The effect of long term oestradiol implantation on bone mineral density in postmenopausal women who have undergone hysterectomy and bilateral oophorectomy

Abstract

Twelve women who had received oestradiol implantation on demand for at least 15 years following hysterectomy with bilateral oophorectomy, underwent bone densitometry of hip and spine. Bone mass of hip and spine was significantly elevated above that of both the age matched mean to a degree hitherto undocumented. This suggests that oestrogen in high doses or over a long period may produce a true anabolic effect on bone mass.Osteoporosis remains a formidable challenge to medicine, with the prevalence of fracture being augmented by the ageing of the population and the absence of an effective treatment. Future advances are likely to come from the fields of screening and prevention. The principal therapeutic means to retard bone loss in postmenopausal women is oestrogen, although serious doubts remain as to the optimal mode and duration of delivery. Oestrogen decreases the rate of bone resorption, principally by cytokine-mediated inhibition of osteoclastic activity. This leads to the correction of the imbalance between bone resorption and bone formation at bone remodelling sites.Non-oral oestrogens avoid the first pass effect on the liver and allow direct delivery into the systemic circulation'. Transdermal oestrogen can cause skin reactions and compliance is not guaranteed. Percutaneous oestrogen implants which guarantee compliance and are relatively cheap have been used in the prevention and treatment of osteoporosis. There is, however, disagreement as to whether this form of therapy simply arrests bone loss, or whether it also causes a prolonged gain in bone mineral density. Oestradiol has been shown to increase spinal and femoral neck bone mineral density when given in a dose of 75 mg every six months for one year to women with a bone mineral density below the 50th centile2.The use of oestrogen replacement therapy following abdominal hysterectomy and bilateral salpingo-

Bone marrow and bone: a functional unit

“…Bord et al (2000) reported significantly higher megakaryocyte numbers in the bone marrow of postmenopausal women treated with conventional hormone replacement therapy when compared with baseline, and even greater numbers in a group of postmenopausal women who had received long-term high-dose parenteral oestradiol therapy. In this latter group, high bone mineral density in the spine and proximal femur (Wahab et al 1997) was associated with histological evidence of increased osteoblast activity, demonstrated by measurement of wall width in iliac crest biopsies (Vedi et al 1999). Immunolocalisation studies revealed expression of both oestrogen receptor subtypes in megakaryocytes (Fig.…”

Estrogen Added Intermittently, but Not Continuously, Stimulates Differentiation and Bone Formation in SaOS-2 Cells

“…This stimulatory effect of E 2 provides strong in vitro evidence that a direct effect of E 2 on human osteoblasts via ERa maybe one of the mechanisms involved in its stimulatory effect on bone formation in vivo, seen both in lower species [7][8][9][10][11] and in postmenopausal women. [12][13][14][15] Furthermore, our data demonstrating the formation of mineralized bone-like structures in long-term cultures of SaOS-2 cells in the presence of dexamethasone, ascorbic acid and bglycerophosphate make the SaOS-2 cell culture a valid human cell system for quantitative study of estrogen action on bone formation in vitro.…”

“…It is thought that the major effect of estrogen in vivo is inhibition of resorption, 6) but effects on bone formation have been reported in lower species. [7][8][9][10][11] More recently, studies 12,13) showing a sustained stimulation of osteoblast function in postmenopausal women who were exposed for prolonged period to relatively high doses of estrogen, may suggest that estrogen also has an effect on bone formation in humans. 6,14,15) Others still view the anabolic effect of estrogen as being controversial.…”

The impact of subcutaneous oestradiol implants on biochemical markers of bone turnover and bone mineral density in postmenopausal women

“…For example, Naessen et al 2 described an increase of 20 -25% in distal radius, lumbar spine (LS) and femoral neck (FN) BMD in postmenopausal subjects that received oestradiol implants for a mean period of 16 years. Wahab et al 1 reported an increase of 40% and 45% in FN and LS BMD, respectively, in 12 oophorectomised postmenopausal women treated with subcutaneous oestradiol during a similar period. Tobias and Compston 3 have suggested that osteoblast activity may be increased as a result of prolonged exposure to high doses of oestrogen as observed with oestradiol implants.…”

“…Previous non-randomised studies have suggested that oestradiol given as subcutaneous implant might be anabolic to bone 1,2 . In these studies, long term treatment resulted in significantly higher bone mineral density (BMD) than that in age matched controls.…”