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Bisphosphonates promote apoptosis in murine osteoclasts in vitro and in vivo

Hughes, David E., Wright, Kenneth R., Uy, Harry L., Sasaki, Akira, Yoneda, Toshiyuki, Roodman, David G., Mundy, Gregory R., Dr. Boyce, Brendan F.·1995·Journal of Bone and Mineral Research
DOI 10.1002/jbmr.5650101008
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Abstract

Bisphosphonates inhibit bone resorption and are therapeutically effective in diseases of increased bone turnover, such as Paget's disease and hypercalcemia of malignancy. The mechanisms by which they act remain unclear. Proposed mechanisms include inhibition of osteoclast formation from precursors and inhibitory or toxic effects on mature osteoclasts. We have developed a new in vitro model to study osteoclast survival and in this paper present in vitro and in vivo evidence that may explain both the observed reduction in osteoclast numbers and in bone resorption by mature osteoclasts, namely that bisphosphonates induce programmed cell death (apoptosis). Three bisphosphonates (risedronate, pamidronate, and clodronate) caused a 4- to 24-fold increase in the proportion of osteoclasts showing the characteristic morphology of apoptosis in vitro. This observation was confirmed in vivo in normal mice, in mice with increased bone resorption, and in nude mice with osteolytic cancer metastases, with similar-fold increases to those observed in vitro. Of the three compounds, risedronate, the most potent inhibitor of bone resorption in vivo, was the strongest inducer of osteoclast apoptosis in vitro. Osteoclast apoptosis may therefore be a major mechanism whereby bisphosphonates reduce osteoclast numbers and activity, and induction of apoptosis could be a therapeutic goal for new antiosteoclast drugs.

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Metadata

Authors
Hughes, D. E., Wright, K. R., Uy, H. L., Sasaki, A., Yoneda, T., Roodman, D. G., Mundy, G. R., & Dr. Boyce, B. F.
Venue
Journal of Bone and Mineral Research
Publisher
Oxford University Press (OUP)
Published
1995-10-01
Volume
10
Issue
10
Pages
1478-1487
ISSN
  • 0884-0431 (ISSN-L)
  • 1523-4681
DOI
10.1002/jbmr.5650101008
OpenAlex
W2161690532
Cited by
1,040
References
2
FWCI
10.54
Type
journal article
Language
en
Open access
closed
Licence
academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
Funders
  • NIH (DE 08569, CA 40035, AR-41336)
  • American Cancer Society (IRG-116)

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CoChat. (2026). Citation check: Bisphosphonates promote apoptosis in murine osteoclasts in vitro and in vivo. https://app.cochat.ai/papers/10.1002/jbmr.5650101008
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Hughes, D. E., Wright, K. R., Uy, H. L., Sasaki, A., Yoneda, T., Roodman, D. G., Mundy, G. R., & Dr. Boyce, B. F. (1995). Bisphosphonates promote apoptosis in murine osteoclasts in vitro and in vivo. Journal of Bone and Mineral Research. https://doi.org/10.1002/jbmr.5650101008

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