High-dose estrogen-induced osteogenesis in the mouse is partially suppressed by indomethacin

We recently found that high-dose estrogen induces the formation of new site s of cancellous bone formation within the long bones of intact female mice. To examine whether prostaglandins play a role in mediating this response, we studied whether this is inhibited by coadministration of the cyclooxygen ase inhibitor, indomethacin, Eight-week-old intact female mice were divided into four groups of ten, and administered vehicle, 17 beta-estradiol (E-2) , at 500 mu g/animal per week and/or indomethacin at 2 mg/kg per day. Anima ls were killed after treatment for 24 days, and histomorphometric indices s ubsequently analyzed on longitudinal sections of the proximal tibial metaph ysis, As found previously, E-2 treatment caused a striking increase in canc ellous bone volume, associated with an equivalent increase in the extent of cancellous doubIelabeled surfaces, In mice treated with both indomethacin and E-2, significant reductions in cancellous bone volume and cancellous do uble-labeled surfaces were observed as compared with animals treated with E -2 alone, In contrast, indomethacin did not significantly influence these p arameters when given alone, Subregional analysis within the proximal tibial metaphysis revealed that this inhibitory effect of indomethacin was more m arked distally as compared with proximally, with the estrogen-induced gain in cancellous bone volume at these sites being reduced by 50% and 25%, resp ectively. We conclude that estrogen-induced osteogenesis in female mice is partially suppressed by treatment with indomethacin, suggesting that prosta glandin synthesis plays a significant role in mediating this response, (C) 1999 by Elsevier Science Inc. All rights reserved.