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Rich dietary sources of fluoride include teas and marine fish. Many medications contain <br /> fluoride such as quinolone antibiotics and statins,but the exposure is probably minimal as <br /> long as their metabolism does not release free fluoride. One inhalational drug exposure <br /> example is the hepatic biotransformation of the anesthetic methoxyflurane to release free <br /> fluoride, resulting in nephrotoxicity.12'13 However, other anesthetics that resulted in <br /> commensurately increased systemic fluoride levels were not associated with <br /> nephrotoxicity. One recent paper concluded that the nephrotoxicity of methoxyflurane is <br /> related at least in part to the dichloroacetic acid metabolite.13 <br /> Fluoride Health Risks: Dental or enamel fluorosis is a hypomineralization of the <br /> enamel surfact of the tooth that develops in children 8 years old and younger exposed to <br /> excess fluoride levels from any source during critical periods of tooth development. This <br /> affects the appearance of the teeth. Milder forms are primarily cosmetic, but may have <br /> effects on self-esteem. Severe forms include pitting of the enamel. <br /> Skeletal fluorosis is a rare condition associated with high levels of fluoride exposure over <br /> many years. There are six cases reported in the US,two of which had CKD.2 Symptoms <br /> may include bone pain and arthralgias.14,"5 Characteristics include increased bone mass <br /> and increased radiographic bone density or osteosclerosis. Renal osteodystrophy may be <br /> difficult to distinguish from skeletal fluorosis on imaging studies. The mechanism of <br /> renal osteodystrophy development is complex including calcium, phosphorus, <br /> parathyroid hormone and vitamin D interactions. A bone biopsy series to assess the <br /> effects of trace metals in 153 CKD patients treated with hemodialysis or peritoneal <br /> dialysis revealed that increased fluoride was associated with poor mineralization and <br /> increased osteoid content.15 There were no cases of skeletal fluorosis in this series.15 <br /> Fluoride may interact with aluminum to worsen osteomalacia. The interaction of fluoride <br /> with magnesium is poorly understood. <br /> The NRC committee noted that under certain conditions fluoride can weaken bone and <br /> increase the risk of fractures. The committee concluded that lifetime exposure to fluoride <br /> at drinking water concentrations of 4 mg/L or higher is likely to increase fracture rates in <br /> the population compared to exposure of 1 mg/L,particularly in subgroups that are prone <br /> to accumulate fluoride into their bones(e.g.,people with CKD).2 However, there is <br /> insufficient evidence to validate the concerns regarding persons with CKD, even at <br /> fluoride concentrations of 4 mg/L. <br /> Fluoride Risks in CKD: <br /> CKD Stages 1-3: Patients with an estimated GFR of 30 ml/min/1.73 m2 or more <br /> probably have a similar risk to individuals without CKD, although there is little <br /> specific data to support this conclusion. <br /> CKD Stages 4, 5 and 5 D: Patients with an estimated GFR less than <br /> approximately 25 ml/min/1.73m2 retain more fluoride than healthy individuals <br /> based on older studies that used creatinine clearance to assess kidney <br /> function.2°16'17 Fluoride blood levels are approximately 4-fold higher or about 4 <br /> umol/L in patients with CKD stages 4 and 5. The significance of this fmding is <br />