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Alendronate disturbs vesicular trafficking in osteoclasts
A Alakangas1, K Selander, M Mulari
1Institute of Biomedicine, Department of Anatomy, University of Turku, Kiinamyllynkatu 10, 20520 Turku, Finland.
Calcified Tissue International
|March 22, 2002
Summary
Alendronate, a bisphosphonate drug, stops bone breakdown by disrupting osteoclast vesicle transport. This impairs osteoclast function, leading to reduced bone resorption without decreasing osteoclast numbers.
Area of Science:
- Biochemistry
- Cell Biology
- Pharmacology
Background:
- Nitrogen-containing bisphosphonates like alendronate inhibit bone resorption.
- Alendronate targets the mevalonate pathway, affecting protein prenylation and small GTPase function in osteoclasts.
Purpose of the Study:
- To investigate alendronate's interference with vesicle transport in isolated rat osteoclasts.
- To elucidate the cellular mechanisms underlying alendronate's inhibition of bone resorption.
Main Methods:
- Isolated rat osteoclasts were treated with alendronate.
- Bone resorption was assessed on alendronate-coated bone slices.
- Ultrastructural changes in osteoclasts were examined using electron microscopy.
Main Results:
- Alendronate treatment led to the accumulation of tartrate-resistant acid phosphatase- and electron-dense material-containing tubular vesicles.
- Osteoclast changes included widened sealing zones, disorganized attachments, and incomplete ruffled borders.
- Bone resorption was inhibited, with dissolution limited to pit edges, and osteoclast numbers remained unchanged.
Conclusions:
- Alendronate inactivates osteoclasts by impairing intracellular vesicle transport.
- Apoptosis is a secondary effect, not the primary mechanism of alendronate-induced osteoclast inactivation.