Abstract:
Alendronate is a powerful therapeutic agent for the treatment of hypercalcemia in malignancy and osteoporosis and has recently been developed as a treatment for hypercalcemia of malignancy. In this study, time-lapse cinemicrography was used to investigate the effects of this agent on the morphology and the motility of human osteoclast-like multinucleated cells (MNCs) from human bone marrow. Alendronate at 10−5 M induced contraction of the cells starting 7.5 h after its addition. contraction was markedly induced immediately after alendronate removal. However, contraction almost disappeared 18 h after removal, and osteoclast-like MNCs recovered their original sizes and shape. There was only partial recovery from contraction after alendronate treatment at 10−4 M. In contrast, untreated control cells did not change their morphology after washing with culture medium. Motility analysis showed that osteoclast-like MNCs treated with 10−5 M alendronate moved actively after washing, but at 10−4 M the motility locus was very narrow. At 10−4 M, the actin ring in the cells began to break down, beginning 6 h after addition. The effects of alendronate on human osteoclast-like MNCs morphology and motility were reversible at 10−5 M, suggesting that alendronate dose not cause any cellular damages in human osteoclasts up to 10−5 M, which is an effective dose for bone resorption.
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Received: June 18, 1998/Accepted: Oct. 30, 1998
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Koshihara, Y., Kodama, S., Ishibashi, H. et al. Reversibility of alendronate-induced contraction in human osteoclast-like cells formed from bone marrow cells in culture. J Bone Miner Metab 17, 98–107 (1999). https://doi.org/10.1007/s007740050071
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DOI: https://doi.org/10.1007/s007740050071