Appraisal Bone Cancer

No association between bone fluoride and osteosarcoma

Publication reviewed:

An assessment of bone fluoride and osteosarcoma

Kim FM, Hayes C, Williams PL, Whitford GM, Joshipura KJ, Hoover RN, Douglass CW, and the National Osteosarcoma Etiology Group — 2011 Journal of Dental Research 90(10): 1171-6


The purpose of this study was to assess whether fluoride levels in bone were associated with osteosarcoma. A case-control design was used to compare bone fluoride levels in 137 subjects with primary osteosarcoma (cases) with 51 controls that had other malignant bone tumors. The median age of cases was 17.6 years old. The median age of controls was 41.3 years old. The gender distribution also differed with 53 percent of cases being male compared to 71 percent of controls. A subset of 32 cases was matched with controls based on gender and age. The study did not demonstrate an association between fluoride levels in bone and osteosarcoma. This was true even after adjusting for age and gender in the statistical analysis in the unmatched cases and controls.


  • A – Strong methodology and unbiased, appeared in peer-reviewed in respected science journal
  • B – Strong methodology and unbiased, not in peer-reviewed journal
  • C – Weak methodology and/or biased
  • F – Not a scientific finding


  • High – All the peer-reviewed research to date support these findings, and a significant amount of research has been done in this area.
  • Medium – Most, but not all, peer-reviewed research to date support these findings, and a significant amount of research has been done in this area.
  • Low – Not a lot of research has been done in this area, or some, but not most, other peer-reviewed research supports these findings.
  • Not Supported – No other studies support this study’s conclusions.
  • Contradicted – Most studies contradict this study’s conclusions.


Direct measurement of fluoride in bone. A large sample of cases (n=200) and controls (n=114) were recruited. A careful assessment to rule out bias and alternative explanation. A thorough discussion of the limitations.


Age-matching of controls was abandoned early in the study, so only 32 age-matched pairs were available for analysis. If risk of osteosarcoma is related to exposures at a specific time in life rather than total accumulated dose, then this study would not be able to detect the risk.


This is a hospital-based case control study involving 9 hospitals across the US. The initial study protocol called for matching controls on gender and age. Because it was difficult to recruit controls, this was abandoned early in the study.