Anabolic Effect of Estrogen Replacement on Bone in Postmenopausal Women with Osteoporosis: Histomorphometric Evidence in a Longitudinal Study1

Abstract

It is well recognized that estrogen (E2) prevents postmenopausal bone loss by suppressing bone resorption. Despite evidence that E2 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 E2 replacement therapy (ERT) [75 mg percutaneous E2 replaced 6-monthly plus oral medroxy progesterone acetate (5 mg daily) for 10 days each calendar month]. The mean serum E2 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 E2 treatment was 38.30 μm compared with 31.20 μm 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 E2 is capable of exerting an anabolic effect in women with osteoporosis, even when started well into the menopause.