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

Department of Gynaecology (G.K., J.S. N.H.), Chelsea & Westminster Hospital, London SW10 9NH; Department of Chemical Pathology (J.A.-Z.), Charing Cross Hospital, London W6 8RP; and Department of Histopathology (S.F., J.C.), St. George’s Hospital Medical School, London SW17 ORE, United Kingdom

Address correspondence to: Dr. J. W. M. Chow, Department of Histopathology, St. George’s Hospital Medical School, Cranmer Terrace, London SW17 ORE, United Kingdom. E-mail: j.chow{at}sghms.ac.uk

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.

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