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

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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.

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References

  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 16:392–398

    Google Scholar 

  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 16:198–203

  3. Peacock M, Heyburn P (1977) Effect of vitamin D3 metabolites on proximal muscle weakness. Calcif Tiss Res [Suppl] 24:R20–23

  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 80:54–58

    Article  CAS  PubMed  Google Scholar 

  5. Verhaar HJJ, Samson MM, Jansen PAF et al (2000) Muscle strength, functional mobility and vitamin D in older women. Aging Clin Exp Res 12:455–460

    CAS  Google Scholar 

  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 17:891–897

    CAS  PubMed  Google Scholar 

  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:S168

    Google Scholar 

  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:S34–35

    Article  Google Scholar 

  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 56:157–161

    PubMed  Google Scholar 

  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 11:260–266

    Google Scholar 

  11. Bonjour JP, Rizzoli R, Caverzasio J (1992) Phosphate homeostasis, 1, 25-dihydroxyvitamin-D3, and hyperparathyroidism in early chronic failure. Trends Endocrinol Metab 3:301–305

    Article  Google Scholar 

  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 6:162–169

    CAS  PubMed  Google Scholar 

  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 29:496–502

    CAS  PubMed  Google Scholar 

  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 7:439–443

    Article  CAS  PubMed  Google Scholar 

  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 569–570

  16. Poor G, Atkinson EJ, O’Fallon WM et al (1995) Predictors of hip fracture in elderly men. J Bone Miner Res 10:1900–1907

    CAS  PubMed  Google Scholar 

  17. Nguyen TV, Eisman JA, Kelly PJ et al (1996) Risk factors for osteoporotic fractures in elderly men. Am J Epidemiol 144:255–263

    CAS  PubMed  Google Scholar 

  18. Youm T, Koval KJ, Kummer FJ et al (1999) Do all hip fractures result from a fall? Am J Orthop 28:190–194

    CAS  PubMed  Google Scholar 

  19. K/DOQI (2003) K/DOQI practice guidelines for bone metabolism and disease in chronic kidney disease. Am J Kidney Dis 42:S7–S28

    Google Scholar 

  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 14:570–576

    Article  CAS  PubMed  Google Scholar 

  21. Cockcroft DW, Gault MH (1976) Prediction of creatinine clearance from serum creatinine. Nephron 16:31–41

    CAS  PubMed  Google Scholar 

  22. Winer BJ (1971) Statistical principles in experimental design, 2nd edn. McGraw-Hill, New York, p 14

  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 15:993–1000

    PubMed  Google Scholar 

  24. Cohen A, Shane E (2003) Osteoporosis after solid organ and bone marrow transplantation. Osteoporos Int 14:617–630

    Article  PubMed  Google Scholar 

  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 26:231–243

    CAS  PubMed  Google Scholar 

  26. Pilon D, Castilloux AM, Dorais M, LeLorier J (2004) Oral anticoagulants and the risk of osteoporotic fractures among elderly. Pharmacoepidemiol Drug Saf 13:289–294

    Article  CAS  PubMed  Google Scholar 

  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 31:23–29

    CAS  PubMed  Google Scholar 

  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 11:552–559

    CAS  PubMed  Google Scholar 

  29. Michel BA, Bloch DA, Wolfe F, Fries JF (1993) Fractures in rheumatoid arthritis: an evaluation of associated risk factors. J Rheumatol 20:1666–1669

    CAS  PubMed  Google Scholar 

  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 51:291–299

    Article  Google Scholar 

  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]:S8

  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 305:372–374

    CAS  PubMed  Google Scholar 

  33. Epstein S, Bryce G, Hinman JW et al (1986) The influence of age on bone mineral regulating hormones. Bone 7:421–425

    Article  CAS  PubMed  Google Scholar 

  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 73:1668–1672

    CAS  PubMed  Google Scholar 

  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:S35

    Google Scholar 

  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 18:2440–2445

    Article  CAS  Google Scholar 

  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 62:193–198

    Article  CAS  PubMed  Google Scholar 

  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 86:3618–3628

    Article  CAS  PubMed  Google Scholar 

  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 52:230–236

    Article  Google Scholar 

  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 60:236–239

    Article  PubMed  Google Scholar 

  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 88:2019–2025

    Article  CAS  PubMed  Google Scholar 

  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 47:1195–1201

    CAS  Google Scholar 

  43. Boland R (1986) Role of vitamin D in skeletal muscle function. Endocr Rev 784:434–448

    Google Scholar 

  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–M119

    CAS  PubMed  Google Scholar 

  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 144:5138–5144

    Article  CAS  PubMed  Google Scholar 

  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 33:19–24

    Article  CAS  Google Scholar 

  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 19:265–269

    CAS  PubMed  Google Scholar 

  48. Ringe JD, Schacht E (2004) Prevention and therapy of osteoporosis: the roles of plain vitamin D and alfacalcidol. Rheumat Int 24:189–197

    CAS  Google Scholar 

  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 28:34–39

    CAS  PubMed  Google Scholar 

  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 18:343–351

    CAS  Google Scholar 

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Acknowledgements

The study was supported by GRY Pharma GmbH, Germany.

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Correspondence to Laurent Dukas.

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Dukas, L., Schacht, E. & Stähelin, H.B. 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 16, 1683–1690 (2005). https://doi.org/10.1007/s00198-005-1903-7

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