Soy and Osteoporosis/Bone Loss Prevention Abstracts
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AUTHOR: Head KA
TITLE: Ipriflavone: an important bone-building isoflavone.
SOURCE: Altern Med Rev (C2X), 1999 Feb; 4 (1): 10-22
LANGUAGE: English
COUNTRY PUB.: UNITED STATES
ABSTRACT:
Ipriflavone, an isoflavone synthesized from the soy
isoflavone daidzein, holds great promise in the prevention
and treatment of osteoporosis and other metabolic bone
diseases. It has been widely studied in humans and found
effective for inhibiting bone resorption and enhancing bone
formation, the net result being an increase in bone density
and a decrease in fracture rates in osteoporotic women.
While ipriflavone appears to enhance estrogen's effect, it
does not possess intrinsic estrogenic activity, making it an
attractive adjunct or alternative to conventional hormone
replacement therapy. Preliminary studies have also found
ipriflavone effective in preventing bone loss associated
with chronic steroid use, immobility, ovariectomy, renal
osteodystrophy, and gonadotrophin hormone-releasing hormone
agonists. In addition, it holds promise for the treatment of
other metabolic diseases affecting the bones, including
Paget's disease of the bone, hyperparathyroidism, and
tinnitus caused by otosclerosis.
AUTHOR: Harrison E; Adjei A; Ameho C; Yamamoto S; Kono S
ADDRESS: Department of Adult Health, Faculty of Medicine, University
of the Ryukyus, Okinawa, Japan.
TITLE: The effect of soybean protein on bone loss in a rat model of
postmenopausal osteoporosis.
SOURCE: J Nutr Sci Vitaminol (Tokyo) (JFD), 1998 Apr; 44 (2): 257-68
LANGUAGE: English
COUNTRY PUB.: JAPAN
ABSTRACT:
This study was designed to investigate the modulatory effect
of dietary soybean protein on the skeleton of an
ovariectomized rat model with postmenopausal osteoporosis.
Thirty-two female Sprague-Dawley rats were weight matched
and divided into the following four experimental groups: Soy
group, ovariectomized and fed soy protein diet; Estrogen
group, ovariectomized, fed casein diet and injected with
estrogen; Casein group, ovariectomized and fed casein diet;
and Sham group, sham-operated and fed casein diet. The diets
and estrogen were started two weeks after surgery, and
continued for four weeks. Rats in the Sham, Soy and Estrogen
groups had significantly higher (p < 0.05) femur and tibia
ash content than those in the Casein group. Accordingly, the
calcium content of the tibia and femur were also
significantly higher (p < 0.05) in the Soy, Estrogen and
Sham groups as compared to the Casein group. Serum total and
bone-type alkaline phosphatase levels were both
significantly lower (p < 0.05) in the Estrogen and Sham
groups in relation to the Soy and Casein groups. This study
demonstrated that a 22% soybean protein diet could be just
as effective as daily estrogen administration in suppressing
bone loss due to ovariectomy. However, unlike estrogen, soy
protein diet did not have any uterotrophic effect and did
not decrease the markers of bone turnover measured,
suggesting a possible difference in the mechanism of action.
AUTHOR: Anderson JJ; Garner SC
ADDRESS: Department of Nutrition, Schools of Public Health and
Medicine, University of North Carolina, Chapel Hill, USA.
TITLE: Phytoestrogens and bone.
SOURCE: Baillieres Clin Endocrinol Metab (9JL), 1998 Dec; 12 (4):
543-57
LANGUAGE: English
COUNTRY PUB.: ENGLAND
ABSTRACT:
Practically all plant foods contain small amounts of the
diverse phytoestrogen molecules that have the potential to
improve health. Phytoestrogens, especially the soy-derived
isoflavones, are receiving great scrutiny as food
supplements for the purposes of both enhancing the health of
tissues and preventing several common diseases, such as
cardiovascular diseases, cancers of reproductive tissues and
osteoporosis. Investigations of isoflavones, in particular,
have recently become more prominent because of their
oestrogenic activities. These actions may be as either
partial oestrogen agonists or anti-oestrogens (inhibitors of
natural oestrogen activity). For example, the isoflavones of
soy, mainly genistein and daidzein, have been shown by at
least three different laboratories to conserve bone in
ovariectomized rodent models, and they probably have similar
conservatory effects in higher mammalian species.
Nevertheless, the only positive effects of phytoestrogens on
bone observed so far in post-menopausal women have been
small and limited to the lumbar vertebrae. Additional
information on human studies currently in progress is needed
before the efficacy of these preparations in human subjects
is known.
AUTHOR: Arjmandi BH; Getlinger MJ; Goyal NV; Alekel L; Hasler CM;
Juma S; Drum ML; Hollis BW; Kukreja SC
ADDRESS: Department of Nutritional Sciences, Oklahoma State
University, Stillwater 74078-6141, USA.
TITLE: Role of soy protein with normal or reduced isoflavone
content in reversing bone loss induced by ovarian hormone
deficiency in rats.
SOURCE: Am J Clin Nutr (3EY), 1998 Dec; 68 (6 Suppl): 1358S-1363S
LANGUAGE: English
COUNTRY PUB.: UNITED STATES
ABSTRACT:
Soy protein, a rich source of isoflavones, fed immediately
after an ovariectomy prevents bone loss in rats. Reports of
the effectiveness of natural and synthetic isoflavones in
preventing or treating osteoporosis led us to examine the
effect of soy protein in reversing established bone loss.
Seventy-two 95-d-old female Sprague-Dawley rats were
assigned to 6 groups. The rats were either sham operated
(SHAM; 2 groups) or ovariectomized (OVX; 4 groups) and then
fed a casein-based, semipurified diet. Thirty-five days
after surgery, 1 SHAM and 1 OVX group were killed to examine
the occurrence of bone loss. Thereafter, the other SHAM and
1 OVX groups continued to receive the casein-based diet.
Whereas the remaining 2 OVX groups received diets in which
casein was replaced by soy protein with normal (OVX+SOY) or
reduced (OVX+SOY-) isoflavone content for 65 days. The OVX
control group had significantly lower femoral and fourth
lumbar vertebral bone densities than the SHAM group. Femoral
density of rats fed SOY or SOY- diets were not significantly
different from SHAM or OVX controls. This suggests a slight
reversal of cortical bone loss that may be partially due to
higher femoral insulin-like growth factor I mRNA transcripts
resulting from both the SOY and SOY- diets. The ovariectomy-
induced increases in indexes of bone turnover were not
ameliorated by either of the soy diets, suggesting that any
positive effect of soy was achieved through enhanced bone
formation rather than slowed bone resorption. Long-term
consumption of soy or its isoflavones may be needed to
produce small but continued increments in bone mass.
AUTHOR: Kardinaal AF; Morton MS; Bruggemann-Rotgans IE; van
Beresteijn EC
ADDRESS: Department of Consumer Research and Epidemiology, TNO
Nutrition and Food Research Institute, Zeist, The
Netherlands.
TITLE: Phyto-oestrogen excretion and rate of bone loss in
postmenopausal women.
SOURCE: Eur J Clin Nutr (EJC), 1998 Nov; 52 (11): 850-5
LANGUAGE: English
COUNTRY PUB.: ENGLAND
ABSTRACT:
OBJECTIVE: The hypothesis was tested that the rate of
postmenopausal bone loss is inversely associated with long-
term 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 < or = 0.5% over the first 5 years of
the study and 35 women with a rate of > or = 2.5% per year.
METHODS: The isoflavonoids 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 isoflavonoids
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 significantly 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 fibre.
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.
AUTHOR: Kimira M; Arai Y; Shimoi K; Watanabe S
ADDRESS: Department of Applied Bioscience, Tokyo University of
Agriculture, Japan.
TITLE: Japanese intake of flavonoids and isoflavonoids from foods.
SOURCE: J Epidemiol (CL8), 1998 Aug; 8 (3): 168-75
LANGUAGE: English
COUNTRY PUB.: JAPAN
ABSTRACT:
The intake of flavonoids and isoflavonoids was estimated
based upon a preliminary database of 40 food items, covering
at least 80% of total food consumption. Fifty volunteer
women in "I-City" recorded the weight of all dietary intake
for 3 days in September 1996, and received a health check-
up, as well as laboratory examination. The data was analyzed
in relation to the various food factors. Average daily
intake per capita of flavonoids was as follows: 4.9 mg
kaempferol, 8.3 mg quercetin, 1.5 mg rutin, 0.6 mg
myricetin, 0.3 mg luteolin, 0.01 mg myricitrin, 0.4 mg
fisetin, and 0.3 mg eriodictyol. Total intake from
vegetables and fruits was less than 10 mg 16.2 mg (range:
3.18-35.61 mg) and 23.27 mg (4.62-52.12 mg) of isoflavones,
such as daidzein and genistein, respectively, were taken per
day, and total isoflavone intake was 39.46 mg (7.80-87.73
mg). Chief component analysis on ingested vitamins,
flavonoids and isoflavonoids was carried out. Factor 1 was
mainly composed of flavonoids and antioxidant vitamins.
Factor 1 was positively associated with age and the level of
HDL cholesterol and negatively related to the level of
triglycerides. Factor 2, which was mainly composed of
isoflavonoids, was positively associated with creatinine and
uric acid levels. So far, these factors did not show a
significant association with bone density and other health
indices, such as BMI and blood pressure.
AUTHOR: Arjmandi BH; Birnbaum R; Goyal NV; Getlinger MJ; Juma S;
Alekel L; Hasler CM; Drum ML; Hollis BW; Kukreja SC
ADDRESS: Department of Nutritional Sciences, Oklahoma State
University, Stillwater 74078-6141, USA.
TITLE: Bone-sparing effect of soy protein in ovarian hormone-
deficient rats is related to its isoflavone content.
SOURCE: Am J Clin Nutr (3EY), 1998 Dec; 68 (6 Suppl): 1364S-1368S
LANGUAGE: English
COUNTRY PUB.: UNITED STATES
ABSTRACT:
Our previous studies showed that a soy-protein diet prevents
ovariectomy-induced bone loss. The purpose of this study was
to determine whether isoflavones in soy protein are
responsible for this bone-protective effect. Forty-eight 95-
d-old Sprague-Dawley rats were divided into 4 groups: sham-
operated fed a casein-based diet (SHAM), ovariectomized fed
a casein-based diet (OVX+CASEIN), ovariectomized fed soy
protein with normal isoflavone content (OVX+SOY), and
ovariectomized fed soy protein with reduced isoflavone
content (OVX+SOY-). The OVX+SOY group had significantly
greater femoral bone density (in g/cm3 bone vol) than the
OVX+CASEIN group, whereas OVX+SOY- was similar to OVX+CASEIN
(mean +/- SD; SHAM, 1.522 +/- 0.041; OVX+CASEIN, 1.449 +/-
0.044; OVX+SOY, 1.497 +/- 0.030; OVX+SOY-, 1.452 +/- 0.030).
Ovariectomy resulted in greater bone turnover as indicated
by higher serum alkaline phosphatase activity, serum insulin-
like growth factor I and insulin-like growth factor binding
protein 3 concentrations, and urinary hydroxyproline. These
increases were not affected by soy with either normal or
reduced isoflavone content. Similarly, histomorphometry
revealed a greater bone formation rate with ovariectomy, and
this was not altered by the soy diets. The findings of this
study suggest that isoflavones in soy protein are
responsible for its bone-sparing effects. Further studies to
evaluate the mechanism of action of isoflavones on bone are
warranted.
AUTHOR: Barnes S
ADDRESS: Department of Pharmacology and Toxicology, University of
Alabama at Birmingham, 35294, USA.
TITLE: Evolution of the health benefits of soy isoflavones.
SOURCE: Proc Soc Exp Biol Med (PXZ), 1998 Mar; 217 (3): 386-92
LANGUAGE: English
COUNTRY PUB.: UNITED STATES
ABSTRACT:
Soy is a unique dietary source of the isoflavones, genistein
and daidzein. It has been part of the Southeast Asian diet
for nearly five millenia, whereas consumption of soy in the
United States and Western Europe has been limited to the
20th century. Heavy consumption of soy in Southeast Asian
populations is associated with reduction in the rates of
certain cancers and cardiovascular disease. Recent
experimental evidence suggests that phytochemicals in soy
are responsible for its beneficial effects, which may also
include prevention of osteoporosis, a hereditary chronic
nose bleed syndrome, and autoimmune diseases. Exposure of
soy formula-fed infants to the potential estrogenizing
effects of the isoflavones is limited by the first pass
effect of the liver following the uptake of isoflavones from
the gut. Several mechanisms of action of isoflavones have
been proposed-both through estrogen-dependent and estrogen-
independent pathways.
AUTHOR: Ishimi Y; Miyaura C; Ohmura M; Onoe Y; Sato T; Uchiyama Y;
Ito M; Wang X; Suda T; Ikegami S
ADDRESS: Department of Food Science, The National Institute of Health
and Nutrition, Tokyo, Japan.
TITLE: Selective effects of genistein, a soybean isoflavone, on B-
lymphopoiesis and bone loss caused by estrogen deficiency.
SOURCE: Endocrinology (EGZ), 1999 Apr; 140 (4): 1893-900
LANGUAGE: English
COUNTRY PUB.: UNITED STATES
ABSTRACT:
Genistein, an isoflavone abundantly present in soybeans, has
structural similarity to estrogen, suggesting that genistein
may act as a phytoestrogen. To examine the possible role of
genistein in hemopoiesis and bone metabolism, female mice
were either sham-operated or ovariectomized (OVX), and
selected OVX mice were administered genistein for 2-4 weeks
(0.1-0.7 mg/day) or 17beta-estradiol (E2; 0.01-0.1
microg/day) s.c., using a miniosmotic pump (Alza Corp., Palo
Alto, CA). In OVX mice, uterine weight declined but was
completely restored by E2 administration. In contrast,
genistein did not demonstrate a reversal of the OVX-induced
uterine atrophy. The number of bone marrow cells markedly
increased, 2-4 weeks after OVX, and most of these were B220-
weakly positive pre-B cells. The increased B-lymphopoiesis
was completely restored, not only by E2 but also by
genistein administration. In OVX mice, the trabecular bone
volume of the femoral distal metaphysis, measured by
microcomputed tomography scanning and dual-energy x-ray
absorptiometry, was markedly reduced; and genistein restored
this, as did E2. These results indicate that genistein
exhibits estrogenic action in bone and bone marrow, to
regulate B-lymphopoiesis and prevent bone loss, without
exhibiting estrogenic action in the uterus. Phytoestrogens
may be useful for preventing bone loss caused by estrogen
deficiency in females.
AUTHOR: Ishida H; Uesugi T; Hirai K; Toda T; Nukaya H; Yokotsuka K;
Tsuji K
ADDRESS: School of Pharmaceutical Science, University of Shizuoka,
Yada, Japan.
TITLE: Preventive effects of the plant isoflavones, daidzin and
genistin, on bone loss in ovariectomized rats fed a calcium-
deficient diet.
SOURCE: Biol Pharm Bull (BPZ), 1998 Jan; 21 (1): 62-6
LANGUAGE: English
COUNTRY PUB.: JAPAN
ABSTRACT:
The effects of the plant isoflavones, daidzin and genistin,
on bone loss in ovariectomized (ovx) rats fed a calcium-
deficient diet were investigated. Daidzin and genistin were
orally administered to ovx rats for 4 weeks. The femurs of
these rats showed significantly lower density, strength
(breaking forces), ash weight and calcium and phosphorus
content (p<0.01) in comparison with those of sham-operated
rats. These changes were largely prevented in animals
receiving oral daidzin or genistin for 4 weeks at a dose of
50 mg/kg/d and in animals receiving subcutaneous estrone
(7.5 microg/kg/d) as a positive control. Ovariectomy caused
atrophy of the uterus and increased the ratio of the urinary
excretion of pyridinoline and deoxypyridinoline to
endogenous creatinine excretion. This was prevented by
administration of daidzin or estrone, but, interestingly,
not genistin. The preventive effect of daidzin treatment on
bone loss in ovariectomized rats appears to be due to
suppression of bone turnover. Genistin has a different
mechanism of action from daidzin.
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