Critical Review

The abnormal bone denseness resulting from fluoride is of poor quality and, while the increased density helps compression strength, it generally leads to weakness of tensile strength. Thus, previous tests ^2-4 of fluoride "treatment" for osteoporosis finds a decrease in vertebral (compression) fractures but an increased incidence of hip and long bone fracture, compared to control patients, after four years or so of the treatment. Other researchers have advised abandoning fluoride as a legitimate treatment of osteoporosis for that reason and fluoride's toxicity ⁵. Dr Pak et al are intent on detecting a difference in vertebral compression fractures, no matter how minor and insignificant that is in treating osteoporosis.

In clinical practice, the occurrence of atraumatic minor compression fractures of vertebra is common in postmenopausal osteoporotic women and is frequently asymptomatic, being found only by radiographs though the patient may have noted a slight decrease in her height over time. The more morbid consequence of osteoporosis is hip fracture which has the potential for seriously disabling patients. Thus, the goal of osteoporosis research should be directed to prevention of loss of tensile strength of bones, not merely compression strength. The protocol for Dr Pak's USPH funded and FDA approved investigational new drug application for Mission Pharmacal Company seems limited to demonstrating the obvious, i.e., that excessive fluoride causes osteofluorosis.

In his study, Dr Pak is administering about 25 mg of fluoride per day in a slow release form to postmenopausal women in order to raise their serum fluoride levels from 50 ng/ml to slightly over 100 ng/ml while avoiding fluoride's known gastric inflammatory effects such as mucosal erosions, ulcers, and bleeding which regularly accompany usual oral fluoride supplementation at this dosage. While the slow release form of administration will protect against these particular gastric symptoms of fluoride toxicity, it will likely have little or no effect on the later connective tissue abnormalities routinely resulting from fluoride intake at this level. In this report, the average duration of fluoride supplement exposure of the treated women is a little under two and one-half years. Since bone turnover time in postmenopausal women is relatively slow, one would not expect the decrease of bone tensile strength (and increase in incidence of hip fractures) to occur for several more years.

The one interesting finding in Dr Pak's interim report is the fact that fluoride supplementation did not cause any reduction in vertebral fractures in women on estrogen supplementation compared to controls. Among estrogen-treated women, the fracture-free rate of placebo (no fluoride) group compared to that of the fluoride group was 75.0% and 76.9% respectively, an inconsequential difference. Dr Pak et al. in commenting on this non-difference, rather obliquely state that "No statistical differences related to estrogen treatment were noted between the slow-release sodium fluoride and placebo groups in estrogen-treated patients, probably because of the small sample size." Unstated is corollary that, in women on estrogen replacement therapy, fluoride treatment offers no possible benefit, regardless of how minor it is or regardless of the potential toxicity of fluoride.

Further, if one looks at the reasoning underlying the context of fluoride treatment for osteoporosis in the light of multiple trials in the US and world-wide, the idea of a therapeutic window for fluoride dosage appears quite remote. As mentioned above, prior studies of "therapeutic" fluoride supplementation found an increase in hip fractures in the treated groups compared to controls, and a number of good studies ^6-9 have shown hip fracture incidence is statistically significantly correlated with even the lower fluoride levels as found in fluoridated communities, compared to non-fluoridated communities. To believe that some dosage range between these two ranges of fluoride intake will be effective in preventing osteoporotic hip fractures is a true stretch of the imagination. Certainly no one believes that osteoporosis is a disease of fluoride deficiency.

Finally, regardless of the ultimate outcome of this study, it obviously has no bearing on the question of water fluoridation. In summary: Dr Pak's trial of inducing what is essentially a controlled form of osteofluorosis (osteosclerosis) in postmenopausal women, and attempting to prove its effectiveness by measuring the incidence of radiographically-identifiable vertebral fractures is inherently flawed and has little relevance to effective treatment of osteoporosis.

2 Riggs BL, Hodgson SF, O'Fallon WM et al. Effect of fluoride treatment on the fracture rate in postmenopausal women with osteoporosis, New England Journal of Medicine 322 802-809 1990.

3 Kleerekoper M, Peterson E, Philips E et al. Continuous sodium fluoride therapy does not reduce vertebral fracture rate in postmenopausal osteoporosis, Journal of Bone and Mineral Research 4 (Suppl 1) S376 1989 (Abstract).

4 Hedlund LR, Gallagher JC, Increased incidence of hip fracture in osteoporotic women treated with sodium fluoride, Journal of Bone and Mineral Research 4 223-225 1989.

5 Avioli LV, Fluoride treatment of osteoporosis, Postgraduate Medicine: Special Report 26-27 September 1987.

6 Sowers MFR, Clark MK, Jannausch ML, Wallace RB, A prospective study of bone mineral content and fracture in communities with differential fluoride exposure, American Journal of Epidemiology 133 649-660 1991.

7 Jacobsen SJ, Goldberg J, Miles TP et al. Regional variation in the incidence of hip fracture among white women aged 65 years and older, Journal of the American Medical Association 264 500-502 1990.

8 Cooper C, Wickham C, Lacey RF, Barker DJP, Water fluoride concentration and fracture of proximal femur, Journal of Epidemiology and Community Health 44 17-19 1990.

9 Danielson C, Lyon JL, Egger M, Goodenough GK, Hip fractures and fluoridation in Utah's elderly population, Journal of the American Medical Association 268 746-748 1992.

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