Fluoride toxicity: A tale of two sources

Abstract

The aim of this study was to identify the cause and source of two patients’ clinical manifestations. Case#1 was a 47-year-old male with diffuse bone pain and weakness aggravated by exertion. Past medical history revealed two surgeries for a left fibular fracture with eventual resection of installed hardware. Current medications included: oxycodone, montelukast, and vitamin D3. Magnetic resonance imaging and x-ray showed L5–6 fusion and diffuse trabecular thickening. A pelvic bone biopsy showed features consistent with severe skeletal fluorosis. Case#2 was a 61-year-old male post-heart transplant patient. His medications included: cyclosporine A, prednisone, rosuvastatin, amlodipine, and voriconazole. He complained of joint pain, his alkaline phosphatase was 222 U/L (reference range 40–129 U/L), and his bone density scan showed periostitis. Fluoride was measured in heparinized-plasma in both patients using a fluoride ion-selective-electrode on an Orion™ Dual Star pH/ISE meter (Thermo Scientific). The analytical measurement range is 4.0–21.0 μmol/L with an upper reporting limit of 105 μmol/L. Case#1 and case#2 had plasma fluoride concentrations of 11.3 and 17.5 μmol/L, respectively (reference-range < 4 μmol/L). Fluoride is often added to drinking water, toothpastes, and mouth rinses to prevent dental cavities. While food generally contains low levels of fluoride, tea and seafood have been found to have higher levels. Several medications containing fluorine are used for treating skin diseases and cancer. Following ingestion, plasma concentrations peak within an hour and up to 50% is stored in bones/teeth while the rest is primarily eliminated in the urine. The average person ingests ∼2–3 mg fluoride per day with a recommended daily intake of 3–4 mg/day by the United States Department of Agriculture. Chronic ingestion exceeding 20 mg/day can pose a risk to bone health leading to denser brittle bones, joint pain, and limited joint movement. In case#1, the source of fluoride was identified as excessive consumption of strong black tea (> 10 servings per day). In case#2, voriconazole (trifluorinated antifungal) was associated with the development of excess fluoride and periostitis. Plasma fluoride testing can be useful for diagnosing acute environmental toxicity, as well as, monitoring those taking fluorine-containing drugs. Detailed patient histories are required to identify common (voriconazole) or less-common (tea) sources. Patient#1 limited his tea consumption to one cup/day and his fluoride levels returned to normal on follow-up three months later. Patient#2 was switched from voriconazole to itraconazole (nonfluorinated triazole) and fluoride levels returned to normal. Pain resolution or improvement was also noted in both cases.