In chronic renal insufficiency (CRI), serum levels of fluoride (F-) are elevated. However, there is limited information about the effects of F- on bone in CRI. In this study, we determined whether F- content in mineralizing tissue (growth plate, cortical bone, and bone marrow of the femur) is affected by uremia. Adult rats were divided into two groups [sham-operated (S) and 5/6 nephrectomized (Nx)]. At sacrifice, the serum creatinine (mg/dl) in the S and 5/6 Nx animals was 0.37+/-0.09 (mean+/-SD) and 1.10+/-0.34 at 4 weeks, and 0.38+/-0.04 and 0.90+/-0.36 at 8 weeks, respectively. The serum calcium, phosphorus, and parathyroid hormone levels were lower and the serum 1, 25-dihydroxyvitamin D levels were higher in S animals than Nx animals at both 4 and 8 weeks. F- urinary excretion (ppm/24 h) was reduced in Nx animals at 4 weeks (34.0+/-19.2) versus S animals (50.7+/-12.9) (P<0.05). F content (ppm) was significantly increased in the growth plate in Nx animals compared with S animals both at 4 weeks (550+/-167 vs. 353+/-63) and at 8 weeks (654+/-135 vs. 396+/-97), respectively (P<0.01). The F- content in cortical bone was similarly increased in Nx animals compared with S animals, but was only statistically increased at 8 weeks. There was no difference in bone marrow F- content between the two groups. In conclusion, this study suggests that in CRI, there is a rapid increase in F- content of the distal femur in the growth plate region, with a subsequent slower increase of F- content in cortical bone.
In summary, we demonstrate an increased F– content in the growth plate region of the femur at 4 weeks and 8 weeks, and in cortical bone at 8 weeks, in rats with experimental
CRI. We hypothesize that elevated serum F– levels might contribute to the disturbances in mineral ion homeostasis that are observed in patients with CRI. This is of particular concern since the incidence of dental fluorosis has increased due to increased F– uptake from multiple fluoridated sources . The ubiquitous presence of F– in food and beverage products regardless of the degree of water fluoridation suggests that the overall F– exposure in individuals with CRI may need to be more closely monitored. Furthermore, investigations are underway in younger animals to determine if high serum F– levels associated with CRI interfere with normal mineralization at the level of the growth plate, and possibly contribute to the growth retardation that occurs during the active growth period.