Calcified Tissue International

, Volume 81, Issue 2, pp 99–106 | Cite as

Effect of L-Carnitine Supplementation on Secondary Hyperparathyroidism and Bone Metabolism in Hemodialyzed Patients

  • Roman Cibulka
  • Jaroslav Racek
  • Richard Pikner
  • Daniel Rajdl
  • Ladislav Trefil
  • Eugenie Vesela
  • Marie Studenovska
  • Romana Siroka
Article
First Online:
Received:
Accepted:

Abstract

The aim of our work was to test the influence of L-carnitine supplementation on secondary hyperparathyroidism and bone metabolism in hemodialyzed patients in a randomized study. Eighty-three chronically hemodialyzed patients were observed; 44 were supplemented with L-carnitine (15 mg/kg intravenously after each hemodialysis for 6 months), while 39 took placebo. Levels of free carnitine (CAR), calcium (Ca), inorganic phosphate (P), Ca x P product, parathormone (PTH), bone-specific alkaline phosphatase (b-ALP), osteocalcin (OC), and osteoprotegerin (OPG) were monitored. In comparison with pretreatment values, changes of some selected parameters occurred in the supplemented patients after 6 months (data are expressed as medians; NS, nonsignificant change): PTH, 186.0 vs. 135.5 ng/L (NS); b-ALP, 13.9 vs. 13.2 μg/L (P < 0.05); OC, 78.3 vs. 68.8 μg/L (NS); OPG, 144.0 vs. 182.0 ng/L (P < 0.05). In the controls, there were the following changes: PTH, 148.0 vs. 207.0 ng/L (NS); b-ALP, 15.2 vs. 13.2 μg/L (P < 0.05); OC, 62.7 vs. 79.8 μg/L (P < 0.05); OPG, 140.0 vs. 164.0 ng/L (NS). A significant correlation was found between CAR and OPG changes (r = 0.51, P < 0.001) in the supplemented patients. The supplementation led to a significant increase of serum OPG concentration. Nevertheless, we observed only nonsignificant tendencies to correction of secondary hyperparathyroidism and reduction of bone turnover in hemodialyzed patients supplemented with L-carnitine in contrast to controls. At this point, the use of L-carnitine does not seem to be justified.

Keywords

L-Carnitine Hemodialysis Secondary hyperparathyroidism Bone metabolism Osteoprotegerin 
This is a preview of subscription content, log in to check access.

Notes

Acknowledgement

This study was supported by the Internal Grant Agency (IGA) grant NB/7350-3 from the Ministry of Health, Czech Republic.

References

  1. 1.
    Schonekess BO, Allard MF, Lopaschuk GD (1995) Propionyl L-carnitine improvement of hypertrophied heart function is accompanied by an increase in carbohydrate oxidation. Circ Res 77:726–734PubMedGoogle Scholar
  2. 2.
    Vaz FM, Wanders R (2002) Carnitine homeostasis and human disease: advances in metabolite analysis. LabMedica 19:14–17Google Scholar
  3. 3.
    Battistella PA, Angelini C, Vergani L, Bertoli M, Lorenzi S (1978) Carnitine deficiency induced during hemodialysis. Lancet 1:939PubMedCrossRefGoogle Scholar
  4. 4.
    Bohmer T, Bergrem H, Eiklid K (1978) Carnitine deficiency induced during intermittent haemodialysis for renal failure. Lancet 1:126–128PubMedCrossRefGoogle Scholar
  5. 5.
    Evans AM, Faull R, Fornasini G, Lemanowicz EF, Longo A, Pace S, Nation RL (2000) Pharmacokinetics of L-carnitine in patients with end-stage renal disease undergoing long-term hemodialysis. Clin Pharmacol Ther 68:238–249PubMedCrossRefGoogle Scholar
  6. 6.
    Suzuki Y, Nariata M, Yamazaki N (1982) Effects of L-carnitine on arrhythmias during hemodialysis. Jpn Heart J 23:349–359PubMedGoogle Scholar
  7. 7.
    Goral S (2001) Levocarnitine’s role in the treatment of patients with end-stage renal disease: a review. Dial Transplant 30:530–538Google Scholar
  8. 8.
    Horl WH (2004) The clinical consequences of secondary hyperparathyroidism: focus on clinical outcomes. Nephrol Dial Translpant 19(suppl 5):V2–V8CrossRefGoogle Scholar
  9. 9.
    Portale AA, Halloran BP, Morris RC Jr (1989) Physiologic regulation of the serum concentration of 1,25-dihydroxyvitamin D3 by phosphorus in normal men. J Clin Invest 83:1494–1499PubMedGoogle Scholar
  10. 10.
    Portale AA, Booth BE, Halloran BP, Morris RC Jr (1984) Effect of dietary phosphorus on circulating concentrations of 1,25-dihydroxyvitamin D and immunoreactive parathyroid hormone in children with moderate renal insufficiency. J Clin Invest 73:1580–1589PubMedCrossRefGoogle Scholar
  11. 11.
    Combe C, Aparicio M (1994) Phosphorus and protein restriction and parathyroid function in chronic renal failure. Kidney Int 46:1381–1386PubMedCrossRefGoogle Scholar
  12. 12.
    Slatopolsky E, Brown A, Dusso A (2001) Role of phosphorus in the pathogenesis of secondary hyperparathyroidism. Am J Kidney Dis 37(suppl 2):S54–S57PubMedGoogle Scholar
  13. 13.
    Adamek G, Felix R, Guenther HL, Fleisch H (1987) Fatty acid oxidation in bone tissue and bone cells in culture. Characterization and hormonal influences. Biochem J 248:129–137PubMedGoogle Scholar
  14. 14.
    Ahmad S, Robertson HT, Golper TA, Wolfson M, Kurtin P, Katz LA, Hirschberg R, Nicora R, Ashbrook DW, Kopple JD (1990) Multicenter trial of L-carnitine in maintenance hemodialysis patients. II. Clinical and biochemical effects. Kidney Int 38:912–918PubMedCrossRefGoogle Scholar
  15. 15.
    Nakazawa R, Furuhashi S, Shioda T, Kawamura K, Kimura K, Azuma N, Suzuki M (2002) Effect of long-term L-carnitine supplementation on hyperphosphatemic hemodialysis patients [abstract]. Presented at the 11th International Congress on Nutrition and Metabolism in Renal Disease, Nagoya, Japan, March 29–31, 2002Google Scholar
  16. 16.
    Vesela E, Racek J, Trefil L, Jankových V, Pojer M (2001) Effect of L-carnitine supplementation in hemodialysis patients. Nephron 88:218–223PubMedCrossRefGoogle Scholar
  17. 17.
    Khosla S (2001) The OPG/RANKL/RANK system. Endocrinology 142:5050–5055PubMedCrossRefGoogle Scholar
  18. 18.
    Kostenuik PJ (2005) Osteoprotegerin and RANKL regulate bone resorption, density, geometry and strength. Curr Opin Pharmacol 5:618–625PubMedCrossRefGoogle Scholar
  19. 19.
    Seim H (1998) Carnitine. In: Lothar T (ed), Clinical Laboratory Diagnostics. TH-Books Verlagsgesellschaft, Frankfurt, 202–207Google Scholar
  20. 20.
    National Kidney Foundation (2003) Kidney Disease Quality Outcomes Initiative (K/DOQI) clinical practice guidelines. Bone metabolism and disease in chronic kidney disease. Am J Kidney Dis 42(suppl 3):S1–S201Google Scholar
  21. 21.
    Locatelli F (2004) The need for better control of secondary hyperparathyroidism. Nephrol Dial Translpant 19(suppl 5):V15–V19CrossRefGoogle Scholar
  22. 22.
    Guarnieri G, Toigo G, Crapesi L, Situlin R, Del Bianco MA, Corsi M, LoGreco P, Paviotti G, Mioni G, Campanacci L (1987) Carnitine metabolism in chronic renal failure. Kidney Int 32(suppl 22):S116–S127Google Scholar
  23. 23.
    Urena P, De Vernejoul MC (1999) Circulating biochemical markers of bone remodeling in uremic patients. Kidney Int 55:2141–2156PubMedCrossRefGoogle Scholar
  24. 24.
    Martin KJ, Olgaard K; Bone Turnover Work Group (2004) Diagnosis, assessment, and treatment of bone turnover abnormalities in renal osteodystrophy. Am J Kidney Dis 43:558–565PubMedCrossRefGoogle Scholar
  25. 25.
    Charhon SA, Delmas PD, Malaval L, Chavassieux PM, Arlot M, Chapuy MC, Meunier PJ (1986) Serum bone Gla-protein in renal osteodystrophy: comparison with bone histomorphometry. J Clin Endocrinol Metab 63:892–897PubMedCrossRefGoogle Scholar
  26. 26.
    Sebert JL, Ruiz JC, Fournier A, Fardellone P, Gueris J, Marie A, Moriniere P, Codet MP, Renaud H (1987) Plasma bone Gla-protein: assessment of its clinical value as an index of bone formation in hemodialyzed patients. Bone Miner 2:21–27PubMedGoogle Scholar
  27. 27.
    Simonet WS, Lacey DL, Dunstan CR, Kelley M, Chang MS, Luthy R, Nguyen HQ, Wooden S, Bennett L, Boone T, Shimamoto G, DeRose M, Elliott R, Colombero A, Tan HL, Trail G, Sullivan J, Davy E, Bucay N, Renshaw-Gegg L, Hughes TM, Hill D, Pattison W, Campbell P, Sander S, Van G, Tarpley J, Derby P, Lee R, Boyle WJ (1997) Osteoprotegerin: a novel secreted protein involved in the regulation of bone density. Cell 89:309–319PubMedCrossRefGoogle Scholar
  28. 28.
    Steddon SJ, Fan SL, Cunningham J (2005) New prospects for the management of renal bone disease. Nephron Clin Pract 99:c1–c7PubMedCrossRefGoogle Scholar
  29. 29.
    Bekker PJ, Holloway D, Nakanishi A, Arrighi M, Leese PT, Dunstan CR (2001) The effect of a single dose of osteoprotegerin in postmenopausal women. J Bone Miner Res 16:348–360PubMedCrossRefGoogle Scholar
  30. 30.
    Nakashima A, Yorioka N, Doi S, Takasugi N, Shigemoto K, Kohno N (2006) Osteoprotegerin and bone mineral density in hemodialysis patients. Osteoporos Int 17:841–846PubMedCrossRefGoogle Scholar
  31. 31.
    Kazama JJ, Kato H, Sato T, Shigematsu T, Fukagawa M, Iwasaki Y, Gejyo F (2002) Circulating osteoprotegerin is not removed through haemodialysis membrane. Nephrol Dial Transplant 17:1860–1861PubMedCrossRefGoogle Scholar
  32. 32.
    Avbersek-Luznik I, Malesic I, Rus I, Marc J (2002) Increased levels of osteoprotegerin in hemodialysis patients. Clin Chem Lab Med 40:1019–1023PubMedCrossRefGoogle Scholar
  33. 33.
    Lee SK, Lorenzo JA (1999) Parathyroid hormone stimulates TRANCE and inhibits osteoprotegerin messenger ribonucleic acid expression in murine bone marrow cultures: correlation with osteoclast-like cell formation. Endocrinology 140:3552–3561PubMedCrossRefGoogle Scholar
  34. 34.
    Avbersek-Luznik I, Balon BP, Rus I, Marc J (2005) Increased bone resorption in HD patients: is it caused by elevated RANKL synthesis? Nephrol Dial Transplant 20:566–570PubMedCrossRefGoogle Scholar
  35. 35.
    Colucci S, Mori G, Vaira S, Brunetti G, Greco G, Mancini L, Simone GM, Sardelli F, Koverech A, Zallone A, Grano M (2005) L-Carnitine and isovaleryl L-carnitine fumarate positively affect human osteoblast proliferation and differentiation in vitro. Calcif Tissue Int 76:458–465PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Roman Cibulka
    • 1
  • Jaroslav Racek
    • 1
  • Richard Pikner
    • 2
  • Daniel Rajdl
    • 1
  • Ladislav Trefil
    • 1
  • Eugenie Vesela
    • 3
  • Marie Studenovska
    • 3
  • Romana Siroka
    • 1
  1. 1.Institute of Clinical Biochemistry and Hematology, Charles University Medical Faculty and Faculty HospitalPilsenCzech Republic
  2. 2.2nd Department of Internal MedicineCharles University Medical Faculty and Faculty HospitalPilsenCzech Republic
  3. 3.Dialysis Centers EuroCarePilsen and TepliceCzech Republic

Personalised recommendations