Glycosaminoglycan alterations in rat bone due to growth and fluorosis

Evidence in the literature has suggested that alterations in bone glycosaminoglycans (GAGs) are at least partially responsible for the defective calcification in skeletal fluorosis. The major objectives of this study were to quantitate the GAGs of bone from normal and fluorotic rats and to characterize the change in bone GAGs that occurred during maturation. Weanling male rats were fed a semipurified diet and deionized water with or without fluoride (125 ppm) for 1 or 2 months. Also, a control group of rats was pair-fed to the rats receiving fluoride. GAGs were isolated from dry, fat-free tibias and then quantitated by digestion with chondroitinases and chondrosulfatases. Chondroitin-4-sulfate (C4S) comprised 90% of the bone GAGs, while chondroitin-6-sulfate (C6S), dermatan sulfate (DS) and hyaluronic acid (HA) together comprised about 10% of the total bone GAGs. With increasing age, total GAGs, C4S and HA decreased in amount, but DS remained constant. Fluorotic bone (containing in excess of 5000 ppm of fluoride) had three times as much C6S and twice as much DS as bone from weight- and age-matched control rats. Thus, using a controlled experimental animal model, we have demonstrated that specific alterations of bone GAGs result from fluorosis independently of changes in body weight and age.