Antiestrogen and antiandrogen administration reduce bone mass in the rat

Feldmann, Sascha; Minne, H. W.; Parvizi, Saeed; Pfeifer, Michael; Lempert, U.G.; Bauss, Frieder; Ziegler, Reinhard

doi:10.1016/0169-6009(89)90081-0

Cited by 49 publications

(10 citation statements)

References 42 publications

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“…These and more recent studies (Frolik et al 1996;Li et al 1996;Sibonga et al 1996;Ke et al 1997) have shown that tamoxifen prevents ovariectomy-induced bone loss. In intact female rats the results are somewhat conflicting, some studies show no effect (Jordan et al 1987;Moon et al 1991) whereas others show a slight tamoxifen-related decrease of bone tissue (Feldmann et al 1989;Hard et al 1993;Sibonga et al 1996). In postmenopausal women, tamoxifen has been shown to lack negative effects on bone metabolism (Nakanishi et al 1995;Barni et al 1996;Kalef-Ezra et al 1996;Powles et al 1996) and some studies even indicate a weak antiosteoporotic effect (Nakanishi et al 1995;Barni et al 1996).…”

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confidence: 91%

“…In the late 1980's when it was demonstrated that normal human osteoblast-like cells exhibit oestrogen receptors (Eriksen et al 1988), several studies were performed to evaluate the effect of tamoxifen on bone homeostasis in intact rats (Jordan et al 1987;Feldmann et al 1989;Moon et (11. 1991) and ovariectomised rats (Feldmann et al 1989;Kalu et al 1991 b;Moon et ul.…”

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confidence: 99%

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The Effect of Toremifene on Bone and Uterine Histology and on Bone Resorption in Ovariectomised Rats

Karlsson¹,

Mäntylä²,

Hirsimäki³

et al. 1999

Pharmacology & Toxicology

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The effect of the selective oestrogen receptor modulator, toremifene, to inhibit ovariectomy-induced bone loss was studied in rats. The oral doses were 0.3, 3.0 or 30 mg/kg/day for 2 months. 17P-oestradiol ( 5 pgikgiday, subcutaneously) was used as positive control. One group was also treated with a combination of 17P-oestradiol (5 pgikg) and toremifene (3.0 mgikg). Biochemical markers were urinary hydroxyproline and calcium (adjusted with urinary creatinine levels) and the serum level of pyridinoline cross-linked carboxy terminal telopeptide, a bone specific collagen breakdown product. The femoral and sternal trabecular bone thickness served as histological parameters. Ovarectomy increased the levels of hydroxyproline and pyrodinoline and decreased the trabecular bone thickness compared to the sham-operated control group. This was inhibited by both test compounds but 17P-oestradiol was more efficient. Toremifene did not reverse the ovariectomy-induced reduction of urinary calcium but inhibited the 17P-oestradiol-related increase. When administered together with oestradiol, toremifene did not reverse the positive effect of 17P-oestradiol on bone, however toremifene reversed the oestradiol-related uterothrophic effects. These findings indicate that the antagonistic features of toremifene dominate in the rat uterus the agonistic properties do in the bone.

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confidence: 91%

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confidence: 99%

The Effect of Toremifene on Bone and Uterine Histology and on Bone Resorption in Ovariectomised Rats

Karlsson¹,

Mäntylä²,

Hirsimäki³

et al. 1999

Pharmacology & Toxicology

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“…However, studies in ovary-intact animals, which would address the interaction between TAM and endogenous estrogen, are few in number. Based upon various interpretations of skeletal effects, these studies report that TAM maintains bone density in intact, adult rats while it antagonizes growth in the uterus [13]; significantly reduces cancellous bone area when high doses (30 mg/3 weeks) are infused in intact young animals [14]; antagonizes estrogen's maximum ability to suppress bone loss in the OVX rat when administered in combination with estrogen [15]; and is antiestrogenic for bone and sex organs in young rats [16]. These studies however are limited by the relatively insensitive methods used to assay the skeleton [13,16], the use of rapidly growing animals [14,15], or both [16].…”

Section: Introductionmentioning

confidence: 97%

Ovarian status influences the skeletal effects of tamoxifen in adult rats

Sibonga

Evans

Hauck

et al. 1996

Breast Cancer Res Tr

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Tamoxifen (TAM), an antiestrogen used in adjuvant therapy for breast cancer, is currently being evaluated for prevention of breast cancer in premenopausal and postmenopausal disease-free women. In light of this clinical application in young women, the skeleton's potential predisposition for osteoporosis following long-term treatment with an antiestrogen is a concern. In postmenopausal women being treated for breast cancer TAM was shown to prevent bone loss. There is little information, however, about the skeletal effects of TAM in premenopausal women. Previous animal studies in ovariectomized (OVX'd) rats have consistently reported TAM to prevent cancellous and cortical bone loss. The effects of TAM on ovary-intact animals, however, are not well established. We have performed a histomorphometric analysis in order to evaluate the influence of ovarian function on the skeletal effects of long-term TAM treatment in the laboratory animal model. Six-month-old rats were implanted subcutaneously with pellets designed for the controlled release of TAM at a dose (5 mg/3 wks) previously shown to be effective at antagonizing short-term bone loss in OVX'd growing rats. TAM acted as an estrogen agonist on cortical bone measurements in tibia of ovary-intact as well as OVX'd rats. In cancellous bone of OVX'd rats, TAM reduced indices of bone formation and resorption and reduced the bone loss from over 90 percent to less than 50 percent. In ovary-intact rats, however, TAM produced a 31 percent loss of cancellous bone, a deficit associated with a 26 percent reduction in the trabecular number. These results clearly demonstrate an interaction between TAM and ovarian status whereby TAM partially prevents estrogen-deficient bone loss in OVX'd animals but antagonizes selective actions of estrogen on the skeleton of ovary-intact animals.

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“…Controversial results have been reported on the influence of tamoxifen on bone minerals in animal models [19][20][21][22][23][24]. Various investigators applying absorptiometric techniques reported that tamoxifen lacks adverse effects on the amount of bone minerals.…”

Section: Discussionmentioning

confidence: 96%

Elemental composition of bone minerals in women with breast cancer treated with adjuvant tamoxifen

Kalef-Ezra

Pavlidis

Klouvas

et al. 1996

Breast Cancer Res Tr

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Oestrogen levels play a major role in conditioning the rates of bone changes in women. Tamoxifen is a synthetic oestrogen antagonist commonly used as an adjuvant therapy for breast cancer. The goal of the present study was to study the amount and the elemental composition of bone minerals in the appedicular skeleton of women with breast cancer treated with adjuvant tamoxifen, as well as to investigate the possibility of increased risk for osteoporosis. Forty-two patients, aged 41-65 years, without skeletal metastases were studied. The mean duration of tamoxifen administration on a daily dose of 20 mg was 21 months (range 1-59 months). It was found that neither the amount of phosphorus in hands (HBP) nor forearm bone mineral content (BMC) differ statistically from those of age-matched healthy subjects. This was confirmed by reassessing bone mineral status after 30 months in 17 postmenopausal patients treated with tamoxifen for a mean time of 52 months. In conclusion, our data support that long-term tamoxifen treatment has no adverse or protective effect on the amount and elemental composition of the appedicular skeleton.

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Antiestrogen and antiandrogen administration reduce bone mass in the rat

Cited by 49 publications

References 42 publications

The Effect of Toremifene on Bone and Uterine Histology and on Bone Resorption in Ovariectomised Rats

The Effect of Toremifene on Bone and Uterine Histology and on Bone Resorption in Ovariectomised Rats

Ovarian status influences the skeletal effects of tamoxifen in adult rats

Elemental composition of bone minerals in women with breast cancer treated with adjuvant tamoxifen

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