The strain imposed by mechanical loading on bone tissue normally stimulates a response by bone cells that results in an adjustment of bone architecture that enables the bone to withstand reasonable loads. But it is unclear why this process should become less effective in some 50 per cent of postmenopausal women, who suffer fractures as a result. Here we show that bone in vivo undergoes an adaptive response to loading that is less effective in the absence of the α-form of the oestrogen receptor (ER-α) and that osteoblast-like cells require ER-α to proliferate in response to mechanical strain in vitro. As ER-α expression in osteoblasts and osteocytes depends on oestrogen concentration^,,,, a failure to maintain bone strength after the menopause might be due to a reduction in the activity of ER-α in bone cells, thereby limiting their anabolic response to mechanical loading and allowing a loss of bone tissue comparable to that associated with disuse.