Alendronate, a double-edged sword acting in the mevalonate pathway

Tricarico,Paola  Maura; Girardelli,Martina; Kleiner,Giulio; Knowles,Alessandra; Valencic,Erica; Crovella,Sergio; Marcuzzi,Annalisa

doi:10.3892/mmr.2015.3957

Alendronate, a double-edged sword acting in the mevalonate pathway

Authors:
- Paola Maura Tricarico
- Martina Girardelli
- Giulio Kleiner
- Alessandra Knowles
- Erica Valencic
- Sergio Crovella
- Annalisa Marcuzzi
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Affiliations: Department of Medicine, Surgery and Health Science, University of Trieste, Trieste I‑34127, Italy, Department of Advanced Diagnostic and Clinical Trials, Institute for Maternal and Child Health, IRCCS ‘Burlo Garofolo’, Trieste I‑34137, Italy
Published online on: June 18, 2015 https://doi.org/10.3892/mmr.2015.3957
Pages: 4238-4242
Copyright: © Tricarico et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

Aminobisphosphonate aledronate is a compound commonly used clinically for the treatment of osteoporosis and other bone diseases, as a result of it preventing bone resorption. However, in previous years it has also been used to obtain cellular and animal models of a rare genetic disorder termed Mevalonate Kinase Deficiency (MKD). MKD is caused by mutations affecting the mevalonate kinase enzyme, in the cholesterol pathway and alendronate can be used to biochemically mimic the genetic defect as it inhibits farnesyl pyrophosphate synthase in the same pathway. Despite evidence in favor of the inhibition exerted on the mevalonate pathway, there is at least one clinical case of MKD in which alendronate improved not only skeletal and bone fractures, as expected, but also MKD clinical features. Based on this finding, the present study assessed the anti‑inflammatory properties of this aminobisphosphonate in vitro. No anti‑inflammatory effects of alendronate were observed in the in vitro experiments. Since MKD lacks specific treatments, these results may assist scientists and physicians in making the decision as to the most suitable choice of therapeutic compounds for this neglected disease.

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