Preliminary evidence for impaired estrogen receptor-α protein expression in osteoblasts and osteocytes from men with idiopathic osteoporosis

Although osteoporosis is usually associated with women, 1 in 12 men in the UK have the disease, and a third of these cases are idiopathic. Estrogen is now known to be associated with bone loss in older men, but we found, previously, that levels of this hormone were normal in younger cases of male idiopathic osteoporosis (MIO) in the age range 33–61 years. We therefore hypothesized that their estrogen responses in bone might be defective, through impaired estrogen receptor-α (ER)-α expression. Consequently, in the present study, we compared expression of ER-α by indirect immunofluorescence, semiquantitative image analysis, and in situ reverse transcription-polymerase chain reaction in bone sections from MIO patients (33–56 years) (N = 7); age-matched control men (N = 7); and, for reference, ovarian steroid (OS)-replete (N = 7) and OS-deficient women (N = 6). In the control men, 23 ± 6% (mean ± SEM) of osteoblasts and 14 ± 2% of osteocytes expressed ER-α protein, similar to OS-replete women. Although receptor expression decreased in OS-deficient women, the loss of ER-α protein in MIO patients was more severe (1 ± 0.5% osteocytes, 2 ± 1% osteoblasts expressed receptor); however, ER-α messenger RNA (mRNA) was still expressed in controls and MIO patients. Bone loss in these patients may be due to deficient ER-α protein expression.