Appraisal Bone Cancer

Osteosarcoma fluoride study only provided hypotheses to explore

Publication reviewed:

Age-specific fluoride exposure in drinking water and osteosarcoma (United States)

Bassin EB, Wypij D, Davis RB — 2006 Cancer Causes and Control 17(4):421-8


The authors of this osteosarcoma fluoride study examined age-specific and gender-specific effects of fluoride level in drinking water and the incidence of osteosarcoma using a matched case–control study design. The study was conducted through 11 hospitals in the United States that included a complete residential history for each patient and type of drinking water (public, private well, bottled) used at each address. Their exploratory analysis, based on 103 cases under the age of 20 and 215 matched controls, plotted the impact of different assessments of exposure for the cases and controls. This method showed that by using fluoride level at each of the ages 4 to 12 years as the exposure definition, there was an increased adjusted odds ratio for males in the higher fluoride exposure group. The adjusted odds ratio was highest for males when exposure to fluoride at age 7 was used. This exploratory approach did not find a similar pattern among females. The authors concluded that their analysis found an association between fluoride exposure in drinking water during childhood and the incidence of osteosarcoma among males but not among females. The authors urged further research to confirm or refute this observation.


  • 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.


Hospital-based case-control study involving 11 hospitals in the United States. Age-matched controls. Telephone interviews. Good sample size. Exploratory approach allows hypothesis generation for future investigation.


Case-control studies are prone to selection bias. Recalling residence history in an interview can be difficult for some people.


The authors used an exploratory approach to assess different age-specific definitions of exposure to fluoride in terms of the strength of association with osteosarcoma status. The association was positive when fluoride exposure was defined as exposure for any age from 4 to 12 years, but only for males. Since the same subjects are used in the analysis, a limitation of the exploratory assessment is that any random error in the sampling of controls, or errors in reporting fluoride exposure in the interview may undermine the findings. Since it is exploratory, the statistical inference is not the same as hypothesis testing.