Presentations

Abstract

Introduction:

Environmental exposure to industrial chemicals including per- and polyfluoroalkyl substances (PFAS) may play a role in bone development and future risk of osteoporosis. We aim to develop an up-to-date understanding of the effects of PFAS on bone mineral density (BMD) and identify the gaps in current literature that can be explored in future studies.

Main Body:

A PubMed search was performed using the terms PFAS, bone density and osteoporosis, yielding 44 results. Titles and abstracts were screened for relevance. Of the remaining articles (22), we reviewed studies related to pediatric (9) and adult (8) populations. Three articles discussed the biochemical effects of PFAS on physiologic receptors and cell types. Significant findings were extracted and synthesized. Studies included both cross-sectional and longitudinal samples.

The current literature demonstrates gaps in current knowledge about the pharmacokinetic and pharmacodynamic properties of PFAS in both animal models and human studies. There is limited data on what receptors, cells, and bones PFAS may impact. Even fewer studies exist that directly examine potential correlations between physiological changes induced by PFAS and the long term clinically significant effects of these changes.

Animal models and in vitro studies have found that PFAS are able to bind to and influence the activity of different transcription factors, receptors, and cells. PFAS were also shown to alter the differentiation andactivity of human bone cells. However, deposition and cellular effects of PFAS differed across different tissue types and body compartments. The literature revealed a significant inverse correlation between the serum concentration of PFAS and BMD in both adult and pediatric populations. However, one study did not find a significant association, and results were inconsistent across sexes.

Additionally, few studies demonstrated a clinically significant effect on bone pathologies, such as osteoporosis and pathological fractures. This is especially apparent in the dearth of studies that include adults over the age of 80, for whom bone pathologies pose a risk of considerable morbidity and mortality.

The studies reviewed rarely divided adults into smaller cohorts of exposure to PFAS mediates downstream pathophysiological effects. Many studies' statistical analyses. It is unknown how length treated adults with a wide age distribution, and therefore varying lengths of exposure, as a homogenous sample; this may have modified the observed correlations between PFAS and BMD based on age ranges.

These studies also struggled to explore the interaction between socioeconomic status (SES) and PFAS. One study demonstrated higher levels of PFAS in individuals of higher SES. However, SES was not used as a predictor of the strength of the relationships between PFAS and BMD. Further research should be conducted to examine how protective factors (such as access to healthcare, diet, and occupational hazards) associated with higher SES may mitigate the harmful effects of PFAS.

Conclusions:

The inverse correlation of PFAS and BMD has been extensively demonstrated across different populations and age groups. Nonetheless, significant correlations are inconsistent across studies. Further research should be done to elucidate the true relationships between BMD and PFAS. Understanding how factors such as age and SES affect the strength of known correlations between PFAS and BMD, and how these translate to clinical outcomes, are areas that merit further investigation. Large gaps still exist in our understanding of the potential effects, and their underlying mechanisms, that these ubiquitous substances have on normal physiology and various bone pathologies. More cause-and-effect relationships need to be brought to light by further research in order to educate healthcare providers in the development of meaningful clinical recommendations.