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We have previously found that administration of oestradiol-17β (OE₂) to intact adult female rats of 19 days stimulates cancellous bone formation. However, this effect is not observed following longer periods of OE₂ treatment, suggesting that the responsiveness of the skeleton to oestrogen's anabolic action is reduced after prolonged administration. A possible explanation for this is that oestrogen also suppresses bone resorption, which is an important stimulus for bone formation. We therefore investigated the effect of omitting OE₂ for short periods, on the proximal tibial metaphysis of intact female rats. We found that, unlike continuous treatment with OE₂ (40 pg/kg) for 56 days, omission of OE₂ for 4 days out of every 20 was associated with a significant increase in cancellous bone volume. Although continuous and intermittent OE₂ were both associated with a reduction in osteoclast surface, a decrease in the proportion of double fluorochrome-labelled surface was only seen after continuous OE₂ treatment. We then studied the effects of longer periods of OE₂ omission by giving OE₂ (40 pg/kg) for three repeated cycles of: (1) OE₂ for 16 days/vehicle for 4 days, (2) OE₂ for 12 days/vehicle for 8 days, (3) OE₂ for 8 days/vehicle for 12 days, or (4) OE₂ for 4 days/vehicle for 16 days. We found a significant increase in cancellous bone volume when OE₂ was stopped for either 4 or 8 days at a time. However, longer periods of OE₂ omission did not affect bone volume, possibly because these were associated with an increase in bone resorption and/or a reduction in bone formation during the OE₂-free period. In conclusion, we observed an increase in cancellous bone volume after prolonged treatment with oestrogen only if OE₂ was omitted for short periods. This may be due, at least in part, to bone formation being maintained at a higher rate by such treatment than by either continuous OE₂ administration or by intermittent administration where OE₂ is discontinued for longer periods.

Journal of Endocrinology (1993) 139, 267–273

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