Exposure to fluoride and risk of primary bone cancer: A systematic review

Fluoride has long been considered essential in the prevention of dental caries, however, its relationship with bone cancer remains unclear. With little improvements in survival from primary bone cancers, it is important to understand the underlying drivers. The focus of this systematic review was, therefore, to assess the association between fluoride exposure and the development of primary bone cancer. The review was conducted as per the PRISMA guidelines and was registered on PROSPERO (CRD42021296109) with a search cut-off of March 2024. In total, 14 studies, involving 8680 participants across all age groups, were identified examining the effects of fluoride exposure on humans investigated for primary bone cancer. Of the 14 studies, only two reported a positive association between fluoride and primary bone cancer. One study including 88 participants reported a positive association between water fluoridation and osteosarcoma development (in young males between 0 and 20 years of age), and the second study, with an unreported number of participants, reported this positive association with bone cancers in males. No association between fluoridation and bone cancer development was reported in the remaining studies. Across all 14 studies, data was presented in a narrative synthesis with subgroup analysis conducted on study design, age, sex, fluoride level and quality score. Both studies reporting a positive association between fluoride and bone cancer identified this association in males, however, both studies concluded that further research is needed. Here we report the most comprehensive systematic review to date examining associations between fluoride exposure and primary bone cancer. We also highlight some of the methodological limitations of some studies, and identify the need, and opportunity, to conduct a large, prospective study to address this and other health issues associated with fluoride.