Bahram H. Arjmandi

Bone-sparing effect of soy protein in ovarian hormone-deficient rats is related to its isoflavone content.

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.

Role of soy protein with normal or reduced isoflavone content in reversing bone loss induced by ovarian hormone deficiency in rats.

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.

One year soy protein supplementation has positive effects on bone formation markers but not bone density in postmenopausal women

BackgroundAlthough soy protein and its isoflavones have been reported to reduce the risk of osteoporosis in peri- and post-menopausal women, most of these studies are of short duration (i.e. six months). The objective of this study was to examine if one year consumption of soy-containing foods (providing 25 g protein and 60 mg isoflavones) exerts beneficial effects on bone in postmenopausal women.MethodsEighty-seven eligible postmenopausal women were randomly assigned to consume soy or control foods daily for one year. Bone mineral density (BMD) and bone mineral content (BMC) of the whole body, lumbar (L1-L4), and total hip were measured using dual energy x-ray absorptiometry at baseline and after one year. Blood and urine markers of bone metabolism were also assessed.Results and DiscussionSixty-two subjects completed the one-year long study. Whole body and lumbar BMD and BMC were significantly decreased in both the soy and control groups. However, there were no significant changes in total hip BMD and BMC irrespective of treatment. Both treatments positively affected markers of bone formation as indicated by increased serum bone-specific alkaline phosphatase (BSAP) activity, insulin-like growth factor-I (IGF-I), and osteocalcin (BSAP: 27.8 and 25.8%, IGF-I: 12.8 and 26.3%, osteocalcin: 95.2 and 103.4% for control and soy groups, respectively). Neither of the protein supplements had any effect on urinary deoxypyridinoline excretion, a marker of bone resorption.ConclusionOur findings suggest that although one year supplementation of 25 g protein per se positively modulated markers of bone formation, this amount of protein was unable to prevent lumbar and whole body bone loss in postmenopausal women.

Evidence for estrogen receptor-linked calcium transport in the intestine

Intestinal calcium malabsorption in postmenopausal osteoporotic women is often linked indirectly to decreased serum 1,25(OH)2 vitamin D or to intestinal resistance to its action, rather than directly to the low circulating estrogen that results following menopause. The studies presented indicate that the intestinal mucosal cells of rats contain estrogen receptor immunoreactivity, express the mRNA for estrogen receptors, and respond directly to 17 beta-estradiol with enhanced calcium transport that is suppressed by gene transcription and protein synthesis inhibitors. These findings suggest that estrogen has a physiological role in the regulation of intestinal calcium absorption and that its deficiency in postmenopausal osteoporosis, and following therapeutic oophorectomy, may result directly in calcium malabsorption that is believed to be an important factor in the bone loss that occurs in these conditions.

Effects of ovariectomy and estrogen on the serum levels of insulin-like growth factor-I and insulin-like growth factor binding protein-3

To determine the effects of ovariectomy and 17 beta-estradiol (E2) on serum IGF-I and its binding proteins, female Sprague-Dawley rats, aged 95 days, were divided into four groups. Group 1 was sham-operated; groups 2, 3, and 4 were ovariectomized. Groups 3 and 4 received daily injections of 200 ng (low dose) and 5000 ng (high dose) E2/kg body wt./day, respectively and the others were given solvent vehicle. Ovariectomy resulted in a significant increase in serum IGF-I (P < 0.001) at 30 and 35 days post-surgery; the increase was prevented in animals that received low-dose E2 while high-dose E2 reduced serum IGF-I levels below those of the sham-operated controls (P < 0.01). Serum IGF-binding proteins (IGFBPs) were determined by IGF-ligand blot analysis, and the resulting autoradiograms quantified by laser densitometry. The intensity of the IGFBP-3 bands changed in parallel with serum IGF-I levels. Ovariectomy increased, low-dose E2 restored, and high-dose E2 reduced serum IGFBP-3 levels compared to the levels for the sham-operated controls. The intensities of binding protein bands smaller than those of IGFBP-3 appeared unchanged by the treatment regimens. A Western immunoblot analysis with IGFBP-3 antiserum confirmed the ligand-blot data. The changes in the levels of IGF-I and its binding proteins were accompanied by ovariectomy-induced increase in osteoblast and osteoclast numbers and loss of cancellous bone that were attenuated by E2 administration. We conclude that there is a possible role for IGF-I in the pathogenesis of the increased bone turnover that occurs early in ovarian hormone deficiency.

Soy isoflavones' osteoprotective role in postmenopausal women: mechanism of action

Ovarian hormone deficiency is a major risk factor for osteoporosis. Current therapies emphasize the use of antiresorptive agents, such as estrogen, calcitonin, and bisphosphonates. These therapies are associated with certain risks and side effects making compliance a major obstacle. Recent findings suggest that a class of synthetic and naturally occurring compounds, selective estrogen receptor modulators, e.g. raloxifene and soy isoflavones can offer attractive alternatives. Evidence for bone-sparing effects of isoflavones relies mainly on animal findings supported by a limited number of human studies. These observations suggest that isoflavones exert their effects on bone by stimulating bone formation and at the same time suppressing bone resorption. However, the precise osteoprotective mechanism of isoflavones remains uncertain and awaiting further clarification. From a clinical point of view, larger and longer duration studies are warranted to enable us to draw clear conclusions in regards to the role of isoflavones on bone.

Dried Plums Improve Indices of Bone Formation in Postmenopausal Women

Menopause drastically increases the risk of osteoporosis. Aside from drug therapy, lifestyle and nutritional factors play an important role in the maintenance of skeletal health. Our recent findings suggest that dried plums, a rich source of phenolic and flavonoid compounds, are highly effective in modulating bone mass in an ovarian hormone-deficient rat model of osteoporosis. The objective of this study was to examine whether the addition of dried plums to the diets of postmenopausal women positively influences markers of bone turnover. Fifty-eight postmenopausal women not on hormone replacement therapy (HRT) were randomly assigned to consume either 100 g dried plums or 75 g dried apples daily for 3 months. Both dried fruit regimens provided similar amount of calories, fat, carbohydrate, and fiber. Serum and urinary biochemical markers of bone status were assessed before and after treatment. In comparison with corresponding baseline values, only dried plums significantly increased serum levels of insulin-like growth factor-I (IGF-I) and bone-specific alkaline phosphatase (BSAP) activity. Higher levels of both serum IGF-I and BSAP are associated with greater rates of bone formation. Serum and urinary markers of bone resorption, however, were not affected by either dietary regimen. The results of this study suggest that dried plums may exert positive effects on bone in postmenopausal women. Longer duration studies are needed to confirm the beneficial effects of dried plum on bone mineral density (BMD) and the skeletal health of postmenopausal women.

Whole flaxseed consumption lowers serum LDL-cholesterol and lipoprotein(a) concentrations in postmenopausal women

Abstract We conducted a double-blind cross-over study to compare the effects of whole flaxseed and sunflower seed, as part of the daily diet, on the lipid profile of postmenopausal women. During two 6-wk periods, thirty-eight mild, moderate, or severely (5.85–9.05 mmol/L) hypercholesterolemic postmenopausal women were randomly assigned to one of the two regimens: flaxseed or sunflower seed. The subjects were provided with 38 g of either treatment in the forms of breads and muffins. The first treatment period lasted six weeks and was followed by a two-wk washout phase. After the washout phase, subjects switched regimens and treatments continued for another 6 weeks. Blood samples were collected at baseline, 6, 8, and 14th wk of the study periods. Significant ( p p p

Dried plum reverses bone loss in an osteopenic rat model of osteoporosis.

Objective:We previously reported the efficacy of dried plum (Prunus domestica L.) in preventing ovariectomy-induced bone loss in a rat model of osteoporosis and improving bone biomarkers in postmenopausal women. The present study evaluated whether dried plum was able to restore bone mass in osteopenic ovariectomized rats. Design:Ninety-day-old Sprague-Dawley rats were either sham-operated (Sham; one group) or ovariectomized (Ovx; five groups) and were fed a standard diet for 40 days to establish bone loss and subsequently experimental treatments were initiated. Sham, Ovx control, and Ovx + 17β-estradiol (E2; 10 μg/kg body weight per day) animals continued to receive the standard diet, whereas the remaining three Ovx groups received the following dietary treatments: Ovx + 5% dried plum (low dose), Ovx + 15% dried plum (medium dose), and Ovx + 25% dried plum (high dose). After 60 days, blood and bone specimens were collected for analyses. Results:Dried plum, as low as 5%, was effective in restoring femoral and tibial bone density. Dried plum increased lumbar bone density as well, with HD achieving a statistical significance. The increase in femoral bone density of dried plum-fed rats resulted in improved bone quality as indicated by 6.9% and 6.0% improvement in overall yield and ultimate force, respectively. Varying doses of dried plum were also able to significantly improve trabecular microarchitectural properties in comparison with ovariectomized controls. Conclusions:The improvement in biomechanical properties of long bones due to dried plum, in part, may be due to the favorable microstructural changes as evident by enhanced tibial bone volume and connectivity. Loss of bone volume accompanied by loss of trabecular connectivity is generally believed to be an irreversible process, but our observations suggest that dried plum improves trabecular microstructure of tibia after losses have already occurred.

Blueberry prevents bone loss in ovariectomized rat model of postmenopausal osteoporosis

The objective of the present study was to explore the bone protective role of blueberry in an ovariectomized rat model. Thirty 6-month-old female Sprague-Dawley rats were either sham-operated (Sham) or ovariectomized (Ovx) and divided into three groups: Sham, Ovx (control), Ovx+blueberry (5% blueberry w/w). After 100 days of treatment, rats were euthanized, and blood and tissues were collected. Bone mineral density (BMD) and content of whole body, right tibia, right femur and fourth lumbar vertebra were assessed via dual-energy X-ray absorptiometry. As expected, Ovx resulted in loss of whole-body, tibial, femoral, and 4th lumbar BMD by approximately 6%. Blueberry treatment was able to prevent the loss of whole-body BMD and had an intermediary effect on prevention of tibial and femoral BMD when compared to either Sham or Ovx controls. The bone-protective effects of blueberry may be due to suppression of Ovx-induced increase in bone turnover, as evident by lowered femoral mRNA levels of alkaline phosphatase, collagen type I and tartrate-resistant acid phosphatase to the Sham levels. Similarly, serum osteocalcein levels were also lower in the blueberry group when compared to the Ovx control group, albeit not significantly. In summary, our findings indicate that blueberry can prevent bone loss as seen by the increases in BMD and favorable changes in biomarkers of bone metabolism.