title: Alendronate, a double-edged sword acting in the mevalonate pathway.
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.
authors.affiliation: Department of Medicine, Surgery and Health Science, University of Trieste, Trieste I‑34127, Italy.
authors.forename: Paola Maura
authors.initials: PM
authors.lastname: Tricarico
authors.affiliation: Department of Advanced Diagnostic and Clinical Trials, Institute for Maternal and Child Health, IRCCS 'Burlo Garofolo', Trieste I‑34137, Italy.
authors.forename: Martina
authors.initials: M
authors.lastname: Girardelli
authors.affiliation: Department of Advanced Diagnostic and Clinical Trials, Institute for Maternal and Child Health, IRCCS 'Burlo Garofolo', Trieste I‑34137, Italy.
authors.forename: Giulio
authors.initials: G
authors.lastname: Kleiner
authors.affiliation: Department of Advanced Diagnostic and Clinical Trials, Institute for Maternal and Child Health, IRCCS 'Burlo Garofolo', Trieste I‑34137, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Knowles
authors.affiliation: Department of Advanced Diagnostic and Clinical Trials, Institute for Maternal and Child Health, IRCCS 'Burlo Garofolo', Trieste I‑34137, Italy.
authors.forename: Erica
authors.initials: E
authors.lastname: Valencic
authors.affiliation: Department of Medicine, Surgery and Health Science, University of Trieste, Trieste I‑34127, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Crovella
authors.affiliation: Department of Advanced Diagnostic and Clinical Trials, Institute for Maternal and Child Health, IRCCS 'Burlo Garofolo', Trieste I‑34137, Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Marcuzzi
mesh_terms: D019386:Alendronate / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D017209:Apoptosis; D053898:Biosynthetic Pathways; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis / Q000378:metabolism; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D008798:Mevalonic Acid / Q000378:metabolism*; D051379:Mice; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000172:deficiency
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D008070:Lipopolysaccharides; D017853:Phosphotransferases (Alcohol Group Acceptor); C021796:mevalonate kinase; D008798:Mevalonic Acid; D019386:Alendronate