Skeletal fluorosis: Histomorphometric analysis of bone changes and bone fluoride content in 29 patients

Abstract

Bone fluoride content (BFC) was measured and histomorphometric analysis of undecalcified sections was performed in transiliac biopsy cores from 29 patients (16 men, 13 women, aged 51 ± 17 years) suffering from skeletal fluorosis due to chronic exposure to fluoride. The origin of the exposure, known in 20 patients, was either hydric (endemic or sporadic) or industrial, or in a few cases iatrogenic. Measured on calcined bone using a specific ion electrode, BFC was significantly high in each specimen ( mean ± SD; 0.79 ± 0.36% on bone ash). The radiologically evident osteosclerosis observed in each patient was confirmed by a significant increase in cancellous bone volume (40.1 ± 11.2% vs. 19.0 ± 2.8% in controls, p < 0.0001). There were significant increases in cortical width (1292 ± 395 mem vs. 934 ± 173 mcm, p < 0.0001) and porosity (14.4 ± 6.4% vs. 6.5 ± 1.7%, p < 0.002), but without reduction of cortical bone mass. Cancellous osteoid volume and perimeter, as well as width of osteoid seams, were significantly increased in fluorotic patients. The increase in cancellous osteoid perimeter was almost three-fold greater than that noted in cancellous eroded perimeter. In 15 patients doubly labeled with tetracycline, the mineral apposition rate was significantly decreased, mineralization lag time was significantly increased. The fluorotic group had a greater number of osteoblasts than controls with a very high proportion of flat osteoblasts. The ultrastructural characteristics reflecting the activity of the bone cells were clearly visible on electron microscopy. Bone formation rate and adjusted apposition rate were significantly decreased in skeletal fluorosis. On stained sections and microradiographs, bone tissue showed typical modifications for skeletal fluorosis (linear formation defects, mottled bone). The volume of cancellous interstitial mineralization defects and the proportion of mottled periosteocytic lacunae were markedly increased in skeletal fluorosis. These two parameters were significantly correlated together but neither of these was significantly correlated with BFC. Renal function did not significantly influence the changes in BFC and histomorphometry of fluorotic patients. Skeletal fluorosis is thus characterized by an unbalanced coupling in favor of bone formation, and a great number of osteoblasts with a high proportion of flat osteoblasts. This may explain the mineralization impairment proven by thick osteoid seams and reduced mineral apposition rate, and supports the view that fluoride may have a dual effect on osteoblasts: a probable increased birthrate at the tissue-level due to a mitogenic effect of fluoride on precursors of osteoblasts, and a toxic effect at the individual cell-level. The addition of these two effects represents, however, a marked increase of bone formation at the organ level.