Sex steroids and osteoporosis: effects of deficiencies and substitutive treatments

Abstract

Adult mammalian bone is continuously renewed by the process of remodelling. In young healthy adults the amount of bone that is resorbed by osteoclasts is replaced by osteoblasts so that no net loss of bone occurs. In a situation of reduced sex hormone levels, such as in females after menopause or ovariectomy, in males after orchidectomy, or in patients of either sex with gonadal dysfunction, there is an imbalance between bone resorption and bone formation resulting in bone loss. The various hypotheses to explain the aetiology of this imbalance are reviewed. Substitution therapy of females with oestrogen results in the prevention of oestrogen deficiency-induced bone loss. It is generally agreed that the effect is due to inhibition of bone resorption. Recent in vitro data, however, indicate that oestrogens also have the capacity to stimulate the proliferation and functioning of bone-forming cells. Prevention of oestrogen deficiency-induced bone loss can also be achieved by treatment with high doses of progestagens. Available data suggest that this too is caused by resorption inhibition. The aim of treatment of females, who have lost so much bone that there is an increased risk of fractures after minimal trauma, is to increase bone mass rather than to prevent further bone loss. This can be accomplished by treatment with anabolic steroids. Both biochemical and histological data indicate that anabolics stimulate the activity of functioning osteoblasts. The increase in bone mass during continuous treatment is temporary because anabolics most probably also inhibit bone resorption. Substitution therapy with anabolics or androgens in males is equally effective and increases trabecular bone mass in the spine.