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 sites 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 cyclooxygenase inhibitor, indomethacin. Eight-week-old intact female mice were divided into four groups of ten, and administered vehicle, 17beta-estradiol (E2), at 500 microg/animal per week and/or indomethacin at 2 mg/kg per day. Animals were killed after treatment for 24 days, and histomorphometric indices subsequently analyzed on longitudinal sections of the proximal tibial metaphysis. As found previously, E2 treatment caused a striking increase in cancellous bone volume, associated with an equivalent increase in the extent of cancellous double-labeled surfaces. In mice treated with both indomethacin and E2, significant reductions in cancellous bone volume and cancellous double-labeled surfaces were observed as compared with animals treated with E2 alone. In contrast, indomethacin did not significantly influence these parameters when given alone. Subregional analysis within the proximal tibial metaphysis revealed that this inhibitory effect of indomethacin was more marked distally as compared with proximally, with the estrogen-induced gain in cancellous bone volume at these sites being reduced by 50% and 25%, respectively. We conclude that estrogen-induced osteogenesis in female mice is partially suppressed by treatment with indomethacin, suggesting that prostaglandin synthesis plays a significant role in mediating this response.
Samuels
A
A
Rheumatology Unit, University of Bristol Division of Medicine, UK.
Perry
M J
MJ
Tobias
J H
JH
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology*; D004965:Estrogen Antagonists / Q000494:pharmacology*; D005260:Female; D007213:Indomethacin / Q000494:pharmacology*; D051379:Mice; D008808:Mice, Inbred CBA; D009929:Organ Size / Q000187:drug effects; D010012:Osteogenesis / Q000187:drug effects* / Q000502:physiology; D011448:Prostaglandin Antagonists / Q000494:pharmacology; D011453:Prostaglandins / Q000096:biosynthesis; D013977:Tibia / Q000187:drug effects / Q000254:growth & development; D014599:Uterus / Q000033:anatomy & histology / Q000187:drug effects
D016861:Cyclooxygenase Inhibitors; D004965:Estrogen Antagonists; D011448:Prostaglandin Antagonists; D011453:Prostaglandins; D004958:Estradiol; D007213:Indomethacin