Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2004) 8 P5

SFE2004 Poster Presentations Bone (5 abstracts)

The effects of Simvastatin on the human osteoblast-like cell, SaOS-2

A Abdulkhaliq 1 , L Mancini 2 & SI Girgis 1


1Department of Metabolic Medicine,Hammersmith Campus, Imperial College London, UK; 2Department of Biochemical Pharmacology, William Harvey Research Institute, London, Uk.


Background: Statins are widely prescribed cholesterol-lowering drugs. They inhibit cholesterol synthesis through inhibition of 3-hydroxy-3-methylglutaryl coenzyme A reductase. They have also been recently identified as bone stimulatory agents (Mundy et al., 1999). They have been found to increase the expression of BMP-2 that triggers a cascade of events leading to increased bone formation. However, the exact mechanism for the stimulatory action of statins is not fully elucidated. The aim of this study was to explore the possible mechanisms responsible for the enhanced bone formation. Our hypothesis is that the anabolic effect of statins on bone may be mediated in part by stimulation of osteoblast proliferation and differentiation and/or by inhibition of osteoblast apoptosis.

Methods: The effect of different concentrations of simvastatin 10-3 to 10-9 Molar) at different incubation times on the human osteoblast-like cells SaOS-2 was examined. Alkaline phosphatase (ALP) activity of the cell lysate was measured using a colorimetric method. Osteoprotegrin (OPG) concentration of the culture medium was measured using an ELISA assay. Cell apoptosis was determined using a DNA fragmentation method.

Results and conclusion: Simvastatin (10-7 Molar) caused a significant (p<0.01) increase in OPG concentration of the culture medium after 3 days incubation (0.327 versus 0.393 nanograms per millilitre[ng/ml]) Simvastatin (3 micromolar) caused a significant (p<0.01) increase in ALP activity after 18 h incubation (230 versus 650 Units/100,000 cells/ml). Simvastatin (10-7Molar) significantly (p<0.01) inhibited apoptosis of SaOS-2 cells as early as at 6 h incubation (0.15 versus 0.10 OD at 405/495 nanometer). Interestingly, higher doses of simvastatin (3 and 5 micromolar) resulted in increased apoptosis of SaOS-2 cells

In conclusion, these results suggest that the anabolic effect of simvastatin may be mediated in part through an inhibition of osteoblast apoptosis and stimulation of osteoblast activity.

Volume 8

195th Meeting of the Society for Endocrinology joint with Diabetes UK and the Growth Factor Group

Society for Endocrinology 

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