Abstract
The crucial role of estrogen (E) in the normal growth and development of the skeleton in girls has been known for decades. Recent studies in a man with estrogen receptor (ER) deficiency has underscored an equally important role for E in boys. Similarly the role of declining ovarian E production in bone loss in women has been well documented since the initial hypothesis of Albright in the 1940’s (1). Important studies in the last several years have provided insight into possible mechanisms underlying these clinical observations, particularly the role of E in modulating local cytokine production in skeletal tissues. The finding of ER-β as the dominant ER in bone (2) answers many questions regarding the previously documented low ER density in this clearly E-dependent tissue.
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References
Albright F, Smith, PH, Richardson AM (1941) Postmenopausal osteoporosis. J Am Med Ass 116:2465–2473.
Grandien K, Berkenstam A, Gustafsson JA (1997) The estrogen receptorgene: promoter organization and expression. Int J Biochem & Cell Biol 29:1343–1369.
Nelson DA, Simpson PM, Johnson CC et al. (1997) The accumulation of whole body skeletal mass in third- and fourth-grade children: effects of age, gender, ethnicity, and body composition. Bone 20:73–78.
Gilsanz V, Roe TF, Mora S et al. (1991) Changes in vertebral bone density in black girls and white girls during childhood and puberty. N Engl J Med 325:1597–1600.
Gilsanz V, Skaggs DL, Kovanlikaya A et al. (1998) Differential effects of race on the axial and appendicular skeletons of children. J Clin Endocrinol Metab 83:1420–1427.
Takahashi Y, Minamitani K, Kobayashi Y et al. (1996) Spinal and femoral bone mass accumulation during normal adolescence: comparison with female patients with sexual precocity ad hypogonadism. J Clin Endocrinol Metab 81:1248–1253.
Theintz G, Buchs B, Rizzoli R et al. (1992) Longitudinal monitoring of bone mass accumulation in healthy adolescents: evidence for a marked reduction after 16 years of age at the levels of lumber spine and femoral neck in female subjects. J Clin Endocrinol Metab 79:1060–1065.
Holmes SJ, Shalet SM (1996) Role of growth hormone and sex steroids in achieving and maintaining normal bone mass. Hormone Res 45:86–93.
Smith EP, Boyd J, Frank GR et al. (1994) Estrogen resistance caused by a mutation in the estrogen-receptor gene in a man. N Engl J Med 331:1056–1061.
Schot LP, Schuurs AH (1990) Pathophysiology of bone loss in castrated animals. J Steroid Biochem & Mol Biol 37:461–465.
Ershler WB, Harman SM, Keller ET (1997) Immunologic aspects of osteoporosis. Develop & Comp Immunol 21:487–499.
Pacifici R (1998) Cytokines, estrogen, and postmenopausal osteoporosis - the second decade. Endocrinol 130:2659–2661.
Stein B, Yang MX (1995) Repression of the interleukin-6 promoter by estrogen receptor is mediated by NF-kappa B and C/EBP beta. Mol & Cell Biol 15:4971–4979.
Lindsay R, Hart DM, Forrest C etal. (1980) Prevention of spinal osteoporosis in oophorectomized women. Lancet 2:1151–1154.
SlemendaC, Longcope C, Peacock M etal. (1996) Sex steroids, bone mass, and bone loss: A prospective study of pre-, peri-, and postmenopausal women. J Clin Invest 97:14–21.
Riggs BL, Melton LJ (1986) Medical progress series: Involutional osteoporosis. N Engl J Med 314:1676–1686.
Han ZH, Palnitkar S, Rao DS etal. (1997) Effects of ethnicity and age or menopause on the remodeling and turnover of iliac bone: implications for mechanisms of bone loss. J Bone Miner Res 12:498–508.
Cummings SR, Browner WS, Bauer D etal. (1998) Endogenous hormones and the risk of hip and vertebral fractures among older women. N Engl J Med 339:733–738.
Stepan JJ, Lachman M, Zverina J et al. (1989) Castrated men exhibit bone loss. Effect of calcitonin treatment on biochemical indices of bone remodeling. J Clin Endocrinol Metab 69:523–527.
Riggs BL, Khosla H, Melton LJ (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 13:763–773.
Falch JA, Oftebro H, Haug E (1987) Early postmenopausal bone loss is not associated with a decrease in circulating levels of 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D or vitamin D binding protein. J Clin Endocrinol Metab 64:836–841.
Anonymous (1996) Effects of hormone therapy on bone mineral density: results of the postmenopausal estrogen/progestin interventions (PEPI) trial. The writing group for PEPI. J Am Med Ass 276:1389–1396.
Rosen CJ, Chesnut CH, Mallinak NJ (1997) The predictive value of biochemical markers of bone turnover for bone mineral density in early postmenopausal women treated with hormone replacement or calcium supplementation. J Clin Endocrinol Metab 82:1904–1910.
Looker AC, Orwoll ES, Johnston CC Jr et al. (1997) Prevalence of low femoral bone density in older U.S. adults from NHANES III. J Bone Miner Res 12:1761–1768.
Michaelsson K, Baron JA, Farahmand BY et al. (1998) Hormone replacement therapy and risk of hip fracture: population based case-control study. The Swedish hip fracture study group. Brit Med J 316:1858–1863.
Felson DT, Zhang Y, Hannan MT et al. (1993) The effect of postmenopausal estrogen therapy on bone density in elderly women. N Engl J Med 329:1141–1146.
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Kleerekoper, M. (2001). Estrogen and the Skeleton. In: Li, J.J., Li, S.A., Daling, J.R. (eds) Hormonal Carcinogenesis III. Springer, New York, NY. https://doi.org/10.1007/978-1-4612-2092-3_35
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DOI: https://doi.org/10.1007/978-1-4612-2092-3_35
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