All fluoride activity is local. High concentrations in the stomach can irritate gastric tissue, and excessive concentrations at bone sites, where it slowly accumulates, can excessively stimulate bone formation, such that there is an overwhelming calcium demand, resulting in a mineralization defect(1). By using a very low, and slow, bioavailable dosage system (and a two-month withdrawal after each year of daily treatment), Pak et al. have avoided local toxicities, while retaining maximum antifracture benefits, depending on the severity of the disease. A favorable confirmatory study is in process.
Pioneering fluoride researchers demonstrated many years ago that when F-treatment is withdrawn, accumulated bone-F is slowly mobilized and excreted in the urine. This has recently been confirmed by Pak in 1995 (2).
All fluoride activity is local, mainly at the bone. Bone provides a
"reservoir" of F, but when retention increases beyond a threshold level,
toxicity results. It is not the administered or absorbed dosage per
se, but the accumulated retained dosage at the bone that is
crucial for safety. When bone-F exceeds 0.6%-0.7% bone ash (Accumulative
Overdosage), bone formation becomes overstimulated, resulting in a
mineralization defect. The Pak four-year dosage system, unlike that of
all others, results in a safe accumulated bone-F content, well below
the toxic bone level (3). [See Figure 1 below]. Withdrawal of
F-treatment causes slow mobilization of retained bone-F, which can be
detected in the urine indicating a loosely-bound phase of fluoride at
the bone site. [See Figure 2 below].