Alendronate is an amino bisphosphate that has recently been approved for treatment of both osteoporosis and Paget's disease of bone due to its potency to inhibit osteoclastic bone resorption. We tested the effects of alendronate on osteoclast formation induced by the marrow stromal cells and on cytokine production in human bone marrow cultures. We recently immortalized a human marrow stromal cell line (Saka) that supports osteoclast formation in vitro and have shown that Saka cells mediate their effects by production of interleukin-1 and interleukin-6, as well as membrane-bound factor. We have also developed a marrow stromal cell line from an affected bone from a patient with Paget's disease and shown that it also enhances osteoclast formation, but does not require cell-to-cell contact for its effects. It also produces stem cell factor, leukemia inhibitory factor, factors not produced by Saka cells, as well as interleukin-1, interleukin-6 and high concentrations of granulocyte macrophage colony-stimulating factor. First, we studied the effect of alendronate on osteoclast-like cell formation in long-term human marrow cultures at various concentrations ranging from 10-5 M to 10-9 M. Alendronate significantly inhibited osteoclast-like cell formation in the presence of 10-8 M 1,25-dihydroxyvitamin D3 at 10-9 M concentration in long-term marrow cultures. However, there was no significant inhibition of osteoclast formation by alendronate at concentrations ranging from 10-6 M to 10-7 M, suggesting a biphasic effect of this compound on osteoclast-like cell formation in human bone marrow cultures. These results were seen in multiple experiments. Further experiments to understand this biphasic effect of alendronate on stromal cell mediated osteoclast formation in human bone marrow cultures are currently ongoing.
|Original language||English (US)|
|Journal||Journal of Investigative Medicine|
|State||Published - Feb 1999|
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)