A comparison of the action of progestins and estrogen on the growth and differentiation of normal adult human osteoblast-like cells in vitro

Estrogen/gestagen replacement therapy prevents excess bone loss in postmenopausal women. The mode of action by which these sex steroids exert their anabolic effects on bone has not been completely clarified yet. In this study, 17β-estradiol (E₂), as well as the progestins progesterone (P), dydrogesterone (DD), 20α-dihydroxydydrogesterone (DHD), medroxyprogesterone acetate (MPA), and cyproterone acetate (CPA) were able to stimulate the mitogenesis and differentiation of normal adult human osteoblast-like (HOB) cells harvested from female trabecular bone explants. The different progestins exerted a more pronounced stimulatory effect on HOB proliferation than E₂ did. The combination of E₂ with P, DD, or DHD did not result in a statistically significant further increase of HOB proliferation, as compared with the progestins alone. In general, E₂ showed a stronger differentiation-inducing effect than the progestins, as measured by histochemical staining of the HOB cells for alkaline phosphatase activity. Combining E₂ and the progestins did not result in a further increase of the number of alkaline phosphatase positive cells, compared with E₂ alone. The different progestins proved to be equally potent in stimulating HOB proliferation and differentiation. In conclusion, progestins as well as E₂ exerted anabolic but differential effects on normal adult human osteoblasts in vitro.