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Preventing the decrease in bone mineral density (BMD) is significant for postmenopausal women. We previously discovered that rhamnose, a deoxy monosaccharide used as a food additive, could suppress bone resorption; however, studies confirming this effect in postmenopausal women are lacking. Therefore, this pilot study aimed to explore whether rhamnose could help maintain BMD via bone resorption suppression in postmenopausal women. The participants consumed either 1.0 or 0.5 g/day of rhamnose or placebo for 24 weeks, and BMD (lumbar spine and femur) and bone turnover markers were measured. After 24 weeks, the group consuming rhamnose 1.0 g/day exhibited a significantly higher BMD of the lumbar spine than the placebo group. Furthermore, the levels of tartrate-resistant acid phosphatase 5b, a bone resorption marker, were significantly lower in both rhamnose groups. These results indicated that rhamnose might contribute to the maintenance of BMD by suppressing bone resorption in healthy postmenopausal women (UMIN000046570).

This study aimed to investigate the effects of blackcurrant (BC) on gut microbiota abundance and composition, inflammatory and immune responses, and their relationship with bone mass changes. The effects of BC on bone mineral density (BMD), gut microbiota, and blood inflammatory and immune biomarkers were evaluated using DXA, stool and fasting blood collected from a pilot three-arm, randomized, double-blind, placebo-controlled clinical trial. Fifty-one peri- and early postmenopausal women aged 45-60 years were randomly assigned into one of three treatment groups for 6 months: control, low BC (392 mg/day) and high BC (784 mg/day); and 40 women completed the trial. BC supplementation for 6 months effectively mitigated the loss of whole-body BMD (P<.05). Six-month changes (%) in peripheral IL-1β (P=.056) and RANKL (P=.052) for the high BC group were marginally significantly lower than the control group. Six-month changes in whole-body BMD were inversely correlated with changes in RANKL (P<.01). In proteome analysis, four plasma proteins showed increased expression in the high BC group: IGFBP4, tetranectin, fetuin-B, and vitamin K-dependent protein S. BC dose-dependently increased the relative abundance of Ruminococcus 2 (P<.05), one of six bacteria correlated with BMD changes in the high BC group (P<.05), suggesting it might be the key bacteria that drove bone protective effects. Daily BC consumption for 6 months mitigated bone loss in this population potentially through modulating the gut microbiota composition and suppressing osteoclastogenic cytokines. Larger-scale clinical trials on the potential benefits of BC and connection of Ruminococcus 2 with BMD maintenance in postmenopausal women are warranted. Trial Registration: NCT04431960, https://classic.clinicaltrials.gov/ct2/show/NCT04431960., Competing Interests: Declaration of competing interests The authors declare no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Ethnopharmacological Relevance: Siwu decoction (SWD) is widely used in gynecological diseases, such as peripheral menopause syndrome, premature ovarian failure, and menstrual disorder. However, the mechanism of SWD on postmenopausal osteoporosis (PMOP) remains unclear., Aim of the Study: To discover the phytoestrogenic osteoprotective effect of SWD on PMOP., Materials and Methods: The potential mechanism of SWD on PMOP was filtered through network pharmacology research. The potential mechanism was verified in MC3T3-E1 cell lines in vitro. CCK8 assay was conducted to assess cell proliferation and the expressions of ER/PI3K/AKT pathway were analyzed using Western blot. Female F-344 rats were chosen to set up the PMOP model. The osteoprotective effect of SWD in vivo was evaluated using Hematoxylin-eosin staining, TRAP staining, Goldner staining and DXA. The potential mechanism was verified in vivo through Western blot and immunohistochemistry. RT-qPCR was conducted to unveil the expressions of osteogenesis genes., Results: Network pharmacology research showed that ER/PI3K/AKT pathway may be the potential mechanism of SWD on PMOP. SWD promoted the proliferation of osteoblasts and regulated the protein expressions of ER/PI3K/AKT pathway in vitro. SWD improved the morphological structure, bone mineralization and bone mineral density of femurs and suppressed osteoclastogenesis in PMOP rat model via ER/PI3K/AKT pathway in vivo. In addition, SWD regulated the mRNA expressions of osteogenesis-related genes., Conclusions: SWD exerts a phytoestrogenic osteoprotective on PMOP by regulating ER/PI3K/AKT pathway, which marks it as a valuable medicine or supplement of PMOP., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Postmenopausal osteoporosis (PMOP) arises from the disruption in bone remodeling caused by estrogen deficiency, leading to a heightened susceptibility to osteoporotic fractures in aging women. Tetrahydroberberine (THB) is a chemical compound extracted from Corydalis yanhusuo , a member of the traditional Chinese medicine series "Zhejiang eight taste", possessing a variety of pharmacological functions such as lowering lipids and preventing muscle atrophy. However, the impact of THB on PMOP has not been systematically explored. In vitro experiments supported that THB suppresses osteoclast formation and resorption of bone concentration-dependently. Further experiments confirmed that these inhibitory effects of THB were related to inhibition on expressions of osteoclast-specific genes, the mitogen-activated protein kinase (MAPK) pathway, and the nuclear factor kappa-B (NF-κB) pathway and an increased apoptosis level in mature osteoclasts. Additionally, THB treatment mitigated the ovariectomy-induced bone loss and improved the skeletal microarchitecture in vivo. In conclusion, THB has such potential to improve the PMOP status.

Ethnopharmacological Relevance: Postmenopausal osteoporosis (PMOP) has been considered as a major causative factor for bone-joint pain and inducing pathologic fractures. Bu-Sui-Dan (BSD), a classic ancient herbal formula, has been shown to exhibit osteoprotective effects by promoting bone marrow development and bone growth. However, the exact mechanism of BSD are still unexplored., Aim of Study: The study aimed to investigate the protective effect of BSD against osteoporotic injury, and to explore whether BSD regulated BMSCs' osteogenic differentiation by targeting VGLL4, which in turn improved PMOP., Materials and Methods: The anti-osteoporotic effect of BSD was studied in ovariectomized (OVX) rats and bone marrow mesenchymal stem cells (BMSCs). Micro-CT imaging and HE staining were performed, and the levels of osteogenic protein RUNX2 and osteogenesis-related factor VGLL4 were determined. Co-immunoprecipitation (Co-IP) was further employed to delve into the effects of BSD on the interactions between TEAD4 and RUNX2. The key osteogenic factors 1ALP, COLl1A1, and Osterix expression were detected by RT-qPCR. Co-IP and proximity ligation assay (PLA) were employed to scrutinize the influence of BSD on TEAD4 and RUNX2 inter-binding. Moreover, VGLL4 knockdown in BMSCs was conducted to confirm the role of VGLL4 in the therapeutic mechanism of BSD., Results: BSD showed a dose-dependent protective effect against osteoporotic injury, as evidenced by improvement in bone volume, bone microarchitecture, and histomorphometry. Additionally, BSD treatment increased the levels of RUNX2 and its downstream target genes including ALP, COL1A1, and Osterix. Moreover, BSD upregulated VGLL4 expression and lessened TEAD4-RUNX2 interactions. In BMSCs experiment, BSD-containing serum could promote osteogenic differentiation of BMSCs, boosted the expression of osteogenesis-related factors and VGLL4 level. The knockdown of VGLL4 in BMSCs diminished the promotion effect of BSD in osteoblast differentiation, suggesting that VGLL4 play a vital role in the therapeutic effects exerted by BSD., Conclusion: BSD ameliorated osteoporosis injury and promoted osteoblast differentiation through upregulation of VGLL4 levels, which in turn antagonized TEAD4-mediated RUNX2 transcriptional repression. Our study implied that BSD may be an osteoporosis therapeutic agent., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: The bone status of postmenopausal women is worsening. In fact, postmenopausal period is the high incidence stage of osteoporosis and falls. Notably, a recent study has pointed out that exercise can improve bone health in postmenopausal women. However, the effect of Tai Chi exercise on postmenopausal women is controversial. Therefore, a meta-analysis was designed to analyze the effect of Tai Chi exercise on bone health and fall prevention in postmenopausal women., Methods: The researches on Tai Chi improving the bone health of postmenopausal women before August 31, 2023 were collected from Chinese and English databases, such as PubMed, Embase, and Web of Science, etc. The risk of bias of the included studies was assessed using the Cochrane risk-of-bias tool for randomized trials. Besides, R software 4.3.1 was employed to analyze the effect sizes in the meta-analysis to summarize the impact of Tai Chi on vertebral bone mineral density, serum calcium, clinical balance scores, the number of falls, total falls, and health status scores in postmenopausal women., Results: There were 12 studies eventually included in this meta-analysis. A total of 1,272 postmenopausal women were involved, including 628 in the experimental group (intervention with Tai Chi exercise) and 644 in the control group (without any intervention). Briefly, postmenopausal women practicing Tai Chi presented a significant increase in vertebral bone density [standardized mean difference (SMD) = 0.37, 95% confidence interval (CI) (0.04-0.71), P = 0.03] and health status score [SMD = 0.25, 95% CI (0.01-0.49), P = 0.04]. In contrast, there were no significant differences for postmenopausal women between the two groups in terms of serum calcium [SMD = -0.01, 95% CI (-0.39, 0.36), P = 0.77], clinical balance [SMD = 0.17, 95% CI (-0.01, 0.46), P = 0.23], number of falls [SMD = -0.61, 95% CI (-1.24, 0.02), P = 0.06] and total falls [odds ratio = 0.35, 95% CI (0.11-1.12), P = 0.07]., Conclusion: Tai Chi exercise can improve the bone mineral density of postmenopausal women, thereby maintaining bone health. Hence, Tai Chi exercise is necessary to prevent osteoporosis., (© 2024. The Author(s).)

Objective: The aim of this study is to evaluate the findings of existing systematic reviews (SRs) and provide scientific evidence on the efficacy and safety of whole-body vibration (WBV) in improving bone mineral density (BMD) in postmenopausal women, to provide recommendations and guidance for future high-quality clinical research and SRs., Methods: We conducted searches in six databases (SinoMed, CNKI, Cochrane Library, Embase, PubMed, Web of Science) from the inception of the databases until July 31, 2023. The language was limited to Chinese or English. The methodological quality, risk of bias, and evidence grade of outcomes were evaluated using AMSTAR-2, ROBIS, and GRADE, respectively. Additionally, the degree of overlap in randomized controlled trials (RCTs) among the SRs was calculated using corrected covered area (CCA). Furthermore, we performed quantitative synthesis or descriptive analysis of the relevant data. All relevant operations were independently conducted by two individuals., Results: A total of 15 SRs were included in the analysis, out of which three were qualitative descriptions and 12 were meta-analyses. According to AMSTAR-2, only two SRs were rated as low or moderate, while the remaining 13 SRs were rated as critically low quality. The ROBIS assessment indicated that seven SRs had a low risk of bias, while 8 SRs had a high risk of bias. The overall findings suggest that WBV does not have a significant advantage in improving BMD in postmenopausal women. Furthermore, the CCA results revealed a high overlap in RCTs across five outcomes among the 15 SRs. Only five SRs reported specific adverse reactions/events experienced by participants after WBV interventions, and none of the SRs reported any severe adverse events., Conclusion: The existing evidence cannot establish definitive advantages of WBV in improving BMD in postmenopausal women. Therefore, we do not recommend the use of WBV for improving BMD in postmenopausal women. However, WBV may have potential value in maintaining BMD in postmenopausal women, further research is needed to confirm these findings., (© 2024. The Author(s).)

Background: Postmenopausal osteoporosis (PMO) is a chronic condition characterized by decreased bone strength. This study aims to investigate the effects and mechanisms of the combination of Butyricicoccus pullicaecorum (Bp) and 3-hydroxyanthranilic acid (3-HAA) on PMO., Methods: The effects of Bp and 3-HAA on PMO were evaluated in ovariectomized (OVX) rats by assessing stereological parameters, femur microstructure, and autophagy levels. The T helper (Th) 17/Regulatory T (Treg) cells of rats were detected using flow cytometric analysis. Furthermore, the impact of Bp and 3-HAA on the gut microbiota of rats was assessed using 16S rRNA gene sequencing. The correlation between the gut microbiota of rats and Th17/Treg immune factors, as well as femoral stereo parameters, was separately assessed using Spearman rank correlation analysis., Results: Bp and 3-HAA treatments protected OVX rats by promoting osteogenesis and inhibiting autophagy. Compared to the Sham group, OVX rats showed an increase in Th17 cells and a decrease in Treg cells. Bp and 3-HAA reversed these changes. Enterorhabdus and Pseudomonas were significantly enriched in OVX rats. Bp and 3-HAA regulated the gut microbiota of OVX rats, enriching pathways related to nutrient metabolism and immune function. There was a correlation between the gut microbiota and the Th17/Treg, as well as femoral stereo parameters. The concurrent administration of Bp and 3-HAA medication facilitated the enrichment of gut microbiota associated with the improvement of PMO., Conclusion: The combination therapy of Bp and 3-HAA can prevent PMO by modulating the gut microbiota and restoring Th17/Treg immune homeostasis., (© 2024. The Author(s).)

Background: Postmenopausal osteoporosis (PMO) is associated with dysregulation of bone metabolism and gut microbiota. Quinoa is a grain with high nutritional value, and its effects and potential mechanisms on PMO have not been reported yet. Therefore, the purpose of this study is to investigate the bone protective effect of quinoa on ovariectomy (OVX) rats by regulating bone metabolism and gut microbiota., Results: Quinoa significantly improved osteoporosis-related biochemical parameters of OVX rats and ameliorated ovariectomy-induced bone density reduction and trabecular structure damage. Quinoa intervention may repair the intestinal barrier by upregulating the expression of tight junction proteins in the duodenum. In addition, quinoa increased the levels of Firmicutes, and decreased the levels of Bacteroidetes and Prevotella, reversing the dysregulation of the gut microbiota. This may be related to estrogen signaling pathway, secondary and primary bile acid biosynthesis, benzoate degradation, synthesis and degradation of ketone bodies, NOD-like receptor signaling pathway and biosynthesis of tropane, piperidine and pyridine alkaloids. Correlation analysis showed that there is a strong correlation between gut microbiota with significant changes in abundance and parameters related to osteoporosis., Conclusion: Quinoa could significantly reverse the high intestinal permeability and change the composition of gut microbiota in OVX rats, thereby improving bone microstructure deterioration and bone metabolism disorder, and ultimately protecting the bone loss of OVX rats. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Importance: Daily supplementation with the probiotic Limosilactobacillus reuteri ATCC PTA 6475 (L reuteri) vs placebo has previously been demonstrated to reduce bone loss in an estrogen deficiency mice model and older women, although the magnitude of the effect was small. We hypothesized that long-term treatment with L reuteri could result in clinically relevant skeletal benefits in postmenopausal osteoporosis., Objective: To evaluate whether daily supplementation with L reuteri vs placebo could reduce early postmenopausal bone loss and whether the effects remained or increased over time during 2 years of treatment., Design, Setting, and Participants: A double-blind, randomized, placebo-controlled clinical trial was conducted between December 4, 2019, and October 6, 2022, at a single center in Gothenburg, southwestern Sweden. Participants were recruited by online advertisements, and letters were sent to 10 062 women aged 50 to 60 years. Responding women (n = 752) underwent telephone screening, resulting in 292 women being invited to a screening visit. Of those who were screened, 239 women met all inclusion criteria and had no exclusion criteria., Interventions: Capsules with L reuteri in 2 doses, 5 × 108 (low dose) or 5 × 109 (high dose) colony-forming units, taken twice daily or placebo were administered. All capsules also included cholecalciferol, 200 IU., Main Outcomes and Measures: The primary outcome was the relative change in tibia total volumetric bone mineral density (vBMD) over 2 years. Secondary outcomes included relative change in areal BMD of the lumbar spine and total hip, bone turnover markers C-terminal telopeptide cross-links of collagen type I and type I procollagen intact N-terminal propeptide, as well as tibia trabecular bone volume fraction and cortical vBMD. Both intention-to-treat and per-protocol analyses were conducted., Results: A total of 239 postmenopausal women (median age, 55 [IQR, 53-56] years) were included. Tibia vBMD (primary outcome), hip and spine vBMD, and tibia cortical area and BMD decreased significantly in all groups, with no group-to-group differences (percent change tibia vBMD high dose vs placebo least-squares means, -0.08 [95 CI, -0.85 to 0.69] and low dose vs placebo least-squares means, -0.22 [95% CI, -0.99 to 0.55]). There were no significant treatment effects on any other predefined outcomes. A prespecified sensitivity analysis found a significant interaction between body mass index (BMI) and treatment effect at 2 years. No significant adverse effects were observed., Conclusions and Relevance: In this randomized clinical trial of 239 early postmenopausal women, supplementation with L reuteri had no effect on bone loss or bone turnover over 2 years. The observed interaction between BMI and treatment effect warrants further investigation., Trial Registration: ClinicalTrials.gov Identifier: NCT04169789.

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.

Objective: Menopausal hormone therapy (MHT) has consistently shown a bone protective effect by reducing the risk of vertebral, non-vertebral, and hip fractures in postmenopausal women regardless of baseline fracture risk. However, the optimal sequential treatment after MHT discontinuation has not been determined. This systematic review aimed to obtain the best evidence regarding the effect of antiresorptive or osteoanabolic treatment on bone mineral density (BMD) and/or fracture risk following MHT., Methods: A comprehensive search was conducted in the PubMed, Scopus, and Cochrane databases up to October 31, 2023. Randomized-controlled trials (RCTs) and observational studies conducted in postmenopausal women were included., Results: After the exclusion of duplicates, 717 studies were identified. Two were eligible for qualitative analysis, one RCT and one retrospective cohort study. The RCT showed that alendronate 10 mg/day for 12 months further increased lumbar spine (LS) BMD by 2.3% following MHT and maintained femoral neck (FN) BMD in postmenopausal women (n = 144). It also decreased bone anabolic and resorption markers by 47 and 36%, respectively. In the retrospective study (n = 34), raloxifene 60 mg/day increased both LS and FN BMD at 12 months by 3 and 2.9%, respectively. No fractures were reported., Conclusions: Antiresorptive therapy with either a bisphosphonate (i.e., alendronate) or raloxifene could be considered a sequential antiosteoporosis therapy after MHT withdrawal since they have been shown in studies to further increase BMD. However, no safe conclusions can be drawn from the existing literature., (© 2024. The Author(s).)

Importance: Approximately 55 million people in the US and approximately 1.1 billion people worldwide are postmenopausal women. To inform clinical practice about the health effects of menopausal hormone therapy, calcium plus vitamin D supplementation, and a low-fat dietary pattern, the Women's Health Initiative (WHI) enrolled 161 808 postmenopausal US women (N = 68 132 in the clinical trials) aged 50 to 79 years at baseline from 1993 to 1998, and followed them up for up to 20 years., Observations: The WHI clinical trial results do not support hormone therapy with oral conjugated equine estrogens plus medroxyprogesterone acetate for postmenopausal women or conjugated equine estrogens alone for those with prior hysterectomy to prevent cardiovascular disease, dementia, or other chronic diseases. However, hormone therapy is effective for treating moderate to severe vasomotor and other menopausal symptoms. These benefits of hormone therapy in early menopause, combined with lower rates of adverse effects of hormone therapy in early compared with later menopause, support initiation of hormone therapy before age 60 years for women without contraindications to hormone therapy who have bothersome menopausal symptoms. The WHI results do not support routinely recommending calcium plus vitamin D supplementation for fracture prevention in all postmenopausal women. However, calcium and vitamin D are appropriate for women who do not meet national guidelines for recommended intakes of these nutrients through diet. A low-fat dietary pattern with increased fruit, vegetable, and grain consumption did not prevent the primary outcomes of breast or colorectal cancer but was associated with lower rates of the secondary outcome of breast cancer mortality during long-term follow-up., Conclusions and Relevance: For postmenopausal women, the WHI randomized clinical trials do not support menopausal hormone therapy to prevent cardiovascular disease or other chronic diseases. Menopausal hormone therapy is appropriate to treat bothersome vasomotor symptoms among women in early menopause, without contraindications, who are interested in taking hormone therapy. The WHI evidence does not support routine supplementation with calcium plus vitamin D for menopausal women to prevent fractures or a low-fat diet with increased fruits, vegetables, and grains to prevent breast or colorectal cancer. A potential role of a low-fat dietary pattern in reducing breast cancer mortality, a secondary outcome, warrants further study.

Bone strength estimates are important for fracture prevention. This study compared bone strength changes in postmenopausal women with low bone mass who were assigned to 12 months of exercise, a bone medication, or control. Exercise and bone medications benefited structure at the hip. Structure should be considered in fracture prevention research., Purpose: Exercise and bisphosphonates reduce fracture risk, but their impact on estimates of bone strength remains uncertain. This study compared changes in tibial bone strength using peripheral quantitative computed tomography (pQCT) and hip structure analysis (HSA) outcomes from dual-energy X-ray absorptiometry (DXA) scans in postmenopausal women with low bone mass assigned to 12 months of exercise, risedronate, or control., Methods: In this RCT, 276 postmenopausal women within 6 years of menopause were randomly assigned to three groups: exercise (92), risedronate (91), or control (93). Exercise included weighted jogging and progressive resistance exercises; risedronate treatment was 150 mg monthly; all groups received calcium and vitamin D. pQCT and DXA images were obtained at baseline and 6 and 12 months and compared between groups over time., Results: Participants had a mean (± SD) age of 54.5 (± 3.2) years with an average of 36.7 (± 40.7) months postmenopause. No significant differences were found between groups for the change in pQCT outcomes (volumetric bone mineral density, area, and strength estimates). At 12 months, mean percent differences (95% CI) in HSA measures between exercise and controls were as follows: intertrochanteric, cross-sectional area 2.25% (0.28, 4.12) (p = .03), cross-sectional moment of inertia (CSMI) 5.67% (1.47, 9.87) (p < .01), and section modulus (SM) 4.38% (1.02, 7.74) (p = .01), and narrow neck, average cortical thickness 2.37% (-0.08, 4.83) (p = .031). Mean percent differences (95% CI) in HSA measures between risedronate and control were as follows: intertrochanteric, CSMI 4.28% (-0.24, 8.81) (p = .03) and SM 3.35% (-0.21, 6.91) (p = .03), and shaft, subperiosteal width 0.82% (0.05, 1.58) (p = .047), CSMI 2.53% (0.88, 4.18) (p = .004), and SM 1.57% (0.34, 2.8) (p = .008). Exercise maintained neck-shaft angle compared to both control 1.27% (0.13, 2.41) (p = .04) and risedronate 1.31% (0.23, 2.39) (p = .03). All other differences for changes in HSA outcomes over time were not significantly different between the exercise and risedronate groups., Conclusion: Exercise and bisphosphonates may influence structural and strength estimates at the hip, but not at peripheral sites (tibia). Neither exercise nor bisphosphonates were found to be superior in improving estimates of hip bone strength., (© 2024. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

Osteoporosis affects one in three women over the age of 50 and results in fragility fractures. Oestrogen deficiency during and after menopause exacerbates bone loss, accounting for higher prevalence of fragility fractures in women. The gut microbiota (GM) has been proposed as a key regulator of bone health, as it performs vital functions such as immune regulation and biosynthesis of vitamins. Therefore, GM modulation via probiotic supplementation has been proposed as a target for potential therapeutic intervention to reduce bone loss. While promising results have been observed in mouse model studies, translation into human trials is limited. Here, we present the study protocol for a double-blind randomized controlled trial that aims to examine the effectiveness of three lactobacilli strains on volumetric bone mineral density (vBMD), trabecular, and cortical microstructure, as measured using High Resolution peripheral Quantitative Computed Tomography (HR-pQCT). The trial will randomize 124 healthy early postmenopausal women (up to 8 years from menopause) to receive either probiotic or placebo administered once daily for 12 months. Secondary outcomes will investigate the probiotics' effects on areal BMD and specific mechanistic biomarkers, including bone metabolism and inflammatory markers. The trial is registered with Australian New Zealand Clinical Trials Registry (ACTRN12621000810819).

Calcium and vitamin D deficiencies have been ongoing problems in Koreans due to a lack of food sources of calcium and vitamin D. Postmenopausal women aged 50 to 64 years ( n = 25) were randomly assigned to consume three home meal replacements (HMRs)/week with (treatment) and without (control) eggshell powder and vitamin D for 6 months. Additionally, subjects who agreed to continue the study consumed the same three HMRs/week for an additional 6 months in this randomized double-blind study. We confirmed the high compliance of the study participants by analyzing carotenoids, the bioactive substances of HMRs, in the blood. The treatment group consumed an additional 261 mg/d of calcium and 10.3 μg/d of vitamin D from the HMRs, thus meeting the recommended intakes of calcium and vitamin D for Koreans. As a result of consuming fortified HMRs for 6 months, the decline in femoral neck bone density was significantly reduced in the treatment group ( p = 0.035). This study indicates that inexpensive eggshell powder may be a good source of calcium for populations with low consumption of milk and dairy products. Additionally, functional HMRs fortified with eggshell powder and vitamin D can be a good dietary strategy for bone health.

It is important for postmenopausal women to acquire bone health protective behaviors to protect them from fractures. For this reason, it is necessary to evaluate bone health during menopause and to inform women., Purpose: This study was conducted to examine osteoporotic fracture protection behaviors, quality of life, and self-efficacy in postmenopausal women., Methods: In the study, the data were evaluated with the socio-demographic data form, Osteoporotic Fracture Protection Scale, Osteoporosis Self-Efficacy-Efficacy Scale, European Osteoporosis Foundation Quality of Life Questionnaire-41, which includes introductory information on socio-demographic characteristics., Results: It was determined that the postmenopausal women included in our study were between the ages of 45-92; more than half of them had chronic diseases; their average BMI was 29; and their DEXA score was - 3.00 ± 0.41. Among the people included in our study, those with a history of fractures had lower self-efficacy scores. It was determined that the fracture prevention scale scores of the participants were above the average, and the average of the osteoporosis-related quality of life score was high. In addition, it was determined that there was a strong positive correlation between self-efficacy and fracture prevention scale., Conclusion: It is important to determine behaviors to prevent osteoporotic fractures in postmenopausal women, to raise the necessary awareness and to inform patients about the precautions to be taken. It is thought that it will increase patients' quality of life by increasing their disease-related self-efficacy. Therefore, there is a need for research on providing education to op patients and examining the results., (© 2024. The Author(s).)

Background . Bone Health and Osteoporosis Foundation (BHOF) reports that as of 2023, approximately 10 million of older Americans have osteoporosis and another 44 million have low bone density. Osteoporosis is a serious handicap for the elderly and, in particular, for estrogen-deficient postmenopausal women, as it increases the risk of debilitating bone weakness and fractures. The BHOF recommendations for prevention of osteopenia, osteoporosis and bone fractures are to perform weight-bearing and muscle-strengthening exercises and to take recommended amounts of daily calcium and vitamin D. Methods . The purpose of this review is to describe and discuss recent evidence-based research on how to effectively utilize timing of exercise and calorie intake for stimulation of postmenopausal bone anabolism, and to provide this new information in the form of specific and actionable recommendations. Results . The five evidence-based recommendations are as follows: 1. Select an appropriate circadian time of day for exercise; 2. Increase walking speed to raise the movement momentum; 3. Eat a weight-maintenance meal one or two hours before the exercise bout; 4. Sustain the duration of walking activity (impulse) for 40 to 45 min; and 5. Repeat effective exercise stimulus 7 to 8 h after the first one to double the anabolic effect. Osteogenesis can also be increased with subthreshold mechanical loading, where needed, under several special circumstances. Conclusions . This review should provide pragmatic actionable pointers on how to utilize the idiosyncratic bone responsiveness to timing of movement and meals to prevent osteoporosis and encourage research toward a better understanding of how bone detects adequacy of a mechanical stimulus and determines duration of necessary rest to recover its sensitivity to mechanical stimulation and nutrients.

Due to estrogen deficiency, postmenopausal women may suffer from an imbalance in bone metabolism that leads to bone fractures. Isoflavones, a type of phytoestrogen, have been suggested to improve bone metabolism and increase bone mass. Therefore, isoflavones are increasingly recognized as a promising natural alternative to hormone replacement therapy for postmenopausal women who face a heightened risk of osteoporosis and are susceptible to bone fractures., Purpose: This study aimed to evaluate the efficacy of isoflavone interventions on bone mineral density (BMD) in postmenopausal women by means of systematic review and meta-analysis., Methods: The electronic database searches were performed on PubMed, Embase, Scopus, and Cochrane Library databases, covering literature up to April 20, 2023. A random-effects model was used to obtain the main effect estimates, with a mean difference (MD) and its 95% confidence interval (CI) as the effect size summary. The risk of bias assessment was conducted using the Risk of Bias 2 (RoB2) tool., Results: A total of 63 randomized controlled trials comparing isoflavone interventions (n = 4,754) and placebo (n = 4,272) were included. The results indicated that isoflavone interventions significantly improved BMD at the lumbar spine (MD = 0.0175 g/cm 2 ; 95% CI, 0.0088 to 0.0263, P < 0.0001), femoral neck (MD = 0.0172 g/cm 2 ; 95% CI, 0.0046 to 0.0298, P = 0.0073), and distal radius (MD = 0.0138 g/cm 2 ; 95% CI, 0.0077 to 0.0198, P < 0.0001) in postmenopausal women. Subgroup analysis showed that the isoflavone intervention was effective for improving BMD when the duration was ≥ 12 months and when the intervention contained genistein of at least 50 mg/day., Conclusion: This systematic review and meta-analysis suggests that isoflavone interventions, especially those containing genistein of at least 50 mg/day, can effectively enhance BMD in postmenopausal women., (© 2023. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

Postmenopausal osteoporosis is a major concern for women worldwide due to increased risk of fractures and diminished bone quality. Recent research on gut microbiota has suggested that probiotics can combat various diseases, including postmenopausal bone loss. Although several preclinical studies have explored the potential of probiotics in improving postmenopausal bone loss, the results have been inconsistent and the mechanism of action remains unclear. To address this, a meta-analysis was conducted to determine the effect of probiotics on animal models of postmenopausal osteoporosis. The bone parameters studied were bone mineral density (BMD), bone volume fractions (BV/TV), and hallmarks of bone formation and resorption. Pooled analysis showed that probiotic treatment significantly improves BMD and BV/TV of the ovariectomised animals. Probiotics, while not statistically significant, exhibited a tendency towards enhancing bone formation and reducing bone resorption. Next, we compared the effects of Lactobacillus sp. and Bifidobacterium sp. on osteoporotic bone. Both probiotics improved BMD and BV/TV compared with control, but Lactobacillus sp. had a larger effect size. In conclusion, our findings suggest that probiotics have the potential to improve bone health and prevent postmenopausal osteoporosis. However, further studies are required to investigate the effect of probiotics on postmenopausal bone health in humans.

We aimed to evaluate the clinical efficacy of five traditional Chinese fitness exercises (Baduanjin, Taijiquan, Wuqinxi, Yijinjing, and Liuzijue), as well as their efficacy when combined with drug therapy, in the treatment of decreased bone mineral density in postmenopausal women., Methods: This study strictly followed the evaluation guidelines of PRISMA and followed the "PICOS" principle outlined in the Cochrane Handbook. We performed a systematic search on Web of Science, Springer Link, Scopus, EMBASE, EBSCO, PubMed, the Cochrane Library, CNKI, Wanfang, CBMdisc, and the VIP Database, and we targeted RCTs studying the effect of TCE on BMD in postmenopausal women published prior to September 2023. The quality of the literature and the risk of bias of the included studies were assessed according to ROB2 and GRADE criteria, and data analysis was performed using Stata 14., Results: A total of 33 RCTs (3658 post-menopausal women) were included. Network meta-analysis showed that Taiji (SMD=0.72, 95% CI: 0.22, 1.21, P<0.01) and Yijinjing (SMD=0.51, 95% CI: 0.03, 0.99, P<0.05) were significantly superior to conventional rehabilitation in lumbar BMD. In terms of improvement of femoral neck BMD, Baduanjin (SMD=1.63, 95% CI: -3.58, 6.85, P<0.001) and Taiji (SMD=0.46, 95% CI: 0.14, 0.79, P<0.05) had statistically different outcomes to conventional rehabilitation. Regarding Ward's triangle BMD, Taiji (SMD= 0.32, 95% CI: 0.14, 0.50, P< 0.05) had statistically different outcomes to conventional rehabilitation. The results of the SUCRA probability ranking showed that Baduanjin + drug interventions achieved the most significant improvement in lumbar BMD (SUCRA=83.6%) and femoral neck BMD (SUCRA=90.2%). Taiji + drug interventions most effectively improved Ward's triangle BMD (SUCRA=86.0%). In terms of traditional Chinese fitness exercises alone, Taiji was the most effective in improving lumbar BMD (SUCRA=64.4%) and Ward's triangle BMD (SUCRA=46.8%), and Baduanjin was the most effective in treating femoral neck BMD (SUCRA=89.9%)., Conclusion: Traditional Chinese fitness exercises can significantly improve the BMD levels of postmenopausal women. Taiji, Yijinjing, and Baduanjin combined with medication showed better intervention effects overall. However, due to the limitations of the number of studies and sample sizes of individual interventions, definitive conclusions need to be verified by more high-quality studies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Liu, Wu, Qi and Wang.)

Probiotics have been found to have beneficial effects on bone metabolism. In this randomized, double-blind, placebo-controlled trial, the effects of multispecies probiotic supplementation on bone turnover markers were evaluated after 12 weeks. Forty postmenopausal women with osteopenia were included and randomly divided into two groups. The intervention group received multispecies probiotics, while the control group received identical placebo sachets daily. The baseline characteristics of both groups were similar. Still, the median serum bone resorption marker C-terminal telopeptide of type I collagen (CTX) was slightly higher in the multispecies probiotic group than in the placebo group (0.35 (0.12, 0.53) vs. 0.16 (0.06, 0.75); p -value = 0.004). After 12 weeks, the mean difference in serum CTX at baseline versus 12 weeks was significantly different between the multispecies probiotic and placebo groups (-0.06 (-0.29, 0.05) vs. 0.04 (-0.45, 0.67); p -value < 0.001). The multispecies probiotic group showed a significant decrease in serum CTX at 12 weeks compared with baseline ( p -value 0.026). However, the placebo group showed no significant change in serum CTX ( p -value 0.18). In conclusion, multispecies probiotics may have a preventive effect on bone through their antiresorptive effect in osteopenic postmenopausal women.

Estrogen deficiency is one of the main causes of postmenopausal osteoporosis in elderly women. Hormone replacement therapy has been employed to manage postmenopausal osteoporosis; however, it has raised concerns related to heart attacks and breast cancer. Sesame oil has been reported to affect sex hormone status. The aim of the present study is to evaluate the effect of sesame oil supplement on postmenopausal osteoporosis in rats. We used female Sprague Dawley rats that underwent bilaterally ovariectomy (OVX) as an experimental postmenopausal osteoporosis animal model. These rats were orally administrated sesame oil (0.25 or 0.5 mL/kg/day) for four months as the therapeutic group. We assessed bone mineral density (BMD) and the levels of osteocalcin, procollagen-I C-terminal propeptide (PICP), collagen cross-linked N-telopeptide (NTx), estradiol, and aromatase in the sera. The daily supplementation of sesame oil significantly increased BMD, serum osteocalcin levels, and trabecular areas in the OVX-treated rats. Sesame oil also elevated serum PICP levels and decreased NTx levels in these rats. Furthermore, sesame oil effectively maintained serum estradiol and aromatase levels in the OVX-induced osteoporosis rats. In conclusion, daily supplementation of sesame oil prevents postmenopausal osteoporosis by maintaining serum estrogen and aromatase levels, while also modulating the imbalance between bone formation and resorption in osteoporosis rats., (© 2024. The Author(s).)

Osteoporosis is a systemic skeletal disease manifesting as weak and fragile bones. Dietary patterns have been described as an affecting constituent of bone metabolism. There is no consensus on the advantages or harms of vegetarian diets on bone health. This study aimed to design a lacto-vegetarian dietary score (LVDS) to evaluate the similarity of an individual's dietary pattern to the lacto-vegetarian dietary pattern and assess its association with postmenopausal osteoporosis (PMO). We hypothesized that individuals with greater LVDS will have a lower risk for PMO. In this hospital-based, case-control study, 220 cases (definitively diagnosed with osteoporosis) and 220 age-matched controls were registered. Usual dietary intakes were evaluated by a validated 147-item semiquantitative food frequency questionnaire. To design the LVDS, the energy-adjusted intakes of 12 food groups were categorized into quintiles, and positive or reverse points were assigned. To determine the association between the LVDS and PMO, binary logistic regression was used. Those in the top tertile of the LVDS had a lower chance of PMO compared with those in the bottom tertile (odds ratio, 0.11; 95% confidence interval, 0.06-0.22). An inverse relation was obtained between vegetables, fruits, legumes, nuts, dairy, soy protein, and egg consumption and PMO. Higher consumption of vegetable and animal oils significantly increased the risk of PMO. A dietary pattern similar to the lacto-vegetarian dietary pattern and concentrated on greater consumption of legumes, nuts, dairy, fruits, vegetables, and soy protein can be suggested as a protective method against PMO. Further, longitudinal studies are required to confirm these findings., Competing Interests: Author Declarations None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

We assessed women's perspectives regarding early preventative therapy for osteoporosis. More than a third of early menopausal women were concerned about bone loss and future fractures, and approximately half were willing to take an intravenous or oral bisphosphonate around the time of menopause to preserve bone health., Purpose: Bisphosphonate medications can prevent the substantial bone loss that occurs during early menopause, but little is known about whether women would accept bisphosphonate treatment at this time in their life, when imminent fracture risk is low. We assessed women's perspectives regarding bone loss, fracture risk, and preventative pharmacotherapy in early menopause., Methods: In this cross-sectional study, Canadian women aged ≥ 45 years were recruited via Facebook advertisement to complete an electronic survey. Primary outcome was the proportion of early menopausal respondents (≤ 5 years since final menstrual period) who were worried about bone loss and fractures. Secondary outcomes were the proportion of early menopausal women willing to accept pharmacologic intervention aimed at preventing either bone loss or future fractures. We compared responses between early menopausal women and older women (> 5 years since final menstrual period)., Results: 2033 women responded to the Facebook advertisement, 1195 eligible women (aged: 45 to 89 years) started the survey, and 966 completed it. Among early menopausal respondents (N = 98), 38 (42%) were worried about future fractures and 9 of 25 (36%) who had a prior bone mineral density scan were worried about their results. A total of 42 (47%) were willing to start medication to prevent fractures, and 48 (54%) would start medication to prevent bone loss. Responses were comparable between early menopausal women and older women., Conclusion: Menopausal women are concerned about bone loss and fractures. Many women would consider early menopausal pharmacotherapy, with the goals of preserving bone health and lowering their risk of fractures., (© 2023. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

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.

Context: Fructus Ligustri Lucidi (FLL), a commonly used herb of traditional Chinese medicine (TCM), is the fruit of Ligustrum lucidum Ait. (Oleaceae). The ethanol extract of FLL is a potential candidate for preventing and treating postmenopausal osteoporosis (PMOP) by nourishing the liver and kidneys., Objective: This study determines whether an ethanol extract of FLL has anti-osteoporotic effects in ovariectomized (OVX) mice and explores the underlying mechanism., Materials and Methods: The OVX model of eight-week-old C57BL/6J female mice was taken, and ovariectomy was used as PMOP. Mice were divided into five groups: sham-operated group ( n  = 10), OVX group ( n  = 10), OVX + E 2 group ( n  = 10; 0.039 mg/kg), OVX + FLL group ( n  = 10; 2 g/kg) and OVX + FLL group ( n  = 10; 4 g/kg). Mice were treated by gavage with FLL or CMCNa once daily for 8 weeks. We harvested uteri, femur, and tibias from mice; bone mineral density (BMD) and bone microstructure were obtained by X-ray absorptiometry and micro-CT. Furthermore, the effect of FLL on the balance of osteoblast and adipocyte differentiation was investigated using bone marrow mesenchymal stem cells (BMMSCs)., Results: The results indicated that FLL did not affect OVX-induced estradiol reduction. Compared with OVX mice, FLL significantly increased BMD (63.54 vs. 61.96), Conn. D (86.46 vs. 57.00), and left tibial strength (13.91 vs. 11.27), decreased Tb. Sp (0.38 vs. 0.44) and body fat content (4.19% vs. 11.24%). FLL decreased osteoclast activity and enhanced RUNX2 expression; inhibited perilipin peroxisome proliferator-activated receptor gamma (PPARγ) expression and adipocyte differentiation from BMMSCs., Conclusions: FLL prevented additional bone loss and improved bone microstructure in OVX mice by modulating bone and fat balance, suggesting that FLL might be a therapeutic agent for PMOP.

Objective: Hormone therapy can positively impact bone mineral density after menopause. We explored bone mineral density change in postmenopausal women who discontinued hormone therapy after the Women's Health Initiative landmark 2002 trial results were published. We secondarily explored whether usual physical activity modified the results., Methods: Postmenopausal women participating in the Buffalo OsteoPerio study with information on hip bone density, hormone therapy use, and self-reported physical activity at two time points (1997-2001; 2002-2007) were included (N = 961). Hormone therapy included three groups according to use at baseline and year 5 (non/non; current/non; current/current)., Results: At baseline (mean age, 65.9 years; SD, 6.7 years), 480 women were not using hormone therapy, while 481 were current users. Between the baseline and 5-year visits, 336 women using hormone therapy discontinued. Baseline total hip bone density was highest in current users. After 5 years, those who continued hormone therapy exhibited no bone loss; those who discontinued exhibited the greatest loss at the total hip of -0.021 gm/cm2. Women who never used hormone therapy exhibited some loss of -0.012 gm/cm2. Usual physical activity did not appreciably impact change in bone density in any group., Conclusions: This prospective observational study explored the 5-year change in bone mineral density among older postmenopausal women after the landmark 2002 hormone therapy trial findings were released. We found bone density decreased in never-users and in women who discontinued use. Bone density was maintained in current users. Although usual physical activity did not mitigate bone loss, targeted physical activity regimens should be investigated., Competing Interests: Financial disclosure/conflicts of interest: None reported., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The Menopause Society.)

Postmenopausal osteoporosis is associated with bone formation inhibition mediated by the impaired osteogenic differentiation potential of bone marrow mesenchymal stem cells (BMSCs). However, identifying and confirming the essential genes in the osteogenic differentiation of BMSCs and osteoporosis remain challenging. The study aimed at revealing the key gene that regulated osteogenic differentiation of BMSCs and led to osteoporosis, thus exploring its therapeutic effect in osteoporosis. In the present study, six essential genes related to the osteogenic differentiation of BMSCs and osteoporosis were identified, namely, fibrillin 2 (Fbn2), leucine-rich repeat-containing 17 (Lrrc17), heat shock protein b7 (Hspb7), high mobility group AT-hook 1 (Hmga1), nexilin F-actin-binding protein (Nexn), and endothelial cell-specific molecule 1 (Esm1). Furthermore, the in vivo and in vitro experiments showed that Hmga1 expression was increased during the osteogenic differentiation of rat BMSCs, while Hmga1 expression was decreased in the bone tissue of ovariectomized (OVX) rats. Moreover, the expression of osteogenic differentiation-related genes, the activity of alkaline phosphatase (ALP), and the number of mineralized nodules were increased after Hmga1 overexpression, which was partially reversed by a Wnt signaling inhibitor (DKK1). In addition, after injecting Hmga1-overexpressing lentivirus into the bone marrow cavity of OVX rats, the bone loss, and osteogenic differentiation inhibition of BMSCs in OVX rats were partially reversed, while osteoclast differentiation promotion of BMSCs in OVX rats was unaffected. Taken together, the present study confirms that Hmga1 prevents OVX-induced bone loss by the Wnt signaling pathway and reveals that Hmga1 is a potential gene therapeutic target for postmenopausal osteoporosis., (© 2023 Federation of American Societies for Experimental Biology.)

Postmenopausal osteoporosis is the main cause of fractures in women. Resistance exercise has a positive effect on bone mineral density in postmenopausal osteoporosis patients, but its mechanism is unclear. The purpose of this study was to explore the mechanism of resistance exercise in improving ovariectomized osteoporotic rats based on the transcriptome sequencing technique. Eighteen female Sprague-Dawley rats were randomly divided into the sham-operated group, the non-exercise group, and the resistance exercise group. The rat model of postmenopausal osteoporosis was established by bilateral ovariectomy. Ten weeks after the operation, the resistance exercise group received 2 weeks of adaptive training, and 12 weeks of resistance exercise began in the 13th week. The rats were trained 5 days per week, in 4 sets of 3 repetitions per day. After the intervention, all rats were sacrificed, and the body weight, bone mineral density, trabecular bone microarchitecture, and bone biomechanics were examined. At the same time, RNA-seq and enrichment analysis of gene ontology and Kyoto Encyclopedia of Genes and Genomes were performed on the left tibias, followed by Elisa and RT-qPCR verification. It had been found that resistance exercise can effectively counteract the weight gain of ovariectomized osteoporotic rats, and has a good effect on bone mineral density and trabecular bone microarchitecture. Enrichment analysis showed that regulation of gene expression and osteoclast differentiation is the most closely related biological process and signaling pathway shared by RE/Ovx and NE/Ovx groups. Our results revealed that resistance exercise can play a role in inhibiting osteoclast activation and preventing the enhancement of osteoclast bone resorption function in ovariectomized osteoporotic rats by inhibiting Fos/Fosb-regulated TRAP activation and relieving Calcr inhibition, which has important application value in preventing bone loss caused by estrogen deficiency., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wang, Weng, Xu, Ye, Liang, Wang, Zhang, Gao, Wang, Xu, Sun and Xu.)

Background: Preclinical studies suggest that blueberry consumption is associated with improved bone health., Objectives: We conducted a blueberry dose-response study in ovariectomized (OVX)-rats that informed a study in postmenopausal women using the urinary appearance of calcium (Ca) tracers from prelabeled bone to reflect changes in bone balance. We hypothesized that blueberry consumption would reduce bone loss in a dose-dependent manner compared with no treatment., Methods: OVX rats were fed 4 doses of blueberry powder (2.5%, 5%, 10%, and 15%) in randomized order to determine bone 45 Ca retention. Fourteen healthy, nonosteoporotic women ≥4 y past menopause were dosed with 50 nCi of 41 Ca, a long-lived radioisotope, and equilibrated for 5 mo to allow 41 Ca deposition in bone. Following a 6-wk baseline period, participants were assigned to a random sequence of 3 6-wk interventions, a low (17.5 g/d), medium (35 g/d), or high (70 g/d) dose of freeze-dried blueberry powder equivalent to 0.75, 1.5, or 3 cups of fresh blueberries incorporated into food and beverage products. Urinary 41 Ca:Ca ratio was measured by accelerator mass spectrometry. Serum bone resorption biomarkers and urinary polyphenols were measured at the end of each control and intervention period. Data were analyzed using a linear mixed model and repeated measures analysis of variance., Results: In both OVX rats and postmenopausal women, blueberry interventions benefited net bone calcium balance at lower but not at higher doses. In women, net bone calcium retention increased by 6% with the low (95% CI: 2.50, 8.60; P < 0.01) and 4% with the medium (95% CI: 0.96, 7.90; P < 0.05) dose compared with no treatment. Urinary excretion of hippuric acid increased dose-dependently with blueberry consumption. No significant relationships were found between bone resorption biomarkers, 25-hydroxyvitamin D, and interventions., Conclusions: Moderate consumption (<1 cup/d) of blueberries may be an effective strategy to attenuate bone loss in healthy postmenopausal women. This trial was registered at clinicaltrials.gov as NCT02630797., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Physical activity (PA) is generally encouraged for the treatment of osteoporosis. However, epidemiological statistics on the level of physical activity required for bone health are scarce. The purpose of this research was to analyze the association between PA and total spine bone mineral density (BMD) in postmenopausal women., Methods: The research study included postmenopausal women aged ≥ 50 from the National Health and Nutrition Examination Survey. The metabolic equivalent (MET), weekly frequency, and duration of each activity were used to calculate PA. Furthermore, the correlations between BMD and PA were investigated by multivariable weighted logistic regression., Results: Eventually, 1681 postmenopausal women were included, with a weighted mean age of 62.27 ± 8.18 years. This study found that performing ≥ 38MET-h/wk was linked to a lower risk of osteoporosis after controlling for several covariates. Furthermore, the subgroup analysis revealed that the connection between total spine BMD and moderate-to-vigorous PA was more obvious among postmenopausal women aged < 65 years or individuals with normal BMI (< 25 kg/m 2 )., Conclusion: Physical activity ranging from moderate to vigorous was linked to higher total spine BMD in postmenopausal women., (© 2023. The Author(s).)

Background: Osteoporosis (OP) is one of the diseases that endanger the health of the elderly population. Klotho protein is a hormone with anti-aging effects. A few studies have discussed the relationship between Klotho and OP. However, there is still a lack of research on larger populations. This study aims to evaluate the association between OP and Klotho in American postmenopausal women., Methods: This is a retrospective study. We searched the National Health and Nutrition Examination Survey (NHANES) database and collected data of 3 survey cycles, finally involving 871 postmenopausal women over 50 years old in the present study. All participants took dual-energy X-ray absorptiometry examination and serum Klotho testing at the time of investigation. After adjusting the possible confounding variables, a multivariate regression model was employed to estimate the relationship between OP and Klotho proteins. Besides, the P for trend and restricted cubic spline (RCS) were applied to examine the threshold effect and calculate the inflection point., Results: Factors influencing the occurrence of OP included age, ethnicity, body mass index and Klotho levels. Multivariate regression analysis indicated that the serum Klotho concentration was lower in OP patients than that in participants without OP (OR[log 2 Klotho] = 0.568, P = 0.027). The C-index of the prediction model built was 0.765, indicating good prediction performance. After adjusting the above-mentioned four variables, P values for trend showed significant differences between groups. RCSs revealed that when the Klotho concentration reached 824.09 pg/ml, the risk of OP decreased drastically., Conclusion: Based on the analysis of the data collected from the NHANES database, we propose a correlation between Klotho and postmenopausal OP. A higher serum Klotho level is related to a lower incidence of OP. The findings of the present study can provide guidance for research on diagnosis and risk assessment of OP., (© 2023. The Author(s).)

Objective: This case-control study was to explore the effect of Bushen Zhuanggu tablet combined with routine regimen on bone mineral density (BMD) improvement, functional recovery, and fracture prevention in postmenopausal osteoporosis (PMOP) patients., Methods: 180 postmenopausal osteoporosis patients were randomly selected from communities A, B, and C cohorts as research subjects from January to May 2021. The study subjects were divided into three groups. The groups were in a 1 : 1 ratio according to the principles of nonrandomised, concurrent controlled trials, and methods. There were 60 participants in each group (group A, group B, and group C). Group A was treated with Bushen Zhuanggu tablet for antiosteoporosis + basic treatment (calcium supplement and vitamin D). Group C was given Bushen Zhuanggu tablet for antiosteoporosis intervention. Group B was given basic treatment (calcium supplement and vitamin D supplementation) as a control group. The follow-up time was 6 months after treatment. Finally, we compare the differences in calcium and phosphorus metabolism indexes, BMD, bone metabolism indexes, upper and lower limb muscle strength, and quality of life scores., Results: Group A, B, and C's effective rate was 98.33%, 80.00%, and 93.33%, respectively. The group A's effective rate was significantly higher than that in group B and C, and the difference was statistically significant ( P < 0.05). After 6 months intervention, the levels of serum Ca 2+ , serum phosphorus (P), serum creatinine (Cr), and parathyroid hormone (PTH) in 3 groups decreased. Ca, P, Scr, and PTH levels in group A were the lowest among study groups, and the difference was statistically significant ( P < 0.05). The increase in the BMD of lumbar spine, the left femoral neck, and Ward's triangle area of the three groups were observed with the highest data in group A. After 6 months of treatment, the levels of serum N-terminal propeptide of type I procollagen, PINP, and serum osteocalcin (OC) increased, while the levels of β -cross-linked C-terminal telopeptide of type I collagen ( β -CTX) and alkaline phosphatase (ALP) decreased in the three groups. The improvement of all bone metabolic indexes in group A was significantly better than that in B and C groups, and the difference was statistically significant ( P < 0.05). The enhanced upper limb muscle strength and the shorter standing-walking timing test (TUGT) time were observed after 6 months of treatment. The improvement effect of upper and lower limb muscle strength in group A was significantly better than that in B and C groups, and the difference was statistically significant ( P < 0.05). There were significant differences in physiological function, life function, general health status, physical pain, mental state, emotional function, vitality, and social function among the three groups after 6 months treatment, and the difference was statistically significant ( P < 0.05). The score of quality of life in group A was higher than that in B and C groups, and the difference was statistically significant ( P < 0.05)., Conclusion: Bushen Zhuanggu tablet combined with conventional therapy is effective in the postmenopausal osteoporosis treatment, which effectively increase the BMD, regulate calcium and phosphorus metabolism, promote the recovery of limb function, prevent the recurrence of fracture, and improve the patients' quality of life. This treatment scheme is worth popularizing., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2023 Tianliang Chen et al.)

The aim of this systematic review and meta-analysis was (1) to determine exercise effects on bone mineral density (BMD) in postmenopausal women and (2) to address the corresponding implication of bone and menopausal status or supervision in postmenopausal women. A comprehensive search of eight electronic databases according to the PRISMA statement up to August 9, 2022, included controlled exercise trials ≥ 6 months. BMD changes (standardized mean differences: SMD) at the lumbar spine (LS), femoral neck (FN), and total hip (TH) were considered as outcomes. Study group comparisons were conducted for osteopenia/osteoporosis versus normal BMD, early versus late postmenopausal women, and predominantly supervised versus predominantly non-supervised study arms. We applied an inverse heterogeneity (IVhet) model. In summary, 80 studies involving 94 training and 80 control groups with a pooled number of 5581 participants were eligible. The IVhet model determined SMDs of 0.29 (95% CI: 0.16-0.42), 0.27 (95% CI: 0.16-0.39), and 0.41 (95% CI: 0.30-0.52) for LS, FN, and THBMD, respectively. Heterogeneity between the trial results varied from low (I 2 = 20%, TH BMD) to substantial (I 2 = 68%, LS-BMD). Evidence for publication bias/small study effects was negligibly low (FN-, TH-BMD) to high (LSBMD). We observed no significant differences (p > .09) for exercise effects on LS-, FN-, or TH-BMD-LS between studies/study arms with or without osteopenia/osteoporosis, early versus late postmenopausal women, or predominantly supervised versus non-supervised exercise programs. Using robust statistical methods, the present work provides further evidence for a positive effect of exercise on BMD in postmenopausal women. Differences in bone status (osteopenia/osteoporosis versus normal bone), menopausal status (early versus late postmenopausal), and supervision (yes versus no) did not significantly affect the exercise effects on BMD at LS or proximal femur., (© 2023. The Author(s).)

Postmenopausal osteoporosis, an epidemic disorder is defined as a loss in bone mineral density and a greater possibility of fractures in older women. It is a multifactorial disease under the control of various genetic, hormonal, and environmental factors. Insufficiency of estrogen hormone, leads to postmenopausal osteoporosis. Hormone replacement therapy (HRT), despite being the most effective treatment, it is associated with the risk of breast cancer and cardiovascular disorders. This review seeks to compile the most recent information on medicinal plants and natural compounds used to treat and prevent postmenopausal osteoporosis. Furthermore, the origin, chemical constituents and the molecular mechanisms responsible for this therapeutic and preventive effect are also discussed. Literature research was conducted using PubMed, Science direct, Scopus, Web of Science, and Google Scholar. Different plant extracts and pure compounds exerts their antiosteoporotic activity by inhibition of RANKL and upregulation of OPG. RANKL signaling regulates osteoclast formation, characterized by increased bone turnover and osteoprotegrin is a decoy receptor for RANKL thereby preventing bone loss from excessive resorption. In addition, this review also includes the chemical structure of bioactive compounds acting on NFκB, TNF α, RUNX2. In conclusion, we propose that postmenopausal osteoporosis could be prevented or treated with herbal products., Competing Interests: Declaration of Competing Interest The authors declares no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

This study assessed whether vitamin K, given with oral bisphosphonate, calcium and/or vitamin D has an additive effect on fracture risk in post-menopausal women with osteoporosis. No difference in bone density or bone turnover was observed although vitamin K 1 supplementation led to a modest effect on parameters of hip geometry., Purpose: Some clinical studies have suggested that vitamin K prevents bone loss and may improve fracture risk. The aim was to assess whether vitamin K supplementation has an additive effect on bone mineral density (BMD), hip geometry and bone turnover markers (BTMs) in post-menopausal women with osteoporosis (PMO) and sub-optimum vitamin K status receiving bisphosphonate, calcium and/or vitamin D treatment., Methods: We conducted a trial in 105 women aged 68.7[12.3] years with PMO and serum vitamin K 1  ≤ 0.4 µg/L. They were randomised to 3 treatment arms; vitamin K 1 (1 mg/day) arm, vitamin K 2 arm (MK-4; 45 mg/day) or placebo for 18 months. They were on oral bisphosphonate and calcium and/or vitamin D. We measured BMD by DXA, hip geometry parameters using hip structural analysis (HSA) software and BTMs. Vitamin K 1 or MK-4 supplementation was each compared to placebo. Intention to treat (ITT) and per protocol (PP) analyses were performed., Results: Changes in BMD at the total hip, femoral neck and lumbar spine and BTMs; CTX and P1NP did not differ significantly following either K 1 or MK-4 supplementation compared to placebo. Following PP analysis and correction for covariates, there were significant differences in some of the HSA parameters at the intertrochanter (IT) and femoral shaft (FS): IT endocortical diameter (ED) (% change placebo:1.5 [4.1], K 1 arm: -1.02 [5.07], p = 0.04), FS subperiosteal/outer diameter (OD) (placebo: 1.78 [5.3], K 1 arm: 0.46 [2.23] p = 0.04), FS cross sectional area (CSA) (placebo:1.47 [4.09],K 1 arm: -1.02[5.07], p = 0.03)., Conclusion: The addition of vitamin K 1 to oral bisphosphonate with calcium and/or vitamin D treatment in PMO has a modest effect on parameters of hip geometry. Further confirmatory studies are needed., Trial Registration: The study was registered at Clinicaltrial.gov:NCT01232647., (© 2023. The Author(s).)

Wnt signaling is a positive regulator of bone formation through the induction of osteoblast differentiation and down-regulation of osteoclast differentiation. We previously reported that muramyl dipeptide (MDP) increases bone volume by increasing osteoblast activity and attenuating osteoclast activity in receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoporotic model mice. In this study, we investigated whether MDP could alleviate post-menopausal osteoporosis through Wnt signaling regulation in an ovariectomy (OVX)-induced mouse osteoporosis model. MDP-administered OVX mice exhibited higher bone volume and bone mineral density than mice of the control group. MDP significantly increased P1NP in the serum of OVX mice, implying increased bone formation. The expression of pGSK3β and β-catenin in the distal femur of OVX mice was lower than that in the distal femur of sham-operated mice. Yet, the expression of pGSK3β and β-catenin was increased in MDP-administered OVX mice compared with OVX mice. In addition, MDP increased the expression and transcriptional activity of β-catenin in osteoblasts. MDP inhibited the proteasomal degradation of β-catenin via the down-regulation of its ubiquitination by GSK3β inactivation. When osteoblasts were pretreated with Wnt signaling inhibitors, DKK1 or IWP-2, the induction of pAKT, pGSK3β, and β-catenin was not observed. In addition, nucleotide oligomerization domain-containing protein 2-deficient osteoblasts were not sensitive to MDP. MDP-administered OVX mice exhibited fewer tartrate-resistant acid phosphatase (TRAP)-positive cells than did OVX mice, attributed to a decrease in the RANKL/OPG ratio. In conclusion, MDP alleviates estrogen deficiency-induced osteoporosis through canonical Wnt signaling and could be an effective therapeutic for the treatment of post-menopausal bone loss. © 2023 The Pathological Society of Great Britain and Ireland., (© 2023 The Pathological Society of Great Britain and Ireland.)

Objective: This study aimed to evaluate the associations of hormone preparations with lumbar spine bone mineral density (BMD), osteopenia, and osteoporosis in postmenopausal women, and whether these impacts persisted after hormone preparations were discontinued., Methods: A total of 6,031 postmenopausal women were enrolled and divided into seven groups based on the types of hormone preparations. Among them, 1,996 participants were further divided into a current users (CU) group and a past users (PU) group. Multivariable linear regression models or logistic regression models were used to evaluate the associations of hormone preparation with lumbar spine BMD, osteopenia, and osteoporosis., Results: Combined oral contraceptive pills, estrogen-only pills, estrogen/progestin combo pills, estrogen-only patches, or the use of more than two kinds of hormone preparations were positively associated with lumbar spine BMD (all P < 0.05). Except for estrogen-only patches, other hormone preparations also had a protective effect against osteopenia (all OR < 1, all P < 0.05), but none of them were associated with osteoporosis prevalence (all P > 0.05). The BMD increased by 0.10 and 0.04 g/cm 2 in the CU and PU groups, respectively, compared with the nonusers group (all P < 0.05). In both the CU and PU groups, the risk of osteopenia was reduced (OR, 0.34 and 0.57, respectively)., Conclusions: Hormone preparations increase lumbar spine BMD in postmenopausal women and exert a protective effect against osteopenia. These impacts persisted after hormone preparations were discontinued. Hormone preparations, however, were not associated with osteoporosis prevalence., Competing Interests: Financial disclosure/conflicts of interest: None reported., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The North American Menopause Society.)

Objective: Osteoporosis is a skeletal disease characterized by low bone mass, reduced bone strength, and increased fracture risk. We aimed to investigate the association between combined dietary antioxidant intake and the likelihood of osteoporosis in premenopausal and postmenopausal women, based on data from the National Health and Nutrition Examination Survey., Methods: Nutrient intake data were obtained using two 24-hour recalls. Composite dietary antioxidant index (CDAI), which refers to the intake amounts of β-carotene, vitamin A, vitamin C, vitamin E, selenium, zinc, copper, and iron, was then constructed. Prevalent osteoporosis was defined according to bone mineral density T scores of ≤ -2.5 and self-reports. Multiple logistic and Poisson regression models were used for association analyses., Results: A total of 3,418 participants (1,157 premenopausal and 2,261 postmenopausal women) 40 years or older were included, 776 (22.70%) of whom had prevalent osteoporosis. In terms of individual nutrients, postmenopausal women in the highest CDAI quartiles for dietary β-carotene, vitamin A, vitamin C, and iron intakes had a low likelihood of osteoporosis. Regarding the CDAI-osteoporosis association, postmenopausal women in the highest quartile were less likely to have osteoporosis (OR Q3 vs Q1 , 0.64; 95% CI, 0.43-0.96; OR Q4 vs Q1 , 0.56; 95% CI, 0.35-0.89; P for trend = 0.013), after controlling for covariates., Conclusions: CDAI was negatively associated with the likelihood of osteoporosis in postmenopausal women. Our findings suggest that the combined intake of antioxidant nutrients can help reduce the likelihood of osteoporosis in women., Competing Interests: Financial disclosure/conflicts of interest: None reported., (Copyright © 2023 by The North American Menopause Society.)

Objective: This study evaluated the cost effectiveness of denosumab versus alendronate for secondary prevention of osteoporotic fractures among post-menopausal women in China., Methods: A validated individual-level simulation model of osteoporotic fractures in the Chinese setting was adapted. Allowing both treatment discontinuation and waning effects, the analysis aimed to evaluate the incremental cost-effectiveness ratio of denosumab compared to alendronate by simulating a cohort of previously fractured individuals over the residual lifetime from the healthcare system perspective. Hip, vertebral, and wrist/humeral fractures were tracked along with the associated medical costs and quality-adjusted life-years. Age-related health state utility values, health state utility values of fractures, costs, fracture incidence, and mortality risks for Chinese were used whenever available. Comparative effectiveness data were obtained from a published network meta-analysis. One-way and probabilistic sensitivity analyses were conducted., Results: In the base case, denosumab was dominated by alendronate with incremental costs of CN¥2743 (US$425) and incremental health outcomes of - 0.20 quality-adjusted life-years at its current price in mainland China. It remained dominated in all one-way sensitivity analysis robustness checks. However, denosumab was cost effective if both drugs did not carry any waning effects. In the probabilistic sensitivity analysis, denosumab remained dominated in all replications., Conclusions: Denosumab is not cost effective for preventing secondary fractures among overall postmenopausal women in China. It is advisable to identify alternative denosumab regimens for high-risk subgroups among previously fractured postmenopausal women., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

The main objective of this work was to explore the association of dietary phytate intake with bone mineral density (BMD) in a Mediterranean population of postmenopausal women. For this purpose, a cross-sectional analysis of 561 women aged 55-75 years with overweight/obesity and metabolic syndrome from a Mediterranean area and with data on dual-energy X-ray absorptiometry (DXA) scans in femur and lumbar spine was performed. Estimated phytate intake was calculated using a validated food frequency questionnaire. Our results indicated that phytate intake was associated with BMD [β(95%CI) per each 25 mg/100 kcal] in femoral neck [0.023(0.060-0.040) g/cm 2 ], femoral Ward's triangle [0.033(0.013-0.054) g/cm 2 ], total femur [0.018(0.001-0.035) g/cm 2 ], and all the analyzed lumbar spine sites [L1-L4: 0.033(0.007-0.059) g/cm 2 ] after adjusting for potential confounders. The sensitivity analysis showed that phytate intake was directly associated with lumbar spine BMD in women younger than 66 years, with a body mass index higher than 32.6 kg/cm 2 and without type 2 diabetes (all p -for interactions < 0.05). The overall results indicated that phytate, a substance present in food as cereals, legumes and nuts, was positively associated with BMD in Mediterranean postmenopausal women. Phytate may have a protective effect on bone resorption by adsorbing on the surfaces of HAP. Nevertheless, large, long-term, and randomized prospective clinical studies must be performed to assess the possible benefits of phytate consumption on BMD in postmenopausal women.

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.

Osteoporosis is a prevalent issue among postmenopausal women, who have a higher incidence of the condition than men. This study aimed to examine the relationship between phytochemical-rich food intake and osteoporosis incidence in premenopausal and postmenopausal women. The data analyzed included 4600 women aged 40-69 who were free of osteoporosis at baseline, with dietary intake evaluated through a semi-quantitative food frequency questionnaire and osteoporosis prevalence determined using interviewer-administered questionnaires and bone mineral density tests. The phytochemical index (PI) was calculated to reflect the intake levels of phytochemical-rich foods. Postmenopausal women in the highest PI quartile had a 16% lower risk of osteoporosis (95% confidence interval (CI): 0.71 to 0.99, p for trend = 0.02) than those in the lowest quartile, while no significant association was observed among premenopausal women (hazard ratio: 0.98, 95% CI: 0.78 to 1.24, p for trend = 0.8). These findings suggest that consuming phytochemical-rich foods may have a protective effect against osteoporosis in postmenopausal women, offering valuable scientific insights. However, additional research is needed to validate these findings using biochemical data. Overall, this study highlights the potential of dietary interventions to reduce the risk of osteoporosis in postmenopausal women.