TAMOXIFEN ATTENUATES THE EFFECTS OF EXOGENOUS GLUCOCORTICOID ON BONE-FORMATION AND GROWTH IN PIGLETS

Tamoxifen (Tam) has been shown to inhibit dexamethasone (Dex)-mediated effects on bone formation in vitro. Our objective was to determine wh ether Tam would block Dex-induced osteopenia and growth inhibition in growing piglets. Four-day-old male Yorkshire piglets were adapted to a liquid formula diet (400 ml/kg.day) and randomized to one of four gro ups (n = 5/group): Dex (0.5 mg/kg.day), Tam (1 mg/kg.day), Dex plus Ta m, or placebo control (vehicle only). Both drugs were administered by orogastric gavage twice daily for 12 days. At baseline and at the end of treatment, whole body bone mineral density (BMD) was determined by dual energy x-ray absorptiometry (Hologic QDR1000W). Plasma osteocalci n and PTH were measured on days 0 and 12, and urinary N-telopeptide wa s measured on day 12. Changes in axial length and daily weight were al so measured. Delta whole body BMD was 29% lower (P < 0.05) in Dex alon e treated piglets than in controls (0.033 vs. 0.047 g/cm(2), respectiv ely), whereas the maximum change in BMD in Dex plus Tam group (0.046 g /cm(2)) was similar to that in controls. Concurrent Tam administration reduced the Dex-induced deficit in weight gain by 56% (P < 0.05) and the deficit in axial length gain by 72% (P < 0.01). In Dex alone treat ed piglets, PTH was significantly elevated (7-fold), whereas osteocalc in and N-telopeptide were significantly reduced compared with control values. These effects were prevented by Tam. These data suggest that t he suppression of growth and other changes in parameters of bone metab olism induced by glucocorticoids in vivo can be attenuated by Tam.