The Oxidative Metabolism of Estradiol Conditions Postmenopausal Bone Density and Bone Loss

Leelawattana, Rattana; Ziambaras, Konstantinos; Roodman-Weiss, Jane; Lyss, Christine; Wagner, Danielle; Klug, Thomas L.; Armamento-Villareal, Reina; Civitelli, Roberto

doi:10.1359/jbmr.2000.15.12.2513

Cited by 37 publications

(50 citation statements)

References 57 publications

(67 reference statements)

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“…Disorders of estrogen metabolism have been implicated in the etiology of certain estrogen-dependent conditions, such as breast, endometrial, and ovarian cancers (5-7) and, recently, osteoporosis (8). For instance, it has been reported that women with increased 16␣-hydroxylation, as indicated by a low ratio of 2-hydroxyestrone (2OHE 1 ) to 16␣-hydroxyestrone (16␣OHE 1 ), have a high risk of breast cancer (5,9), most likely because of a relatively higher estrogenic state.…”

Section: Introductionmentioning

confidence: 99%

Effects of dietary calcium compared with calcium supplements on estrogen metabolism and bone mineral density

Napoli

Thompson

Civitelli

et al. 2007

The American Journal of Clinical Nutrition

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Background: High calcium intake has been associated with both high bone mineral density (BMD) and high urinary estrogen metabolites. However, the role of dietary calcium and calcium supplements on estrogen metabolism and BMD remains unknown. Objective: The objective was to investigate the importance of the source of calcium intake on estrogen metabolism and BMD. Design: The average total daily calcium intake from supplements and diet, urinary estrogen metabolites, and spine and proximal femur BMD were studied in 168 healthy postmenopausal white women. Results: Women who obtained calcium primarily from the diet or from both the diet and supplements had significantly (P ҃ 0.03) lower ratios of nonestrogenic to estrogenic metabolites (2-hydroxyestrone 1/16␣-hydroxyestrone) than did those who obtained calcium primarily from supplements. Adjusted BMD z scores were significantly greater in the subjects who obtained calcium primarily from the diet or from both the diet and supplements than in those who obtained calcium primarily from calcium supplements at the spine (P ҃ 0.012), femoral neck (P ҃ 0.02), total femur (P ҃ 0.003), and intertrochanter (P ҃ 0.005). This difference was evident especially in those who obtained calcium primarily from the diet, whose total calcium intake was lower than that in those who obtained calcium primarily from supplements. Conclusion: Calcium from dietary sources is associated with a shift in estrogen metabolism toward the active 16␣-hydroxyl metabolic pathway and with greater BMD and thus may produce more favorable effects in bone health in postmenopausal women than will calcium from supplements.

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Section: Introductionmentioning

confidence: 99%

Effects of dietary calcium compared with calcium supplements on estrogen metabolism and bone mineral density

Napoli

Thompson

Civitelli

et al. 2007

The American Journal of Clinical Nutrition

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“…Furthermore, African-American women, who had a greater bone mass and lower risk for developing osteoporosis compared with European-American women, have been reported to have a higher urinary 16 -OHE 1 /2-OHE 1 ratio (Cauley et al 1994, Taioli et al 1996. More recent data suggested that women in the lowest quartile of urinary 2-OHE 1 / 16 -OHE 1 appeared to be protected from early postmenopausal bone loss (Leelawattana et al 2000).…”

Section: Introductionmentioning

confidence: 99%

Tissue-selective effects of continuous release of 2-hydroxyestrone and 16alpha-hydroxyestrone on bone, uterus and mammary gland in ovariectomized growing rats

Lotinun

Westerlind²,

Rt³

2001

Journal of Endocrinology

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Abstract2-Hydroxyestrone (2-OHE 1 ) and 16 -hydroxyestrone (16 -OHE 1 ) have been reported to be risk factors for negative bone balance and breast cancer, respectively. The roles of these two metabolites of estrone as estrogen agonists or antagonists with respect to estrogen target tissues, or both, are poorly defined. The purpose of this study was to characterize metabolite and tissue-specific differences between the actions of hydroxylated estrones on selected reproductive and non-reproductive estrogen target tissues in growing rats. First, the effects of ovariectomy were determined. Ovariectomy had the expected effects, including increases in all dynamic bone measurements at the proximal tibial epiphysis, without induction of bone loss. Second, ovariectomized growing rats were continuously treated for 3 weeks with 2-OHE 1 , 16 -OHE 1 , 17 -estradiol (E 2 ), a combination of E 2 and 2-OHE 1 (E 2 +2-OHE 1 ), or a combination of E 2 and 16 -OHE 1 (E 2 +16 -OHE 1 ), using controlled release subcutaneous implanted pellets containing 5 mg 2-OHE 1 , 5 mg 16 -OHE 1 , 0·05 mg E 2 or placebo. E 2 reduced body weight gain and radial and longitudinal bone growth as well as indices of cancellous bone turnover, and increased serum cholesterol, uterine wet weight and epithelial cell height, and proliferative cell nuclear antigen labeling in mammary gland. The hydroxylated estrones did not alter uterine wet weight and 16 -OHE 1 antagonized the E 2 -stimulated increase in epithelial cell height. 2-OHE 1 had no effect on cortical bone, whereas 16 -OHE 1 was an estrogen agonist with respect to all cortical bone measurements. 16 -OHE 1 also behaved as an estrogen agonist with respect to serum cholesterol and cancellous bone measurements. 2-OHE 1 had no effect on most E 2 -regulated indices of cancellous bone growth and turnover, but was a weak estrogen agonist with respect to mineral apposition rate and bone formation rate. Neither estrogen metabolite influenced body weight gain. Third, weanling rats were treated for 1 week with vehicle, E 2 (200 µg/kg per day) or 16 -OHE 1 (30, 100, 300, 1000 and 3000 g/kg per day) to confirm uterotropic effects of daily subcutaneous (s.c.) administration of 16 -OHE 1 . 16 -OHE 1 increased uterine weight in a dose-response manner to values that did not differ from rats treated with E 2 . We conclude that the estrogen metabolites 2-OHE 1 and 16 -OHE 1 have target tissue-specific biological activities which differ from one another as well as from E 2 . These findings add further support to the concept that there are several classes of estrogens with distinct biological activities. Furthermore, differences in the route of administration could influence the tissue specificity of estrogen metabolites.

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“…This study has shown that hormones and exercise interact to influence bone adaptations, and thus raise E 3 level related to increased BMD following exercise in female athletes. For example, serum E 2 , cortisol, PTH and T 3 levels in the athlete group were higher than those of the controls, and the major finding of this study was that increased radius BMD (K<0.05) and calcaneus BMD (K<0.01, P<0.05) were significantly and positively related to serum E 3 (K<0.01, P<0.01) concentrations [10][11][12] . Therefore, a clear understanding the interaction suggested by the present data between E 3 concentration and the adaptation of bone to exercise is important, and provides an interaction through which the estrogen receptors involved in the early response of bone cells might increase their responsiveness to loading [11,12] .…”

Section: Discussionmentioning

confidence: 48%

“…Consequently, lifelong physical exercise is recommended to optimize health-related benefits [2][3][4][5][6][7][8] . And the influence of physical activity and exercise training on BMD in females previously has been assessed in cross-sectional, retrospective longitudinal and controlled trial studies [3][4][5][6][7][8][9][10][11][12][13] . Even though no relationship about growth hormone and BMD was found.…”

Section: Introductionmentioning

confidence: 99%

“…Longitudinal information on associations between life style factors and age-related bone loss remains quite controversial. Some studies have found no relationship between bone loss and body composition or body weight, while others have shown them to predict bone mass changes [3][4][5][6][7][8][9][10][11][12][13][14][15][16] . Therefore, the purpose of this study was to explore the physiological function of female athletes, including BMD, renal function, liver function, hormone status, bone marker assay, lipid metabolism and muscle biology related to the effectiveness of exercise intervention for the health status of female athletes compared with controls.…”

Section: Introductionmentioning

confidence: 99%

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Effects of exercise on lipid metabolism and musculoskeletal fitness in female athletes

Chen¹,

Yang²

2004

WJG

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AIM:This study investigated the effects of intense training on lipid metabolism, bone metabolism and bone mineral density (BMD) in female athletes. METHODS:Sixty-six female subjects participated in this study, age ranging from 18 to 55 years. The sample group included thirty-six athletic subjects and the control group comprised thirty non-athletic individuals. Five athletes competed with national level (5/36) and nine non-athletic subjects (9/30) were postmenopausal women. The assessment items included body composition, radius BMD, calcaneus BMD, lung function, muscular endurance, renal and liver function, bone marker assay and hormone status. All data were analysed, using SPSS 10.0 software, and were presented as mean rank statistical difference, using the Kurskal-Wallis (K-W) test. After that the non-parameter statistics were used. Either K value or P value below 0.05 was considered significant. RESULTS: CONCLUSION:Postmenopausal athletes (5/36) who no longer took competing exercises had reduced levels of physical activity, faced increased risk of cardiovascular disease compared to active athletes (31/36) and the postmenopausal controls (9/30). We may thus concluded that long term exercise effectively improves musculoskeletal fitness and prevents BMD loss in female athletes.Chen KT, Yang RS. Effects of exercise on lipid metabolism and musculoskeletal fitness in female athletes.

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The Oxidative Metabolism of Estradiol Conditions Postmenopausal Bone Density and Bone Loss

Cited by 37 publications

References 57 publications

Effects of dietary calcium compared with calcium supplements on estrogen metabolism and bone mineral density

Effects of dietary calcium compared with calcium supplements on estrogen metabolism and bone mineral density

Tissue-selective effects of continuous release of 2-hydroxyestrone and 16alpha-hydroxyestrone on bone, uterus and mammary gland in ovariectomized growing rats

Effects of exercise on lipid metabolism and musculoskeletal fitness in female athletes

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