Journal of Bone and Mineral Research

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Abstract
Histomorphometric analysis of undecalcified sections was performed in transiliac biopsy cores taken 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, bone fluoride content was significantly high in each specimen (mean ± SD: 0.79 ± 0.36% of bone ash) as compared to control values (< 0.10%). The radiologically evident osteosclerosis observed in each patient was confirmed by the significant increase of 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 vs. 934 ± 173 μm, p < 0.0001) and porosity (14.4 ± 6.4 vs. 6.5 ± 1.7%, p < 0.002), but without reduction of cortical bone mass. Osteoid parameters were significantly increased in fluorotic patients. The increase in cancellous osteoid perimeter was almost threefold greater than that noted in cancellous eroded perimeter. The fluorotic group had a greater number of osteoblasts than controls, with a very high proportion of flat osteoblasts. In 15 patients doubly labeled with tetracycline, the mineral apposition rate was significantly decreased, while mineralization lag time significantly increased. Bone formation rate and adjusted apposition rate were significantly decreased in skeletal fluorosis. Cancellous wall width was normal in fluorosis but the formation period and active formation period were significantly increased. Skeletal fluorosis is thus characterized by an unbalanced coupling in favor of bone formation, and also by a great number of osteoblasts with a high proportion of flat osteoblasts. These osteoblasts have a very increased formation period mainly due to a prolonged inactive formation period. Our results support the view that fluoride may have a dual effect on osteoblasts: an increased birthrate at the tissue level, 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.

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