L-carnitine and isovaleryl L-carnitine fumarate positively affect human osteoblast proliferation and differentiation in vitro

Calcif Tissue Int. 2005 Jun;76(6):458-65. doi: 10.1007/s00223-004-0147-4. Epub 2005 May 19.


Age-related bone loss is characterized by decreased osteoblast activity, possibly related to the reduction of energy production. Carnitine promotes energy availability and its concentration declines with age; Therefore, two Carnitine derivatives, L-carnitine fumarate (LC) and isovaleryl L-carnitine fumarate (Iso-V-LC), have been tested on several parameters of human osteoblasts in vitro. Both compounds significantly increased osteoblast activity, but the new compound Iso-V-LC was more efficient than LC at lower concentrations. They both significantly enhanced cell proliferation, [3H]-proline incorporation and the expression of collagen type I (COLLI), and the bone sialoproteins (BSPs) and osteopontin (OPN). The percentage of alkaline phosphatase (ALP)-positive cells and the secretion of osteocalcin were not modified by LC and Iso-V-LC. Both molecules increased the formation of mineralized nodules, but Iso-V-LC reached the maximum effect at a concentration 10-fold lower than that of LC. Furthermore, we showed that insulin-like growth factor (IGF)-I and IGF-II mRNA levels were not modified by the treatment. However, the two compounds induced an increase of insulin-like growth factor binding protein (IGFBP)-3 and a decrease of IGFBP-5 in both osteoblast lysates and the extracellular matrix (ECM). In conclusion these data suggest that carnitine and, in particular, its new derivative, Iso-V-LC supplementation in the elderly may stimulate osteoblast activity and decrease age-related bone loss.

Publication types

  • Comparative Study

MeSH terms

  • Alkaline Phosphatase / drug effects
  • Alkaline Phosphatase / metabolism
  • Blotting, Western
  • Calcification, Physiologic / drug effects
  • Carnitine / analogs & derivatives*
  • Carnitine / pharmacology*
  • Cell Differentiation / drug effects
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Collagen Type I / drug effects
  • Collagen Type I / metabolism
  • Humans
  • In Vitro Techniques
  • Osteoblasts / cytology*
  • Osteoblasts / drug effects*
  • Osteocalcin / drug effects
  • Osteocalcin / metabolism
  • Osteopontin
  • Receptors, Somatomedin / drug effects
  • Receptors, Somatomedin / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sialoglycoproteins / drug effects
  • Sialoglycoproteins / metabolism
  • Somatomedins / drug effects
  • Somatomedins / metabolism


  • Collagen Type I
  • Receptors, Somatomedin
  • SPP1 protein, human
  • Sialoglycoproteins
  • Somatomedins
  • Osteocalcin
  • Osteopontin
  • Alkaline Phosphatase
  • Carnitine