Skip to main content

Advertisement

Log in

l-Carnitine Fumarate and Isovaleryl-l-Carnitine Fumarate Accelerate the Recovery of Bone Volume/Total Volume Ratio after Experimetally Induced Osteoporosis in Pregnant Mice

Calcified Tissue International Aims and scope Submit manuscript

Abstract

Anabolic skeletal agents have recently broadened the therapeutic options for osteoporosis by directly stimulating bone formation and improving bone turnover, bone density, bone size, and bone microarchitecture. We recently demonstrated that two new l-carnitine derivatives, l-carnitine fumarate (LC) and isovaleryl-l-carnitine fumarate (Iso-V-LC), stimulated osteoblast proliferation and differentiation. We here investigated, by histomorphometry in a mouse model of osteoporosis, the impact of these compounds on the repair of trabecular bone and the osteoblast involvement in this process. Fifty-nine inbred adult female CD1 mice in pregnancy were assigned to four treatment groups: (1) controls, mice fed a standard normocalcemic pre- and postpartal diet; (2) Hypo, mice fed a low-calcium isocaloric prepartal diet and a standard postpartal diet; (3) LC, mice fed a group 2-type diet supplemented post-partum with LC; (4) Iso-V-LC, mice fed a group 2-type diet supplemented post-partum with Iso-V-LC. Bone volume/total volume ratio (BV/TV), bone perimeter, osteoblast surface/bone surface, and osteoblast number/bone surface were measured from sections of L3 and L4 vertebral bodies obtained from animals killed on the day of delivery (controls and Hypo) and on days 7, 14, and 21 after delivery (all groups). BV/TV and all osteoblast-based indexes were significantly higher in LC and Iso-V-LC than in Hypo mice at each time point, and Iso-V-LC at the end of the treatment attained levels observed in controls. In conclusion, Iso-V-LC and, to a lesser extent, LC accelerated the recovery of normal BV/TV level after a hypocalcemic diet.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Borum PR (1980) Regulation of carnitine concentration in plasma. In: Frenkel RA, McGarry JD (eds) Carnitine biosynthesis, metabolism and functions. Academic Press, New York, pp 115–126

    Google Scholar 

  2. Evangeliou A, Vlassopoulos D (2003) Carnitine metabolism and deficit—when is supplementation necessary? Curr Pharm Biotechnol 4:211–219

    Article  PubMed  CAS  Google Scholar 

  3. Maccari F, Arseni A, Chiodi P, Ramacci MT, Angelucci L (1990) Levels of carnitines in brain and other tissues of rats of different ages: effect of acetylitine administration. Exp Gerontol 25:127–134

    Article  PubMed  CAS  Google Scholar 

  4. Costell M, O’Connor JE, Grisolia S (1989) Age-dependent decrease of carnitine content in muscle of mice and humans. Biochem Biophys Res Commun 161:1135–1143

    Article  PubMed  CAS  Google Scholar 

  5. Costell M, Grisolia S (1993) Effect of carnitine feeding on the levels of heart and skeletal muscle carnitine of elderly mice. FEBS Lett 315:43–46

    Article  PubMed  CAS  Google Scholar 

  6. Adamek G, Felix R, Guenther HL, Fleisch H (1987) Fatty acid oxidation in bone tissue and bone cells in culture. Biochem J 242:129–137

    Google Scholar 

  7. 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 76:458–465

    Article  PubMed  CAS  Google Scholar 

  8. Chiu KM, Keller ET, Crenshaw TD, Gravenstein S (1999) Carnitine and dehydroepiandrosterone sulphate induced protein synthesis in porcine osteoblast-like cells. Calcif Tissue Int 64:527–533

    Article  PubMed  CAS  Google Scholar 

  9. Riggs BL, Parfitt AM (2005) Drugs used to treat osteoporosis: the critical need for a uniform nomenclature based on their action on bone remodeling. J Bone Miner Res 20:177–184

    Article  PubMed  CAS  Google Scholar 

  10. Neer RM, Arnaud CD, Zanchetta JR, Prince R, Gaich GA, Reginster J-Y, Hodsman AB, Eriksen EF, Ish-Shalom S, Genant HK, Wang O, Mitlak BH (2001) Effect of parathyroid hormone (1–34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N Engl J Med 344:1434–1441

    Article  PubMed  CAS  Google Scholar 

  11. Benvenga S, Ruggeri RM, Russo A, Lapa D, Campenni A, Trimarchi F (2001) Usefulness of l-carnitine, a naturally occurring peripheral antagonist of thyroid hormone action, in iatrogenic hyperthyroidism: a randomized, double-blind, placebo-controlled clinical trial. J Clin Endocrinol Metab 86:3579–3594

    Article  PubMed  CAS  Google Scholar 

  12. Parfitt AM, Drezner MK, Glorieux FH, Kanis JA, Malluche H, Meunier PJ, Ott SM, Recker RR (1987) Bone histomorphometry: standardization of nomenclature, symbols, and units. Report of the ASBMR Histomorphometry Nomenclature Committee. J Bone Miner Res 2:595–610

    Article  PubMed  CAS  Google Scholar 

  13. Salomon CD, Volpin G (1970) Fine structure of bone resorption in experimental osteoporosis caused by calcium deficient diet in rats. An electron microscopic study of compact bone. Calcif Tissue Res 4:80–82

    Article  Google Scholar 

  14. Ornoy A, Wolinsky I, Guggenheim K (1974) Structure of long bones of rats and mice fed a low calcium diet. Calcif Tissue Res 15:71–76

    Article  PubMed  CAS  Google Scholar 

  15. Shen V, Birchman R, Xu R, Lindsay R, Dempster DW (1995) Short term changes in histomorphometric and biochemical turnover markers and bone mineral density in estrogen- and/or dietary calcium-deficient rats. Bone 16:149–156

    Article  PubMed  CAS  Google Scholar 

  16. Kunkel ME, Powers DL, Hord NG (1990) Comparison of chemical, histomorphometric, and absorptiometric analyses of bones of growing rats subjected to dietary calcium stress. J Am Coll Nutr 9:633–640

    PubMed  CAS  Google Scholar 

  17. Thomas ML, Simmons DJ, Kidder L, Ibarra MJ (1991) Calcium metabolism and bone mineralization in female rats fed diets marginally sufficient in calcium: effects of increased dietary calcium intake. Bone Miner 12:1–14

    Article  PubMed  CAS  Google Scholar 

  18. Weinreb M, Rodan GA, Thompson DD (1991) Immobilization related bone loss in the rat is increased by calcium deficiency. Calcif Tissue Int 48:93–100

    Article  PubMed  CAS  Google Scholar 

  19. Shen V, Birchman R, Xu R, Lindsay R, Dempster DW (1995) Short term changes in histomorphometric and biochemical turnover markers and bone mineral density in estrogen- and/or dietary calcium-deficient rats. Bone 16:149–156

    Article  PubMed  CAS  Google Scholar 

  20. Kovacs CS, Kronenberg HM (1997) Maternal–fetal calcium and bone metabolism during pregnancy, puerperium, and lactation. Endocr Rev 18:832–872

    Article  PubMed  CAS  Google Scholar 

  21. Kiefer MC, Schmid C, Waldvogel M, Schlapfer I, Futo E, Masiarz FR, Green K, Barr PJ, Zapf J (1992) Characterization of recombinant human insulin-like growth factor binding proteins 4, 5, and 6 produced in yeast. J Biol Chem 267:12692–12699

    PubMed  CAS  Google Scholar 

  22. Ernst M, Rodan GA (1990) Increased activity of insulin-like growth factor (IGF) in osteoblastic cells in the presence of growth hormone (GH): positive correlation with the presence of the GH-induced IGF-binding protein BP-3. Endocrinology 127:807–814

    Article  PubMed  CAS  Google Scholar 

  23. Conover CA, Kiefer MC (1993) Regulation and biological effect of endogenous insulin-like growth factor binding protein-5 in human osteoblastic cells. J Clin Endocrinol Metab 76:1153–1159

    Article  PubMed  CAS  Google Scholar 

  24. Benvenga S, Ruggeri RM, Russo A, Lapa D, Campenni A, Trimarchi F (2001) Usefulness of l-carnitine, a naturally occurring peripheral antagonist of thyroid hormone action, in iatrogenic hyperthyroidism: a randomized, double-blind, placebo-controlled clinical trial. Clin Endocrinol Metab 86:3579–3594

    Article  CAS  Google Scholar 

  25. Benvenga S, Amato A, Calvani M, Trimarchi F (2004) Effects of carnitine on thyroid hormone action. Ann N Y Acad Sci 1033:158–167

    Article  PubMed  CAS  Google Scholar 

  26. Sener G, Eksioglu-Demiralp E, Cetiner M, Ercan F, Sirvanci S, Gedik N, Yegen BC (2006) l-Carnitine ameliorates methotrexate-induced oxidative organ injury and inhibits leukocyte death. Cell Biol Toxicol 2006:47–60

    Article  CAS  Google Scholar 

  27. Abd-Allah AR, Al-Majed AA, Al-Yahya AA, Fouda SI, Al-Shabana OA (2005) l-Carnitine halts apoptosis and myelosuppression induced by carboplatin in rat bone marrow cell cultures (BMC). Arch Toxicol 79:406–413

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to M. Grano.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Patano, N., Mancini, L., Settanni, M.P. et al. l-Carnitine Fumarate and Isovaleryl-l-Carnitine Fumarate Accelerate the Recovery of Bone Volume/Total Volume Ratio after Experimetally Induced Osteoporosis in Pregnant Mice. Calcif Tissue Int 82, 221–228 (2008). https://doi.org/10.1007/s00223-008-9109-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00223-008-9109-6

Keywords

Navigation