Advertisement

Osteoporosis International

, Volume 16, Issue 12, pp 1683–1690 | Cite as

In elderly men and women treated for osteoporosis a low creatinine clearance of <65 ml/min is a risk factor for falls and fractures

  • Laurent Dukas
  • Erich Schacht
  • Hannes B. Stähelin
Original Article

Abstract

Recently, a low creatinine clearance (CrCl) of <65 ml/min was described as a new significant and independent risk factor for the number of fallers and falls in a community-dwelling elderly population. In this study we investigated if a low creatinine clearance of <65 ml/min is also a risk factor for falls and fractures in elderly men and women treated for osteoporosis. In a cross-sectional study with the help of questionnaires we assessed the prevalence of having experienced falls within the last 12 months according to renal function in 5,313 German men and women receiving treatment for osteoporosis. The CrCl was calculated using the established Cockcroft-Gault formula. The prevalence of falls and fractures was assessed in multivariate-controlled logistic regression models according to a CrCl cut off of 65 ml/min. The P -values were two-sided. In this study of elderly men and women treated for osteoporosis ( n =5,313), 60.9% ( n =3,238) had a CrCl of <65 ml/min, which was associated in multivariate controlled analyses, compared to a CrCl of ≥65 ml/min ( n =2,075), with a significant increased risk of experiencing falls (1,775/3,238 vs. 773/2,075, OR 1.69, 95% CI 1.50–1.91, P <0.0001) and an increased risk for multiple falls (37.1 vs. 22.6%, OR 1.63, 95% CI 1.42–1.87, P <0.0001). Furthermore, compared to a creatinine clearance of ≥65 ml/min, a creatinine clearance of <65 ml/min was also associated with a significant increased multivariate controlled risk for hip fractures (OR 1.57, 95%CI 1.18–2.09, P =0.002), for radial fractures (OR 1.79, 95%CI 1.39–2.31, P =<0.0001), for total vertebral fractures (OR 1.31, 95%CI 1.19–1.55, P =0.003) and for fall-associated vertebral fractures (OR 1.24, 95% CI 1.03–1.54, P =0.031). Similar to community-dwelling elderly, in elderly men and women treated for osteoporosis a CrCl of less than 65 ml/min is a significant and independent risk factor for falls. Furthermore, we could show for the first time that a low creatinine clearance in elderly men and women treated for osteoporosis is also associated with a significantly increased risk of vertebral, hip and radial fractures.

Keywords

Creatinine clearance Osteoporosis treatment Falls Fractures 

Notes

Acknowledgements

The study was supported by GRY Pharma GmbH, Germany.

References

  1. 1.
    Dukas L, Schacht E, Mazor Z, Stähelin HB (2005) A new significant and independent risk factor for falls in elderly men and women: A low creatinine clearance of less than 65 ml/min. Osteoporos Int 16:392–398Google Scholar
  2. 2.
    Dukas L, Schacht E, Mazor Z, Stähelin HB (2005) Treatment with alfacalcidol in elderly people significantly decreases the high risk of falls associated with low creatinine clearance of <65 ml/min. Osteoporos Int 16:198–203Google Scholar
  3. 3.
    Peacock M, Heyburn P (1977) Effect of vitamin D3 metabolites on proximal muscle weakness. Calcif Tiss Res [Suppl] 24:R20–23Google Scholar
  4. 4.
    Bischoff, HA, Stähelin HB, Urscheler N et al (1999) Muscle strength in the elderly: its relation to vitamin D metabolites. Arch Phys Med Rehabil 80:54–58CrossRefPubMedGoogle Scholar
  5. 5.
    Verhaar HJJ, Samson MM, Jansen PAF et al (2000) Muscle strength, functional mobility and vitamin D in older women. Aging Clin Exp Res 12:455–460Google Scholar
  6. 6.
    Dhesi JK, Bearne LM, Monitz C, Hurley MV, Jackson SHD, Swift CG, Allain TJ (2002) Neuromuscular and psychomotor function in elderly subjects who fall and the relationship with vitamin D status. J Bone Miner Res 17:891–897PubMedGoogle Scholar
  7. 7.
    Koike T, Okawa T, Wada M, Kita T, Takaoka K (2003) Effects of a long-term alfacalcidol or calcitonin administration on body sway in japanese elderly women. J Bone Miner Res 18:S168Google Scholar
  8. 8.
    Dukas L, Schacht E, Bischoff HA (2003) Better functional mobility in community dwelling elderly is related to D-hormone and a minimal calcium intake of more than 512 mg/day. Osteoporos Int 14:S34–35CrossRefGoogle Scholar
  9. 9.
    Sörensen OH, Lund BI, Saltin B, Lund BJ, Andersen RB, Hjorth L, Melson F, Mosekilde F (1979) Myopathy in bone loss of ageing: Improvement by treatment with 1-alpha- hydroxycholecalciferol and calcium. Clin Sci 56:157–161PubMedGoogle Scholar
  10. 10.
    Trombetti A, Stoermann-Chopard C, Ferrari S, Saudan P, Chevalley T, Binet I, Uebelhart B, Rizzoli R, Martin PY (2003) Prävention von Knochenkomplikationen bei Patienten mit chronischer Niereninsuffizienz (1.Teil). Swiss Med Forum 11:260–266Google Scholar
  11. 11.
    Bonjour JP, Rizzoli R, Caverzasio J (1992) Phosphate homeostasis, 1, 25-dihydroxyvitamin-D3, and hyperparathyroidism in early chronic failure. Trends Endocrinol Metab 3:301–305CrossRefGoogle Scholar
  12. 12.
    Reichel H, Deibert B, Schmidt-Gayk H, Ritz E (1991) Calcium metabolism in early chronic renal failure: implications for the pathogenesis of hyperparathyroidism. Nephrol Dial Transplant 6:162–169PubMedGoogle Scholar
  13. 13.
    Martinez I, Saracho R, Montenegro J, Liach F (1997) The importance of dietary calcium and phosporus in the secondary hyperparathyroidism of patients with early renal failure. Am J Kidney Dis 29:496–502PubMedGoogle Scholar
  14. 14.
    Chapuy MC, Preziosi P, Maamer M, Arnaud S, Galan P, Hersberg S, Meunier PJ (1997) Prevalence of vitamin D insufficiency in an adult normal population. Osteoporos Int 7:439–443CrossRefPubMedGoogle Scholar
  15. 15.
    Peacock M, Selby PL, Francis RM, Brown WB, Hordon L (1985) Vitamin D deficiency, insufficiency, sufficiency and intoxication. What do they mean? In: Norman A et al (eds) Sixth workshop on vitamin D. de Gruyter, Berlin, pp 569–570Google Scholar
  16. 16.
    Poor G, Atkinson EJ, O’Fallon WM et al (1995) Predictors of hip fracture in elderly men. J Bone Miner Res 10:1900–1907PubMedGoogle Scholar
  17. 17.
    Nguyen TV, Eisman JA, Kelly PJ et al (1996) Risk factors for osteoporotic fractures in elderly men. Am J Epidemiol 144:255–263PubMedGoogle Scholar
  18. 18.
    Youm T, Koval KJ, Kummer FJ et al (1999) Do all hip fractures result from a fall? Am J Orthop 28:190–194PubMedGoogle Scholar
  19. 19.
    K/DOQI (2003) K/DOQI practice guidelines for bone metabolism and disease in chronic kidney disease. Am J Kidney Dis 42:S7–S28Google Scholar
  20. 20.
    Klawansky S, Komaroff E, Cavanaugh PF, Mitchell DY, Gordon MJ, Connelly JE, Ross SD (2003) The relationship between age, renal function and bone mineral density in the US population. Osteoporos Int 14:570–576CrossRefPubMedGoogle Scholar
  21. 21.
    Cockcroft DW, Gault MH (1976) Prediction of creatinine clearance from serum creatinine. Nephron 16:31–41PubMedGoogle Scholar
  22. 22.
    Winer BJ (1971) Statistical principles in experimental design, 2nd edn. McGraw-Hill, New York, p 14Google Scholar
  23. 23.
    Van Staa TP, Leufkens HGM, Abenhaim A, Zhang B, Cooper C (2000) Use of oral corticosteroids and risk of fractures. J Bone Miner Res 15:993–1000PubMedGoogle Scholar
  24. 24.
    Cohen A, Shane E (2003) Osteoporosis after solid organ and bone marrow transplantation. Osteoporos Int 14:617–630CrossRefPubMedGoogle Scholar
  25. 25.
    Nacher M, Aubia J, Serrano S, Marinoso ML, Hernandez J, Bosch J, Diez A, Puig JM, Lloveras J (1994) Effect of cyclosporine A on normal human osteoblasts in vitro. Bone Miner 26:231–243PubMedGoogle Scholar
  26. 26.
    Pilon D, Castilloux AM, Dorais M, LeLorier J (2004) Oral anticoagulants and the risk of osteoporotic fractures among elderly. Pharmacoepidemiol Drug Saf 13:289–294CrossRefPubMedGoogle Scholar
  27. 27.
    Walsmith J, Abad L, Kehayias J, Roubenoff R (2004) Tumor necrosis factor-α production is associated with less body cell mass in women with rheumatoid arthritis. J Rheumatol 31:23–29PubMedGoogle Scholar
  28. 28.
    Argiles JM, Alvarez B, Carbo N, Busquets S, Van Royen M, Lopez-Soriano FJ (2000) The divergent effects of tumour necrosis factor-alpha on skeletal muscle: implications in wasting. Eur Cytokine Netw 11:552–559PubMedGoogle Scholar
  29. 29.
    Michel BA, Bloch DA, Wolfe F, Fries JF (1993) Fractures in rheumatoid arthritis: an evaluation of associated risk factors. J Rheumatol 20:1666–1669PubMedGoogle Scholar
  30. 30.
    Latham NK, Anderson CS, Lee A, Bennett DA, Moseley A, Cameron ID (2003) A randomized, controlled trial of quadriceps resistance exercise and vitamin D in frail older people: the Frailty Interventions Trial in Elderly Subjects (FITNESS). JAGS 51:291–299CrossRefGoogle Scholar
  31. 31.
    Smith H, Anderson F, Raphael H, Crozier S, Cooper C (2004) Effect of annual intramuscular vitamin D supplementation on fracture risk: population-based, randomised, double-blind, placebo-controlled trial. Osteoporos Int 15 [Suppl 1]:S8Google Scholar
  32. 32.
    Slovik DM, Adams JS, Neer RM et al (1981) Deficient production of 1,25-dihydroxyvitamin D in elderly osteoporotic patients. N Engl J Med 305:372–374PubMedGoogle Scholar
  33. 33.
    Epstein S, Bryce G, Hinman JW et al (1986) The influence of age on bone mineral regulating hormones. Bone 7:421–425CrossRefPubMedGoogle Scholar
  34. 34.
    Tsai KS, Heath H III, Kumar R et al (1984) Impaired vitamin D metabolism with aging in women: a possible role in the pathogenesis of senile osteoporosis. J Clin Invest 73:1668–1672PubMedGoogle Scholar
  35. 35.
    Dukas L, Bischoff HA, Schacht E et al (2002) Normal 25(OH) vitamin D serum levels do not exclude D-hormone deficiency in community-dwelling elderly. Osteoporos Int 13:S35Google Scholar
  36. 36.
    Ebert R, Jovanovic M, Ulmer M, Schneider D, Meißner-Weigl J, Adamski J, Jakob F (2004) Downregulation by nuclear factor κB of human 25-hydroxyvitamin D3 1α-hydroxylase promoter. Mol Endrocrinol 18:2440–2445CrossRefGoogle Scholar
  37. 37.
    Oelzner P, Muller A, Deschner F, Huller M, Abendroth K, Hein G, Stein G (1998) Relationship between disease activity and serum levels of vitamin D metabolites and PTH in rheumatoid arthritis. Calcif Tissue Int 62:193–198CrossRefPubMedGoogle Scholar
  38. 38.
    Gallagher JC, Fowler SE, Detter JR et al (2001) Combination treatment with estrogen and calcitriol in the prevention of age-related bone loss. J Clin Endocrinol Metab 86:3618–3628CrossRefPubMedGoogle Scholar
  39. 39.
    Dukas L, Bischoff HA, Lindpaintner LS, Schacht E, Birkner-Binder D. Thalmann B, Stähelin HB (2004) Alfacalcidol reduces the number of fallers in a community-dwelling elderly population with a minimum calcium intake of 500 mg daily. J Am Ger Soc 52:230–236CrossRefGoogle Scholar
  40. 40.
    Zofkovà I, Kancheva RL, Bendlovà B (1997) Effect of 1, 25(OH)2 Vitamin D3 on circulating insulin-like growth factor-I and β2 microglobulin in patients with osteoporosis. Calcif Tissue Int 60:236–239CrossRefPubMedGoogle Scholar
  41. 41.
    Cappola AR, Xue QL, Ferrucci L, Guralnik JM, Volpato S, Fried LP (2003) Insulin-like growth factor I and interleukin-6 contribute synergistically to disability and mortality in older women. J Clin Endocrinol Metab 88:2019–2025CrossRefPubMedGoogle Scholar
  42. 42.
    Stein MS, Wark JD, Scherer SC, Walton SL, Chick P, Di Carlantonio M, Zajac JD, Flicker L (1999) Falls related to vitamin D and parathyroid hormone in Australian nursing home and hostel. J Am Ger Soc 47:1195–1201Google Scholar
  43. 43.
    Boland R (1986) Role of vitamin D in skeletal muscle function. Endocr Rev 784:434–448Google Scholar
  44. 44.
    Tinetti ME, Williams CS (1998) The effect of falls and fall injuries on functioning in community-dwelling older persons. J Gerontol A Biol Sci Med Sci 53:M112–M119PubMedGoogle Scholar
  45. 45.
    Endo I, Inoue D, Mitsui T, Umaki, Y, Akaike M, Yoshizawa T, Kato S, Matsumoto T (2003) Deletion of vitamin D receptor gene in mice results in abnormal skeletal muscle development with deregulated expression of myoregulatory transcription factors. Endocrinology 144:5138–5144CrossRefPubMedGoogle Scholar
  46. 46.
    Bischoff HA, Borchers M, Gudat F, Duermueller U, Theiler R, Stähelin HB, Dick W (2001) In situ detection of 1,25-dihydroxyvitamin D receptor in human skeletal muscle tissue. Histochemistry 33:19–24CrossRefGoogle Scholar
  47. 47.
    Bischoff-Ferrari HA, Borchers M, Gudat F, Dürmüller U, Stähelin HB, Dick W (2004) Vitamin D receptor expression in human muscle tissue decreases with age. J Bone Miner Res 19:265–269PubMedGoogle Scholar
  48. 48.
    Ringe JD, Schacht E (2004) Prevention and therapy of osteoporosis: the roles of plain vitamin D and alfacalcidol. Rheumat Int 24:189–197Google Scholar
  49. 49.
    Miya K, Morimoto S, Fukuo K, Imanaka S, Shiraishi T, Yamamato H, Kitano S, Miyashita Y, Inoue T, Hirotani J, et al (1991) Cognitive function and calcium related factors in elderly female subjects. Nippon Ronen Igakkai Zasshi 28:34–39PubMedGoogle Scholar
  50. 50.
    Bischoff HA, Stähelin HB, Dick W (2003) Fall prevention by vitamin D and calcium supplementation: a randomized controlled trial. Am J Bone Min Res 18:343–351Google Scholar

Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2005

Authors and Affiliations

  • Laurent Dukas
    • 1
    • 3
  • Erich Schacht
    • 2
  • Hannes B. Stähelin
    • 1
  1. 1.Geriatric University ClinicKantonsspitalBaselSwitzerland
  2. 2.Department of Rheumatology and RehabilitationUniversity Clinic BalgristZurichSwitzerland
  3. 3.Acute Geriatric University Clinic and Ambulatorium WiesendammBaselSwitzerland

Personalised recommendations