THE EFFECT OF OLPADRONATE IN OVARIECTOMIZED THYROXINE-TREATED RATS

Hyperthyroidism increases bone turnover and induces bone loss. This st udy examines the effect of thyroid hormone excess on two biochemical m arkers of bone turnover (hydroxyproline and bone alkaline phosphatase) as well as on bone mineral content (BMC) and bone mineral density (BM D). The possible protective role of dimethyl-APD (olpadronate, OLP), o n both suppression of hone turnover and bone mineral loss in ovariecto mized (ovx) rats, was also studied. Female Sprague-Dawley rats, were a ssigned to five groups of eight rats each: sham, ovx, ovx OLP treated (0.3 mg/kg per week), ovx T-4 treated (250 mu g/kg per day), and ovx T -4-OLP rats. Rats were killed after 5 weeks of treatment. At the end o f the study, blood samples were analyzed for serum calcium, phosphorus , T-4, total and bone alkaline phosphatase (ALP and b-ALP), and urinar y 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, o vx, and sham rats (p < 0.05). Ovx increased HOProl/creat excretion com pared with sham (p < 0.05), but it was similar compared with ovx T-4-t reated 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 w as lower than in the sham group, but the difference was not statistica lly significant (p < 0.08). The lowest BMC was observed in ovx T-4 rat s (p < 0.05). When final BMC was expressed per body weight (BMC/W), ov x rats presented a significantly lower BMC/W than sham rats (p < 0.09) . (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), hut not significantly differe nt than the ovx T-4 rats. BMC and BMD of OLP ovx rats, whether they re ceived T-4 or not. was similar to the sham group. The highest final BM D 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 BM D and BMC in OLP-treated animals were comparable to sham control rats may reflect that OLP administration could inhibit bone resorption in b oth T-4-treated or -untreated rats. Although further studies are neces sary, these findings may have clinical relevance in estrogen-depleted patients to whom medical management other than the reduction of T-4 ad ministration would be desirable. (C) 1997 by Elsevier Science Inc. All rights reserved.