Preliminary report of impaired oestrogen receptor-alpha expression in bone, but no involvement of androgen receptor, in male idiopathic osteoporosis.

Abstract

In western countries, osteoporosis affects at least 1 in 12 of all adult males and a third of osteoporotic men have idiopathic disease (MIO). Both oestrogen and testosterone are now known to be important to the male skeleton. As normal oestrogen levels have been found in younger MIO cases, it is hypothesized that, in bone, their responses to gonadal steroids may be defective, through impaired receptor expression. This study therefore compared oestrogen receptor (ER)-alpha and androgen receptor (AR) expression, by indirect immunofluorescence and semi-quantitative image analysis, in undecalcified fresh frozen bone sections from MIO patients (33-56 years), age-matched control men (n=7), and, for reference, ovarian steroid-replete (n=7) and -deficient women (n=6). In normal men, 23%+/-SEM 6% osteoblasts and 14%+/-SEM 2% osteocytes expressed ERalpha protein, similar to hormone-replete women. Although receptor expression decreased in hormone-deficient women, loss of ERalpha protein in MIO patients was more severe (1%+/-SEM 0.5% osteocytes, 2%+/-SEM 1% osteoblasts expressed receptor). In all four groups, there was little osteocyte AR expression, but in the women, a proportion of osteoblasts were receptor-positive. Deficient osteoblast and osteocyte ERalpha protein expression could explain the bone loss in these MIO patients.