Safety Control of Fluoride in Osteoporosis

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Pioneering fluoride researchers demonstrated many years ago that when F-treatment is withdrawn, accumulated bone-F is slowly mobilized and excreted in the urine.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].

[Figure 1]

[Figure 2]


  1. MW Lundy et al: Histomorphometric Analysis of Illiac Crest Bone Biopsies in Placebo-Treated Versus Flouride-Treated Subjects. Osteoporosis Intl 5:115-129, 1995.
  2. CYC Pak: in Transcript of FDA Advisory Committee Meeting #61 on November 15, 1995, P. 24.
  3. CYC Pak et al: Sustained-Release Sodium Fluoride in the Management of Established Postmenopausal Osteoporosis. AmJ Med Sci 313:23-32, 1997.
  4. EJ Largent in World Health Organization Monograph Series No. 59: "Fluorides and Human Health", Geneva, 1970, P. 158.
  5. ME Cohen-Solal et al: Osteomalacia Is Associated with High Bone Fluoride Content In Dialysis Patients. Bone 19(Suppl):135S, Abstract #24, 1996.
  6. LH Turner et al: High Fluoride Intakes Cause Osteomalacia and Diminished Bone Strength in Rats with Renal Deficiency. Bone 19:595-601, 1996.