Effects of 1-year treatment with ipriflavone on bone in postmenopausal women with low bone mass

Valente, Michele; Bufalino, L.; Castiglione, G. N.; D’Angelo, Roberto; Mancuso, A.; Gabriela, Paola; Zichella, L

doi:10.1007/bf00305522

Cited by 67 publications

(19 citation statements)

References 15 publications

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“…The usual dose in these studies was 600 mg per day, often given in three daily doses of 200 mg. In placebo-controlled studies with a duration of 1 or 2 years, this dose has been shown to inhibit the loss of bone mineral density of the spine (Valente et al, 1994;Agnusdei et al, 1997;de Aloysio et al, 1997;Gambacciani et al, 1997;Gennari et al, 1997) and radius Gennari et al, 1997) that was observed in the control groups. Several studies (Agnusdei et al, 1995;de Aloysio et al, 1997;Gambacciani et al, 1997) have also evaluated the effect of ipri¯avone in combination with low-dose conjugated oestrogens.…”

Section: Discussionmentioning

confidence: 99%

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Phyto-oestrogen excretion and rate of bone loss in postmenopausal women

et al. 1998

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Objective: The hypothesis was tested that the rate of postmenopausal bone loss is inversely associated with longterm urinary excretion of phyto-oestrogens, as a marker of habitual dietary intake. Design: Secondary analysis of a 10-year follow-up study (1979 ± 1989) among postmenopausal women in the Netherlands. Subjects: From the original population of 154 women, 32 women were selected with an annual rate of radial bone loss of 0.5% over the ®rst 5 years of the study and 35 women with a rate of ! 2.5% per year. Methods: The iso¯avonoids genistein, daidzein and equol, and the lignan enterolactone were determined by gas chromatography ± mass spectrometry in aggregate samples from annually collected urine samples. Cortical bone density of the radius had previously been measured annually by single-photon absorptiometry. Results: Excretion of iso¯avonoids did not differ between both groups, although in multivariate analysis equol excretion was weakly positively associated with rate of bone loss in the 5 years after the menopause. Enterolactone excretion was signi®cantly higher in the group with high rate of bone loss. This positive association remained in multivariate linear regression analysis after adjustment for age, years since menopause, body mass index and intake of calcium, vegetable protein and dietary ®bre. Conclusions: Enterolactone excretion is likely to be an indicator of consumption of grains and legumes; it is not clear whether the observed positive association with rate of bone loss is a causal one. Our results do not support a preventive effect of low, unsupplemented dietary intake of phyto-oestrogens on postmenopausal cortical bone loss. However, no conclusions can be drawn about effects of higher doses of phyto-oestrogens. Sponsorship: This study was supported by the Dutch Prevention Fund, a charity organisation.

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Section: Discussionmentioning

confidence: 99%

“…In Italy, a number of trials support the preventive effect of ipri¯avone on postmenopausal bone loss Agnusdei et al, 1997;Valente et al, 1994). Ipri¯avone is a synthetic iso¯avone; iso¯avones are natural plant hormones with an oestrogen-like structure, with soy products as their predominant source.…”

Section: Introductionmentioning

confidence: 99%

Phyto-oestrogen excretion and rate of bone loss in postmenopausal women

et al. 1998

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“…Ipriflavone, (IPR; 7-isopropoxyisoflavone), an isoflavone derivative, has been the phytoestrogen most studied as a therapeutic agent in osteoporosis. Daily oral doses of 3-10 mg/kg/day IPR prevent bone turnover and loss in bone density in women who are postmenopausal or who have been treated with gonadotropinreleasing hormone (GnRH) agonists (132)(133)(134). These doses produce plasma concentrations (135) similar to the in vitro concentrations (≥ 100 nM) required for inhibition of osteoclast differentiation (136) and bone resorption (137).…”

Section: Bone Densitymentioning

confidence: 99%

Cross-species and interassay comparisons of phytoestrogen action.

Whitten

Patisaul

2001

Environ Health Perspect

174

105

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This paper compiles animal and human data on the biologic effects and exposure levels of phytoestrogens in order to identify areas of research in which direct species comparisons can be made. In vitro and in vivo assays of phytoestrogen action and potency are reviewed and compared to actions, dose-response relationships, and estimates of exposure in human subjects. Binding studies show that the isoflavonoid phytoestrogens are high-affinity ligands for estrogen receptors (ERs), especially ER beta, but have lower potency in whole-cell assays, perhaps because of interactions with binding proteins. Many other enzymatic actions require concentrations higher than those normally seen in plasma. In vivo data show that phytoestrogens have a wide range of biologic effects at doses and plasma concentrations seen with normal human diets. Significant in vivoresponses have been observed in animal and human tests for bone, breast, ovary, pituitary, vasculature, prostate, and serum lipids. The doses reported to be biologically active in humans (0.4--10 mg/kg body weight/day) are lower than the doses generally reported to be active in rodents (10--100 mg/kg body weight/day), although some studies have reported rodent responses at lower doses. However, available estimates of bioavailability and peak plasma levels in rodents and humans are more similar. Steroidogenesis and the hypothalamic-pituitary-gonadal axis appear to be important loci of phytoestrogen actions, but these inferences must be tentative because good dose-response data are not available for many end points. The similarity of reported proliferative and antiproliferative doses illustrates the need for fuller examination of dose-response relationships and multiple end points in assessing phytoestrogen actions.

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“…First clinical trials indicate that the compound exerts a beneficial effect in osteopenic diseases [1][2][3]. It is not clear yet whether ipriflavone acts primarily by inhibiting bone resorption or by stimulating bone formation.…”

mentioning

confidence: 99%

“…For measuring bone resorption, we used a technique based on long-term prelabeling with [ 3 H]-tetracycline and the subsequent determination of urinary excretion of the tracer (Fig. 1).…”

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Ipriflavone inhibits bone resorption in intact and ovariectomized rats

1997

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Abstract. The aim of this study was to investigate the possible inhibitory effect of ipriflavone on bone resorption in rats. For this purpose, 10-week-old, intact and ovariectomized (OVX) rats, prelabeled from birth with [3 H]-tetracycline, were used. Bone resorption was monitored by measuring the urinary excretion of [ 3 H]. The animals were fed a purified diet devoid of naturally occurring flavonoids. In the intact rats, the daily meal was given either as a single portion or divided into four portions, a procedure known to lead by itself to a decrease in bone resorption. Ipriflavone, given 7 days after OVX at the dose of 400 mg/kg B.W. daily mixed with the food, led within 2-3 days to a significant decrease in bone resorption equivalent to that of 27.2 p g/kg S.C. of 1713-estradiol. The inhibition was sustained for the length of the experiment, up to 21 days. Ipriflavone given 7 days before OVX prevented the increase in bone resorption induced by castration, the effect being dose-dependent between 50 and 400 mg/kg B.W. In contrast to 1713-estradiol, a 5-week treatment with ipriflavone failed to prevent the OVX-induced uterine atrophy. Significant inhibition of bone resorption was also seen in intact animals, provided they rapidly ingested the daily meal. Actually, the decrease in bone resorption induced by portioning the daily food masked the inhibitory effect of ipriflavone in intact animals. In conclusion, ipriflavone can decrease bone resorption in both intact and OVX animals given a purified diet as a single daily meal. In the OVX model, ipriflavone mimics the osteoprotective effect of estrogen. However, the lack of a uterotropic effect suggests that the compound can discriminate between bone and reproductive tissues.Key words: Ipriflavone -Bone resorption -Ovariectomized rats.Ipriflavone is a synthetic derivative of a natural isoflavone. First clinical trials indicate that the compound exerts a beneficial effect in osteopenic diseases [1][2][3]. It is not clear yet whether ipriflavone acts primarily by inhibiting bone resorption or by stimulating bone formation. Inhibition of osteoclast recruitment in both in vitro [4,5] and in vivo [6], and induction of markers of the osteoblast phenotype in vitro [7,8] have been demonstrated. However, in the rat model of osteopenia following ovariectomy [9], ipriflavone did not reduce bone resorption when administered alone, but it did enhance the therapeutic effects of estrogen. Confounding factors may explain the lack of the protective effect of ipriflavone per se on bone loss due to estrogen withdrawal in animals. Therefore, we investigated in vivo the modalities by which an intrinsic inhibitory activity of ipriflavone on bone resorption can be disclosed.For measuring bone resorption, we used a technique based on long-term prelabeling with [ 3 H]-tetracycline and the subsequent determination of urinary excretion of the tracer (Fig. 1). This technique allows monitoring of bone resorption, daily or at shorter intervals, over extended periods of time [10].According to t...

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Effects of 1-year treatment with ipriflavone on bone in postmenopausal women with low bone mass

Cited by 67 publications

References 15 publications

Phyto-oestrogen excretion and rate of bone loss in postmenopausal women

Phyto-oestrogen excretion and rate of bone loss in postmenopausal women

Cross-species and interassay comparisons of phytoestrogen action.

Ipriflavone inhibits bone resorption in intact and ovariectomized rats

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