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Implications of mevalonic acid, Wnt and oestrogen pathways in osteoporosis and response to antiresorptive drugs

14th national competition for scientific and technical research

Genetic and pharmacogenetic markers

Senior Researcher : José A. Riancho Moral

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Research Centre or Institution : Hospital Universitario Marqués de Valdecilla. Universidad de Cantabria. Santander.


Osteoporosis is a frequent disorder, particularly among menopausal women. It is characterised by a reduction of bone mass and increased bone fragility, making the skeleton less resistant and more susceptible to fractures with the slightest knock and even without any. The causes of osteoporosis are complex. Although some acquired factors come into play (nutrition, physical activity, etc.), the disease has a significant hereditary component. However, up to now the genes directly involved have not been clearly identified. That is why this project aims to analyse the influence of several polymorphisms (specific variations in the DNA sequence) on bone mass. The genes studied will include some related to the metabolism of oestrogens (female sexual hormones) and others related to bone cell activity, in particular the modulating genes of the Wnt pathway, which plays an important role in osteoblast (bone forming cells) activity, and the mevalonate pathway, which modulates the osteoclast (bone destruction cells) activity. How these polymorphisms affect the response to the drugs used in osteoporosis treatment will also be studied. The study will be carried out in two stages. The first stage will consist of studying a group of 1,100 post-menopausal women from Cantabria. In the second stage, carried out in collaboration with Dutch researchers, the positive results will be confirmed in a different population, specifically that of the Rotterdam cohort. The aim of this project is to identify a series of genetic characteristics that predispose the development of osteoporosis, which will in turn help to identify women at risk who are especially suitable for receiving preventive treatment. On the other hand, the identification of genetic markers that affect the response to the drugs will help to personalise treatment, selecting the most suitable drug for each patient.

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