Effects of combination therapy with PTH and 17 beta-estradiol on long bones of female mice

Parathyroid hormone (PTH) is thought to increase trabecular bone mass in po stmenopausal 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 osteogeni c response. In the present investigation, we used this model to determine w hether an interaction exists between stimulatory effects of PTH and estroge n on osteoblast function in, cancellous bone. An initial dose response stud y was performed where PTH (hPTH, 1-38) was administered to ten-week-old, in tact female mice by daily se injection for 28 days, at doses of 1, 10 100 m ug/kg. In a subsequent study, intact, female mice were given PTH and/or 17 beta -estradiol (E-2) 10 and 40 mug/kg/day respectively. Femoral BMD was as sessed by peripheral DXA (PIXImus), and histomorphometry was performed to a nalyse 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, E-2 produced a large increase in femoral BMD, s timulated cancellous and endocortical bone formation, but inhibited periost eal bone formation. In mice treated with combination therapy, a greater inc rease in femoral BMD was observed compared to that following treatment with either agent alone. No; differences in indices of cancellous bone were fou nd between animals treated with E-2 compared to the combination group. Howe ver, cortical area and periosteal bone formation rate were significantly gr eater in the latter group. We conclude that PTH and E-2 exert an additive e ffect on bone mass in long bones of female mice, possibly reflecting an abi lity of PTH to oppose E-2-induced suppression of periosteal bone formation.