The effect of prolonged fluoride therapy for osteoporosis: bone composition and histology.

To examine the long-term effects of fluoride therapy in osteoporosis, we obtained iliac crest biopsies from 11 osteoporotic patients 6 to 12 years after they had started fluoride therapy. Although basal biopsies were not obtained, nine subjects had been biopsied 4 years prior to the second biopsy. In addition, 4 subjects had stopped fluoride therapy prior to the second biopsy. Biopsy samples were divided and analyzed: (a) histomorphometrically for bone formation and mineralization; and (b) for mineral content. Parameters of bone formation were increased in the first biopsy of all patients; they remained elevated in the second biopsy of subjects still receiving fluoride, but decreased to normal values in subjects who stopped fluoride therapy. Parameters of mineralization (i.e., osteoid width and osteocytic osteoid) were elevated in the first biopsy, but had decreased in the second biopsy whether fluoride was stopped or not. There was no woven bone in these biopsies. Bone mineral content, whether measured as density or by summation of the individual ions (% mineral), was higher than normal in all subjects, whether or not they were still receiving fluoride. These results suggest that prolonged fluoride therapy of osteoporosis continues to stimulate bone formation, but does not cause a progressive mineralization defect. Mineral content is acutely increased following fluoride therapy, and persists after therapy is discontinued.