Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are a class of compounds widely used in industry and consumer products. They are resistant to degradation and tend to accumulate in the environment and in living beings with possible toxic effects. These contaminants are a public health problem, especially in some areas of the Veneto Region, but have recently been isolated in waters from other parts of Italy. Perfluorooctanoic acid (PFOA) is the predominant form in human samples and has been shown to induce serious health consequences, such as neonatal alterations, neurotoxicity and immunotoxicity. Toxicological studies indicate that PFAS accumulate in bone tissue and alter bone development. Epidemiological studies have reported an inverse relationship between PFAS blood levels and bone health, especially in terms of bone mineral density (BMD). Osteopenia and osteoporosis have been shown in several cohorts, ranging from post-menopausal women to young men. Since the interaction between this class of compounds and certain nuclear hormone receptors (such as the thyroid hormone receptor and the androgen receptor) has already been demonstrated, an interaction with the vitamin D receptor has also been hypothesised, which is essential for the proper regulation of phosphocalcic metabolism, the main determinant of bone density. This study summarises the experimental and clinical evidence supporting the interference of PFOA with the vitamin D signalling pathway.
