Imatinib as a potential antiresorptive therapy for bone disease.

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Dewar AL, Farrugia AN, Condina MR, Bik To L, Hughes TP, Vernon-Roberts B, Zannettino AC

Imatinib as a potential antiresorptive therapy for bone disease.

Blood. 2006 Jun 1;107(11):4334-7. Epub 2006 Jan 31.

PubMed ID

16449525 [ View in PubMed

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Abstract

Osteoclasts (OCs) are large multinucleated cells derived from progenitor cells of the monocyte-macrophage lineage. Signal transduction via the macrophage-colony-stimulating factor (M-CSF) receptor, c-fms, is essential for OC formation. Since we have previously demonstrated inhibition of c-fms by imatinib, we examined the effect of imatinib on OC formation and activity. OC formation was not affected by concentrations of 1.0 microM imatinib and lower, but was reduced by 75% at 3.0 microM imatinib. In contrast, both the area of resorption and the number of resorption lacunae were reduced by 80% at 0.3 microM imatinib, and no resorption was observed at concentrations above 3.0 microM. A dose-dependent decrease in receptor activator of nuclear factor kappaB (RANK) expression was observed in OCs when cultured in the presence of imatinib, providing a mechanism for the decrease in OC function. In vivo analysis of the effect of imatinib on OC activity in adult mice following 8 weeks of imatinib treatment also demonstrated a decrease in OC activity. These results suggest that imatinib may have therapeutic value as an antiosteolytic agent in diseases such as osteoporosis, metastatic bone disease, and multiple myeloma.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Imatinib	Macrophage colony-stimulating factor 1 receptor	Protein	Humans	Unknown	Antagonist	Details