Inhibition of bone resorption by bisphosphonates: Interactions between bisphosphonates, osteoclasts, and bone

@article{Flanagan1991InhibitionOB,
  title={Inhibition of bone resorption by bisphosphonates: Interactions between bisphosphonates, osteoclasts, and bone},
  author={Adrienne Margaret Flanagan and Timothy J. Chambers},
  journal={Calcified Tissue International},
  year={1991},
  volume={49},
  pages={407-415}
}
Bisphosphonates are nonbiodegradable pyrophosphate analogues that are being used increasingly to inhibit bone resorption in disorders characterized by excessive bone loss. We have previously found that dichloromethylene bisphosphonate (Cl2MBP) inhibits bone resorption through injury to the cells that resorb Cl2MBP-contaminated surfaces. 3-amino-1-hydroxypropylidene-1,1-bisphosphonate (AHPrBP) is a more potent inhibitor of bone resorptionin vivo, and we have attempted to identify a step in the… CONTINUE READING

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Inhibition of bone resorption by bisphosphonates : Interactions between bisphosphonates , osteoclasts , and bone .
These observations suggest that AHPrBP inhibits bone resorption through injury to osteoclasts when they solubilize bisphosphonate - contaminated bone .
The greater sensitivity of resorption to AHPrBPin vivo could neither be attributed to an effect of AHPrBP on the ability of osteoblastic cells to stimulate resorption in response to calcium - regulating hormonesin vitro nor to an effect on osteoclast generation : osteoclast formation was unaffected by concentrations of AHPrBP 10-fold higher than those of Cl2MBP which inhibit bone resorption in the bone slice assay .
The greater sensitivity of resorption to AHPrBPin vivo could neither be attributed to an effect of AHPrBP on the ability of osteoblastic cells to stimulate resorption in response to calcium - regulating hormonesin vitro nor to an effect on osteoclast generation : osteoclast formation was unaffected by concentrations of AHPrBP 10-fold higher than those of Cl2MBP which inhibit bone resorption in the bone slice assay .
The effect was specific for osteoclasts , could be prevented if bone resorption was suppressed by calcitonin , and was not seen in osteoclasts incubated in AHPrBP on plastic coverslips .
The effect was specific for osteoclasts , could be prevented if bone resorption was suppressed by calcitonin , and was not seen in osteoclasts incubated in AHPrBP on plastic coverslips .
These observations suggest that AHPrBP inhibits bone resorption through injury to osteoclasts when they solubilize bisphosphonate - contaminated bone .
We found that when osteoclasts , isolated from neonatal rat long bones , were incubated on bone slices in the presence of bisphosphonates , AHPrBP was less , rather than more potent as a resorption - inhibitor than Cl2MBP .
These observations suggest that AHPrBP inhibits bone resorption through injury to osteoclasts when they solubilize bisphosphonate - contaminated bone .
We found that when osteoclasts , isolated from neonatal rat long bones , were incubated on bone slices in the presence of bisphosphonates , AHPrBP was less , rather than more potent as a resorption - inhibitor than Cl2MBP .
DiphosphonatesChemical structure ofpamidronate
These observations suggest that AHPrBP inhibits bone resorption through injury to osteoclasts when they solubilize bisphosphonate - contaminated bone .
We found that when osteoclasts , isolated from neonatal rat long bones , were incubated on bone slices in the presence of bisphosphonates , AHPrBP was less , rather than more potent as a resorption - inhibitor than Cl2MBP .
The effect was specific for osteoclasts , could be prevented if bone resorption was suppressed by calcitonin , and was not seen in osteoclasts incubated in AHPrBP on plastic coverslips .
The effect was specific for osteoclasts , could be prevented if bone resorption was suppressed by calcitonin , and was not seen in osteoclasts incubated in AHPrBP on plastic coverslips .
Inhibition of bone resorption by bisphosphonates : Interactions between bisphosphonates , osteoclasts , and bone .
These observations suggest that AHPrBP inhibits bone resorption through injury to osteoclasts when they solubilize bisphosphonate - contaminated bone .
The greater sensitivity of resorption to AHPrBPin vivo could neither be attributed to an effect of AHPrBP on the ability of osteoblastic cells to stimulate resorption in response to calcium - regulating hormonesin vitro nor to an effect on osteoclast generation : osteoclast formation was unaffected by concentrations of AHPrBP 10-fold higher than those of Cl2MBP which inhibit bone resorption in the bone slice assay .
The greater sensitivity of resorption to AHPrBPin vivo could neither be attributed to an effect of AHPrBP on the ability of osteoblastic cells to stimulate resorption in response to calcium - regulating hormonesin vitro nor to an effect on osteoclast generation : osteoclast formation was unaffected by concentrations of AHPrBP 10-fold higher than those of Cl2MBP which inhibit bone resorption in the bone slice assay .
We found that when osteoclasts , isolated from neonatal rat long bones , were incubated on bone slices in the presence of bisphosphonates , AHPrBP was less , rather than more potent as a resorption - inhibitor than Cl2MBP .
OsteoclastsAnatomic structure is physical part ofBone Tissue
Inhibition of bone resorption by bisphosphonates : Interactions between bisphosphonates , osteoclasts , and bone .
These observations suggest that AHPrBP inhibits bone resorption through injury to osteoclasts when they solubilize bisphosphonate - contaminated bone .
We found that when osteoclasts , isolated from neonatal rat long bones , were incubated on bone slices in the presence of bisphosphonates , AHPrBP was less , rather than more potent as a resorption - inhibitor than Cl2MBP .
These observations suggest that AHPrBP inhibits bone resorption through injury to osteoclasts when they solubilize bisphosphonate - contaminated bone .
We found that when osteoclasts , isolated from neonatal rat long bones , were incubated on bone slices in the presence of bisphosphonates , AHPrBP was less , rather than more potent as a resorption - inhibitor than Cl2MBP .
We found that when osteoclasts , isolated from neonatal rat long bones , were incubated on bone slices in the presence of bisphosphonates , AHPrBP was less , rather than more potent as a resorption - inhibitor than Cl2MBP .
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