am 74:961–974

    CAS  PubMed  Google Scholar 

  59. 59.

    Bouillon R (1991) Diabetic bone disease. Calcif Tissue Int 49:155–160

    CAS  PubMed  Google Scholar 

  60. 60.

    Piepkorn B, Kann P, Forst T, Adreas J, Pfützner A, Beyer J (1997) Bone mineral density and bone metabolism in diabetes mellitus. Horm Metab Res 29:584–591

    CAS  PubMed  Google Scholar 

  61. 61.

    Forsén L, Meyer HE, Midthjell K, Edna T-H (1999) Diabetes mellitus and the incidence of hip fracture: results from the Nord-Trøndelag Health Survey. Diabetologia 42:920–925

    Google Scholar 

  62. 62.

    Nicodemus KK, Folsom AR (2001) Iowa Women’s Health Study. Type 1 and type 2 diabetes and incident hip fractures in postmenopausal women. Diabetes Care 24:1192–1197

    CAS  PubMed  Google Scholar 

  63. 63.

    Schwartz AV, Sellmeyer DE, Ensrud KE et al. (2001) Older women with diabetes have an increased risk of fracture: a prospective study. Study of Osteoporotic Fractures Research Group. J Clin Endocrinol Metab 86:32–38

    Google Scholar 

  64. 64.

    Heath H III, Melton LJ III, Chu C-P (1980) Diabetes mellitus and risk of skeletal fracture. N Engl J Med 303:567–570

    Google Scholar 

  65. 65.

    Melchior TM, Sørensen H, Torp-Pedersen C (1994) Hip and distal arm fracture rates in peri- and postmenopausal insulin-treated diabetic females. J Intern Med 236:203–208

    CAS  Google Scholar 

  66. 66.

    Ivers RQ, Cumming RG, Mitchell P, Peduto AJ (2001) Diabetes and risk of fracture: the Blue Mountains Eye Study. Diabetes Care 24:1198–203

    CAS  PubMed  Google Scholar 

  67. 67.

    Seeley DG, Kelsey J, Jergas M, Nevitt MC (1996) Predictors of ankle and foot fractures in older women. The Study of Osteoporotic Fractures Research Group. J Bone Miner Res 11:1347–1355

    CAS  PubMed  Google Scholar 

  68. 68.

    Kalker AJ, Pirsch JD, Heisey D et al. (1996) Foot problems in the diabetic transplant recipient. Clin Transplant 10:503–510

    CAS  PubMed  Google Scholar 

  69. 69.

    Andress DL, Hercz G, Kopp JB et al. (1987) Bone histomorphometry of renal osteodystrophy in diabetic patients. J Bone Miner Res 2:525–631

    CAS  PubMed  Google Scholar 

  70. 70.

    Julian BA, Quarles LD, Niemann KMW (1992) Musculoskeletal complications after renal transplantation: pathogenesis and treatment. Am J Kidney Dis 19:99–120

    CAS  PubMed  Google Scholar 

  71. 71.

    Pei Y, Hercz G, Greenwood C et al. (1993) Renal osteodystrophy in diabetic patients. Kidney Int 44:159–164

    CAS  PubMed  Google Scholar 

  72. 72.

    Inaba M, Nagasue K, Okuno S et al. (2002) Impaired secretion of parathyroid hormone, but not refractoriness of osteoblast, is a major mechanism of low bone turnover in hemodialyzed patients with diabetes mellitus. Am J Kidney Dis 39:1261–1269

    Article  CAS  PubMed  Google Scholar 

  73. 73.

    Coco M, Rush H (2000) Increased incidence of hip fractures in dialysis patients with low serum parathyroid hormone. Am J Kidney Dis 36:1115–1121

    CAS  PubMed  Google Scholar 

  74. 74.

    Epstein S, Shane E, Bilezikian JP (1995) Organ transplantation and osteoporosis. Curr Opin Rheumatol 7:255–261

    CAS  PubMed  Google Scholar 

  75. 75.

    Torres A, Lorenzo V, Salido E (2002) Calcium metabolism and skeletal problems after transplantation. J Am Soc Nephrol 13:551–558

    PubMed  Google Scholar 

  76. 76.

    Monier-Faugere MC, Mawad H, Qi Q, Friedler RM, Malluche HH (2000) High prevalence of low bone turnover and occurrence of osteomalacia after kidney transplantation. J Am Soc Nephrol 11:1093–1099

    CAS  PubMed  Google Scholar 

  77. 77.

    Coen G (1996) Fracturing osteoporosis after kidney transplantation—what are the options? Nephrol Dial Transplant 11:567–569

    CAS  PubMed  Google Scholar 

  78. 78.

    Fan SL, Almond MK, Ball E, Evans K, Cunningham J (2000) Pamidronate therapy as prevention of bone loss following renal transplantation. Kidney Int 57:684–690

    Article  CAS  PubMed  Google Scholar 

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This project was supported in part by grants AG-04875 and AR-30582 from the National Institutes of Health, US Public Health Service. The authors would like to thank Mrs. Cindy Crowson for assistance with data analysis and Mrs. Mary Roberts for help in preparing the manuscript.

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Correspondence to L. Joseph Melton III.

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Presented at the 24th Annual Meeting of the American Society of Bone and Mineral Research in San Antonio, Tex., USA.

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Vautour, L.M., Melton, L.J., Clarke, B.L. et al. Long-term fracture risk following renal transplantation: a population-based study. Osteoporos Int 15, 160–167 (2004). https://doi.org/10.1007/s00198-003-1532-y

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  • Diabetes mellitus
  • Epidemiology
  • Fracture
  • Osteoporosis
  • Renal transplantation