Effects of combination therapy with PTH and 17beta-estradiol on long bones of female mice.
Parathyroid hormone (PTH) is thought to increase trabecular bone mass in postmenopausal women by stimulating osteoblast function. A similar action may contribute to estrogen's protective effect on the skeleton, which we have explored in female mice, in which estrogen induces an exaggerated osteogenic response. In the present investigation, we used this model to determine whether an interaction exists between stimulatory effects of PTH and estrogen on osteoblast function in cancellous bone. An initial dose response study was performed where PTH (hPTH, 1-38) was administered to ten-week-old intact female mice by daily sc injection for 28 days, at doses of 1, 10, 100 microg/kg. In a subsequent study, intact female mice were given PTH and/or 17beta-estradiol (E2) 10 and 40 microg/kg/day respectively. Femoral BMD was assessed by peripheral DXA (PIXImus), and histomorphometry was performed to analyse changes in cancellous and cortical bone. PTH caused a small gain in femoral BMD, and increased the extent of periosteal bone formation surfaces, but had relatively little effect on other skeletal parameters when given alone. As previously found, E2 produced a large increase in femoral BMD, stimulated cancellous and endocortical bone formation, but inhibited periosteal bone formation. In mice treated with combination therapy, a greater increase in femoral BMD was observed compared to that following treatment with either agent alone. No differences in indices of cancellous bone were found between animals treated with E2 compared to the combination group. However, cortical area and periosteal bone formation rate were significantly greater in the latter group. We conclude that PTH and E2 exert an additive effect on bone mass in long bones of female mice, possibly reflecting an ability of PTH to oppose E2-induced suppression of periosteal bone formation.
Samuels
A
A
University of Bristol Division of Medicine, UK.
Perry
M J
MJ
Gibson
R
R
Tobias
J H
JH
D015502:Absorptiometry, Photon; D000818:Animals; D015519:Bone Density / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D005269:Femur / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007091:Image Processing, Computer-Assisted; D007279:Injections, Subcutaneous; D051379:Mice; D023421:Models, Animal; D010012:Osteogenesis / Q000187:drug effects; D010281:Parathyroid Hormone / Q000008:administration & dosage / Q000494:pharmacology*
D010281:Parathyroid Hormone; D004958:Estradiol