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Updated: May 23, 2026
11:52
Differentiation of Functional Osteoclasts from Human Peripheral Blood CD14+ Monocytes
Published on: January 27, 2023
Clodronate acts on human osteoclastic cell proliferation, differentiation and function in a bioreversible manner
Raffaella Recenti1, Giuseppe Leone, Lisa Simi
1Internal Medicine.
Summary
Clodronate
Area of Science:
- Biochemistry
- Cell Biology
- Pharmacology
Background:
- Bisphosphonates are pyrophosphate analogs used to treat bone resorption diseases.
- Clodronate, a non-nitrogen-containing bisphosphonate, was previously considered cytotoxic.
- Its mechanism involves intracellular metabolism to an ATP analog, inhibiting ADP/ATP translocase.
Purpose of the Study:
- To investigate the reversibility of clodronate's effects on human osteoclastic cells.
- To determine if clodronate should be classified as cytotoxic based on its bioeffects.
- To elucidate the mechanism of clodronate's action and its reversal.
Main Methods:
- Used human preosteoclastic (FLG 29.1) and osteoclast-like (HOC) cell lines.
- Assessed cell proliferation, differentiation (TRAcP), apoptosis (TEM), and ATP levels (luciferin-luciferase assay).
- Identified the metabolite adenosine-5 [ β - γ -dichloromethylene] triphosphate (AppCCl(2)p) using HPLC-ESI-MS-MS.
Main Results:
- Clodronate inhibited osteoclastic cell proliferation and differentiation.
- Clodronate induced apoptosis and reduced intracellular ATP levels.
- Adding ATP to the culture medium reversed clodronate's biological actions.
Conclusions:
- Clodronate's inhibition of osteoclastic function is mediated by the intracellular metabolite AppCCl(2)p.
- The observed bioeffects of clodronate in vitro are reversible.
- Clodronate should not be defined as cytotoxic due to the reversibility of its actions.
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