susceptible demographic groups that are more prone to accumulate fluoride in their bones. However, three of the 12 members judged that the evidence only supported a conclusion that the MCLG might not be protective against bone fracture. They judge that more evidence that bone fractures occur at an appreciable frequency in human populations exposed to fluoride at 4 mg/L is needed before drawing a conclusion that the MCLG is likely to be not protective.
Few studies have assessed fracture risk in populations exposed to fluoride at 2 mg/L in drinking water. The best available study was from Finland, which provided data that suggested an increased rate of hip fracture in populations exposed to fluoride at >1.5 mg/L. However, this study alone is not sufficient to determine the fracture risk for people exposed to fluoride at 2 mg/L in drinking water. Thus, the committee finds that the available epidemiologic data for assessing bone fracture risk in relation to fluoride exposure around 2 mg/L are inadequate for drawing firm conclusions about the risk or safety of exposures at that concentration.
A more complete analysis of communities consuming water with fluoride at 2 and 4 mg/L is necessary to assess the potential for fracture risk at those concentrations. These studies should use a quantitative measure of fracture such as radiological assessment of vertebral body collapse rather than self-reported fractures or hospital records. Moreover, if possible, bone fluoride concentrations should be measured in long-term residents.
The effects of fluoride exposure in bone cells in vivo depend on the local concentrations surrounding the cells. More data are needed on concentration gradients during active remodeling. A series of experiments aimed at quantifying the graded exposure of bone and marrow cells to fluoride released by osteoclastic activity would go a long way in estimating the skeletal effects of this agent.
A systematic study of stage II and stage III skeletal fluorosis should be conducted to clarify the relationship of fluoride ingestion, fluoride concentration in bone, and clinical symptoms. Such a study might be particularly valuable in populations in which predicted bone concentrations are high enough to suggest a risk of stage II skeletal fluorosis (e.g., areas with water concentrations of fluoride above 2 mg/L).
More research is needed on bone concentrations of fluoride in people with altered renal function, as well as other potentially sensitive populations (e.g., the elderly, postmenopausal women, people with altered acid-balance), to better understand the risks of musculoskeletal effects in these populations.