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Objectives: This study aimed to investigate the effect and the mechanism of recombinant human fibroblast growth factor 18 (rhFGF18) on postmenopausal osteoporosis., Methods: The effect of rhFGF18 on the proliferation and apoptosis of osteoblasts and the mechanism underlying such an effect was evaluated using an oxidative stress model of the MC3T3-E1 cell line. Furthermore, ovariectomy was performed on ICR mice to imitate estrogen-deficiency postmenopausal osteoporosis. Bone metabolism and bone morphological parameters in the ovariectomized (OVX) mice were evaluated., Results: The results obtained from the cell model showed that FGF18 promoted MC3T3-E1 cell proliferation by activating the extracellular signal-regulated kinase (ERK) and p38 instead of c-Jun N-terminal kinase (JNK). FGF18 also prevented cells from damage inflicted by oxidative stress via inhibition of apoptosis. After FGF18 administration, the expression level of anti-apoptotic protein Bcl-2 in the mice was upregulated, whereas those of the pro-apoptotic proteins Bax and caspase-3 were downregulated. Administering FGF18 also improved bone metabolism and bone morphological parameters in OVX mice., Conclusions: FGF18 could effectively prevent bone loss in OVX mice by enhancing osteoblastogenesis and protecting osteoblasts from oxidative stress-induced apoptosis.

Background: Obesity is associated with an increased risk of fracture in adults, but is unclear in postmenopausal women. We aim to determine the association of obesity with the risk of fracture in postmenopausal women., Methods: PubMed, EMBASE, Cochrane Library and Web of Science were searched up to 11 April 2022 for cohort studies. And the included studies regarding the relationship between obesity with all cause of fracture in postmenopausal women were included in our meta-analysis. Data were screened and extracted independently by two reviewers. The relative risks (RR) were estimated using a random-effects model. Between-study heterogeneity was assessed using Cochran's Q and I 2 statistics., Results: Eight cohort studies comprising 671,532 postmenopausal women and 40,172 fractures were included. Overall, the pooling analysis shows that obesity in postmenopausal women is associated with an increased risk of all-cause fracture (relative ratio (RR) = 1.18; 95% confidence interval (CI):1.09-1.28, I 2 = 86.3%, p  = .000). Sub-analyses for each site of fracture indicate that obesity was associated with an increased risk of vertebral fracture in postmenopausal women (RR = 1.154, 95% CI: 1.020-1.305, I 2 = 94.5%, p  = .023), but reduced the risk of pelvic fracture (RR = 0.575, 95% CI:0.470-0.702, I 2 = 0.0%, p =  .000). There is no statistically significant difference in the risk of hip and humerus fractures associated with obesity in postmenopausal women., Conclusion: Obesity is associated with an increased risk of all-cause and vertebral fractures in postmenopausal women, but is a protective factor for pelvic fractures. Our findings suggest that postmenopausal women who regulate their weight might lower their risk of fractures. Registration: (PROSPERO: CRD42022324973)KEY MESSAGESObesity is associated with an increased risk of all-cause and vertebral fractures in postmenopausal women.Obesity maybe a protective factor for pelvic fractures in postmenopausal women.Postmenopausal women should regulate their weight to prevent fractures.

Objective: Intervertebral discs act as shock absorbers, thereby helping to reduce the risk of vertebral body fractures. Previous studies have shown that estrogen loss following menopause is associated with disc height reduction whereas treatment with hormone replacement therapy (HRT) helps to maintain disc height. This study reports the effect of HRT on disc height from a post hoc analysis of a prospective randomized clinical trial of the effect of HRT on bone density., Methods: A total of 355 healthy postmenopausal women aged (mean ± standard deviation) 55.4 ± 4.8 years were randomized to HRT with oral 1 mg or 2 mg estradiol plus dydrogesterone or placebo. Dual-energy X-ray absorptiometry measurements (Lunar DPX) were obtained at baseline and following 2 years of treatment. Intervertebral disc height was measured in discs between T12 and L3 using the bone densitometer ruler., Results: Compared with baseline, treatment with HRT resulted in a significant increase in total disc height with 1 mg estradiol (0.16 ± 0.65 cm, p  = 0.015) and with 2 mg estradiol (0.21 ± 0.86 cm, p  = 0.006) whilst there was no significant increase with placebo (0.13 ± 0.65 cm, p  = 0.096). Between-group differences were not statistically significant., Conclusions: These results are consistent with previous findings of a beneficial effect of estrogen on discs. This may be in part responsible for the anti-fracture efficacy of HRT on vertebral fractures.

Menopausal hormone therapy (MHT) has been used for prevention and treatment of postmenopausal osteoporosis for several decades. However, public concerns were raised over the safety of MHT after the initial report was published in 2002 by the Women's Health Initiative. We conducted a historical review on this subject, primarily focusing on level I evidence from randomized controlled trials, systematic reviews and meta-analyses, and summarized high-quality evidence on the efficacy and safety of MHT in management of postmenopausal osteoporosis. Clinical issues were also discussed on MHT initiation, identification of treatment candidates and treatment duration, as well as discontinuation of MHT.

Objectives: This study aimed to evaluate the effects of royal jelly (RJ) supplementation on bone metabolism in postmenopausal women., Methods: This was a randomized, double-blind, placebo-controlled clinical trial. Seventy-two healthy postmenopausal women aged 45-60 years within 5 years after menopause were randomized into two groups: women in the RJ group ( n  = 36) received capsules containing dried RJ (equivalent to 3000 mg of fresh RJ); and women in the placebo group ( n  = 36) received placebo daily for 6 months. Bone mineral density (BMD) of the lumbar spine (L2-L4) and left proximal femur, hip structural analysis (HSA) of the left hip, and bone turnover markers were measured., Results: Although women in the placebo group experienced a significant loss of BMD and deterioration in HSA parameters of the femur, no significant differences were found in these parameters in women in the RJ group. The levels of total procollagen type 1 N-terminal propeptide (P1NP) and tartrate-resistant acid phosphatase decreased significantly in the placebo group; however, the total P1NP level, a marker of bone formation, was not significantly different in the RJ group at postintervention compared with baseline., Conclusion: RJ consumption may ameliorate decreases in femoral BMD and strength in postmenopausal women.

Malabsorption due to celiac disease (CD) may contribute to postmenopausal osteoporosis. This study aimed to survey participants with CD regarding their bone density, fractures, and bone-preserving medications; to compare tolerance of bone-preserving medications in participants with and without CD; and to review the evidence for CD screening and osteoporosis therapies in the setting of CD. We recruited 131 participants with CD and 102 participants without CD. Of those with CD, 87% were diagnosed in adulthood and 40% had no recognized gastrointestinal symptoms. In 21% CD was diagnosed after the diagnosis of osteoporosis and in 9% after a fracture. No difference was found in the tolerability of bone medications between participants with CD and those without. Review of the literature found that, although monitoring of bone health is recommended for patients with CD, screening for CD is not generally accepted for patients with osteoporosis, although studies of the prevalence of CD in osteoporosis had incomplete ascertainment methods. There is a lack of well-conducted studies and therefore insufficient data for the efficacy and tolerability of bone medication in CD. In conclusion, both CD and menopause lead to bone loss. Identifying CD in postmenopausal women should lead to modification of osteoporosis management.

Menopause and aging are associated with changes in circulating gonadal steroid hormones, insulin sensitivity, body composition, and also lifestyle and social coordinates. Vitamin D status influences different metabolic adjustments, aside from calcium-phosphorus and bone metabolism. The main blood marker used to measure endogenous vitamin D status is 25-hydroxyvitamin D. Aging is associated with increases in serum parathyroid hormone and alkaline phosphatase, and a decrease of serum calcium, phosphorus, and vitamin D metabolites. 25-Hydroxyvitamin D status is also influenced by the circannual rhythm of sun irradiation. Results of clinical association studies have not correlated with intervention trials, experimental studies, and/or meta-analyses regarding the role of vitamin D on different outcomes in women during their second half of life and the vitamin D supplementation dose needed to improve clinical endpoints. Discordant results have been related to the method used to measure vitamin D, the studied population (i.e., sociodemographics and ethnicity), study designs, and biases of analyses. Vitamin D supplementation with cholecalciferol or calcifediol may improve some metabolic variables and clinical outcomes in young postmenopausal and older women. Studies seem to suggest that calcifediol may have some advantages over other forms of vitamin D supplementation. Further studies are needed to define interventions with supplements and effective food fortification.

Vitamin K 2 (vit K 2 ) belongs to a large group of fat-soluble compounds whose formulation is MK (menaquinone) (MK-2 to MK-14), that seem to be involved in different biological functions. In particular, vit K 2 has been recently recognized as efficacious and safe in treatment of bone loss, as it contributes to structural integrity of osteocalcin (OC), the major non-collagenous protein typically found in bone matrix. Several studies proved low vit K 2 intake is linked to bone loss and to increased fracture risk in both sexes. Nowadays, vit K 2 supplementation is considered a significant manner to enhance the association of calcium and vitamin D whose role on bone health is largely recognized. On the other hand, vit K 2 may be used alone or with other drugs to preserve bone quality/strength from skeletal degradation after menopause and/or in patients affected by secondary osteoporosis. In this paper, we review the most recent data about vit K 2 on skeleton.

Nowadays, postmenopausal women are largely undertreated. Analysis of conflicting results among different studies suggests that hormone replacement therapy (HRT) can prevent osteoporosis and cardiovascular disease in symptomatic, early postmenopausal women. In fact, climacteric symptoms are related to an increased risk of chronic conditions, including hypertension and cardiovascular disease. Different scientific societies have pointed out that patient selection, timing of initiation, and the choice of the type and dose of HRT used are the major determinants of the ultimate effect of HRT on women's health and quality of life in selected women. HRT may prevent chronic conditions when started in symptomatic women before the age of 60 years or within 10 years of the onset of the menopause, taking into consideration the characteristics and risk profiles of each given woman. The bulk of scientific evidence from preclinical, clinical, epidemiological, and also randomized studies indicates that wisely selected HRT is generally useful and rarely dangerous. Following simple and well-established rules, HRT benefits outweigh all of the possible risks. Progestogen choice can make the difference in terms of cardiovascular disease benefits.

Postmenopausal osteoporosis is a frequent health issue in women. Because osteoporosis-related fractures cause a significant increase in mortality and morbidity, it is clinically important to identify as soon as possible women at increased risk for future fracture so that preventive measures can be instituted. At the beginning of menopause, evaluation of the subsequent risk of fracture is not so easy. Most screening tools fail to accurately identify those women who will fracture within the next 10 years. A history of a prior fracture and low bone mineral density are the only major consistently found predictors for the risk of fracture. On the other hand, it is no longer a question whether menopause hormone therapy is efficient not only to prevent postmenopausal bone loss but also the incidence of fragility fracture. Over the last years, utility of menopause hormone therapy for the prevention of osteoporosis has been questioned due to safety concerns. In light of the most recent reports on a more favorable benefit/risk balance than was initially claimed in early postmenopausal women, this needs to be reconsidered. Prevention of bone loss in those women with a moderate or slightly high risk of fracture is likely a strategy to reduce fracture risk in older women. Menopause hormone therapy must be considered as a true primary preventive therapy more than an anti-fracture therapy at an age when the risk of fracture is likely much lower than later in life. Only thereafter should other anti-osteoporotic medications be discussed in women still at high risk for fracture.

The aim of the study is to compare the bone sparing effect of half-dose with standard-dose conjugated equine estrogen (CEE) combined with progestin. A total of 123 participants were administrated with 0.625 mg of CEE and 100 mg of micronized progesterone (MP) in group A, 0.3 mg of CEE and 100 mg of MP in group B, 0.625 mg of CEE and 10 mg of dydrogesterone (DDG) in group C for one year. Percent changes from baseline in BMD at lumbar spine and fracture rate were primary outcomes. Secondary endpoints included changes of BMD at femoral neck, total hip and arm, bone markers (alkaline phosphatase, calcium and phosphorus), serum alanine aminotransferase (ALT) and endometrial thickness. No fractures occurred during the treatment. Standard dose of CEE leads to significant changes in lumbar spine and arm. The 3.78% growth of BMD at femoral neck in group C marked a statistically difference. There was no statistically remarkable bone loss at hip in all three groups. Bone turnover markers and ALT significantly decreased from basic values. Endometrium thickened more with traditional dose of CEE. Both the half and standard dose CEE are effective in BMD preservation among early menopausal women with subtle side effects. Low-dose estrogen is less efficacious than traditional one.

Aim: There is conflicting evidence regarding the effects of omega-3 fatty acids on bone turnover markers in postmenopausal women. Thus, we systematically reviewed the efficacy of omega-3 fatty acids by conducting a meta-analysis of available randomized controlled trials., Methods: PubMed, Embase, Cochrane Library and Scopus were searched in December 2016. The standardized mean difference (SMD) or weighted mean difference (WMD) and the corresponding 95% confidence intervals (CIs) were calculated using a fixed-effects model., Results: Eight trials were included in the present meta-analysis. The pooled findings did not identify significant decreases in bone-specific alkaline phosphatase (SMD -0.08, 95% CI -0.29 to 0.12, p = 0.429) and collagen type I cross-linked C-telopeptide (WMD 0 ng/ml, 95% CI -0.04 to 0.04, p = 0.899). There was a significant decrease in osteocalcin (WMD -0.86 ng/ml, 95% CI -1.68 to -0.04, p = 0.040) as compared with control., Conclusion: Omega-3 fatty acids reduced postmenopausal women's serum osteocalcin. Further well-designed studies are needed to verify the effects of omega-3 fatty acids on bone mass density and other bone turnover markers in postmenopausal women., Clinical Trial Registration Number: CRD42016053219 ( https://www.crd.york.ac.uk/PROSPERO/ ).

Objective: To evaluate risk factors for low bone mineral density (BMD) in postmenopausal breast cancer survivors compared with postmenopausal women without breast cancer (controls)., Method: In this study, 112 breast cancer survivors were compared to 224 women (controls). Inclusion criteria were amenorrhea ≥12 months, age 45-75 years, treated for breast cancer, and metastasis-free for at least 5 years. The control group consisted of women without breast cancer, matched by age and menopause status (in a proportion of 1: 2 as sample calculation). The risk factors for low BMD (osteopenia/osteoporosis) were assessed by interview. BMD was measured by dual-energy X-ray absorptiometry in the lumbar spine (L1-L4) and femoral neck. Logistic regression models (odds ratio, OR) were used to identify factors associated with low BMD., Results: The mean (standard deviation) age of breast cancer survivors was 61.3 (9.7) years, with a mean follow-up of 10.2 (3.9) years. These women had a higher incidence of osteopenia (45.1%) and osteoporosis (22.3%) in the femoral neck than controls (39.3% and 9.0%, respectively) (p = 0.0005). Lumbar spine BMD did not differ between groups (p = 0.332). Univariate analysis adjusted for age and time since menopause revealed that chemotherapy (OR 6.90; 95% confidence interval (CI) 5.57-9.77) was associated with a higher risk of low BMD. Contrarily, regular physical exercise (OR 0.24; 95% CI 0.06-0.98) and a body mass index ≥30 kg/m 2 (OR 0.09; 95% CI 0.02-0.37) reduced the risk among breast cancer survivors., Conclusion: Postmenopausal breast cancer survivors had a higher incidence of osteopenia and osteoporosis in the femoral neck than women without breast cancer. A history of chemotherapy was a risk factor for low BMD, whereas regular physical activity and high body mass index reduced the risk among breast cancer survivors.

Objectives: To observe the effectiveness and safety of menopause-related hormone therapy (MHT) to prevent bone loss in Chinese women during the menopausal transition and early menopause, as well as to evaluate the effects of 5-year MHT on overall health to add Level I evidence for the prevention of osteoporosis using MHT., Design: This clinical study was a prospective, double-blind, randomized, parallel placebo-controlled study. Chinese women in the menopausal transition and early menopause were randomly allocated to the MHT group or the placebo group. All subjects received a 5-year intervention. The effectiveness of MHT for bone mineral density (BMD) and bone metabolism and the safety of MHT in relation to glycolipid metabolism, breast cancer, and cardiovascular disease were studied., Results: In the MHT group, women in both transition and early menopause showed a significant increase in lumbar and femoral neck BMD after the 1st year of therapy; BMD tended to decrease in the 3rd year but ultimately was sustained at stable levels that were near the baseline levels. In the placebo group, BMD decreased at both sites. Metabolism indexes and breast ultrasound examination findings did not differ significantly between the MHT and placebo groups. Three cases of breast cancer and three cases of cardiovascular disease were diagnosed during follow-up. One breast cancer case and two cardiovascular disease cases occurred in the MHT group., Conclusions: Five-year sequential therapy with estrogen and progesterone can increase or maintain the BMD of women in their menopausal transition and early menopause. This regimen had no negative effect on glycolipid metabolism and did not increase the risk of breast cancer or cardiovascular events.

This review describes the evolving role of oral hormone therapy (HT) for treating menopausal symptoms and preventing osteoporosis, focusing on conjugated estrogens/bazedoxifene (CE/BZA). Estrogens alleviate hot flushes and prevent bone loss associated with menopause. In nonhysterectomized women, a progestin should be added to estrogens to reduce the risk of endometrial cancer. Use of HT declined since the Women's Health Initiative (WHI) studies showed that HT does not prevent coronary heart disease (CHD) and that conjugated estrogens/medroxyprogesterone acetate increased the risk of invasive breast cancer after nearly 5 years of use. However, re-analyses of the WHI data suggest that some risks (eg, CHD, all-cause mortality) may be reduced when HT is initiated in women <60 years of age and <10 years since menopause, compared with later. CE/BZA is the first menopausal HT without a progestogen for nonhysterectomized women. Instead, BZA, a selective estrogen receptor modulator, in combination with CE, protects against estrogenic effects on uterine and breast tissue. Data from 5 large, randomized clinical trials show that CE/BZA reduces hot flush frequency/severity, prevents bone loss, reduces bone turnover, improves the vaginal maturation index and ease of lubrication, and improves some measures of sleep and menopause-specific quality of life. In studies of up to 2 years, there was no increase in endometrial hyperplasia, vaginal bleeding, breast density, or breast pain/tenderness compared with placebo. Venous thromboembolism and stroke are risks of all estrogen-based therapies. The choice of HT should be individualized, with consideration of the risk/benefit profile and tolerability of therapy, as well as patient preferences.

Objectives: To evaluate the efficacy of conjugated estrogens/bazedoxifene (CE/BZA) on bone mineral density (BMD), bone turnover markers (BTM), and menopause-specific quality of life (MENQOL) in European women., Methods: Data through 12 months were pooled from two double-blind, randomized, controlled trials in non-hysterectomized postmenopausal women who received CE/BZA or placebo. Women from European study sites with evaluable BMD (n = 60), BTM (n = 56), and MENQOL questionnaire (n = 236) data were included and compared with 1523 women from US study sites (n = 730 with evaluable data for bone outcomes)., Results: At month 12, CE 0.45 mg/BZA 20 mg and CE 0.625 mg/BZA 20 mg, respectively, significantly improved BMD (adjusted difference vs. placebo) in lumbar spine (2.5%, 2.9%; both p ≤ 0.011) and total hip (1.7%, 2.2%, both p ≤ 0.002), significantly improved serum BTMs (osteocalcin: -31.1%, -33.1%; C-telopeptide: -48.5%, -36.8%) vs. placebo (osteocalcin: 6.7%, C-telopeptide: 4.2%; all p < 0.001), and significantly improved MENQOL vasomotor function scores (-2.1, -2.2) vs. placebo (-0.7; both p < 0.001). No significant treatment × subpopulation interactions were observed for any of the outcomes., Conclusions: Twelve-month CE/BZA treatment prevented bone loss and improved vasomotor function in European postmenopausal women. Findings were similar to those in the subpopulation of women enrolled at US study sites.

Objectives: To compare the effects on bone mineral density (BMD) measured by dual-energy X-ray absorptiometry at the lumbar spine, the femoral neck and the total hip following 2 years of treatment with a low-dose combined hormone therapy (HT) comprised of 1 mg estradiol and 0.5 mg norethisterone acetate (E2/NETA) versus 2.5 mg tibolone in postmenopausal women. Additionally, quantitative ultrasonometry (QUS) of the os calcaneus and of the phalanges was performed., Methods: Changes in BMD, QUS and side-effects were assessed at baseline, 6, 12 and 24 months in 50 postmenopausal women who received either E2/NETA (n = 26) or tibolone (n = 24) for 2 years., Results: Compared to women on tibolone, women receiving E2/NETA showed a significant increase in BMD from baseline to 12 and 24 months at the lumbar spine (3.07%, 3.86%; p < 0.01 vs. 1.13%, 2.23%; p < 0.05), and at the total hip (1.33%, 1.69%; p < 0.01 vs. 0.76%, 0.70%) and at the femoral neck from baseline to 24 months (1.10%; p < 0.05). QUS indices only showed a significant change with the ultrasound bone profile index with E2/NETA at 6 months (-2.32%; p < 0.001)., Conclusions: Low-dose E2/NETA showed a significantly higher increase in BMD compared to tibolone. QUS measurement was not considered to comprise beneficial effects in monitoring drug-induced bone changes.

Plasma homocysteine, which is increased after menopause, can be a risk factor for cardiovascular disease and osteoporosis. The purpose of the present study was to determine the effect of folic acid supplementation on plasma homocysteine in postmenopausal women. The study was performed as a randomized placebo controlled trial on 48 healthy postmenopausal women (aged 50-70 years) and plasma homocysteine of all women was measured. In the case group, folic acid, and in the control group, placebo was prescribed. The second plasma homocysteine was measured 16-17 weeks later and was compared in the two groups. There was no significant difference between the two groups according to age, BMI, parity, duration of menopause and the first plasma homocysteine level. Plasma homocysteine level was significantly lower in the case group than control group 16 weeks after folic acid administration (10.33 ± 3.51 μmol/l vs 13.21 ± 3.11 μmol/l, p=0.004). There was no significant correlation between plasma homocysteine level and BMI and parity. However, there was a weak-moderate positive correlation between plasma homocysteine and age (p<0.05, r=0.33), and there was a significant but weak correlation between plasma homocysteine and duration of menopause (p=0.05, r=0.28).

In developed countries, women spend more than one-third of their life in the menopause and at least half of them experience vasomotor symptoms that impair their normal function and well-being. Long-term estrogen replacement therapy (HRT) with estrogen can suppress typical menopausal symptoms and prevents osteoporosis. When estrogen-only HRT is started within 10 years after the menopause, the prevalence of cardiovascular disease is reduced, mortality is lower, and the risk of breast cancer is not significantly increased. Postmenopausal genital and urinary problems with recurrent infections, incontinence, and dyspareunia can effectively be treated by vaginal application of estriol, which seems to be safe for women treated for breast cancer. HRT after the age of 60 years is associated with a lower number needed to treat than number needed to harm, implying that there would be one unfavorable side-effect for up to ten women experiencing a positive effect. However, further studies are needed regarding the risk-benefit ratio of HRT in women over 70 years. It is concluded that transdermal substitution therapy with estradiol may increase the number of quality-adjusted life years of postmenopausal women. The combination with nutriceutical food supplementation may add to this benefit, but complementary prospective trials are still needed.

Background and Objective: The ossein-hydroxyapatite complex (OHC) is a microcrystalline form of calcium which provides a number of additional minerals (magnesium, phosphorus, potassium, zinc), and proteins (osteocalcin, type I collagen, type I insulin growth factor I and II, transforming growth factor beta) associated with bone metabolism. The objective of this review is to examine the role of OHC in preventing bone loss in different conditions., Material and Methods: A review of clinical trials assessing the relationship between OHC and bone loss was made using the following data sources: Medline (from 1966 to December 2013), the Cochrane Controlled Clinical Trials Register, Embase (up to December 2013), contact with companies marketing the supplements studied, and reference lists., Results: Different randomized, clinical trials and meta-analysis suggest that OHC is more effective than calcium supplements in maintaining bone mass in postmenopausal women and in different conditions related to bone loss. In addition, OHC improves pain symptoms and accelerates fracture consolidation in patients with osteopenia or osteoporosis., Conclusion: The ossein-hydroxyapatite complex is significantly more effective in preventing bone loss than calcium carbonate.

The major application of FRAX in osteoporosis is to direct pharmacological interventions to those at high risk of fracture. Whereas the efficacy of osteoporosis treatment, with the possible exception of alendronate, is largely independent of baseline bone mineral density (BMD), it remains a widely held perception that osteoporosis therapies are only effective in the presence of low BMD. Thus, the use of FRAX in the absence of BMD to identify individuals requiring therapy remains the subject of some debate and is the focus of this review. The clinical risk factors used in FRAX have high evidence-based validity to identify a risk responsive to intervention. The selection of high-risk individuals with FRAX, without knowledge of BMD, preferentially selects for low BMD and thus identifies a risk that is responsive to pharmacological intervention. The prediction of fractures with the use of clinical risk factors alone in FRAX is comparable to the use of BMD alone to predict fractures and is suitable, therefore, in the many countries where facilities for BMD testing are sparse. In countries where access to BMD is greater, FRAX can be used without BMD in the majority of cases and BMD tests reserved for those close to a probability-based intervention threshold. Thus concerns surrounding the use of FRAX in clinical practice without information on BMD are largely misplaced.

It is now 75 years since Fuller Albright published his observations on the causal relationship between menopausal estrogen deficiency and osteoporosis. He introduced the concept of menopausal hormone therapy (MHT) for the prevention of osteoporosis. Most of his remarkable observations have stood the test of time and scientific scrutiny. Unfortunately, the uptake of MHT for the prevention of osteoporosis and related fractures remains very low. This can be ascribed to several factors. The availability of new drugs, supported by randomized clinical trials, has increased therapeutic options and created the impression that all new drugs are better compared to MHT. Confusion exists as to the benefit/risk profile of menopausal hormone therapy, limitations on the age of initiation of treatment, limitations on the length of treatment, and the need for treatment in the young menopausal woman with low bone density.

Low-intensity, high-frequency mechanical vibration (LHMV) has shown to increase bone formation. However, studies comparing the effectiveness of early- and late-treatments of LHMV to counteract bone loss have not been documented. This study was designed to compare the effects of early- and late-treatments of LHMV (at 30 Hz/0.6 g, 20 min per day/five days per week, for 12 weeks) on bone parameters in ovariectomized (Ovx) rats. Thirty days after ovariectomy, 40 adult rats were randomly divided into four groups: GI (early control group); GII treated with LHMV 3 weeks after Ovx (early treatment); GIII (late control group) and GIV treated with LHMV twelve weeks after Ovx (late treatment). Bone mineral density (BMD) was analyzed before Ovx and after treatments. Then, animals were killed, and the femurs were collected and their length and diaphysis diameter were measured; the distal femurs were taken and processed for histomorphometry and polarized light microscopy for collagen fibers analysis or subjected to immunohistochemistry of cleaved caspase-3 in osteocytes. Statistical analysis was done by ANOVA followed by the Bonferroni post hoc test (p < 0.05). BMD was similar among the groups before Ovx, but after treatments, it was significantly higher in GII and GIV compared with their control groups (p < 0.05). Femur length and cortical bone thickness were similar among the groups, but the diaphysis diameter of GII was higher compared with GI. Trabecular bone area was higher in the vibrated groups, but it was greater in GII (p < 0.05). Also, the vibrated groups showed the higher content collagen fibers and lower presence apoptotic osteocytes (positive caspase-3 immunoreactivity) when compared with the other groups (p < 0.05). These results suggest that both early- and late-treatments with LHMV counteract bone loss, being the early treatment more effective than the late treatment.

Breast cancer and osteoporosis are common conditions affecting women, particularly following menopause. With increasing breast cancer incidence, effects of therapies and decreasing mortality, issues relating to the preservation of bone health with breast cancer therapy have become a priority. Contributing factors to bone loss and fractures in women with breast cancer include tumor effects, estrogen deprivation secondary to breast cancer therapies (chemotherapy, ovarian ablation or aromatase inhibitors), natural menopause and secondary causes of bone loss, typically from concurrently prescribed medications. Management of osteoporosis and other survivorship care is complex, and a multi-disciplinary approach is recommended with assessment of risk factors for bone loss, optimization of bone health through lifestyle approaches and pharmacological interventions based on evidence-based algorithms. This review examines the pathophysiology of bone loss and gives guidelines for the management of bone disease in women with breast cancer.

Systematic reviews of randomized, controlled trials (RCTs) are considered the highest level of evidence to inform clinical practice. Meta-analyses of large RCTs of calcium and/or vitamin D supplements completed in the last 15 years provide strong evidence for clinical recommendations. These meta-analyses with data for > 50,000 older adults reported that calcium with or without vitamin D has only weak, inconsistent effects on fracture, and that vitamin D without calcium has no effect on fracture. Only one RCT of co-administered calcium and vitamin D in frail, institutionalized, elderly women with low dietary calcium intake and vitamin D levels showed significant reductions in fracture risk. These RCTs have also reported previously unrecognized adverse events of calcium supplements including kidney stones, myocardial infarction, hypercalcemia, and hospitalization with acute gastrointestinal symptoms. The small risk of these important adverse effects, together with the moderate risk of minor side-effects such as constipation, probably outweighs any benefits of calcium supplements on fracture. These data suggest the role for calcium and vitamin D supplements in osteoporosis management is very limited. Neither calcium nor vitamin D supplements should be recommended for fracture prevention in community-dwelling adults, although vitamin D should be considered for prevention of osteomalacia in at-risk individuals.

Women may expect to spend more than a third of their lives after menopause. Beginning in the sixth decade, many chronic diseases will begin to emerge, which will affect both the quality and quantity of a woman's life. Thus, the onset of menopause heralds an opportunity for prevention strategies to improve the quality of life and enhance longevity. Obesity, metabolic syndrome and diabetes, cardiovascular disease, osteoporosis and osteoarthritis, cognitive decline, dementia and depression, and cancer are the major diseases of concern. Prevention strategies at menopause have to begin with screening and careful assessment for risk factors, which should also include molecular and genetic diagnostics, as these become available. Identification of certain risks will then allow directed therapy. Evidence-based prevention for the diseases noted above include lifestyle management, cessation of smoking, curtailing excessive alcohol consumption, a healthy diet and moderate exercise, as well as mentally stimulating activities. Although the most recent publications from the follow-up studies of the Women's Health Initiative do not recommend menopause hormonal therapy as a prevention strategy, these conclusions may not be fully valid for midlife women, on the basis of the existing data. For healthy women aged 50-59 years, estrogen therapy decreases coronary heart disease and all-cause mortality; this interpretation is entirely consistent with results from other randomized, controlled trials and observational studies. Thus. as part of a comprehensive strategy to prevent chronic disease after menopause, menopausal hormone therapy, particularly estrogen therapy may be considered as part of the armamentarium.

Introduction: Two global, double-blind, placebo- and active-controlled, phase-3 studies (2-year prevention (n = 1583) and 3-year treatment (n = 7492)) have shown that bazedoxifene (BZA) is safe and effective for prevention and treatment of postmenopausal osteoporosis., Objective: To evaluate the efficacy/safety of BZA according to baseline kidney function., Methods: Data for the BZA 20- and 40-mg and placebo groups from both studies were integrated for assessment of bone turnover markers (BTMs), bone mineral density (BMD), and fracture incidence (treatment study only). Safety was assessed using integrated data for the BZA, placebo, and raloxifene 60-mg groups from both studies. Baseline glomerular filtration rate (GFR) was estimated by the Modification of Diet in Renal Disease Study equation; among subjects with baseline GFR, renal function categories were defined by GFR (ml/min per 1.73 m(2)): normal (GFR ≥ 90; n = 1982), mild impairment (60 ≤ GFR < 90; n = 6032), or moderate/severe impairment (GFR < 60; n = 723)., Results: Demographics were similar across treatment groups and within GFR subgroups. Across GFR subgroups, BZA 20 and 40 mg reduced BTM levels and improved lumbar spine and total hip BMD versus placebo. At month 24, there were significant treatment-by-GFR (p = 0.003) and treatment-by-serum creatinine (p = 0.034) interactions for the increase in lumbar spine BMD versus placebo. Fracture incidence was lower with BZA than placebo across all GFR categories, with no treatment-by-GFR interaction. There were no significant differences among treatment groups in incidences of overall, serious, or renal-related adverse events across GFR subgroups., Conclusions: Mild to moderate kidney impairment did not affect the efficacy and safety of BZA in postmenopausal women.

In this study, we investigated the synergistic effects of daidzein (Dz) and kiwifruit on bone and equol production in ovariectomised (OVX) rats. Female Sprague-Dawley rats were randomly assigned to one of five groups: sham operated, OVX control, OVX fed 0.1% Dz-supplemented diet (OVX + Dz), OVX fed 0.1% Dz and green kiwifruit (GRK)-supplemented diet (OVX + Dz + GRK) and OVX fed 0.1% Dz and gold kiwifruit (GOK)-supplemented diet (OVX + Dz + GOK). There were no significant differences in whole body and femur bone mineral density (BMD) among groups at week 8. BMD in the OVX group significantly decreased at week 8; however, BMD in the OVX + Dz + GRK was not significantly different from baseline in the end of the study. However, supplementation with kiwifruit did not affect urinary equol concentrations, urinary ratios of equol to Dz and the composition of caecal microbiota. These results suggest that the combination of Dz and GRK may slightly reduce bone loss caused by oestrogen deficiency but does not affect equol production.

The tissue selective estrogen complex (TSEC) pairs a selective estrogen receptor modulator (SERM) with one or more estrogens. Different TSECs are associated with distinct gene expression profiles in mammary gland and endometrial tissue according to the individual SERM and estrogen components. Few TSECs have been evaluated outside the laboratory. In preclinical trials, bazedoxifene (BZA) was distinct from other SERMs, with a neutral effect on mammary gland and endometrial tissue, and an antagonist effect on these tissues when combined with conjugated estrogens (CE). The only TSEC in an advanced stage of clinical development pairs BZA with CE. In large, randomized clinical trials, two doses, BZA 20 mg/CE 0.45 and 0.625 mg, reduced menopausal symptoms and prevented bone loss in postmenopausal women with a favorable safety profile on the breast, endometrium, and ovary, and with cardiovascular and venous thrombosis events similar to placebo. Improvements were seen in sleep, health-related quality of life, and treatment satisfaction. Compared with traditional, progestogen-containing hormone therapy, BZA/CE had higher rates of amenorrhea and reduced breast pain, with changes in breast density from baseline similar to placebo. Future TSECs identified in preclinical studies need to be tested in rigorous phase-3 clinical trials for effectiveness, safety and tolerability.

Introduction: Bazedoxifene is a third-generation Selective Estrogen Receptor Modulator, developed on raloxifene's model, and investigated as treatment for postmenopausal osteoporosis and menopause management. Clinical trial have shown that bazedoxifene is effective as raloxifene in preventing bone loss in women at risk of osteoporosis and that in patients with osteoporosis it is effective in reducing the incidence of new vertebral fracture with a protection maintained for up 7 years., Areas Covered: This drug evaluation presents the antifracture efficacy of bazedoxifine and evidence that it, unlike raloxifene, can reduce the rate of non-vertebral fractures in high-risk patients. The authors also review the effects of bazedoxifine has on reproduction tissues as well as the on lipid pattern. Additionally, the authors present the safety profile of bazedoxifine and discuss its prospects, specifically in relation to conjugated estrogen., Expert Opinion: Despite its peculiar profile, bazedoxifene could be considered as a second-line therapy for women < 65 - 70 years of age, where bisphopshonates are contraindicated or not well tolerated. Furthermore, the authors believe that bazedoxifene could also have its place as a first-line therapy for younger postmenopausal patients in the management of menopause and prevention of osteoporosis; this could be prescribed either by itself or in combination with conjugated estrogen. The authors also highlight the fact that the association of bazedoxifene and conjugated estrogen could also be beneficial in the treatment of climacteric syndrome in patients with menopausal symptoms.

Objectives: Bazedoxifene/conjugated estrogens (BZA/CE) has demonstrated efficacy in improving vasomotor and vulvar/vaginal atrophy symptoms in postmenopausal women. This study evaluated the endometrial safety of BZA/CE and effects on bone mineral density (BMD) compared with CE/medroxyprogesterone acetate (MPA) and placebo., Methods: The Selective estrogens, Menopause, And Response to Therapy (SMART)-4 trial was a 1-year, multicenter, double-blind, randomized, placebo- and active-controlled, phase-3 study in non-hysterectomized, postmenopausal women (n = 1061; aged 40 -< 65 years). Subjects received BZA 20 mg/CE 0.45 or 0.625 mg, CE 0.45 mg/MPA 1.5 mg, or placebo daily. Primary endpoints were the incidence of endometrial hyperplasia and the change in lumbar spine BMD at 1 year. Secondary endpoints included the change in total hip BMD and rates of amenorrhea and breast pain., Results: At 1 year, no cases of endometrial hyperplasia were identified in the BZA 20-mg/CE 0.45-mg group, while three cases (1.1%) were confirmed for the BZA 20-mg/CE 0.625-mg group (95% one-sided confidence interval upper limit < 4%). Both BZA/CE doses significantly increased lumbar spine and total hip BMD versus placebo (p ≤ 0.001) and showed low incidences of bleeding and breast tenderness, similar to placebo and significantly lower than for CE 0.45 mg/MPA 1.5 mg (p < 0.05). BZA/CE treatment was generally safe and well tolerated., Conclusions: BZA 20 mg/CE 0.45 and 0.625 mg significantly improved BMD while maintaining endometrial safety and showed a favorable safety/tolerability profile over 1 year. BZA/CE may be a promising therapy for treating menopausal symptoms and preventing osteoporosis in non-hysterectomized, postmenopausal women.

The following Consensus Statement is endorsed by The American Society for Reproductive Medicine, The Asia Pacific Menopause Federation, The Endocrine Society, The European Menopause and Andropause Society, The International Menopause Society, The International Osteoporosis Foundation and The North American Menopause Society.

We hypothesized that adherence to the Mediterranean diet measured as a Mediterranean diet score (MDS) has a beneficial effect on bone mineral density (BMD). For the purposes of this study, a sample of healthy women from Southern Spain was chosen. Subjects were grouped into two major groups: a first group consisted of women of reproductive age (premenopausal, pre-M) and a second group consisted of postmenopausal women (pos-M). The consumption of vegetables and fruit was found to be significantly related to BMD in both groups of subjects studied. In the pre-M group, the lipid ratio was positively associated with BMD and in pos-M women nuts intake was also associated with BMD. After implementing the analysis of covariance analysis, significant linear trends between the MDS and BMD were observed in all subjects studied. Our results indicate that a varied diet based on Mediterranean diet patterns may be beneficial in the prevention of osteoporosis.

Background: According to the 2010 Osteoporosis Canada Clinical Practice Guidelines, denosumab is a first-line option for the pharmacological management of postmenopausal osteoporosis (PMO), along with several therapeutics that may be more familiar to family practice doctors: bisphosphonates, raloxifene, teriparatide, and hormone therapy. Denosumab is indicated for postmenopausal patients at high risk for fracture or others who have failed, or are intolerant to, other osteoporosis therapies., Scope: We undertook a review of the efficacy and safety of denosumab in PMO, searching the English-language literature on this drug via PubMed queries as of July 2012., Findings: Although established treatments reduce fracture risk among osteoporotic postmenopausal women in trials, their effectiveness in clinical practice is limited by patient adherence. Twice-yearly denosumab treatment is associated with markedly improved bone mineral density (BMD) and cortical and trabecular bone strength, and significantly reduced osteoporotic fracture. Inhibition of bone resorption is fully reversible following discontinuation. Placebo-controlled and open-label extension studies showed similar adverse event (AE) and serious AE rates, relative to placebo, over up to 5 years. Data indicate a potential advantage of denosumab over the bisphosphonate alendronate for BMD and patient adherence and preference., Conclusion: Owing to its efficacy, safety, and potential to improve adherence rates, denosumab is an appropriate first-line pharmacologic option for PMO management.

Selective estrogen receptor modulators (SERMs), which exhibit estrogen receptor agonist or antagonist activity based on the target tissue, have evolved through multiple generations for the prevention and/or treatment of postmenopausal osteoporosis. An ideal SERM would protect bone without stimulating the breast or endometrium. Raloxifene, lasofoxifene, and bazedoxifene have demonstrated unique preclinical profiles. Raloxifene, lasofoxifene, and bazedoxifene have shown significant reduction in the risk of vertebral fracture and improvement in bone mineral density versus placebo in postmenopausal women with osteoporosis. Raloxifene has been shown to reduce the risk of non-vertebral fractures in women with severe prevalent fractures at baseline. Lasofoxifene 0.5 mg, but not lasofoxifene 0.25 mg, has shown reduction in the incidence of non-vertebral fractures. Bazedoxifene 20 mg has been associated with a significant reduction in the risk of non-vertebral fracture versus placebo and raloxifene 60 mg in women at higher baseline fracture risk. Neither raloxifene, lasofoxifene, nor bazedoxifene has shown an increase in the incidence of endometrial hyperplasia or carcinoma. All SERMs have been associated with increased venous thromboembolic events and hot flushes. SERMs are effective alternatives for women who cannot tolerate or are unwilling to take bisphosphonates and may be appropriate for women at higher risk of fracture, particularly younger women who expect to remain on therapy for many years and are concerned about the long-term safety of bisphosphonates.

Introduction: The aim of this study was to evaluate an oral low-dose estrogen therapy on bone mineral density (BMD) and quantitative ultrasonometry (QUS) in osteopenic postmenopausal women., Material and Methods: This prospective, open-label cohort study investigated 120 postmenopausal hysterectomized women. Forty-seven women had been treated with 0.3 mg conjugated equine estrogen daily (ET). Primary end point was the change in BMD at the spine after 24 months. Secondary end points were among other changes in QUS at the os calcis and phalanges., Results: After matching 42 participants in the ET group, 42 controls were analyzed. The change in BMD differed significantly after 24 months (p = 0.019). Women on ET showed significant increase of spine and hip Z-score, whereas controls showed significant decreases in spine and total hip BMD. In QUS of the os calcis and the phalanges, a number of variables showed a significant improvements with ET., Conclusion: Our results comprised a positive effect of an oral low-dose estrogen therapy on BMD. Limitations of the study are the small sample size and the open-label, non-randomized cohort study design. The findings are in accordance to the common literature and support the use of ET in the primary prevention of postmenopausal bone loss.

The risk for fragility fracture represents a problem of enormous magnitude. It is estimated that only a small fraction of women with this risk take the benefit of preventive measures. The relationship between estrogen and bone mass is well known as they are the other factors related to the risk for fracture. There are precise diagnostic methods, including a tool to diagnose the risk for fracture. Yet there continues to be an under-diagnosis, with the unrecoverable delay in instituting preventive measures. Women under the age of 70 years, being much more numerous than those older, and having risk factors, are a group in which it is essential to avoid that first fragility fracture. Today it is usual not to differentiate between the treatment and the prevention of osteoporosis since the common aim is to prevent fragility fractures. Included in this are women with osteoporosis or with low bone mass and increased risk for fracture, for whom risk factors play a primary role. There is clearly controversy over the type of treatment and its duration, especially given the possible adverse effects of long-term use. This justifies the concept of sequential treatment, even more so in women under the age of 70, since they presumably will need treatment for many years. Bone metabolism is age-dependent. In postmenopausal women under 70 years of age, the increase in bone resorption is clearly predominant, related to a sharp drop in estrogens. Thus a logical treatment is the prevention of fragility fractures by hormone replacement therapy (HRT) and, in asymptomatic women, selective estradiol receptor modulators (SERMs). Afterwards, there is a period of greater resorption, albeit less intense but continuous, when one could utilise anti-resorptive treatments such as bisphosphonates or denosumab or a dual agent like strontium ranelate. Bone formation treatment, such as parathyroid hormone (PTH), in women under 70 years will be uncommon. That is because it should be used in cases where the formation is greatly diminished and there is a high risk for fracture, something found in much older women.

Objective: Generic medicines are often used in public hospitals. However, data on the quality of generic alendronate, its efficacy, side-effects and medication adherence in clinical practice is scarce. Therefore, this study aimed to compare the side-effects and medication adherence of generic (apo-alendronate*) and proprietary alendronate (Fosamax†)., Research Design and Methods: This prospective study involved two groups of patients: (1) postmenopausal osteoporotic women prescribed once-weekly Fosamax (proprietary group) but were switched to apo-alendronate after 2 years ('switched over' group); and (2) patients initiated with once-weekly apo-alendronate (generic group). Participants were recruited from the Osteoporosis Clinic of a tertiary hospital. Data were collected through interviews., Main Outcome Measures: Side-effects and medication adherence., Results: A total of 131 participants were recruited: proprietary group = 64 and generic group = 67. An intergroup and a within-group comparison were made. Side-effects were reported by 6 (9.4%), 30 (44.8%) and 12 (18.8%) participants in the proprietary, generic and 'switched over' groups, respectively. Participants who were on generic alendronate were at a significantly higher risk of experiencing side-effects compared to those who were taking proprietary alendronate [odds ratio (OR):7.84 (95% CI: 2.98-20.65), p < 0.001]. However, no significant statistical difference was found between the 'switched over' and the proprietary group [OR: 2.23 (95% CI: 0.78-6.37), p = 0.127]. Four out of 12 (33.3%) patients who experienced side-effects immediately after switching to generic alendronate discontinued generic alendronate due to intolerable gastrointestinal side-effects. There was no difference in medication adherence to generic or proprietary alendronate., Conclusions: Medication adherence to both generic and proprietary alendronate appeared similar although patients who were taking generic alendronate* were significantly more likely to experience side-effects than those on proprietary alendronate. Therefore, the switch from proprietary alendronate to the generic forms should not only consider the cost of the products but must also ensure that the generic and proprietary alendronate are equivalent in all aspects of efficacy and safety.

A new study by Karim and colleagues has highlighted the intriguing issue of the consequences of cessation of long-term postmenopausal hormone use. While potential reductions in breast cancer risk and in the incidence of newly diagnosed breast cancer in the era after the Women's Health Initiative study have been heavily debated, the implications of withdrawal from hormone therapy for bone health and fracture risk have remained outside the main scope. This new study has now demonstrated that there is a very clear downside in skeletal outcome that should be considered while evaluating the pros and cons of discontinuing hormone therapy. During 532 686 person-years of observation and a follow-up period of 6.5 years, a 55% increased risk for hip fracture was observed in women who stopped hormone therapy. In view of the dramatic decline in the number of hormone users all around the world, this mini-review discusses the 'neglected' skeletal outcomes of such global trends.

A new analysis from the Women's Health Initiative included data on breast cancer incidence over a 11-year period from the randomized trial of conjugated equine estrogens (CEE) plus medroxyprogesterone acetate (MPA) and a subsequent observational follow-up. The conclusions were that CEE/MPA use was associated with an increase in both breast cancer incidence and mortality. We have concerns over the validity of their statistical analyses, as adjustments for baseline characteristics or for multiple comparisons demonstrate no significant differences in incidence between those allocated to CEE/MPA or placebo. We suspect that the apparent increase in mortality is the result of surveillance and detection bias rather than a true cause and effect. Even if such an effect were true, mortality from breast cancer would still be a very rare event. We also question the clinical relevance and applicability of their findings. The data over the 11 years show no increased risk of breast cancer with CEE/MPA in women who had not previously used hormone replacement therapy (HRT), and the vast majority of women on HRT would not be prior users at initiation. It should be remembered that women using CEE alone showed a significant decrease in breast cancer risk in the WHI trial and follow-up. Even if combined estrogen?progestogen HRT did cause an increase in breast cancer risk, and this is not proven, the magnitude of that risk is small, and less than that risk seen with many lifestyle factors. HRT is a benefit, not a risk, for those women requiring it.

Introduction: Osteoporosis is a well-recognized disease with severe consequences if left untreated. The prevention of osteoporosis-associated fractures should include fall prevention, calcium supplementation and life-style advice, as well as pharmacological therapy using agents with proven antifracture efficacy., Areas Covered: This manuscript offers an evidence-based critical assessment of the currently available efficacy data on all new chemical entities that have been granted a marketing authorization for the management of primary osteoporosis in women., Expert Opinion: The availability of new therapeutic agents makes clinical decision making in osteoporosis more complex. Therapeutic decisions should be based on a balance between the benefits and risks of treatment, which must be carefully considered in each particular case, both by the physician and the patient. Indeed, no single agent is appropriate for all patients. Therefore, treatment decisions should be made on a tailor-made basis, taking into account all measures of treatment effect and risk, before making informed judgments about the best individual treatment option.

A high intake of fruits and vegetables is associated with a lower risk of cancer. In this context, considerable attention is paid to Asian populations who consume high amounts of soy and soy-derived isoflavones, and have a lower risk for several cancer types such as breast and prostate cancers than populations in Western countries. Hence, interest focuses on soyfoods, soy products, and soy ingredients such as isoflavones with regard to their possible beneficial effects that were observed in numerous experiments and studies. The outcomes of the studies are not always conclusive, are often contradictory depending on the experimental conditions, and are, therefore, difficult to interpret. Isoflavone research revealed not only beneficial but also adverse effects, for instance, on the reproductive system. This is also the case with tumor-promoting effects on, for example, breast tissue. Isoflavone extracts and supplements are often used for the treatment of menopausal symptoms and for the prevention of age-associated conditions such as cardiovascular diseases and osteoporosis in postmenopausal women. In relation to this, questions about the effectiveness and safety of isoflavones have to be clarified. Moreover, there are concerns about the maternal consumption of isoflavones due to the development of leukemia in infants. In contrast, men may benefit from the intake of isoflavones with regard to reducing the risk of prostate cancer. Therefore, this review examines the risks but also the benefits of isoflavones with regard to various kinds of cancer, which can be derived from animal and human studies as well as from in vitro experiments.

Introduction: Raloxifene, a non-steroidal selective estrogen receptor modulator (SERM), offers a new dimension for the treatment and prevention of osteoporosis and risk reduction of invasive breast cancer in postmenopausal populations at high risk. Both osteoporosis and breast cancer are important public health issues for postmenopausal women. It is well known that estrogen and estrogen receptors play an important role in the pathogenesis of both diseases. Initially, hormone replacement therapy (HRT) was used for the purpose of preventing and treating postmenopausal osteoporosis. However, HRT significantly contributed to an increase in breast cancer risk. The SERM, raloxifene, is used for the prevention and for the treatment of postmenopausal osteoporosis and reducing the risk of invasive breast cancer in postmenopausal women., Areas Covered: This article reviews the emerging evidence of the efficacy of raloxifene in postmenopausal women, summarizes the results and places in perspective their therapeutic uses for women having either a high risk of osteoporosis or breast cancer. Emerging clinical evidence suggests bisphosphonates, currently used as drugs for the treatment of osteoporosis, may also reduce breast cancer risk. The status of other SERMs and bisphosphonates are included for completeness. A Medline search of raloxifene, osteoporosis, breast cancer and SERMs was used to derive a database of 355 references., Expert Opinion: Readers will understand the value of raloxifene to prevent osteoporosis and breast cancer in postmenopausal women. Although most women do not require pharmacotherapy for menopausal symptoms, many are severely affected by osteoporosis or breast cancer at and beyond menopause and, for such women, pharmacologic intervention is important if they are to retain an acceptable quality of life. It is reasonable to use raloxifene or bisphosphonate as an appropriate drug that targets symptom-free postmenopausal women for treatment and prevention of osteoporosis but raloxifene is proven to reduce the incidence of invasive breast cancer.

Objective: To assess bone mineral density (BMD) in postmenopausal women using estradiol and testosterone hormonal implants comparing to that of patients without hormonal therapy., Design of the Study: Sixty-one patients were followed in prospective cohort study separated in Group 1, 34 women using implants and Group 2, 27 women without implants and BMD assessment through Dual energy X-ray absorptiometry was conducted in the beginning of follow-up and after 1 year., Results: The average lumbar spine BMD in Group 1 was 1.123 ± 0.16 kg/m(2) and 1.144 ± 0.18 kg/m(2) after 1 year, p=0.39 and femur BMD was 0.922 ± 0.16 kg/m(2) and 0.957 ± 0.12 kg/m(2) after 1 year of treatment, p=0.076. In Group 2, the initial lumbar spine BMD average was 1.064 ± 0.2 kg/m(2) and after 1 year, 1.001 ± 0.23 kg/m(2), p=0.112 and femur BMD changed from 0.928 ± 0.14 kg/m(2) to 0.881 ± 0.15 kg/m(2) after 1 year, p=0.046., Conclusion: BMD variance between the groups in the period of 1 year showed that the combination of estradiol and testosterone promoted bone protection in post menopausal women.