Serum Estradiol and Sex Hormone-Binding Globulin and the Risk of Hip Fracture in Elderly Women: The EPIDOS Study

Oxford University Press (OUP) - Tập 15 Số 9 - Trang 1835-1841 - 2000
Roland Chapurlat1, Patrick Garnero2, Gérard Bréart3, Pierre J. Meunier1, Pierre D. Delmas1
1INSERM Unit 403, Hôpital Edouard Herriot, Lyon Cedex 03, France
2Synarc, Lyon, France
3INSERM Research Unit 149, Paris, France

Tóm tắt

Abstract It has been suggested that low serum 17β-estradiol (E2) and sex hormone-binding globulin (SHBG) may predict hip fracture in postmenopausal women. We have investigated the predictive value of serum E2 and SHBG concentrations and urinary deoxypyridinoline (D-Pyr) and type I collagen breakdown products (CTX) in a large prospective cohort of 7598 healthy elderly ambulatory women (EPIDOS study), aged 75 years or more. We performed a nested case control study, by matching 212 patients with incident hip fracture with 636 controls. Mean follow-up was 3.3 years (maximum, 4.9 years). Women having serum E2 below the limit of detection (3 pg/ml), that is, 2% of the population, were not at higher risk, with a relative hazard (RH) of 1.59 (95% CI = 0.45-5.55). Women having serum E2 below 5, 6, 7, or 8 pg/ml, in the lowest quartile, or below the median had no increased risk of hip fracture. In contrast, women having serum E2 in the highest quartile (i.e., ≥10 pg/ml) were protected, with an RH of 0.66 (0.44-0.98) that did not remain significant after adjustment for weight (RH = 0.71 [0.47-1.06]). High serum SHBG values with different cut-offs tended to be associated with an increased risk of hip fracture. Women in the highest quartile had an RH of 2.5 (1.37-4.61), compared with those in the lowest quartile, that decreased markedly after adjustment for body weight (1.61 [0.99-2.62]). The highest quartile of the ratio E2/SHBG, which is an index of free E2, was associated with a lower hip fracture risk (RH = 0.6 [0.4-0.91]) that was no longer significant after adjustment for weight. In contrast, urinary D-Pyr and CTX, when elevated above the upper limit of premenopausal values, were predictive of hip fracture, with an RH of 2.07 (1.49-2.9) and 1.67 (1.19-2.32), respectively, even after adjustment for body weight, serum E2, and SHBG. We conclude that in healthy elderly French women over 75 years of age, serum E2 and E2/SHBG in the highest quartile are associated with a lower risk of hip fracture and that this association is explained by a higher body weight. In addition, serum levels of E2 and SHBG do not account for the increased risk of hip fracture associated with high levels of bone resorption markers.

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Tài liệu tham khảo

Melton, 1992, How many women have osteoporosis ?, J Bone Miner Res, 7, 1005, 10.1002/jbmr.5650070902

Cooper, 1992, Hip fracture in the elderly: A worldwide projection, Osteoporos Int, 2, 285, 10.1007/BF01623184

Dargent-Molina, 1996, Fall-related factors and risk of hip fracture: The EPIDOS prospective study, Lancet, 348, 145, 10.1016/S0140-6736(96)01440-7

Cummings, 1995, Risk factors for hip fracture in white women, N Engl J Med, 332, 767, 10.1056/NEJM199503233321202

Grisso, 1991, Risk factors for falls as a cause for hip fracture in women, N Engl J Med, 324, 1326, 10.1056/NEJM199105093241905

Melton, 1998, A unitary model for involutional osteoporosis: Estrogen deficiency causes both type I and type II osteoporosis in postmenopausal women and contributes to bone loss in aging men, J Bone Miner Res, 13, 763, 10.1359/jbmr.1998.13.5.763

Lindsay, 1980, Prevention of spinal osteoporosis in oophorectomized women, Lancet, 2, 1151, 10.1016/S0140-6736(80)92592-1

Hansen, 1991, Role of peak bone mass and bone loss in postmenopausal osteoporosis: 12 years study, BMJ, 303, 961, 10.1136/bmj.303.6808.961

Riis, 1996, Low bone mass and fast rate of bone loss at menopause-equal risk factors for future fracture. A 15 years follow-up study, Bone, 19, 9, 10.1016/8756-3282(96)00102-0

Johansen, 1988, Plasma BGP: An indicator of spontaneous bone loss effect of estrogen treatment in postmenopausal women, Eur J Clin Invest, 18, 191, 10.1111/j.1365-2362.1988.tb02412.x

Delmas, 1999, A dose-ranging trial of a matrix transdermal 17β-estradiol for the prevention of bone loss in early postmenopausal women, Bone, 24, 517, 10.1016/S8756-3282(99)00076-9

Marshall, 1977, Plasma androstenedione and oestrone levels in normal and osteoporotic postmenopausal women, BMJ, 2, 1177, 10.1136/bmj.2.6096.1177

Longcope, 1984, Androgen and estrogen dynamics in women with vertebral crush fracture, Maturitas, 6, 309, 10.1016/0378-5122(84)90002-1

Davidson, 1983, Endogenous cortisol and sex steroids in patients with osteoporotic spinal fractures, Obstet Gynecol, 61, 275

Riggs, 1973, Serum concentrations of estrogen, testosterone, and gonadotrophins in osteoporotic and nonosteoporotic postmenopausal women, J Clin Endocrinol Metab, 36, 1097, 10.1210/jcem-36-6-1097

Van Hemert, 1989, Sex hormone binding globulin in postmenopausal women: A predictor of osteoporosis superior to endogenous estrogens, Clin Endocrinol (Oxf), 31, 499, 10.1111/j.1365-2265.1989.tb01274.x

Cummings, 1998, Endogenous hormones and the risk of hip and vertebral fractures among older women, N Engl J Med, 339, 733, 10.1056/NEJM199809103391104

Hans, 1996, Ultrasound measurements predict hip fracture in elderly women independently of hip bone density. The EPIDOS study, Lancet, 348, 511, 10.1016/S0140-6736(95)11456-4

Garnero, 1996, Increased bone turnover in late postmenopausal women is a major determinant of osteoporosis, J Bone Miner Res, 11, 337, 10.1002/jbmr.5650110307

Bonde, 1994, Immunoassay for quantifying type I collagen degradation products in urine evaluated, Clin Chem, 40, 2022, 10.1093/clinchem/40.11.2022

Garnero, 1994, Assessment of bone resorption with a new marker of collagen degradation in patients with metabolic bone disease, J Clin Endocrinol Metab, 79, 780

Robins, 1994, Direct, enzyme linked immunoassay for urinary deoxypyridinoline as a specific marker for measuring bone resorption, J Bone Miner Res, 9, 1643, 10.1002/jbmr.5650091019

Abraham, 1975, Reliability criteria for steroid radioimmunoassay, Pathol Biol, 28, 885

Cox, 1972, Regression models and life tables (with discussion), J R Stat Soc, B34, 187

Garnero, 1996, Markers of bone resorption predict hip fracture in elderly women: The EPIDOS prospective study, J Bone Miner Res, 11, 1531, 10.1002/jbmr.5650111021

Garnero, 1998, Do markers of bone resorption add to bone mineral density and ultrasonographic heel measurement for the prediction of hip fracture in elderly women ? The EPIDOS prospective study, Osteoporos Int, 8, 563, 10.1007/s001980050100

Delmas, 1983, Increase in serum bone γ-carboxyglutamic acid protein with aging in women: Implications for the mechanism of age-related bone loss, J Clin Invest, 71, 1316, 10.1172/JCI110882

Epstein, 1984, Differences in serum bone Gla-protein with age and sex, Lancet, 1, 307, 10.1016/S0140-6736(84)90360-X

Chapuy, 1996, Healthy elderly french women living at home have secondary hyperparathyroidism and high bone turnover in winter. EPIDOS Study Group, J Clin Endocrinol Metab, 81, 1129

Van Der Wielen, 1995, Serum 25OHD concentrations among elderly people in Europe, Lancet, 346, 207, 10.1016/S0140-6736(95)91266-5

Gallagher, 1996, Osteoporosis, 1191

Aloia, 1995, To what extent is bone mass determined by fat-free or fat mass?, Am J Clin Nutr, 61, 1110, 10.1093/ajcn/61.5.1110

Chen, 1997, Fat or lean tissue mass: Which one is the major determinant of bone mineral mass in healthy postmenopausal women?, J Bone Miner Res, 12, 144, 10.1359/jbmr.1997.12.1.144

Johnston, 1985, Early menopausal changes in bone mass and sex steroids, J Clin Endocrinol Metab, 61, 905, 10.1210/jcem-61-5-905

Cauley, 1986, The relationship of endogenous estrogen to bone density and bone area in normal postmenopausal women, Am J Epidemiol, 124, 752, 10.1093/oxfordjournals.aje.a114451

Cauley, 1994, Black-White differences in serum sex hormones and bone mineral density, Am J Epidemiol, 139, 1035, 10.1093/oxfordjournals.aje.a116943

Steinberg, 1989, Sex steroids and bone density in pre and perimenopausal women, J Clin Endocrinol Metab, 69, 533, 10.1210/jcem-69-3-533

Rozenberg, 1990, Age, steroids and bone mineral content, Maturitas, 12, 137, 10.1016/0378-5122(90)90092-K

Fentiman, 1994, Bone density of normal women in relation to endogenous and exogenous oestrogens, Br J Rheumatol, 33, 808, 10.1093/rheumatology/33.9.808

Lindsay, 1977, Endogenous oestrogen and bone loss following oophorectomy, Calcif Tissue Res, 22, 213

Manolagas, 1979, Adrenal steroids and the development of osteoporosis in oophorectomized women, Lancet, 314, 597, 10.1016/S0140-6736(79)91663-5

Riis, 1986, The role of serum concentrations of sex steroids and bone turnover in the development and occurrence of postmenopausal osteoporosis, Calcif Tissue Int, 38, 318, 10.1007/BF02555743

Aloia, 1983, 1700

Slemenda, 1987, Steroids and bone mass. A study of changes about the time of menopause, J Clin Invest, 80, 1261, 10.1172/JCI113201

Harris, 1992, Influence of body weight on rates of change in bone density of the spine, hip and radius in postmenopausal women, Calcif Tissue Int, 50, 19, 10.1007/BF00297292

Pelc, 1978, The relation between plasma androstenedione, plasma estrone and androstenedione to estrone conversion rates in postmenopausal women with and without fractures, Clin Sci Mol Med, 54, 125

Davidson, 1982, Total and free estrogens and androgens in postmenopausal women with hip fractures, J Clin Endocrinol Metab, 54, 115, 10.1210/jcem-54-1-115

Laufer, 1983, Physical characteristics and sex hormone levels in patients with osteoporotic hip fractures or endometrial cancer, Am J Obstet Gynecol, 145, 585, 10.1016/0002-9378(83)91201-2

Aloia, 1985, Risk factors for postmenopausal osteoporosis, Am J Med, 78, 95, 10.1016/0002-9343(85)90468-1

Reid, 1993, Circulating insulin levels are related to bone density in normal postmenopausal women, Am J Physiol, 265, E655

Cornish, 1999, Comparison of the effects of calcitonin gene-related peptide and amylin on osteoblasts, J Bone Miner Res, 14, 1302, 10.1359/jbmr.1999.14.8.1302

Goulding, 1998, Plasma leptin values in relation to bone mass and density and to dynamic biochemical markers of bone resorption and formation in postmenopausal women, Calcif Tissue Int, 63, 456, 10.1007/s002239900557

Thomas, 1999, Leptin acts on human marrow stromal cells to enhance differentiation to osteoblasts and to inhibit differentiation to adipocytes, Endocrinology, 140, 1630, 10.1210/endo.140.4.6637