Anabolic effect of estrogen replacement on bone in postmenopausal women with osteoporosis: Histomorphometric evidence in a longitudinal study

It is well recognized that estrogen (E-2) prevents postmenopausal bone loss by suppressing bone resorption. Despite evidence that E-2 may also stimulate bone formation in animals, an anabolic effect in humans is still controversial. To investigate this, we studied 22 older postmenopausal females, with a mean age of 65.4 yr and mean interval of 16.9 yr since menopause and low bone mineral density. Transcortical iliac bone biopsies were performed before and 6 yr after E-2 replacement therapy (ERT) [75 mg percutaneous E-2 replaced 6-monthly plus oral medroxy progesterone acetate (5 mg daily) for 10 days each calendar month]. The mean serum E-2 level after 6 yr of treatment was 1077 (range, 180-2568) pmol/L. Bone mineral density improved in every patient, with a median increase of 31.4% at the lumbar spine and 15.1% at the proximal femur. Bone histomorphometry showed an increase in cancellous bone volume from 10.75% to 17.31% (P < 0.001). The wall thickness after 6 yr of E-2 treatment was 38.30 m compared with 31.20 mum before commencement of ERT (P < 0.0005), indicating net bone gain. This is the first report showing histological evidence for an increase in cancellous bone volume, together with an increase in wall thickness, in a longitudinal follow-up study of ERT in older postmenopausal women. Our results show that E-2 is capable of exerting an anabolic effect in women with osteoporosis, even when started well into the menopause.