Associations between Per- and Polyfluoroalkyl Substances\nExposures and Bone Mineral: A Systematic Review and Best Evidence\nSynthesis

Per-\nand polyfluoroalkyl substances (PFAS) are persistent environmental\npollutants known for their bioaccumulative nature. Reduced bone mineral\ndensity (BMD) is associated with an increased risk of developing osteoporosis.\nThis pioneering study aims to assess the effects of different PFAS\ncompounds on bone mineral. We conducted searches on online databases.\nInclusion criteria included the presence of associations between perfluorooctanoic\nacid (PFOA), perfluorooctanesulfonate (PFOS), perfluorohexanesulfonic\nacid (PFHxS), perfluorononanoic acid (PFNA), and perfluorodecanoic\nacid (PFDA) and BMD, BMD z-score, and bone mineral content (BMC).\nMeta-analyses were performed. Best evidence synthesis (BES) was performed\nto summarize the results. The results of BES showed that the evidence\nof PFOS, PFOA and PFNA with reduced bone mineral were moderate. The\nvariability in methods for assessing bone mineral and sex differences\nare potential sources of heterogeneity in the results. Meta analysis\nshowed that PFOA was associated with BMD (β −0.01, 95%\nCI −0.01 to −0.00; <i>I</i><sup>2</sup> =\n0%). Subgroup analysis by sex showed that PFOS (β −0.01,\n95% CI −0.01 to −0.00; <i>I</i><sup>2</sup> = 50%), PFOA (β −0.01, 95% CI −0.01 to +0.00; <i>I</i><sup>2</sup> = 29%) were negatively correlated with BMD.\nThis systematic review and BES revealed negative correlations between\nexposure to PFOS, PFOA, PFNA and bone mineral. Sex emerged as a potential\nfactor affecting the negative effects of PFAS on bone mineral. The\ndamage of PFAS to bone mineral still requires further exploration.