The effect of the antiestrogen tamoxifen on bone mineral density in normal late postmenopausal women

Grey, Andrew; Stapleton, Joanne P.; Evans, Margaret C.; Tatnell, Michele A.; Ames, Ruth; Reid, Ian R.

doi:10.1016/s0002-9343(99)80251-4

Cited by 144 publications

(62 citation statements)

References 30 publications

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“…Since both drugs have similar effects on bone metabolism and turnover, there is a clear AI class effect on bone health in postmenopausal women with hormone-sensitive breast cancer. Tamoxifen has been reported to have some beneficial effects on bone turnover and fracture risk in AI aromatase inhibitor, CI confidence interval, PINP procollagen type I N terminal propeptide, sCTX serum C-terminal telopeptides, uNTX urinary N-terminal telopeptides, ALP alkaline phosphatase postmenopausal women [4,[20][21][22], but the results here show that these positive effects do not carry over once tamoxifen therapy is discontinued. Our study showed an increase in bone turnover that could eventually lead to bone loss.…”

Section: Discussionmentioning

confidence: 62%

“…Tamoxifen is an antiestrogen that binds to the ER in place of estrogen and thereby blocks estrogen-mediated signaling [3]. Tamoxifen has partial agonist activity and stimulates ER activity in some organs such as bone, resulting in bone-sparing effects; however, in the endometrium, its partial estrogenic agonist activity results in an increased risk of endometrial cancer [4][5][6].…”

Section: Introductionmentioning

confidence: 99%

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A study of the effects of the aromatase inhibitors anastrozole and letrozole on bone metabolism in postmenopausal women with estrogen receptor-positive breast cancer

McCaig

Renshaw

Williams

et al. 2009

Breast Cancer Res Treat

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International audienceALIQUOT (Anastrozole vs. Letrozole, an Investigation of Quality Of Life and Tolerability) was a prospective, open-label, randomized pharmacodynamic study designed to assess the effects of aromatase inhibitors (AIs) on bone turnover in healthy postmenopausal women with estrogen receptor-positive breast cancer. Ninety-four patients were randomized to receive either 12 weeks of letrozole (2.5 mg; = 42) followed by 12 weeks of anastrozole (1 mg), or 12 weeks of anastrozole (1 mg; = 42) followed by 12 weeks of letrozole (2.5 mg). After completion of the study period, patients in the immediate adjuvant group were either switched to tamoxifen ( = 38) or continued on anastrozole or letrozole. In the beginning of the study, 42 patients had taken tamoxifen within 3 months. Patients taking drugs likely to affect bone metabolism, including bisphosphonates, were excluded. Eighty-four patients had complete sample measurements and were included in the analysis. Prior tamoxifen therapy resulted in a significantly lower mean baseline procollagen type 1 N-terminal propeptide (PINP) compared with patients with no prior tamoxifen. There were no significant differences in bone markers between AIs at any time. By 6 months, significant increases were seen in PINP, C-terminal telopeptides (CTX), bone specific alkaline phosphatise (ALP), and urinary N-terminal telopeptides (NTX). Patients with prior tamoxifen had significantly greater increases than patients with no prior tamoxifen. Patients treated with 3 months of tamoxifen following 6 months of an AI showed a significant decrease in markers of bone resorption, serum CTX and urinary NTX. In conclusion, AI-induced bone turnover increases over time. Anastrozole and letrozole produce similar effects on bone metabolism and turnover. Stopping tamoxifen therapy and starting AIs results in a significantly greater increase in bone turnover compared with commencing AIs in tamoxifen-naïve patients. Patients given tamoxifen following AI therapy showed a decrease in markers of bone resorption

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Section: Discussionmentioning

confidence: 62%

Section: Introductionmentioning

confidence: 99%

A study of the effects of the aromatase inhibitors anastrozole and letrozole on bone metabolism in postmenopausal women with estrogen receptor-positive breast cancer

McCaig

Renshaw

Williams

et al. 2009

Breast Cancer Res Treat

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“…We recently carried out a two-year randomized, double-blind, placebo-controlled trial to assess the effects of tamoxifen on bone mass and cardiovascular risk factors in normal postmenopausal women [4,5]. In this study, we incidentally observed changes in biochemical and haematological indices not previously reported with this class of drugs, suggesting that tamoxifen exerts a haemodilutory effect.…”

Section: Introductionmentioning

confidence: 83%

“…Whether this mechanism involves altered volume/osmolarity sensing, increased release of antidiuretic hormone, or increased renal sensitivity to this hormone is unknown. The observation that 20 mg per day of tamoxifen produces less marked effects than standard replacement doses of oestrogen, at least on the skeleton [5], is the likely explanation for the apparently Table 3 Results of biochemical tests in healthy postmenopausal women given tamoxifen or placebo for two years The P-values denote the significance of the between-groups differences in the changes from baseline values, and are derived from the repeated measures analysis of variance.…”

Section: Discussionmentioning

confidence: 99%

“…Studies in women with breast cancer suggest that tamoxifen may substantially reduce the risk of dying from cardiovascular disease [1,6,7]. This effect is likely to be, in part, attributable to favourable effects on serum lipids and haemostatic factors [3,5,13]. Haematocrit, which is an independent risk factor for vascular disease [14][15][16][17] perhaps by influencing blood viscosity [18] and erythrocyte-mediated platelet adhesion [19], has not been assessed in previous studies of the response of cardiovascular risk factors to tamoxifen.…”

Section: Discussionmentioning

confidence: 99%

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The anti‐oestrogen tamoxifen produces haemodilution in normal postmenopausal women

Grey

Evans

Kyle

et al. 1997

Journal of Internal Medicine

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Abstract. Grey AB, Evans MC, Kyle C, Reid, IR (University of Auckland, Auckland, New Zealand). The anti-oestrogen tamoxifen produces haemodilution in normal postmenopausal women. J Intern Med 1997; 242: 383-8. Objectives.To report the effects of the anti-oestrogen tamoxifen on biochemical and haematological parameters. Design. Randomized, double-blind comparison of tamoxifen 20 mg per day and placebo, over two years. Setting. A university hospital. Subjects. Forty-six healthy late-postmenopausal women (mean, SD time since menopause; 11, seven years). Main outcome measures. Blood specimens were drawn in the fasting state at baseline, six months and two years for measurement of haemoglobin, haematocrit, erythrocyte mean cell volume, mean erythrocyte haemoglobin, leucocyte count, platelet count, urea, electrolytes, creatinine and albumin.Results. There was a significant decline in the haemoglobin concentration in the tamoxifen group (Ϫ4.4, 1.2 g/L; mean, SE) and its levels were lower in this group than in those receiving placebo (P ϭ 0.004). Similarly, haematocrit, erythrocyte count and total leucocyte count were lower in those on placebo (P ϭ 0.002, P ϭ 0.01 and P ϭ 0.01, respectively) and platelet count showed a similar trend (P ϭ 0.08). In the tamoxifen group, the level of serum albumin fell significantly (Ϫ2.2, 0.4 g/L) and was lower throughout the study than that in the placebo group (P ϭ 0.006). That of serum urea tended to fall (Ϫ0.4, 0.2 mmol L) but the between-groups comparison was not significant (P ϭ 0.18). Conclusions. These data suggest that tamoxifen exerts a haemodilutory effect in normal postmenopausal women. Since a similar effect has been reported in response to postmenopausal oestrogen therapy, it is likely that the observed changes represent another oestrogenic effect of tamoxifen in postmenopausal women. Haemodilution may contribute to the reduced incidence of cardiovascular disease reported in tamoxifen-treated women, and, therefore, its assessment in the new oestrogen agonists/antagonists being developed for cardiovascular disease prevention may be important.

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The Role of Hormone Replacement Therapy in the Prevention of Postmenopausal Heart Disease

Mosca¹

2000

Arch Intern Med

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Coronary heart disease is the single leading cause of death in women and a significant cause of disability. Menopause adversely affects several risk factors for coronary heart disease, suggesting that hormones influence the risk of coronary heart disease in postmenopausal women. This article reviews the observational and clinical trial data evaluating the relation between cardiovascular disease and hormone replacement therapy. Biological mechanisms of estrogen and the impact of adding progestins are emphasized. Potential risks and benefits of therapy are discussed. The relative effects of other estrogen and lipid-lowering therapies for preventing coronary heart disease in postmenopausal women are highlighted.

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The effect of the antiestrogen tamoxifen on bone mineral density in normal late postmenopausal women

Cited by 144 publications

References 30 publications

A study of the effects of the aromatase inhibitors anastrozole and letrozole on bone metabolism in postmenopausal women with estrogen receptor-positive breast cancer

A study of the effects of the aromatase inhibitors anastrozole and letrozole on bone metabolism in postmenopausal women with estrogen receptor-positive breast cancer

The anti‐oestrogen tamoxifen produces haemodilution in normal postmenopausal women

The Role of Hormone Replacement Therapy in the Prevention of Postmenopausal Heart Disease

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