Zoledronic Acid Is Not Equally Potent on Osteoclasts Generated From Different Individuals

JBMR Plus
Anaïs M J MøllerKent Søe

Abstract

Zoledronic acid is a bisphosphonate commonly used to treat bone diseases such as osteoporosis and cancer-induced bone disease. Patients exhibit a variable sensitivity to zoledronic acid; the underlying explanation for this remains unclear. The objective of this study was to obtain more knowledge in this regard. We hypothesized that osteoclasts generated from different individuals would show a variable sensitivity to zoledronic acid in vitro. Osteoclasts were generated using monocytes from 46 healthy female blood donors (40 to 66 years). Matured osteoclasts were reseeded onto bone slices precoated with different concentrations of zoledronic acid. IC50 values were determined based on total eroded bone surface after 3 days of resorption. The IC50 for inhibition of osteoclastic bone resorption varied from 0.06 to 12.57μM zoledronic acid; thus, a more than 200-fold difference in sensitivity to zoledronic acid among osteoclasts from different individuals was observed. Multiple linear regression analyses showed that the determined IC50 correlated with smoking status, and the average number of nuclei per osteoclast in vitro. Further analyses showed that: (i) increasing protein levels of mature cathepsin K in osteoclast cultures rendere...Continue Reading

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Citations

Apr 17, 2021·Frontiers in Cell and Developmental Biology·Jean-Marie DelaisseNiels Marcussen

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Methods Mentioned

BETA
GTPases
light microscopy
Protein Assay
biopsies

Software Mentioned

GraphPad Prism
Image Lab
SE
GraphPad
STATA

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