ECTS2016 Poster Presentations Osteoporosis: pathophysiology and epidemiology (55 abstracts)
FGF23 and SCL are expressed in carotid plaques and the association between their circulating fractions and fractures differs in relation to comorbidity in elderly individuals
Stefano Rotatori 1 , Claudio Corallo 1 , Daniela Merlotti 1, , Domenico Rendina 3 , Simone Bianciardi 1 , Aurora Patti 1 , Stefano Gonnelli 1 , Isabella Anna Evangelista 1 , Barbara Lucani 1 , Maria Beatrice Franci 1 , Carlo Setacci 1 , Pasquale Strazzullo 3 , Ranuccio Nuti 1 , Francesco Dotta 1 & Luigi Gennari 1
1Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy; 2Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Milan, Italy; 3Department of Clinical and Experimental Medicine, Federico II University, Naples, Italy.
Sclerostin (SCL) and FGF23 are osteocyte-secreted factors with a major role in bone homeostasis. Despite their skeletal effects and their association with fracture risk in some studies, variations in circulating levels were also described in patients with diabetes (DM), chronic renal failure (CRF) and/or cardiovascular disease (CVD). In order to provide further insight on the relationship between these osteocyte-derived factors, osteoporosis and cardio-metabolic disorders we assessed their circulating fractions in 1353 elderly subjects from two cohorts specifically designed to assess the prevalence of cardio-metabolic comorbidities and morphometric vertebral fractures (MVFs). Moreover, serum and tissue samples of 30 patients who underwent carotid endarterectomy were analyzed. In both cohorts, SCL levels were positively correlated with CTX, creatinine and inversely with physical activity score, while FGF23 levels were positively correlated with PTH and creatinine. While SCL did not significantly differ between patients with or without prevalent fractures or MVFs, a significant association was observed between FGF23 and prevalent nonvertebral fractures (P<0.005) but not MVFs. Either SCL or FGF23 levels progressively increased with the increase of comorbid conditions, particularly in subjects with the highest severity for CVD, DM and CRF (as assessed by the ICED score). After exclusion of subjects with all those comorbid conditions, the association between FGF23 levels and fractures became nonsignificant. Conversely, a significant association was observed between SCL and MVF (P<0.01) when patients with the above cardiometabolic-disorders were considered. Remarkably, either SCL or FGF23 were detected by immunohistochemistry in carotid plaques in most samples, and their expression levels correlated negatively and positively with calcification score, respectively. In conclusion, the relationship between circulating SCL or FGF23 levels and fractures is complex and differ in patients with or without major cardiovascular and/or metabolic conditions. Despite their measurement remains of limited value in clinical practice, a better understanding of the mechanisms underlying their increase in DM and CVD is necessary.
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Bone Abstracts
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