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 whether 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 x day) and randomized to one of four groups (n = 5/group): Dex (0.5 mg/kg x day), Tam (1 mg/kg x day), Dex plus Tam, 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 osteocalcin and PTH were measured on days 0 and 12, and urinary N-telopeptide was measured on day 12. Changes in axial length and daily weight were also measured. Delta whole body BMD was 29% lower (P < 0.05) in Dex alone treated piglets than in controls (0.033 vs. 0.047 g/cm2, respectively), whereas the maximum change in BMD in Dex plus Tam group (0.046 g/cm2) 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 treated piglets, PTH was significantly elevated (7-fold), whereas osteocalcin and N-telopeptide were significantly reduced compared with control values. These effects were prevented by Tam. These data suggest that the suppression of growth and other changes in parameters of bone metabolism induced by glucocorticoids in vivo can be attenuated by Tam.
Medical Research Council Group in Periodontal Physiology, Faculty of Dentistry, University of Toronto, Ontario, Canada.
P C
PC
Fritz
W E
WE
Ward
S A
SA
Atkinson
H C
HC
Tenenbaum
D000818:Animals; D001699:Biometry; D001823:Body Composition; D015519:Bone Density; D001846:Bone Development / Q000187:drug effects*; D001851:Bone Diseases, Metabolic / Q000139:chemically induced / Q000517:prevention & control; D003907:Dexamethasone / Q000494:pharmacology; D002149:Energy Intake; D005938:Glucocorticoids; D008297:Male; D015675:Osteocalcin / Q000097:blood; D010281:Parathyroid Hormone / Q000097:blood; D013552:Swine; D013629:Tamoxifen / Q000494:pharmacology*
D005938:Glucocorticoids; D010281:Parathyroid Hormone; D013629:Tamoxifen; D015675:Osteocalcin; D003907:Dexamethasone