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Resumen: Se revisa la evidencia científica en las actividades preventivas de la atención de la mujer en relación con el seguimiento del embarazo, las actividades preventivas en la planificación y seguimiento de los métodos anticonceptivos, actividades preventivas en la menopausia, y la prevención de las fracturas osteoporóticas. Abstract: A review is presented of the scientific evidence on preventive activities in women's care in relation to pregnancy follow-up, preventive activities in the planning and follow-up of contraceptive methods, preventive activities in menopause, and the prevention of osteoporotic fractures.

Objectives: To assess the inclusion of individuals' perspectives in the development of osteoporosis Clinical Practice Guidelines (CPGs) for primary fracture prevention in postmenopausal women., Study Design and Setting: We performed a comprehensive systematic search across guideline databases and (CPGs) developing organizations websites. Using the AGREE II tool, we assessed the quality of the guidelines, with particular emphasis on the inclusion of patients, or representatives in the development process. We also examined if women's perspectives were considered at the recommendations level and explored the potential association between the inclusion of patients' values and preferences with the quality of the CPGs., Results: We retrieved a total of 491 eligible CPGs, of which 33 were finally included. The majority of the CPGs were developed by scientific societies (63.6%), primarily from Europe (39.4%) and North America (30.3%). One in every four (24.2%) guidelines explicitly included individuals' perspectives in their development, and one in ten (12.1%) included research evidence about this aspect to support their recommendations. The domains with the lowest mean scores in the quality assessment were applicability (42.4%), rigor of development (44.7%), and stakeholder involvement (45.7%), and 61% were recommended for use according to our assessment. Guidelines of higher quality were more likely to include women's perspective in their development (mean difference 39.31, P = .003)., Conclusion: The incorporation of women's perspectives into the process of developing guidelines for primary fracture prevention in osteoporosis remains inadequate. Our findings serve as a call for guideline developers to improve this situation, and for users, and policymakers to be aware of these limitations, when using or implementing guidelines in this field., Competing Interests: Declaration of competing interest There are no competing interests for any author., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The objectives of the physician survey component of the MUSIC OS-AP study were to describe physicians' approaches to treatment of women with postmenopausal osteoporosis and to understand the influence of gastrointestinal (GI) events on treatment in clinical practice. Methods: Physicians were recruited from 5 Asia-Pacific countries. Questionnaires collected information about physicians' standard practices for treatment of patients with osteoporosis, as well as their perspectives on the influence of GI events on osteoporosis treatment approaches. Results: A total of 59 physicians participated in the study. The most frequently prescribed or recommended treatments were vitamin D (84% of patients), calcium (82%), and oral bisphosphonates (59%). When choosing a medication for treatment-naïve patients, GI sensitivity was often or always a factor for 79% of physicians. Among physicians not prescribing pharmacologic treatment, a mean of 18% of non-prescriptions were due to GI sensitivity. For patients with pre-existing GI conditions, physicians most frequently ranked use of non-oral osteoporosis medication as the first treatment strategy (47%), followed by co-prescription with a proton pump inhibitor or other gastro-protective agent (31%). For patients developing GI symptoms after starting pharmacologic treatment, the most frequently first-ranked management strategy was to check if patients were taking their osteoporosis medication correctly as prescribed (64%), followed by temporary discontinuation of the medication (i.e., a drug holiday) until GI events have resolved (31%) and co-prescription with a proton pump inhibitor or other gastroprotective agent (24%). Conclusions: These results suggest that GI events influence the prescribing practices of physicians in the Asia-Pacific region and sometimes result in non-treatment of women with osteoporosis.

Purpose: The objective was to investigate the relationships among disease characteristics, sarcopenia risk, bone function, sleep quality, depressive symptoms, and health-related quality of life in menopausal women. Additionally, we also examined the potential mediating role of coping in the relationship between these factors and health outcomes for individuals with osteoporosis., Methods: In a cross-sectional approach, 201 participants were referred by a physician from the Family Medicine Department during their outpatient visits at a general hospital in Southern Taiwan. Data collection involved structured one-on-one interviews, and the analysis included descriptive and inferential statistics, along with a structural equation modeling., Results: The participants' bone function was strongly positively related to coping, physical and mental quality of life (QOL), and negatively related to sleep quality and depressive symptoms. The duration of osteoporosis was positively related to pain, sarcopenia risk, sleep quality, but negatively related to bone function, physical and mental QOL. This structural framework explains 36% of the variance in depressive symptoms, 25% in sleep disturbances, 54% in mental QOL, and 72% in physical QOL. The best-fit structural equation modeling showed that physical function, exercise, sarcopenia, pain, and coping were significant predictors of depressive symptoms, with coping acting as a mediator in these relationships., Conclusion: Individuals who employed more active coping strategies exhibited fewer depressive symptoms, better sleep quality, and superior physical and mental QOL. Further, individuals with osteoporosis had lower pain levels, less sarcopenia risk, and higher engaged in exercise presentation improved physical and mental QOL. Future longitudinal research holds the promise of providing deeper insights into these complex relationships., Competing Interests: Declaration of competing interest Hui-Ling Lai, Chun-I Chen, Yu-Ching Lin, Liu-Chun Lu and Chiung-Yu Huang declare that they have no conflict of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objective: The aim of this study was to investigate the diagnostic efficacy of the radiomorphometric indices of mandibular cortical width (MCW) and mandibular cortical index (MCI) of cortical erosion for osteoporosis screening in adults (≥40 years) and older adults (≥65 years) to determine whether adding a fracture risk assessment tool (FRAX) would improve efficacy., Study Design: One observer measured MCW and assessed MCI on dental panoramic radiographs acquired for patients in the Tromsø study. These indices, alone and with FRAX scores, were evaluated for efficacy in predicting osteoporosis, which was diagnosed by bone density measurement at the femoral necks with dual-energy X-ray absorptiometry., Results: MCW ≤3 mm and MCI indicating heavily eroded cortices (C3) had accuracies of 68.8% and 83.6%, respectively, in identifying osteoporosis. In females >65 years, MCW ≤3 mm and C3 produced higher sensitivities but lower specificities, with slightly lower accuracies (61.4% and 79.8%, respectively) compared with all females. The addition of FRAX scores >15% improved the accuracy of MCW ≤3 mm (81.7%) and C3 (87.9%), resulting in high specificity (86.6% and 95.4%). Combining MCW ≤3 mm or C3 with FRAX >15% increased the probabilities of detecting osteoporosis by increasing positive likelihood ratios., Conclusions: MCW ≤3 mm or MCI C3, when combined with FRAX >15%, showed superior diagnostic efficacy, with high specificity in detecting females without osteoporosis., (Copyright © 2022. Published by Elsevier Inc.)

Purpose: The objective of this study was to analyze changes in serum markers of bone turnover across multiple decades in osteoporotic women compared with nonosteoporotic controls, to determine their utility as potential predictors for osteoporosis. Early prediction of those at risk for osteoporosis can enable early intervention before the irreversible loss of critical bone mass., Methods: Serum samples were obtained from 20 women given the diagnosis of osteoporosis after age 46 years and 20 age-matched women with normal bone mineral density from 4 time points in their life (ages 25-31, 32-38, 39-45, and 46-60 years). Serum levels of bone turnover markers (propeptide of type I collagen, parathyroid hormone, bone-specific alkaline phosphatase, osteocalcin, C-terminal telopeptide of type I collagen, sclerostin, osteoprotegerin, osteopontin, and 25-OH vitamin D) were measured using commercially available arrays and kits. We used logistic regression to assess these individual serum markers as potential predictors of osteoporosis, and mixed-effects modeling to assess the change in bone turnover markers between osteoporotic and control groups over time, then performed fivefold cross-validation to assess the classification ability of the models., Results: Markers of bone turnover, bone-specific alkaline phosphatase, C-terminal telopeptide of type I collagen, sclerostin, and osteocalcin were all independent predictors at multiple time points; osteopontin was an independent predictor in the 39- to 45-year age group. Receiver operating characteristic analyses demonstrated moderately strong classification ability at all time points. Sclerostin levels among groups diverged over time and were higher in the control group than the osteoporotic group, with significant differences observed at time points 3 and 4., Conclusions: Serum markers of bone turnover may be used to estimate the likelihood of osteoporosis development in individuals over time. Although prospective validation is necessary before recommending widespread clinical use, this information may be used to identify patients at risk for developing low bone mineral density long before traditional screening would ostensibly take place., Type of Study/level of Evidence: Diagnostic II., (Copyright © 2022 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.)

Backgroud: Changes in bone mineral density (BMD) are a potential surrogate marker for fracture endpoints in clinical trials. However little is known whether the increase in BMD in response to combination treatment with alendronate plus alfacalcidol is associated with fracture risk reduction. We aimed to evaluate the impact of BMD on fracture risk in osteoporosis patients, using the data from the randomized clinical trial comparing alendronate plus alfacalcidol with alendronate alone., Methods: We selected 412 patients with two or more prevalent vertebral fractures and who had BMD measurements at baseline and after 6, 12, and/or 24 months out of 2022 patients from the database of the Japanese Osteoporosis Intervention Trial. Patients in this subset who received combination treatment with alendronate plus alfacalcidol had shown a lower risk of fracture than patients treated with alendronate alone. We used Poisson regression model analysis to calculate the proportion of treatment effect (PTE) that was attributable to BMD increases in patients receiving combination treatment., Results: The highest PTE attributable to changes in BMD was 1.2% in patients with a BMD increase of 3% or more in the lumbar spine. For BMD measurements of the radius, the highest PTE was 2.8% with a BMD increase of 0% or more. For BMD measurements of the metacarpal bone, the highest PTE was 1.2% with a BMD increase of 3% or more. In patients with a BMD greater than or equal to 70% of the young adult mean in the lumbar spine, the PTE attributable to BMD was 0.2%. In patients with a BMD greater than or equal to 70% of the young adult mean in the radius, the PTE attributable to BMD was 0.3%., Conclusions: The additional effects of alfacalcidol in reducing fracture risk do not likely result from increased BMD; other mechanisms remain a possibility., Competing Interests: Declaration of competing interest Public Health Research Foundation (PHRF) sponsored the JOINT-02 study. PHRF receives financial support from the Japan Arteriosclerosis Prevention Fund, Teijin Pharma Ltd., Asahi Kasei Corporation, Takeda Pharmaceutical Company Ltd., GE Healthcare Japan, Toyo Medic Company Ltd., Banyu Pharmaceutical Company Ltd., and Dainippon Sumitomo Pharma Company Ltd., (Copyright © 2020 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Background: Macro- and micronutrients, such as proteins, vitamin D, and calcium (Ca), are important dietary factors that can modify bone mineral density (BMD). Genetic factors can interact with diet, affecting an individual's predisposition to osteoporosis., Objectives: This study aimed to evaluate the associations between macro- and micronutrient intakes and BMD in Mexican postmenopausal women, and their interactions with genetic polymorphisms involved in the vitamin D metabolic pathway., Methods: We analyzed data from 317 postmenopausal women from the Health Workers Cohort Study, a longitudinal cohort studied in Cuernavaca, Mexico. Postmenopausal women participated in 2 data collection waves (2004-2006 and 2010-2011), with a mean time of 6.4 years. Dietary intake was assessed with a semi-quantitative FFQ. BMD (femoral neck, hip, and lumbar spine) was measured by DXA. Hybrid mixed-effects regression models were used to assess the associations of dietary macro- and micronutrients on BMD, after adjusting for confounding factors and for diet and single nucleotide polymorphism interactions., Results: At baseline, the median age was 57 years (IQR, 50-64). Mean femoral neck, hip, and lumbar spine BMDs decreased over time. We observed statistically significant longitudinal associations for diet (Ca, vitamin D, magnesium, phosphorus, and protein intake) and BMD. Increases of vitamin D, Ca, and protein intakes by 1 SD were associated with mean increases in the femoral neck BMD (0.083 SD, 0.064 SD, and 0.130 SD, respectively). Multiple significant interactions were identified between several loci (CYP2R1, CYP24A1, CYP27B1, VDR, and DHCR7/NADSYN1) and diet for BMDs (femoral neck, hip, and lumbar spine), mainly for protein intake., Conclusions: Our data support associations of vitamin D, Ca, protein, phosphorous, and magnesium consumption with BMD in Mexican postmenopausal women and suggest possible gene-diet interactions. These results could facilitate future personalized nutrition recommendations to help prevent low BMD., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Osteoporosis is characterized by an imbalance between bone formation and resorption rates, resulting in bone loss. For ethical reasons, effects of antiosteoporosis drugs are compared against patients receiving vitamin D and calcium supplementation which is a mild antiresorptive regimen. Bone formation may be resolved into two phases: the initial formation of mineral crystals (primary nucleation) and the subsequent mineral accumulation (secondary nucleation and mineral growth) on them. In this study, we used Raman microspectroscopic analysis of iliac crest biopsies from healthy females (N = 108), postmenopausal osteoporosis patients receiving vitamin D and calcium supplementation (PMOP-S; N = 66), and treatment-naïve postmenopausal osteoporosis patients (PMOP-TN; N = 12) to test the hypothesis that at forming trabecular surfaces, mineral maturity / crystallinity of the youngest crystallites associates with the amount of subsequent mineral accumulation. The surfaces of analysis were chosen based on the presence of fluorescent double labels, defining three distinct tissue ages. The results indicated that when adjusted for age and tissue age, there were no differences in amount of mineral formed between healthy females and either PMOP-S or PMOP-TN, while both PMOP-S and PMOP-TN had larger crystallites compared to healthy females. Moreover, significant differences existed between PMOP-S and PMOP-TN in size of initial crystals formed as well as rate of mineral accumulation and maturation. These findings suggest an additional mechanism that may contribute to the decreased mineral content evident in PMOP, and provide a potential target for the development of new interventions. STATEMENT OF SIGNIFICANCE: We used Raman microspectroscopic analysis of iliac crest biopsies from healthy females and postmenopausal osteoporosis patients (PMOP) receiving placebo to test the hypothesis that at forming trabecular surfaces, mineral maturity / crystallinity (MMC) of the youngest crystallites associates with the amount of subsequent mineral accumulation. This can affect bone mechanical properties as larger crystallites have been shown to result in compromised mechanical attributes; and larger crystallites grow slower compared to smaller ones. The results of the present analysis indicate that increased MMC of the youngest formed mineral may contribute to the bone mineral loss evident in PMOP and the accompanying increased fracture risk independently of bone turnover rate., Competing Interests: Declaration of Competing Interest None of the authors has any conflict of interest., (Copyright © 2021 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Objective: The aim of this study was to evaluate new radiomorphometric indices in cone beam computed tomography (CBCT) for assessing bone mineral density (BMD) status in postmenopausal women., Study Design: Mandibular inferior cortical bone thickness was evaluated in 48 postmenopausal women in cross-sectional images at 4 sites: (1) symphysis (S): cross-sectional image equidistant from the centers of the right and left mental foramina (MF); (2) anterior (A): 10 mm anterior to the MF; (3) molar (M): 10 mm posterior to the MF; and (4) posterior (P): 25 mm posterior to the MF. Participants underwent dual-energy x-ray absorptiometry and were divided into normal, osteopenia, and osteoporosis groups. In the study, t tests with Bonferroni correction were conducted. Statistical significance was set at P < .017. Receiver operator characteristic (ROC) analyses were performed., Results: Mean S index was significantly lower in osteoporosis than in osteopenia (P = .005). Mean M index was significantly lower in osteopenia (P < .001) and osteoporosis (P = .001) than in normal individuals. Mean P index was significantly lower in osteoporosis than in normal patients (P = .008). ROC values ranged between 0.643 and 0.740. Cortical thicknesses separating normal from abnormal varied from 1.73 mm to 3.37 mm., Conclusions: M and P indices in CBCT may be useful for identifying low BMD in postmenopausal women., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Osteoporosis (OP) is a significant public health problem with associated fragility fractures, thereby causing large bone defects and difficulty in self-repair. The introduction of human mesenchymal stem cells (hMSCs) is the most promising platform in bone tissue engineering for OP therapy, which induces less side effects than conventional medication. However, the safety and efficiency of the cell-based OP therapy requires the ability to monitor the cell's outcome and biodistribution after cell transplantation. Therefore, we designed an in vivo system to track hMSCs in real time and simultaneously attempted to obtain a significant therapeutic effect during the bone repair process. In this study, we synthesized Ir(III) complex, followed by encapsulation with biodegradable methoxy-poly(ethylene glycol) poly(lactic-co-glycolic acid) nanospheres through double emulsions strategy. The Ir(III) complex nanospheres did not affect hMSC proliferation, stemness, and differentiation and realized highly efficient and long-term cellular labeling for at least 25 days in vivo. The optimal transplantation conditions were also determined first by injecting a gradient number of labeled hMSCs percutaneously into the cranial defect of the nude mouse model. Next, we applied this method to ovariectomy-induced OP mice. Results showed long-term optical imaging with high fluorescence intensity and computed tomography (CT) scanning with significantly increased bone formation between the osteoporotic and sham-operated bones. During the tracking process, two mice from each group were sacrificed at two representative time points to examine the bony defect bridging via micro-CT morphometric analyses. Our data showed remarkable promise for efficient hMSC tracking and encouraging treatment in bioimaging-guided OP stem cell therapy., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Backgroud: Exercises and vitamin D interventions have shown to improve muscle function and balance, and prevent falls in postmenopausal healthy women and in patients with osteoporosis. However, the effects of eldecalcitol on these factors remain undetermined. The present open-label, randomized, controlled study aimed to investigate the effects of eldecalcitol treatment in reducing falls in postmenopausal women, and improving muscle function and balance., Methods: The study population included 226 Japanese postmenopausal women with osteoporosis. Patients were randomly divided into two groups on the basis of treatment with or without eldecalcitol (0.75 μg/day). Treatment continued for 6 months. Participants in both groups were instructed to perform back extensor muscle exercise. Isometric back extensor and leg extensor strength, grip power, ten-meter walking speed, timed up and go test and time of single leg standing were measured at baseline and 24 weeks. Patients were asked to record the number of falls during the 24-week period., Results: The percentage increase in average bilateral quadriceps muscle strength was significantly higher in the eldecalcitol group compared with the non-eldecalcitol group (right, p = 0.041; left, p = 0.042). In contrast, there were no significant differences in the strength of back muscles and grip power and the parameters of balance and walking abilities between the groups. There was no significant difference in the number of falls between the groups., Conclusions: A 24-week intervention of eldecalcitol improves the strength of the quadriceps muscles in postmenopausal women with osteoporosis. However, eldecalcitol neither improve balance and walking abilities nor reduce the number of falls., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2020 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Background: Osteoporosis is a progressive disease commonly seen in postmenopausal women which is characterized by decreased bone mass. This is becoming an important public health issue in India. This review aimed to evaluate the effect of exercise on quality of life and bone health status among postmenopausal osteoporotic women., Methods: We searched the following databases: Pubmed-Medline, Proquest, CINAHL, Scopus, Cochrane Central and PEDro. The review included randomized controlled trials that examined the use of exercise aimed at improving bone mineral density and quality of life in postmenopausal osteoporotic women without a history of fracture. Risk of bias was assessed by the Cochrane Risk of Bias tool., Results: This review suggests exercise is effective in improving the bone mineral density and quality of life of postmenopausal women with osteoporosis. The exercise interventions included in the studies were heterogeneous and included: Tai Chi, high intensity aerobic exercises, Modified Eight Section Brocade exercises, progressive slow loading low impact exercises, pilates and closed kinetic exercises. Four studies had a small sample size and in three studies, interventions were for a shorter duration. Meta-analysis could not be performed as the studies were not homogenous., Conclusion: There is a need to conduct more experimental trials with robust research methods so that a high risk of bias can be avoided. The available evidence supports the positive effects of exercises on postmenopausal osteoporosis., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objectives: Menopause marks the end of women's reproductive period and can lead to sarcopenia and osteoporosis (OP), increasing the risk of falls and fractures. The aim of this study is to evaluate the influence of normal and low bone mineral density (BMD) on muscular activity, observed through inflammatory edema when mapping using magnetic resonance imaging (MRI) on the quadriceps muscle of postmenopausal women., Methods: This was a cross-sectional study involving 16 older women, who were divided into two groups: osteoporosis group (OG), older women with OP, and control group (CG), older women without OP. The groups were evaluated in terms of nuclear MRI exam before and after carrying out fatigue protocol exercises using an isokinetic dynamometer and squatting exercises., Results: The results of the present study showed that in intragroup comparisons, for both groups, there was a significant increase (p<0.05) in the T2 signal of the nuclear MRI in the quadriceps muscle after carrying out exercises using both thighs. In the intergroup comparison, no statistically significant difference was observed between the OG and CG, pre- (p=0.343) and postexercise (p=0.874)., Conclusion: The acute muscular activation of the quadriceps evaluated by T2 mapping on nuclear MRI equipment is equal in women with and without OP in the postmenopausal phase. BMD did not interfere with muscle response to exercise when muscle fatigue was reached.

Objectives: Previous studies have not shown any correlation between bile acid metabolism and bone mineral density (BMD) in women with postmenopausal osteoporosis. Thus, the current study evaluated the association between bile acid levels as well as BMD and bone turnover marker levels in this group of women., Methods: This single-center cross-sectional study included 150 postmenopausal Chinese women. According to BMD, the participants were divided into three groups: osteoporosis group, osteopenia group, and healthy control group. Serum bile acid, fibroblast growth factor 19 (FGF19), and bone turnover biomarker levels were assessed. Moreover, the concentrations of parathyroid hormone, 25-hydroxy vitamin D [25(OH)D], procollagen type I N-peptide (P1NP), and beta-CrossLaps of type I collagen containing cross-linked C-terminal telopeptide (β-CTX) were evaluated. The BMD of the lumbar spine and proximal femur were examined via dual-energy X-ray absorptiometry., Results: The serum total bile acid levels in the osteoporosis and osteopenia groups (5.28±1.56 and 5.31±1.56 umol/L, respectively) were significantly lower than that in the healthy control group (6.33±2.04 umol/L; p=0.002 and 0.018, respectively). Serum bile acid level was positively associated with the BMD of the lumbar spine, femoral neck, and total hip. However, it negatively correlated with β-CTX concentration. Moreover, no correlation was observed between bile acid and P1NP levels, and the levels of the other biomarkers that were measured did not differ between the groups., Conclusion: Serum bile acid was positively correlated with BMD and negatively correlated with bone turnover biomarkers reflecting bone absorption in postmenopausal women. Thus, bile acid may play an important role in bone metabolism.

Purpose: This study aimed to identify the effect of parity and breastfeeding duration and the occurrence of lumbar vertebral and femoral neck osteoporosis in Korean postmenopausal women., Methods: This study analyzed the data of 1,770 women based on the 2010-2011 results of the Korea National Health and Nutrition Examination Survey. Extracted data concerning bone density included variables known to be associated with osteoporosis. Complex sample multivariate logistic regression analysis was conducted to determine whether parity and breastfeeding duration were associated with osteoporosis in postmenopausal women., Results: Parity was not associated with postmenopausal osteoporosis in the femoral neck or lumbar vertebrae; however, the risk of femoral neck osteopenia was significantly higher in women with a history of 12-24 months of breastfeeding than in women who breastfed for less than 12 months (odds ratio = 2.12, 95% confidence interval = 1.07-4.21). In women who breastfed for 24 months or longer, the risk of lumbar vertebral osteoporosis was significantly higher than in those who breastfed for less than 12 months (odds ratio = 2.73, 95% confidence interval = 1.18-6.32)., Conclusion: Breastfeeding duration may affect the occurrence of lumbar vertebral or femoral neck osteopenia or osteoporosis. Therefore, women who breastfeed for one year or more require education on the risk of bone loss and the need for preventive measures such as adequate calcium intake and physical exercise., (Copyright © 2019. Published by Elsevier B.V.)

This 24-mo randomized, double-blind, controlled trial aimed to examine whether supplementation with a natural marine-derived multi-mineral supplement rich in calcium (Ca) taken alone and in conjunction with short-chain fructo-oligosaccharide (scFOSs) has a beneficial effect on bone mineral density (BMD) and bone turnover markers (BTMs) in postmenopausal women. A total of 300 non-osteoporotic postmenopausal women were randomly assigned to daily supplements of 800 mg of Ca, 800 mg of Ca with 3.6 g of scFOS (CaFOS), or 9 g of maltodextrin. BMD was measured before and after intervention along with BTMs, which were also measured at 12 mo. Intention-to-treat ANCOVA identified that the change in BMD in the Ca and CaFOS groups did not differ from that in the maltodextrin group. Secondary analysis of changes to BTMs over time identified a greater decline in osteocalcin and C-telopeptide of type I collagen (CTX) in the Ca group compared with the maltodextrin group at 12 mo. A greater decline in CTX was observed at 12 mo and a greater decline in osteocalcin was observed at 24 mo in the CaFOS group compared with the maltodextrin group. In exploratory subanalyses of each treatment group against the maltodextrin group, women classified with osteopenia and taking CaFOS had a smaller decline in total-body (P = 0.03) and spinal (P = 0.03) BMD compared with the maltodextrin group, although this effect was restricted to those with higher total-body and mean spinal BMD at baseline, respectively. Although the change in BMD observed did not differ between the groups, the greater decline in BTMs in the Ca and CaFOS groups compared with the maltodextrin group suggests a more favorable bone health profile after supplementation with Ca and CaFOS. Supplementation with CaFOS slowed the rate of total-body and spinal bone loss in postmenopausal women with osteopenia-an effect that warrants additional investigation. This trial was registered at www.controlled-trials.com as ISRCTN63118444.

Background: This study aimed to summarize the existing literature on the benefice-risk balance for ovarian conservation at the time of hysterectomy for benign disease in post menopausal women not at high risk for ovarian cancer., Methods: We searched the published English and French literature using search engines from PUBMED, Medline for studies related to outcomes following hysterectomy with bilateral oophorectomy for benign disease and risk-reducing surgery for ovarian cancer., Results: There are in the literature arguments to support systematic bilateral oophorectomy in post menopausal women not at high risk for ovarian cancer (prevention of ovarian cancer, ovarian benign disease and chronic pelvic pain due to postoperative ovarian adhesions). There are also arguments against postmenopausal oophorectomy (effect on endocrine function, bone density, cardiovascular disease and increased mortality). Before the age of 65, there is no formal argument allowing to recommend an attitude rather than another. On the other hand, beyond the age of 65 years, the literature is clear and a bilateral salpingooophorectomy is recommended., Conclusion: Before the age of 65 years, benefits and relative risks of bilateral oophorectomy at the time of hysterectomy for benign disease even in post menopausal patients should be considered on an individual basis by clinicians and patients. Beyond the age of 65 years, the literature is clear and a bilateral salpingooophorectomy is recommended., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Hormone replacement therapy (HRT) is the most effective treatment currently available for vasomotor and urogenital symptoms and decreased libido. Because harmful effects were evidenced in some clinical trials, health authorities now consider that risk-benefit considerations do not favour the use of HRT for prevention of cardiovascular diseases and bone fractures in postmenopausal women. However, experimental and clinical studies indicate that adverse effects of HRT may largely depend on the estrogen and progesterone/progestin formulation, dosage, mode of administration, patient's age, associated diseases, and duration of treatment. All estrogen formulations and modes of administration have similar beneficial effects on vasomotor and urogenital symptoms and on bone structure. But cardiovascular and invasive breast cancer risks are higher with oral estrogen than with transdermal estradiol, and also higher with many progestin compounds than with micronized progesterone. The combination of transdermal estradiol+micronized progesterone appears to be effective and relatively safe if elementary precautions are taken, and seems to be presently the best choice for HRT in most postmenopausal women. In the author's--heterodox--opinion, HRT may also be a good therapeutic choice to prevent bone loss, since alternative medications, including raloxifene and bisphosphonates, may have dramatic harmful effects in some patients. It might also have beneficial effects on the development of coronary disease in young postmenopausal women. HRT requires careful adjustment to each individual patient and continuous monitoring of clinical evolution. In the future, this adjustment could benefit from genetic screening to maximize in each individual the ratio between positive and adverse effects.

Cardiovascular disease (CVD) is the leading cause of death in the developed world for both men and women. Women experience significant alterations in lipid profiles during the years following menopause, including a reduction in plasma high-density lipoprotein cholesterol and an elevation of plasma low-density lipoprotein cholesterol, and are at an increased risk of CVD. These changes are due in part to the reduction in estrogen production following the onset of the menopause. Therefore, agents that have anti-estrogenic effects, such as most endocrine therapies for breast cancer, may increase the risk of CVD. Tamoxifen, historically the standard endocrine therapy, has an overall beneficial effect on lipid profiles. However, long-term data from clinical trials have failed to demonstrate a cardioprotective effect and patients treated with tamoxifen did not experience fewer cardiovascular events compared with those receiving placebo. Indeed, a number of studies have shown that tamoxifen may have a detrimental effect, with a significantly increased risk of venous thromboembolic events, pulmonary embolism and stroke. The third-generation aromatase inhibitors (AIs) have demonstrated an improvement in efficacy and tolerability over previous treatments. Since they have a different mechanism of action to tamoxifen, they are not anticipated to exert the same impact on lipid profiles. Clinical trials with anastrozole demonstrated no clinically relevant impact on lipid profiles in postmenopausal patients with advanced breast cancer. However, as lipid profiles are surrogate endpoints, the most appropriate endpoint is the incidence of cardiovascular events in long-term studies. This is of particular relevance in the treatment of early breast cancer, where endocrine agents may be used in the adjuvant setting for periods of 5 years or more. Long-term adjuvant anastrozole treatment resulted in significantly fewer thromboembolic and cerebrovascular events and a similar incidence of ischemic cardiovascular events compared with tamoxifen. The effects of the other AIs on lipid levels are variable, and any correlation with cardiovascular events is currently unknown.

Menopause is diagnosed after 12 months of amenorrhoea resulting from the permanent cessation of ovarian function. The mean age at menopause is 51 years. The perimenopause, a time of changing ovarian function, precedes the final menses by several years. The physiology and clinical manifestations of this transition to menopause are not well understood; however, some symptoms, such as hot flashes, certainly begin in the perimenopause. Causal associations between menopause and several symptoms and diseases are proposed. The evidence for these associations varies and is reviewed. Hormone replacement therapy can be directed at symptom relief or at prevention or treatment of chronic diseases. Doses and routes of hormone replacement therapy vary by indication. Complications of hormone replacement therapy depend on the regimen used. Knowing the expected vaginal bleeding pattern for each hormone replacement therapy regimen is important, since unexpected bleeding may signal endometrial hyperplasia. Postmenopausal hormone therapy is a complex intervention that produces positive and negative specific health effects. Overall, based on observational studies, postmenopausal women who use hormones have a 30-50% lower all-cause mortality rate than those who do not use hormones. It is important to recognise that the value that individual women place on various health outcomes associated with hormone replacement therapy may differ. Thus, the decision to use hormone replacement therapy should be made jointly by each woman and her health-care provider, after careful consideration of possible benefits, risks, and her personal preferences.

Estrogen (E2) is known to prevent bone loss and the mechanism is, at least in part, mediated by inhibition of expression of cytokines such as interleukin-6 (IL-6). Expression of IL-6 is tightly regulated and the transcription factor NF kappa B can upregulate IL-6 gene expression by binding to its promoter region. NF kappa B is kept in an inactive state by associating with its cytoplasmic inhibitor I kappa B alpha. Upon mitogenic stimulation, I kappa B alpha becomes phosphorylated, followed by a rapid protein degradation. As a result, NF kappa B is released and translocate to the nucleus where DNA binding occurs. It has been shown that E2 treatment downregulates mitogen-induced IL-6 expression by inhibiting NF kappa B activity. Here, we sought to determine whether E2 regulates IL-6 gene expression by modulating the levels of I kappa B alpha. Our results show that E2 treatment almost completely inhibits phorbol ester-induced I kappa B alpha protein degradation. In addition, E2 inhibits phorbol ester-stimulated I kappa B alpha gene expression. Taken together, our results suggest that E2 maintains steady state levels of I kappa B alpha upon mitogen stimulation, resulting in inhibition of NF kappa B activation and IL-6 gene expression. This may explain the protective effect of E2 on bone loss.

Osteoporosis is characterized by a reduction in bone mineral density (BMD). Women more than men are at risk for osteoporosis-related fractures, especially in the wrists, lumbar spine, and hips. Numerous diet and lifestyle factors, including body weight, influence BMD, and in turn, fracture risk. BMD in the total body, hip, lumbar spine, and radius is weakly to moderately correlated to body weight, fat mass, and lean body mass in adolescent, perimenopausal, and elderly women, possibly as the result of stress on the skeleton from the mechanical loading of body weight alone. In addition, greater lean body mass may be a cause. Other explanations include increased hormonal circulation in obese women and greater conversion of adrenal androgens to estrogens linked to greater mass of adipose tissue. Currently no value is agreed on for weight-to-height versus osteoporosis and related fracture risk, but some extra fat mass yielding a body mass index > 26-28 does confer limited protection, whereas a slender figure yielding a body mass index < 22-24 increases risk.

Epidemiologic results indicate that women who smoke cigarettes are relatively estrogen-deficient. Smokers have an early natural menopause, a lowered risk of cancer of the endometrium, and an increased risk of some osteoporotic fractures. Moreover, women who smoke may have a reduced risk of uterine fibroids, endometriosis, hyperemesis gravidarum, and benign breast disease. Several possible mechanisms for these effects have been identified. Smoking does not appear to be clearly related to estradiol levels, at least in postmenopausal women, although levels of adrenal androgens are increased. Moreover, smoking appears to alter the metabolism of estradiol, leading to enhanced formation of the inactive catechol estrogens.