Current Rheumatology Reports

, Volume 7, Issue 1, pp 53–60 | Cite as

Treatment of metabolic bone disease in patients with chronic renal disease: A perspective for rheumatologists

  • Paul D. Miller
Article

Abstract

As glomerular filtration rate (GFR) declines from age-related bone loss or disease that specifically induces a decline in GFR, there are a number of metabolic bone conditions that may accompany the decline in GFR. These metabolic bone conditions span a spectrum from mild-to-severe secondary hyperparathyroidism in early stages of chronic kidney disease (CKD) to the development of additional heterogeneous forms of bone diseases each with distinctly quantitative bone histomorphometric characteristics. Osteoporosis can also develop in patients with CKD and end-stage renal disease (ESRD) for many reasons beyond age-related bone loss and postmenopausal (PMO) bone loss. Diagnosing osteoporosis in patients with severe CKD or ESRD is not as easy to do as it is in patients with PMO. The diagnosis of osteoporosis in patients with CKD/ESRD must be done by first excluding other forms of renal osteodystrophy, through biochemical profiling or by double tetracycline-labeled bone biopsy and the finding of low trabecular bone volume. In such patients oral bisphosphonates seem to be safe and effective down to GFR levels of 15 mL/min. In patients with stage 5 CKD, who are fracturing because of osteoporosis or who are on chronic glucocorticoids, reducing the oral bisphosphonate dosage to half of its usual prescribed dosing for PMO seems reasonable from known bisphosphonate pharmacokinetics. However, we need better scientific data to fully understand bisphosphonate usage in this population. This paper deals with the evidence available to understand management of patients with CKD and opinions on what might be a reasonable clinical approach where evidence is currently lacking.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References and Recommended Reading

  1. 1.
    Massry SG, Coburn JW: K/DOQI clinical practice guidelines for bone metabolism and disease in chronic kidney disease. Am J Kid Dis 2003, 42(Suppl 3):S10-S135. This is a comprehensive evidence-based or opinion-based guideline development on the assessment and management of bone metabolism in patients with CKD.Google Scholar
  2. 2.
    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, 14:570–576.PubMedCrossRefGoogle Scholar
  3. 3.
    Skagg KG, Emky R, Schnitzer TJ, et al.: Alendronate for the prevention of steroid-induced osteoporosis. New Engl J Med 1998, 339:292–299.CrossRefGoogle Scholar
  4. 4.
    Cohn S, Levy RM, Keller M, et al.: Risedronate therapy prevents corticosteroid-induced bone loss. Arthritis Rheum 1999, 42:2309–2318.CrossRefGoogle Scholar
  5. 5.
    Miller PD: Bisphosphonates for the prevention and treatment of corticoisteroid-induced osteoporosis. Osteoporos Int 2001, 3:S3-S10.CrossRefGoogle Scholar
  6. 6.
    Van Staa TP, Leufkens HG, Abenhaim L, et al.: Use of oral corticosteroids and risk of fractures. J Bone Miner Res 2000, 15:993–1000.PubMedCrossRefGoogle Scholar
  7. 7.
    Lindeman RD: Assessment of renal function in the old. Special considerations. Clin Lab Med 1993, 13:269–277.PubMedGoogle Scholar
  8. 8.
    Ishida K, Ishida H, Narita M, et al.: Factors affecting renal function in 119,985 adults over three years. QJM 2001, 94:541–550.PubMedCrossRefGoogle Scholar
  9. 9.
    Miller PD, Shane E: Management of transplantation renal bone disease: interplay of bone mineral density and decisions regarding bisphosphonate use. In Management of Renal Transplantation. Edited by Weir M. Burlington: Academic Press; 359–375. This chapter discusses the difficulties in the diagnosis of osteoporosis in ESRD along with post-renal transplantation. In addition, the chapter discusses the issues surrounding bisphosphonate use in these populations.Google Scholar
  10. 10.
    WHO Study Group: Assessment of fracture risk and its application to screening for postmenopausal osteoporosis. World Health Organization, Geneva Switzerland; 1994.Google Scholar
  11. 11.
    Elder G: Pathophysiology and recent advances in the management of renal osteodystrophy. J Bone Miner Res 2002, 17:2094–2105. This paper by Professor Elder is the most comprehensive and accurate discussion of all of the recent data surrounding the pros and cons of biochemical marker profiling to discriminate between the various forms of renal bone disease versus osteoporosis. This paper is a must for all interested professionals.PubMedCrossRefGoogle Scholar
  12. 12.
    Ritz E, Schomig M, Bommer J: Osteodystrophy in the millennium. Kidney Int 1999, 56(Suppl 73):S94-S98.CrossRefGoogle Scholar
  13. 13.
    Gerakis A, Hutchison AJ, Apostolou T, et al.: Biochemical markers for non-invasive diagnosis of hyperparathyroid bone disease and adynamic bone in patients on haemodialysis. Nephrol Dial Transplant 1996, 11:2430–2438.PubMedGoogle Scholar
  14. 14.
    Malluche HH, Langub MC, Monier-Fuagere MC: The role of bone biopsy in clinical practice and research. Kidney Int 1999, 73(Suppl 1):S20-S25.CrossRefGoogle Scholar
  15. 15.
    Pecovink BB, Bren A: Bone histomorphometry is still the gold standard for diagnosing renal osteodystrophy. Clin Nephrol 2000, 54:463–469.Google Scholar
  16. 16.
    Ferreria 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):8–14.CrossRefGoogle Scholar
  17. 17.
    Monier-Faugere MC, Geng C, 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, 60:1460–1468. This is a pivotal study that suggests that the ratio of the anabolic 1–84 PTH to the catabolic 7–84 PTH may be predictive of adynamic bone disease.PubMedCrossRefGoogle Scholar
  18. 18.
    Miller PD, Lerma E: Renal bone diseases. In The Bone and Mineral Manual. Edited by Kleerekoper M, McClung M, Siris E. Burlington: Academic Press; 2004.Google Scholar
  19. 19.
    Salusky IB, Goodman WG: Reversible and non-reversible causes of adynamic renal bone disease. J Am Soc Nephrol 2001, 12:1878–1895.Google Scholar
  20. 20.
    Armas LAG, Hollis BW, Heaney RP: Vitamin D2 is much less effective than vitamin D3 in Humans. J Clin Endocrinol Metab 2004, 89:5387–5391.PubMedCrossRefGoogle Scholar
  21. 21.
    Russell RG, Rogers MJ: Bisphosphonates: from the laboratory to the clinic and back again. Bone 1999, 25:97–106.PubMedCrossRefGoogle Scholar
  22. 22.
    Troehler U, Bonjour JP, Fleisch H: Renal secretion of diphosphonates in rats. Kidney Int 1975, 8:6–13.PubMedGoogle Scholar
  23. 23.
    Food and Drug Administration, U.S. Department of Health and Human Services 1998 Guidance for industry: Pharmacokinetics in patients with impaired renal function—study design, data analysis, and impact on dosing and labeling. http://www.fda.gov/ cder/guidance/1449fnl.pdf. Accessed October 5, 2004.Google Scholar
  24. 24.
    Lin JH: Bisphosphonates: a review of their pharmacokinetic properties. Bone 1996, 18:75–85.PubMedCrossRefGoogle Scholar
  25. 25.
    Black DM, Cummings SR, Karpf DB, et al.: Randomized trial of effect of alendronate on risk of fracture in women with existing vertebral fractures. Lancet 1996, 348:1535–1541.PubMedCrossRefGoogle Scholar
  26. 26.
    Harris S, Watts N, Genant H, et al.: Effects of risedronate treatment on vertebral and nonvertebral fractures in women with postmenopausal osteoporosis. A randomized controlled trial. JAMA 1999, 282:1344–1352.PubMedCrossRefGoogle Scholar
  27. 27.
    Reginster J-Y, Minne H, Sorensen OH, et al.: Randomized trial of the effects of risedronate on vertebral fractures in women with established postmenopausal osteoporosis. Osteoporos Int 2000, 11:83–91.PubMedCrossRefGoogle Scholar
  28. 28.
    McClung MR, Geusens P, Miller PD, et al.: Effect of risedronate on the risk of hip fracture in elderly women. N Engl J Med 2001, 344:333–340.PubMedCrossRefGoogle Scholar
  29. 29.
    Sorensen OH, Crawford GM, Mulder H, et al.: Long-term efficacy of risedronate: a 5-year placebo-controlled clinical experience. Bone 2003, 32:120–126.PubMedCrossRefGoogle Scholar
  30. 30.
    Schnitzer T, Bone HG, Crepaldi G, et al.: Two year results of once-weekly administration of alendronate 70 mg for the treatment of postmenopausal osteoporosis. J Bone Miner Res 2002, 17:1988–1996.PubMedCrossRefGoogle Scholar
  31. 31.
    Brown J, Kendler D, McClung M, et al.: The efficacy and tolerability of once-a-week risedronate in the teatment of postemopasual osteoporosis. Calcif Tissue Int 2002, 71:103–111.PubMedCrossRefGoogle Scholar
  32. 32.
    Miller PD, Roux C, Boonen S, et al.: Safety and efficacy of oral risedronate in patients with reduced renal function as assessed by the Cockcroft-Gault method: a pooled analysis from 9 clinical trials. Osteoporos Int 2004, In press. This is the first study showing that oral bisphosphonates in registered doses for PMO and GIOP are safe, do not induce any progression of GFR declines, and are effective to reduce fractures in patients with PMO and GIOP down to GFR of 15 mL/min.Google Scholar
  33. 33.
    Miller PD: Efficacy and safety of long-term bisphosphonates in postmenopausal osteoporosis. Expert Opin Pharmacother 2003, 4:2253–2258.PubMedCrossRefGoogle Scholar
  34. 34.
    Glorieux FH, Bishop NJ, Plotkin H, et al.: Cyclic administration of pamidronate in children with severe osteogenesis imperfecta. N Engl J Med 1998, 339:947–952.PubMedCrossRefGoogle Scholar
  35. 35.
    Bounameaux HM, Schifferli J, Montani JP, et al.: Renal failure associated with the use of intravenous disphosphonates. Lancet 1983, 1:471.PubMedCrossRefGoogle Scholar
  36. 36.
    Chang JT, Green L, Beitz J: Renal failure associated with the use of zolendronic acid. N Engl J Med 2003, 349:1676–1679.PubMedCrossRefGoogle Scholar
  37. 37.
    Markowitz GS, Fine PL, Stack JL, et al.: Toxic acute tubular necrosis following treatment with zolendronic acid (zometa). Kidney Int 2003, 64:281–289.PubMedCrossRefGoogle Scholar
  38. 38.
    Miller PD, Brown JP, Stefan JJ, et al.: Intermittment intraveous ibandronate injections: renal safety profile. Osteoporos Int 2004, In press.Google Scholar

Copyright information

© Current Science Inc 2005

Authors and Affiliations

  • Paul D. Miller
    • 1
  1. 1.Colorado Center for Bone ResearchLakewoodUSA

Personalised recommendations