The effect of olpadronate in ovariectomized thyroxine-treated rats

Abstract

Hyperthyroidism increases bone turnover and induces bone loss. This study examines the effect of thyroid hormone excess on two biochemical markers of bone turnover (hydroxyproline and bone alkaline phosphatase) as well as on bone mineral content (BMC) and bone mineral density (BMD). The possible protective role of dimethyl-APD (olpadronate, OLP), on both suppression of bone turnover and bone mineral loss in ovariectomized (ovx) rats, was also studied. Female Sprague-Dawley rats, were assigned to five groups of eight rats each: sham, ovx, ovx OLP treated (0.3 mg/kg per week), ovx T 4 treated (250 μg/kg per day), and ovx T 4-OLP rats. Rats were killed after 5 weeks of treatment. At the end of the study, blood samples were analyzed for serum calcium, phosphorus, T 4, total and bone alkaline phosphatase (ALP and b-ALP), and urinary samples for hydroxyproline/creatinine ratio (HOProl/creat). Moreover, total BMC, BMD, and scanned area were determined by DXA. Ovx T 4-OLP-treated rats presented higher values of b-ALP than ovx T 4-treated, ovx, and sham rats ( p < 0.05). Ovx increased HOProl/creat excretion compared with sham ( p < 0.05), but it was similar compared with ovx T 4-treated rats. OLP treatment reduced HOProl/creat excretion in both ovx T 4-treated ( p < 0.05) and ovx rats ( p < 0.05). The final BMC in ovx was lower than in the sham group, but the difference was not statistically significant ( p < 0.08). The lowest BMC was observed in ovx T 4 rats ( p < 0.05). When final BMC was expressed per body weight (BMC/W), ovx rats presented a significantly lower BMC/W than sham rats ( p < 0.05). Ovx OLP rats had BMC/W levels higher than ovx ( p < 0.005), ovx T 4 ( p < 0.01), and ovx T 4-OLP rats ( p < 0.01). The ovx group had a final BMD lower than sham animals ( p < 0.05), but not significantly different than the ovx T 4 rats. BMC and BMD of OLP ovx rats, whether they received T 4 or not, was similar to the sham group. The highest final BMD was observed in the ovx T 4-OLP group. In summary, the prevention of an increase in HOProl excretion accompanied by the fact that final BMD and BMC in OLP-treated animals were comparable to sham control rats may reflect that OLP administration could inhibit bone resorption in both T 4-treated or -untreated rats. Although further studies are necessary, these findings may have clinical relevance in estrogen-depleted patients to whom medical management other than the reduction of T 4 administration would be desirable.