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A retrospective study of 121 patients who stopped denosumab (Dmab) then received no treatment (NT), risedronate (RIS), alendronate (ALN), or zoledronic acid (ZOL). Bone density (spine and hip) during and after Dmab discontinuation was measured. Treatment with ALN or ZOL, not NT and RIS, mitigated BMD loss after Dmab discontinuation., Introduction: Denosumab (Dmab) discontinuation is associated with bone loss and multiple vertebral fractures. The purpose was to compare bone mineral density (BMD) change in patients following Dmab discontinuation with no subsequent treatment (NT) and three bisphosphonate (BP) treatments: risedronate (RIS), alendronate (ALN), and zoledronic acid (ZOL)., Methods: In a review of 121 patients aged 71.2 ± 8.1 years, discontinuing Dmab (mean 5.4 doses), 33 received NT and 88 received BP (22 RIS; 34 ALN; 32 ZOL). BMD change after 1 year was compared between groups at the lumbar spine (LS), femoral neck (FN), and total hip (TH). Risk factors for bone loss after Dmab discontinuation were compared between groups and incidence of vertebral fractures was determined., Results: Following Dmab discontinuation, LS mean change (g/cm 2 ; 95% CI) was for NT: - 0.041 (- 0.062 to - 0.021); RIS: - 0.035 (- 0.052 to - 0.017); ALN: - 0.005 (- 0.020 to 0.009); and ZOL: - 0.009 (- 0.025 to 0.008). Differences in LS were found between NT and ALN (p =  0.015), and NT and ZOL (p=0.037), but not between NT and RIS. The only significant difference in TH was found between NT and ZOL (p 0.034) with no group differences in FN. BMD gains during Dmab treatment were associated with BMD loss after Dmab discontinuation. In a subset, discontinuation after Dmab treatment (> 5 doses) followed by ALN (n = 22) and ZOL (n = 11) showed no difference in BMD. Five of 7 vertebral fractures occurred after Dmab discontinuation in NT., Conclusion: Subsequent treatment with ALN or ZOL but not NT and RIS mitigates BMD loss after Dmab discontinuation., (© 2023. The Author(s).)

Background: Percutaneous vertebroplasty was the most common strategy for osteoporotic vertebral compression fracture. However, refracture after vertebroplasty also occurred and bone mineral density (BMD) was one of the main factors associated with refracture after percutaneous vertebroplasty., Aims: To investigate the efficacy of a short-sequential treatment of teriparatide followed by alendronate on prevention of refracture after percutaneous vertebroplasty in osteoporotic patients, and compare it with the therapy of alendronate alone., Methods: From January 2018 to January 2020, we recruited 165 female osteoporosis patients after percutaneous vertebroplasty who were assigned into sequential treatment of teriparatide followed by alendronate group (TPTD + ALN group) and alendronate alone group (ALN group). The vertebral fracture occurred during this process was also recorded in both the groups. A total of 105 participants completed the 1-year follow-up. Furthermore, BMD and serum procollagen type I N-terminal propeptide (PINP) and C-terminal cross-linking telopeptide of type I collagen (CTX) were compared between the two groups during 1-year follow-up., Results: The 105 patients were finally included, with 59 in ALN group and 46 in TPTD + ALN group. During 1-year follow-up, the vertebral refracture rate in TPTD + ALN group was much lower than that in ALN group (2.2% vs. 13.6%, p < 0.05). At 12 months, the BMDs at lumbar in TPTD + ALN group were significantly elevated when compared to the ALN group (0.65 ± 0.10 vs. 0.57 ± 0.07, p < 0.001)., Discussion and Conclusion: A short-sequential administration of teriparatide followed by alendronate was more effective in elevating the BMD and decreasing the refracture rate at 12-month follow-up, compared to the counterpart with alendronate alone., (© 2023. The Author(s).)

Purpose: The immunomodulatory properties of n-3 long chain polyunsaturated fatty acids (LCPUFA) are reported to reduce bone loss through alteration of bone remodelling and n-3 LCPUFA, therefore, may benefit bone health in post-menopausal women, a vulnerable group at high risk of osteoporosis., Methods: Measures of bone mineral density (BMD) were determined using dual energy X-ray absorptiometry (DEXA) in 300 post-menopausal women. The bone turnover markers osteocalcin (OC), C-terminal telopeptides of type 1 collagen (CTX) and total alkaline phosphatase were quantified in serum along with urinary creatinine corrected deoxypyridinoline (DPD/Cr) and CTX/Cr and the CTX:OC ratio calculated. Total serum n-6 PUFA (LA + AA) and n - 3 LCPUFA (ALA + EPA + DPA + DHA) were measured and the n - 6:n - 3 ratio was calculated., Results: Mean (SD) age and body mass index (BMI) were 61 (6.4) years and 27.4 (4.8) kg/m 2 , respectively with participants being 12.6 (7.6) years post-menopause. Multiple regression analysis identified no association between n-3 LCPUFA and any of the measures of T-score or BMD albeit a significant positive association between total n - 3 LCPUFA and femur BMD (β = 0.287; p = 0.043) was observed within those women with a low n - 6:n - 3 ratio. There was a significant inverse association between ALA and urinary DPD/Cr (β = - 0.141; p = 0.016)., Conclusion: A favourable low n - 6:n - 3 ratio was associated with higher femur BMD and a higher n - 3 LCPUFA (ALA) was associated with lower bone resorption. These results support a beneficial role for n - 3 LCPUFA in reducing postmenopausal bone resorption and favourably influencing BMD., Trial Number & Date of Registration: ISRCTN63118444, 2nd October 2009, "Retrospectively registered"., (© 2022. The Author(s).)

Backgroud: Estrogen deficiency is the leading cause of postmenopausal osteoporosis(PMOP) and phytoestrogens soy isoflavones (SI) have been shown to improve PMOP. Equol (Eq), an in vivo metabolite of phytoestrogens soy isoflavones (SI), has a more stable structure and stronger biological activity than its parent compound and has the greatest estrogenic activity. However, there are few studies on the therapeutic effect of Eq on PMOP., Purpose: To explore the therapeutic effect and mechanisms of Eq on POMP., Methods: Osteoblast-like cells ROS1728 were cultured with different doses of Eq, estradiol (E2), separately. The effect of Eq on the proliferation, apoptosis, cell cycle of osteoblasts were detected by CCK-8 and flow cytometry, and the expression of OPG/RANK/RANKL signaling pathway of osteoblasts was detected by Quantitative real-time PCR (qRT-PCR) and Western blot (WB), and RNA silencing technology were carried out to explore the receptors through which Eq plays a role. Then PMOP rat model was established and treated by Eq or E2 to further verification of the effect and mechanism of Eq on PMOP., Result: Eq promoted the proliferation and inhibited the apoptosis of osteoblasts and increased the proportion of osteoblasts in the S phase and G2/M phase in a dose-dependent manner. Mechanistically, Eq treatment upregulated the expression of OPG and OPG/RANKL ratio in osteoblasts and this regulatory effect was mainly mediated through the ERβ receptor. Furthermore, in vivo study, Eq improved microstructure and BMD of the femur of PMOP rat model, which imitated the osteoprotective effect of E2. Moreover, the Eq or E2 treatment increased serum levels of Ca, 1,25(OH)2D3, bone Gla-protein(BGP), and Type I procollagen (PC1), and reduced serum levels of phosphorus (P), parathyroid hormone(PTH), pyridinol (PYD), tartrate-resistant acid phosphatase (TRAP) and urinary level of deoxypyridinoline (DPD) in the treatment OVX group compared with the untreated OVX group. Meanwhile, Eq or E2 markedly induced the mRNA and protein expression of OPG and OPG/RANKL ratio., Conclusion: Eq can combine with ERβ and exert a protective effect on PMOP by upregulating OPG/RANKL pathway., Competing Interests: Declarations of 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 © 2022 The Authors. Published by Elsevier GmbH.. All rights reserved.)

The present study observed significant effects of whole-body vibration (WBV) on bone mineral density (BMD) in postmenopausal women, with high-quality evidence for high-frequency, low-magnitude, and high-cumulative-dose use. The aim was to update a previous systematic review with meta-analysis to observe the effects of WBV on BMD in postmenopausal women. For the meta-analysis, the weighted mean difference between WBV and control groups, or WBV and conventional exercise, was used for the area of bone mineral density (aBMD) of the lumbar spine, femoral neck, total hip, trochanter, intertrochanter, and Ward's area, or volumetric trabecular bone mineral density (vBMDt) of the radius and tibia. Methodological quality was assessed using the PEDro scale and the quality of evidence using the GRADE system. In total, 23 studies were included in the systematic review and 20 in the meta-analysis. Thirteen studies showed high methodological quality. WBV compared with control groups showed significant effects on aBMD in the primary analysis (lumbar spine and trochanter), sensitivity (lumbar spine), side-alternating vibration (lumbar spine and trochanter), synchronous vibration (lumbar spine), low frequency and high magnitude (lumbar spine and trochanter), high frequency and low magnitude (lumbar spine), high frequency and high magnitude (lumbar spine, trochanter, and Ward's area), high cumulative dose and low magnitude (lumbar spine), low cumulative dose and high magnitude (lumbar spine and trochanter), and positioning with semi-flexed knees (trochanter). Of these results, only high frequency associated with low magnitude and high cumulative dose with low magnitude showed high-quality evidence. At this time, considering the high quality of evidence, it is possible to recommend WBV using high frequency (≈ 30 Hz), low magnitude (≈ 0.3 g), and high cumulative dose (≈ 7000 min) to improve lumbar spine aBMD in postmenopausal women. Other parameters, although promising, need to be better investigated, considering, when applicable, the safety of the participants, especially in vibrations with higher magnitudes (≥ 1 g)., (© 2022. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

Postmenopausal women are at significant risk for osteoporotic fractures due to their rapid bone loss. Half of all postmenopausal women will get an osteoporosis-related fracture over their lifetime, with 25% developing a spine deformity and 15% developing a hip fracture. By 2050, more than half of all osteoporotic fractures will occur in Asia, with postmenopausal women being the most susceptible. Early management can halt or even reverse the progression of osteoporosis. Consequently, on October 31, 2020, the Taiwanese Osteoporosis Association hosted the Asia-Pacific (AP) Postmenopausal Osteoporotic Fracture Prevention (POFP) consensus meeting, which was supported by the Asian Federation of Osteoporosis Societies (AFOS) and the Asia Pacific Osteoporosis Foundation (APOF). International and domestic experts developed ten applicable statements for the prevention of osteoporotic fractures in postmenopausal women with low bone mass or osteoporosis but no fragility fractures in the AP region. The experts advocated, for example, that postmenopausal women with a high fracture risk be reimbursed for pharmaceutical therapy to prevent osteoporotic fractures. More clinical experience and data are required to modify intervention tactics., Competing Interests: Declaration of competing interest Chih-Hsing Wu received honoraria for lectures, attending meetings, and/or travel from Eli Lilly, Roche, Amgen, Merck, Servier laboratories, GE Lunar, Harvester, TCM Biotech, and Alvogen/Lotus. E Michael Lewiecki is an investigator, consultant, and speaker for Amgen, and an investigator for Radius., (Copyright © 2023 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Introduction: Postmenopausal osteoporosis, caused by ageing and oestrogen deficiency, seriously threatens women's physical and mental health. Postmenopausal osteopenia is the transition from healthy bone to osteoporosis, and it may be the key period for preventing bone loss. Moxibustion, a physical therapy of Traditional Chinese Medicine, has potential benefits for osteoporosis treatment and prevention, but it has not been adequately studied. This study aims to explore the clinical effects and safety of moxibustion in delaying bone loss in postmenopausal women., Methods and Analysis: In this parallel-design, randomised, patient-blind and assessor-blind, controlled clinical study, 150 women with osteopenia at low fracture risk will be randomly assigned to a moxibustion treatment (MT) group or a placebo-moxibustion control (PMC) group in a 1:1 ratio. In addition to the fundamental measures (vitamin D3 and calcium) as recommended by the guidelines, participants of the two groups will receive MT or PMC treatment for 42 sessions over 12 months. The primary outcome will be the bone mineral density (BMD) of the lumbar spine at the end of the 12-month treatment, and secondary outcomes will be the BMD of the femoral neck and total hip, T-scores, bone turnover markers, serum calcium levels, serum magnesium levels, serum phosphorus levels, serum parathyroid hormone levels and 25-hydroxyvitamin D levels, intensity of bone pain, quality of life, incidence of osteoporosis and fractures, usage of emergency drugs or surgery, participant self-evaluation of therapeutic effects and the rate of adverse events. All statistical analyses will be performed based on the intention-to-treat and per-protocol principle., Ethics and Dissemination: Ethics approval has been obtained from the Ethics Committee on Biomedical Research, West China Hospital of Sichuan University (permission number: 2021-1243). The results are expected to be published in peer-reviewed journals., Trial Registration Number: ChiCTR2100053953., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Context: Ferulic acid ethyl ester (FAEE) is abundant in Ligusticum chuanxiong Hort. (Apiaceae) and grains, and possesses diverse biological activities; but the effects of FAEE on osteoporosis has not been reported., Objective: This study investigated whether FAEE can attenuate osteoclastogenesis and relieve ovariectomy-induced osteoporosis via attenuating mitogen-activated protein kinase (MAPK)., Materials and Methods: We stimulated RAW 264.7 cells with receptor activator of NF-κB ligand (RANKL) followed by FAEE. The roles of FAEE in osteoclast production and osteogenic resorption of mature osteoclasts were evaluated by tartrate resistant acid phosphatase (TRAP) staining, expression of osteoclast-specific genes, proteins and MAPK. Ovariectomized (OVX) female Sprague-Dawley rats were administered FAEE (20 mg/kg/day) for 12 weeks to explore its potential in vivo , and then histology was undertaken in combination with cytokines analyses., Results: FAEE suppressed RANKL-induced osteoclast formation (96 ± 0.88 vs. 15 ± 1.68) by suppressing the expression of osteoclast-specific genes, proteins and MAPK signalling pathway related proteins (p-ERK/ERK, p-JNK/JNK and p-P38/P38) in vitro . In addition, OVX rats exposed to FAEE maintained their normal calcium (Ca) (2.72 ± 0.02 vs. 2.63 ± 0.03, p  < 0.05) balance, increased oestradiol levels (498.3 ± 9.43 vs. 398.7 ± 22.06, p  < 0.05), simultaneously reduced levels of bone mineral density (BMD) (0.159 ± 0.0016 vs. 0.153 ± 0.0025, p  < 0.05) and bone mineral content (BMC) (0.8 ± 0.0158 vs. 0.68 ± 0.0291, p  < 0.01)., Discussion and Conclusions: These findings suggested that FAEE could be used to ameliorate osteoporosis by the MAPK signalling pathway, suggesting that FAEE could be a potential therapeutic candidate for osteoporosis.

Osteoporosis is a common condition in which deteriorating bone tissue results in an increased risk of low trauma fracture. Influenced by the role of estrogen in building and maintaining bone mineral density, women have different patterns of bone accrual and loss compared with men, resulting in a lower peak bone mass and a greater lifetime fracture risk. Moreover, fracture risk increases significantly in postmenopausal women who have depleted estrogen levels. Osteoporotic fractures pose serious consequences-ranging from an inability to perform basic tasks and an increased risk of repeat fracture to the need for assisted living and even death. There is also a large economic toll associated with the health care costs required for post-fracture care. The Society for Women's Health Research (SWHR) convened an interdisciplinary Bone Health Working Group to review the current state of science and practice concerning women's bone health and osteoporosis care and to explore strategies to address gaps in screening, diagnosis, and treatment of bone disease in women. Women's bone health care must shift its paradigm from one of postmenopausal and post-fracture care to a preventive model that engages touchpoints throughout the lifespan. To achieve this paradigm shift, the Working Group recommends prioritizing efforts to build public awareness and clinical education of preventive bone health care for women, increase access to screening tools, improve patient-provider communication, and treat osteoporosis using a broader risk stratification approach.

Beneficial effects of blackcurrant supplementation on bone metabolism in mice has recently been demonstrated, but no studies are available in humans. The current study aimed to examine the dose-dependent effects of blackcurrant in preventing bone loss and the underlying mechanisms of action in adult women. Forty peri- and early postmenopausal women were randomly assigned into one of three treatment groups for 6 months: (1) a placebo (control group, n = 13); (2) 392 mg/day of blackcurrant powder (low blackcurrant, BC, group, n = 16); and (3) 784 mg/day of blackcurrant powder (high BC group, n = 11). The significance of differences in outcome variables was tested by repeated-measures ANOVA with treatment and time as between- and within-subject factors, respectively. Overall, blackcurrant supplementation decreased the loss of whole-body bone mineral density (BMD) compared to the control group (p < 0.05), though the improvement of whole-body BMD remained significant only in the high BC group (p < 0.05). Blackcurrant supplementation also led to a significant increase in serum amino-terminal propeptide of type 1 procollagen (P1NP), a marker of bone formation (p < 0.05). These findings suggest that daily consumption of 784 mg of blackcurrant powder for six months mitigates the risk of postmenopausal bone loss, potentially through enhancing bone formation. Further studies of larger samples with various skeletal conditions are warranted to confirm these findings.

Lophatherum gracile Bronghiart, used in traditional herbal medicine, has many biological properties including antiviral, antipyretic, antitumor, vasorelaxation, and neutrophilic inflammatory effects. However, its modulatory effects on bone metabolism have not been investigated previously. In this study, we examined the effects of a water extract of the leaves of L. gracile (WELG) on osteoclast differentiation and bone loss, and explored its underlying mechanisms. We found that WELG inhibits osteoclastogenesis by suppressing both receptor activator of nuclear factor-κB ligand (RANKL)-induced early activation of mitogen-activated protein kinases (MAPKs) and nuclear factor-κB (NF-κB)- and RANKL-induced modulation of the positive and negative regulators of osteoclastogenesis in osteoclast precursors. In vivo study demonstrated that WELG protects against bone loss, weight gain, and fat accumulation without affecting uterine atrophy in an ovariectomy-induced postmenopausal osteoporosis mice model. In addition, photochemical analysis of WELG identified active constituents known to have bone-protective effects. Overall, the results of this study suggest that WELG can be a potential candidate for therapy and prevention of postmenopausal osteoporosis.

Objectives: Osteoporosis is increasingly prevalent, especially among postmenopausal women, both in China and worldwide. In previous work, soy-whey dual-protein (DP) intervention improved muscle status via regulation of gut microbiota. However, little information is available about the relationship between DP supplementation and osteoporosis., Methods: In this study, the ovariectomized rat model was used to detect the effect of DP on improving osteoporosis., Results: Significant improvement was observed in bone mineral density, bone microstructure, and bone biomechanics with both DP and zoledronic acid (positive control) intervention. DP supplementation dramatically reduced the levels of serum osteocalcin and parathyroid hormone in ovariectomized rats. Ingestion of DP also resulted in a significant decrease in the number of bone marrow adipocytes and a marked increase in the number of osteoblasts, accompanied by elevated expression of the key regulator osteoprotegerin at both mRNA and protein levels. In the analysis of fecal metabolites and intestinal microbiota, the fat metabolism-related molecules chenodeoxycholate, 21-hydroxypregnenolone, and tetrahydrocorticosterone were markedly upregulated with DP treatment, whereas the content of fatty acids such as oleic acid were significantly downregulated. The abundance of three bacterial taxa (upregulated: Ruminococcaceae UCG&#95;002; downregulated: anaerobic digester metagenome and Enterorhabdus) dramatically changed with DP intervention and was closely associated with fat metabolism-related metabolite content CONCLUSION: These results suggest that DP intervention could improve osteoporosis via regulation of bone marrow adipose tissue content and mesenchymal stem cell lineage differentiation. Furthermore, this effect might be mediated by the interaction between intestinal microbiota and metabolites., (Copyright © 2022. Published by Elsevier Inc.)

Purpose: Osteopenia is common in postmenopausal women and effective interventions increasing or stabilizing bone mineral density (BMD) to prevent fractures are urgently needed., Methods: Sixty-five postmenopausal women diagnosed with osteopenia (T-score between -1.0 and -2.5) were randomly assigned to either a vibration training group (VT), a resistance training group (RT), or a control group (CG). BMD T-score values (primary endpoint) were assessed at baseline (T0) and after 12 months (T12), secondary endpoints (muscle strength, postural control, and health-related quality of life) at baseline (T0), after 6 months (T6), after 12 months (T12), and as follow-up after 15 months (T15)., Results: After the intervention period, neither the VT nor the RT showed any significant changes in BMD T-score values compared to the CG. Isokinetic strength improved significantly within all training groups, with the exception of the flexors of VT at an angular velocity of 240°/s. Health-related quality of life as well as postural control improved significantly for the RT only., Conclusions: We conclude that participants of all three groups were able to maintain their BMD. The improvements in quality of life and postural control after resistance training are nevertheless meaningful for postmenopausal osteopenic women and support the importance of regular loadings of the musculoskeletal system. This study was retrospectively registered in January 2022 at the DRKS (S00027816) as clinical trial., (© 2022. The Author(s).)

Background: Dietary consumption of prunes has favorable impacts on bone health, but more research is necessary to improve upon study designs and refine our understandings., Objectives: We evaluated the effects of prunes (50 g or 100 g/d) on bone mineral density (BMD) in postmenopausal women during a 12-mo dietary intervention. Secondary outcomes include effects on bone biomarkers., Methods: The single-center, parallel-arm 12-mo randomized controlled trial tested the effects of 50 g and 100 g prunes compared with a control group on BMD (every 6 mo) and bone biomarkers in postmenopausal women., Results: In total, 235 women (age 62.1 ± 5.0 y) were randomly allocated into control (n = 78), 50-g prune (n = 79), or 100-g prune (n = 78) groups. Compliance was 90.2 ± 1.8% and 87.1 ± 2.1% in the 50-g and 100-g prune groups. Dropout was 22%; however, the dropout rate was 41% for the 100-g prune group (compared with other groups: 10%, control; 15%, 50 g prune; P < 0.001). A group × time interaction for total hip BMD was observed in control compared with 50-g prune groups (P < 0.05) but not in control compared with 100-g prune groups (P > 0.05). Total hip BMD decreased -1.1 ± 0.2% in the control group at 12 mo, whereas the 50-g prune group preserved BMD (-0.3 ± 0.2%) at 12 mo (P < 0.05). Although hip fracture risk (FRAX) worsened in the control group at 6 mo compared with baseline (10.3 ± 0.5% compared with 9.8 ± 0.5%, P < 0.05), FRAX score was maintained in the pooled (50 g + 100 g) prune groups., Conclusions: A 50-g daily dose of prunes can prevent loss of total hip BMD in postmenopausal women after 6 mo, which persisted for 12 mo. Given that there was high compliance and retention at the 50-g dosage over 12 mo, we propose that the 50-g dose represents a valuable nonpharmacologic treatment strategy that can be used to preserve hip BMD in postmenopausal women and possibly reduce hip fracture risk. This trial was registered at clinicaltrials.gov as NCT02822378., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.)

The prevalence of osteoporosis among women aged 50 y and older is expected to reach 13.6 million by 2030. Alternative nonpharmaceutical agents for osteoporosis, including nutritional interventions, are becoming increasingly popular. Prunes (dried plums; Prunus domestica L.) have been studied as a potential whole-food dietary intervention to mitigate bone loss in preclinical models of osteoporosis and in osteopenic postmenopausal women. Sixteen preclinical studies using in vivo rodent models of osteopenia or osteoporosis have established that dietary supplementation with prunes confers osteoprotective effects both by preventing and reversing bone loss. Increasing evidence from 10 studies suggests that, in addition to antiresorptive effects, prunes exert anti-inflammatory and antioxidant effects. Ten preclinical studies have found that prunes and/or their polyphenol extracts decrease malondialdehyde and NO secretion, increase antioxidant enzyme expression, or suppress NF-κB activation and proinflammatory cytokine production. Two clinical trials have investigated the impact of dried plum consumption (50-100 g/d for 6-12 mo) on bone health in postmenopausal women and demonstrated promising effects on bone mineral density and bone biomarkers. However, less is known about the impact of prune consumption on oxidative stress and inflammatory mediators in humans and their possible role in modulating bone outcomes. In this review, the current state of knowledge on the relation between inflammation and bone health is outlined. Findings from preclinical and clinical studies that have assessed the effect of prunes on oxidative stress, inflammatory mediators, and bone outcomes are summarized, and evidence supporting a potential role of prunes in modulating inflammatory and immune pathways is highlighted. Key future directions to bridge the knowledge gap in the field are proposed., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Objectives: To determine the effects of high-intensity multimodal exercise training on bone mineral density and muscle performance in postmenopausal women., Methods: The two-armed, parallel, pilot randomised controlled trial was conducted from November 2020 to July 2021 at Riphah Rehabilitation Centre, Rawalpindi, Pakistan, and comprised women aged 45-70 having been in the post-menopause phase for at least 3 years, with body mass index <30, community ambulant and willing to have exercise therapy. The subjects were randomised into two equal groups. The experimental group A received supervised high-intensity resistance, weight-bearing, balance and mobility training twice weekly for 8 months. The control group B received low-to-moderate intensity exercises. Femoral neck and lumbar spine bone mineral density (g/cm2) were taken through a dual-energy X-ray absorptiometry scan. Muscle performance was measured using 1 repetition maximum for leg and trunk extensors, and 30 sec sit to stand test. Data was analysed using SPSS 21., Results: Of the 101 women screened, 28(27.7%) were enrolled; 14(50%) in group A having mean age 53.36±6.28 years, and 14(50%) in group B having mean age 51.71±4.82 years (p>0.05). Group A showed significantly more improvement than group B both with respect to lumbar spine bone mineral density and muscle performance (p<0.05)., Conclusions: Supervised high-intensity multimodal exercise training protocol had a positive effect on lumbar spine bone mineral density and muscle performance in postmenopausal women., Clinical Trial Number: NCT04653350, Link https://clinicaltrials.gov/ct2/show/NCT04653350.

The purpose was to assess the effects of three interventions on bone mineral density (BMD) to prevent the onset or progression of osteoporosis in postmenopausal women. Specifically, thirty-nine postmenopausal women, diagnosed with osteopenia or osteoporosis, implemented either high-impact training (G1), the same training + calcium and vitamin D intake (G2), or walked at an intense pace + calcium and vitamin D (G3). Baseline change (BC) in BMD was estimated using the femoral neck and lumbar spine T-scores. Participants were classified as having suffered fractures and/or falls before (24-month) and during the 2-year intervention. The participants-aged 61.8 years-were allocated into G1 ( n = 9), G2 ( n = 16), and G3 ( n = 14). The groups evolved similarly over time; however, participants in G2 exhibited the largest T-score improvements with BC over 20%. G1 and G3 maintained BMD levels (BC = -7 to 13.3%; p > 0.05). Falls occurred similarly across the interventions, while the participants in G2 had the lowest percentage of fracture events ( p = 0.037). Overall, the findings suggest that regular physical exercise may be effective in maintaining or improving BMD in postmenopausal women presenting with osteopenia or osteoporosis. Due to the limited sample size, the results are preliminary and warrant future randomized trials to validate the findings.

Introduction: Vitamin K2 supplementation has been revealed to be effective in the prevention and treatment of osteoporosis in Japan, but further proof for the effectiveness of this practice is still needed., Objective: To investigate whether vitamin K2 supplementation plays a role in maintaining bone mineral density (BMD) and reducing the incidence of fractures for postmenopausal women with osteoporosis at a long-term follow-up., Materials and Methods: We searched systematically throughout the databases of PubMed, Cochrane library, and EMBASE from the dates of their inception to November 16 2021 in this meta-analysis and systematic review, using keywords vitamin K2 and osteoporosis., Results: Nine RCTs with 6853 participants met the inclusion criteria. Vitamin K2 was associated with a significantly increased percentage change of lumbar BMD and forearm BMD (WMD 2.17, 95% CI [1.59-2.76] and WMD 1.57, 95% CI [1.15-1.99]). There were significant differences in undercarboxylated osteocalcin (uc-OC) reduction (WMD -0.96, 95% CI [-0.70 to 0.21]) and osteocalcin (OC) increment (WMD 26.52, 95% CI [17.06-35.98]). Adverse reaction analysis showed that there seemed to be higher adverse reaction rates in the vitamin K2 group (RR = 1.33, 95% CI [1.11-1.59]), but no serious adverse events related to vitamin K2 supplementation., Conclusion: This meta-analysis and systematic review seemed to support the hypothesis that vitamin K2 plays an important role in the maintenance and improvement of BMD, and it decreases uc-OC and increases OC significantly at a long-term follow-up. Vitamin K2 supplementation is beneficial and safe in the treatment of osteoporosis for postmenopausal women., (© 2022. The Japanese Society Bone and Mineral Research.)

Background: Postmenopausal osteoporosis (PMOP) has a supernal morbidity rate in elderly females., Objective: To appraise the effects of oleuropein on bone densitometry, bone metabolic index, oxidative stress, and inflammatory index in PMOP. In addition, the mechanism of olive bittersweet preventing bone loss was explored., Methods: We grouped 80 salubrious female Sprague-Dawley rats into four teams: (1) sham operation team (sham, N = 20), (2) ovariectomy (OVX, N = 20), (3) castrated mice fed with oleuropein (OVX+ole, N = 20), and (4) castrated mice fed with estrogen (OVX+E2, N = 20). The ovariectomized SD rats were continuously raised with 200  μ g/kg/dose of oleuropein. Bone mineral density and bone metabolism indexes were recorded. In order to assess the effectiveness of oleuropein on osteopenia, an enzyme-linked immunosorbent assay (ELISA) was devoted to examining the bone marrow indexes. The bone metabolism standards of PMOP rats were appraised by assessing serum levels of calcium, alkaline phosphatase (ALP), phosphorus, malondialdehyde (MDA), and nitrate content by experimental detection methods and levels of osteoclastogenesis inhibitory factor (OPG) and receptor activator for nuclear factor- κ B ligand (RANKL) by ELISA. The OPG-RANK-RANKL signal passage was examined by Western blot (WB). We measured bone mineral density using dual-energy X-rays., Results: Our animal experimental results indicated that oleuropein could significantly improve the bone mineral density of ovariectomized SD rats. In the meantime, it could reduce ending interleukin-6 (IL-6), malondialdehyde (MDA), nitrate, alkaline phosphatase (ALP), and phosphorus (P) serum concentration and would not affect Ca 2+ concentration. In cell experiments, oleuropein also can promote the proliferation of osteoblasts. Furthermore, it can promote the expression of OPG protein and mRNA. In reverse, it inhibits the expression of RANKL protein and mRNA., Conclusion: Oleuropein can not only improve the inflammatory and oxidative indexes of castrated rats but also prevent osteoporosis. Oleuropein avoids bone resorption by regulating OPG/RANKL expression., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Huilan Liu et al.)

Osteoporosis or decreased bone mineral density (BMD) is the most important risk factor for fractures, especially in older postmenopausal women (PMW). However, the interactions between exercise training and bone mineral density are not completely understood. We evaluated the effects of physical exercise on BMD in women aged ≥ 60 years postmenopausal., Purpose: This systematic review and meta-analysis sets out to determine the effects of physical exercise on BMD in older postmenopausal women., Methods: A systematic search was conducted in Medline, Science Direct, Cochrane, PubMed, CINAHL, Google Scholar, Scopus, and ProQuest up to December 25, 2021. Fifty-three studies, which assessed a total of 2896 participants (mean age: between 60 and 82 years), were included and analyzed using a random-effects model to estimate weighted mean differences (WMD) with 95% confidence intervals (CI)., Results: The meta-analysis found that exercise training significantly (p < 0.05) increased femoral neck (WMD: 0.01 g/cm 2 ; 95% CI, 0.00 to 0.01], p = 0.0005; I 2  = 57%; p < 0.0001), lumbar spine (WMD: 0.01 g/cm 2 , 95% CI, 0.01 to 0.02], I 2  = 81%; p = 0.0001), and trochanter (WMD: 0.01 g/cm 2 , 95% CI 0.00, 0.02]; p = 0.009; I 2  = 17%; p = 0.23). There were no significant differences between the intervention and control groups for total body and total hip BMD., Conclusion: Our findings suggest that exercise training may improve bone mineral density in older PMW. This improvement is mediated by increases in the femoral neck, lumbar spine, and trochanter BMD. Further long-term studies are required to confirm these findings., (© 2022. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

Osteoporosis is considered a widespread health problem that affects senior citizens, particularly older women, after the menopause. This national study aimed to estimate the prevalence of osteoporosis among Jordanian postmenopausal women and to determine the association of demographic and nutritional factors, such as calcium and vitamin D supplement intake, with osteoporosis in postmenopausal women. A cross-sectional study was conducted among 884 postmenopausal women aged ≥50 years. A multistage sampling technique was used to select participants from three geographic regions of Jordan (north, middle, and south). The data were collected from the participants by a team of field researchers comprising men and women through a standard questionnaire. The prevalence of osteoporosis was 19.8% among postmenopausal Jordanian women. The study results showed that age (p ˂ 0.001), geographic region (p = 0.019), occupation (p = 0.002), and educational level (p = 0.001) were significantly associated with osteoporosis. Moreover, osteoporosis was significantly associated with calcium and vitamin D supplement intake (p < 0.05). There is a high prevalence of osteoporosis among postmenopausal Jordanian women. Therefore, there is a need to educate women at this age, and probably at an earlier age, to prevent or reduce the development of osteoporosis.

Background: Postmenopausal osteoporosis (PMOP) is a common disease that has decreased bone strength as its main symptom after menopause. Effective treatment for PMOP remains lacking, but traditional Chinese medicine has some advantages in delaying bone loss. Jiangu granule is a traditional Chinese medicine prescription commonly used to treat PMOP. Previous studies have demonstrated its efficacy, but the mechanism of action remains uncharacterized., Purpose: This study aims to observe and discuss the mechanism of Jiangu granule to ameliorate bone loss in OVX rats by regulating the gut microbiota (GM)-short-chain fatty acids (SCFAs)- Treg/Th17 axis., Methods: Female SD rats were divided into the sham operation (S), Jiangu granule (J), and model group (M). Bilateral ovaries were surgically removed from the rats in the J and M groups. After 6 and 12 weeks, rats were sacrificed, and femur, tibia, vertebrae, serum, spleen, colon, and feces samples were collected. We detected the strength of bones, gut microbiota structure, and SCFAs in feces, the Treg and Th17 cell levels in the spleen, and cytokine levels in the serum., Result: Jiangu granule restored the abundance of gut microbiota, increased the content of SCFAs, reduced the permeability of colon epithelium, increased the proportion of Treg cells in the spleen, changed the osteoimmunomodulation-related cytokines, effectively prevented bone loss, and enhanced bone strength., Conclusion: Jiangu granule can effectively improve bone loss in OVX rats, possibly by regulating the "GM-SCFAs-Treg/Th17″ axis., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Overview of: Deardorff WJ, Cenzer I, Nguyen B, et al Time to benefit of bisphosphonate therapy for the prevention of fractures among postmenopausal women with osteoporosis: a meta-analysis of randomised clinical trials. JAMA Intern Med 2022;182:33-41., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Osteoporosis is an abnormal reduction in bone mass and bone deterioration leading to increased fracture risk. Risedronate belongs to the bisphosphonate class of drugs which act to inhibit bone resorption by interfering with the activity of osteoclasts. This is an update of a Cochrane Review that was originally published in 2003., Objectives: We assessed the benefits and harms of risedronate in the primary and secondary prevention of osteoporotic fractures for postmenopausal women at lower and higher risk for fractures, respectively., Search Methods: With broader and updated strategies, we searched the Cochrane Central Register of Control Trials (CENTRAL), MEDLINE and Embase. A grey literature search, including the online databases ClinicalTrials.gov, International Clinical Trials Registry Platform (ICTRP), and drug approval agencies, as well as bibliography checks of relevant systematic reviews was also performed. Eligible trials published between 1966 to 24 March 2021 were identified., Selection Criteria: We included randomised controlled trials that assessed the benefits and harms of risedronate in the prevention of fractures for postmenopausal women. Participants must have received at least one year of risedronate, placebo or other anti-osteoporotic drugs, with or without concurrent calcium/vitamin D. Major outcomes were clinical vertebral, non-vertebral, hip and wrist fractures, withdrawals due to adverse events, and serious adverse events. In the interest of clinical relevance and applicability, we classified a study as secondary prevention if its population fulfilled more than one of the following hierarchical criteria: a diagnosis of osteoporosis, a history of vertebral fractures, low bone mineral density (BMD)T score ≤ -2.5, and age ≥ 75 years old. If none of these criteria was met, the study was considered to be primary prevention., Data Collection and Analysis: We used standard methodology expected by Cochrane. We pooled the relative risk (RR) of fractures using a fixed-effect model based on the expectation that the clinical and methodological characteristics of the respective primary and secondary prevention studies would be homogeneous, and the experience from the previous review suggesting that there would be a small number of studies. The base case included the data available for the longest treatment period in each placebo-controlled trial and a >15% relative change was considered clinically important. The main findings of the review were presented in summary of findings tables, using the GRADE approach. In addition, we looked at benefit and harm comparisons between different dosage regimens for risedronate and between risedronate and other anti-osteoporotic drugs., Main Results: Forty-three trials fulfilled the eligibility criteria, among which 33 studies (27,348 participants) reported data that could be extracted and quantitatively synthesized. We had concerns about particular domains of risk of bias in each trial. Selection bias was the most frequent concern, with only 24% of the studies describing appropriate methods for both sequence generation and allocation concealment. Fifty per cent and 39% of the studies reporting benefit and harm outcomes, respectively, were subject to high risk. None of the studies included in the quantitative syntheses were judged to be at low risk of bias in all seven domains. The results described below pertain to the comparisons for daily risedronate 5 mg versus placebo which reported major outcomes. Other comparisons are described in the full text. For primary prevention, low- to very low-certainty evidence was collected from four studies (one to two years in length) including 989 postmenopausal women at lower risk of fractures. Risedronate 5 mg/day may make little or no difference to wrist fractures [RR 0.48 ( 95% CI 0.03 to 7.50; two studies, 243 participants); absolute risk reduction (ARR) 0.6% fewer (95% CI 1% fewer to 7% more)] and withdrawals due to adverse events [RR 0.67 (95% CI 0.38 to 1.18; three studies, 748 participants); ARR 2% fewer (95% CI 5% fewer to 1% more)], based on low-certainty evidence. However, its preventive effects on non-vertebral fractures and serious adverse events are not known due to the very low-certainty evidence. There were zero clinical vertebral and hip fractures reported therefore the effects of risedronate for these outcomes are not estimable.  For secondary prevention, nine studies (one to three years in length) including 14,354 postmenopausal women at higher risk of fractures provided evidence. Risedronate 5 mg/day probably prevents non-vertebral fractures [RR 0.80 (95% CI 0.72 to 0.90; six studies, 12,173 participants); RRR 20% (95% CI 10% to 28%) and ARR 2% fewer (95% CI 1% fewer to 3% fewer), moderate certainty], and may reduce hip fractures [RR 0.73 (95% CI 0.56 to 0.94); RRR 27% (95% CI 6% to 44%) and ARR 1% fewer (95% CI 0.2% fewer to 1% fewer), low certainty]. Both of these effects are probably clinically important. However, risedronate's effects are not known for wrist fractures [RR 0.64 (95% CI 0.33 to 1.24); three studies,1746 participants); ARR 1% fewer (95% CI 2% fewer to 1% more), very-low certainty] and not estimable for clinical vertebral fractures due to zero events reported (low certainty). Risedronate results in little to no difference in withdrawals due to adverse events [RR 0.98 (95% CI 0.90 to 1.07; eight studies, 9529 participants); ARR 0.3% fewer (95% CI 2% fewer to 1% more); 16.9% in risedronate versus 17.2% in control, high certainty] and probably results in little to no difference in serious adverse events [RR 1.00 (95% CI 0.94 to 1.07; six studies, 9435 participants); ARR 0% fewer (95% CI 2% fewer to 2% more; 29.2% in both groups, moderate certainty)., Authors' Conclusions: This update recaps the key findings from our previous review that, for secondary prevention, risedronate 5 mg/day probably prevents non-vertebral fracture, and may reduce the risk of hip fractures. We are uncertain on whether risedronate 5mg/day reduces clinical vertebral and wrist fractures.  Compared to placebo, risedronate probably does not increase the risk of serious adverse events.  For primary prevention, the benefit and harms of risedronate were supported by limited evidence with high uncertainty., (Copyright © 2022 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Abstract: This narrative review analyzes the customization of menopause hormone therapy (MHT) for osteoporosis prevention and treatment in the context of the patients' age and menopausal age. In short, MHT is indicated in most women suffering from menopause before the age of 45 years except for breast cancer survivors. These women should be treated with MHT until the age of 50 years. For women who have entered menopause at around the age of 50 years, risks associated with MHT are low, and MHT is a safe option, provided there is an indication for it. We suggest that pursuing MHT entails different risks than initiating it, after the age of 60 years. In both cases, advantages and risks should be evaluated. We suggest using risk calculators to assess the magnitude of these risks and choosing regimens that entail the lowest breast and thrombosis risks., Competing Interests: Conflicts of Interest and Source of Funding: S.R. declares to have received funding from Abbott, Pfizer, Will, Gedeon Richter, MSD, Amgen, UCB Bayer, Mithra, Viatris for either research grants, speakers bureau, or advisory board participation. The other authors have no significant relationships with, or financial interest in, any commercial companies., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Postmenopausal women compliance to alendronate therapy is suboptimal due to the complex dosing requirements. The poor compliance may increase their potential of fractures and the prevalence of side effects. In this study, the compliance of osteoporotic women on bisphosphonate therapy to the complex dosing instructions and their knowledge of alendronate-interactions were assessed., Methods: This is a cross-sectional study, using self-administered questionnaire involving 224 osteoporotic women on alendronate therapy, who visited the orthopedic clinics and community pharmacies in the West Bank. Data was collected using a validated questionnaire consisting of 4 sections and analyzed by descriptive statistics. Moreover, associations between patient's socio-demographic characteristics and the extent of compliance and knowledge of alendronate interactions are established in this study., Results: A total of 300 questionnaires were distributed and 224 were completed. The median compliance score to alendronate dosing instructions was 5 out of a possible maximum 7, and the median knowledge score about alendronate interactions was 7 out of a possible maximum 14. Factors found to affect either or both the knowledge and compliance to alendronate dosing instructions were, residency, and the source of instructions., Conclusion: This study identified the importance of compliance and knowledge gaps among postmenopausal women treated with alendronate. Therefore, appropriate knowledge about the importance of proper compliance to dosing instructions and avoidance of interactions is of a great benefit for maximizing clinical effectiveness, lowering fracture risk and prevention of adverse effects of alendronate among patients treated with alendronate in Palestine., (© 2022. The Author(s).)

Background and Purpose: Despite the popularity of Pilates exercises among postmenopausal women, few studies have devoted attention to verifying the effects of the technique on bone mineral density (BMD), and, to date, no systematic review and meta-analysis have been conducted on this topic. Our objective was to conduct a systematic review and meta-analysis of randomized controlled trials examining the effect of Pilates on BMD., Methods: Randomized controlled trials were considered eligible, with follow-up of 6 months and more, which verified the effects of Pilates exercise on the BMD of postmenopausal women. The calculations of the meta-analysis were performed through the weighted mean difference between the Pilates exercise and control groups, through the absolute change between pre- and postintervention in the areal bone mineral density., Results: Three randomized controlled trials met the inclusion criteria and were included in the meta-analysis. Only 1 study presented satisfactory methodological quality. Pilates exercises did not offer significant effects to improve areal bone mineral density of the lumbar spine (0.019 g/cm2 [95% confidence interval (CI), -0.018 to 0.057], P = .32), total hip (0.012 g/cm2 [95% CI, -0.002 to 0.027], P = .10), or femoral neck (0.000 g/cm2 [95% CI, -0.021 to 0.022], P = .97)., Conclusions: Pilates exercises had no significant effects on BMD in postmenopausal women. However, the few studies included in the meta-analysis and the low methodological quality of the majority of the studies do not allow safe extrapolation of the results at this time. More robust randomized controlled trials with high methodological quality are needed so that the results of this meta-analysis can be confirmed., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 APTA Geriatrics, An Academy of the American Physical Therapy Association.)

Bone vasculature influences osteogenesis and haematopoiesis in the bone microenviroment. Mechanical loading has been shown to stimulate the formation of osteogenesis-related type H vessels in an ovariectomy (OVX)-induced osteoporosis mouse model. To determine the loading-driven mechanism of angiogenesis and the formation of type H vessels in bone, we evaluated the roles of PI3K/Akt signaling and erythropoiesis in the bone marrow. The daily application of mechanical loading (1 N at 5 Hz for 6 min/day) for 2 weeks on OVX mice inhibited osteoclast activity, associated with an increase in the number of osteoblasts and trabecular volume ratio. Mechanical loading enhanced bone vasculature and vessel formation, as well as PI3K/Akt phosphorylation and erythropoiesis in the bone marrow. Notably, LY294002, an inhibitor of PI3K signaling, blocked the tube formation by endothelial progenitor cells, as well as their migration and wound healing. The conditioned medium, derived from erythroblasts, also promoted the function of HUVECs with elevated levels of VEGF, CD31, and Emcn. Collectively, this study demonstrates that mechanical loading prevents osteoporotic bone loss by promoting angiogenesis and type H vessel formation. This load-driven preventing effect is in part mediated by PI3K/Akt signaling and erythropoiesis in the bone marrow., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Osteoporosis is caused by enhanced bone resorption and relatively reduced bone formation. There is an unmet need to develop new agents with both antiresorptive and anabolic effects to treat osteoporosis, although drugs with either effect alone are available. A small molecular compound, plumbagin, was reported to inhibit receptor activator of nuclear factor kappa-B ligand-induced osteoclast (OC) differentiation by inhibiting IκBα phosphorylation-mediated canonical NF-κB activation. However, the key transcriptional factor RelA/p65 in canonical NF-κB pathway functions to promote OC precursor survival but not terminal OC differentiation. Here, we found that plumbagin inhibited the activity of NF-κB inducing kinase, the key molecule that controls noncanonical NF-κB signaling, in an ATP/ADP-based kinase assay. Consistent with this, plumbagin inhibited processing of NF-κB2 p100 to p52 in the progenitor cells of both OCs and osteoblasts (OBs). Interestingly, plumbagin not only inhibited OC but also stimulated OB differentiation in vitro. Importantly, plumbagin prevented trabecular bone loss in ovariectomized mice. This was associated with decreased OC surfaces on trabecular surface and increased parameters of OBs, including OB surface on trabecular surface, bone formation rate, and level of serum osteocalcin, compared to vehicle-treated mice. In summary, we conclude that plumbagin is a NF-κB-inducing kinase inhibitor with dual anabolic and antiresorptive effects on bone and could represent a new class of agent for the prevention and treatment of osteoporosis., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Postmenopausal osteoporosis (PMOP) is an estrogen deficiency-induced bone loss, which has been shown an association with an altered gut microbiota (GM). Gut microbiota-bone axis has been recognized as a crucial mediator for bone homeostasis. Icariin (ICA) is an effective agent to delay bone loss by regulating the bone homeostasis. Thus, we hypothesize that ICA can prevent bone loss by modulating GM and regulating metabolite alterations. The effects of ICA on bone metabolism improvement in ovariectomized (OVX) rats and their relationships with the GM and fecal metabolites were investigated. Micro-computed tomography (micro-CT) and hematoxylin-eosin (HE) staining showed a typical bone boss in OVX group, while ICA or estradiol (E2) administration exhibited positive effects on bone micro-architecture improvement. The GM such as Actinobacteria, Gammaproteobacteria, Erysipelotrichi, Erysipelotrichales, Enterobacteriales, Actinomycetales, Ruminococcus and Oscillospira significantly correlated to serum bone Gla-protein (BGP), receptor activator of nuclear factor-κB (RANK), receptor activator of nuclear factor-κB ligand (RANKL), osteoprotegerin (OPG) and tartrate resistant acid phosphatase (TRACP). Further t -test revealed a substantial variation of the GM and fecal metabolites in different treatments. Among them, Lachnoclostridium , Butyricimonas , Rikenella , Paraprevolla , Adlercreutzia , Enterorhabdus , Anaerovorax , Allobaculum , Elusimicrobium , Lactococcus , Globicatella and Lactobacillus were probably the key microbial communities driving the change of bile acid, amino acid and fatty acid, thereby leading to an improvement of PMOP. The significant up-regulation of L-Saccharopine, 1-Aminocyclohexadieneacid and linoleic acid after ICA administration suggested important contributions of amino acid and fatty acid metabolisms in the prevention and treatment of PMOP. Taken together, our study has provided new perspectives to better understand the effects of ICA on PMOP improvement by regulating GM and the associated fecal metabolites. Our findings contribute to develop ICA as a potential therapy for PMOP., Competing Interests: The authors declare that the research was coducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wang, Wang, Wang, Xu, Zhang, Han, Yan, Liu, Wang, Ye and Li.)

Summary: Osteoporosis is an increasing health problem in postmenopausal women. Our findings indicated that long-term brisk walking with a volume greater than 16 per week is effective for improving BMD in premenopausal women., Purpose: To examine the effects of brisk walking on bone mineral density (BMD) in premenopausal women, and further determine the effective frequency, intensity, time and volume (frequency x duration) of brisk walking for training strategy prescription., Methods: 222 healthy premenopausal women were recruited for BMD measurement. According to the survey of their physical activity level, 84 subjects (age: 46±1.8) whose physical activity index ≥40 were categorized into the brisk walking group, and 138 subjects (age: 47±2.2) whose physical activity index <40 were assigned to the sedentary group. The BMD of these two groups were statistically compared with an independent t test. Next, 35 subjects from the original sedentary group were recruited for BMD measurement after 2-year moderate brisk walking. According to the volume of physical activity per week, they were divided into the control group (n = 10, aged 49±0.9), volume 8 group (n = 4, aged 48±1.2), volume 12 group (n = 7, aged 49±1.4), volume 16 group (n = 8, aged 49±1.3), and volume 20 group (n = 6, aged 49±1.5). ANOVA was used to analyze BMD before and after brisk walking among the five groups., Results: The BMD in the brisk walking group (1.00±0.008 g/cm2) was significantly higher than that in the sedentary group (0.89±0.008 g/cm2) (P<0.001). Stepwise regression analysis revealed that the volume of brisk walking was significantly correlated with BMD (P<0.001). In particular, brisk walking with a volume greater than 16 (a score of duration up to 4 and a score of frequency up to 4 or 5) per week is effective for improving BMD in premenopausal women (P = 0.03, P = 0.002, respectively)., Conclusions: Long-term brisk walking is an efficient way to improve BMD. Taking brisk walks for 30 minutes per day 3 or more times per week (volume>16) is recommended to prevent bone loss in premenopausal women., Competing Interests: Yong-Sheng Lan and Yu-Juan Feng declare that they have no conflict of interest.

Osteoporosis is one of the most common bone disorders that seriously affect the health and life quality of elderly individuals. Reduced osteoblast differentiation and bone formation lead to changes in bone volume and microarchitecture, leaving the bones vulnerable to fracture. Bergamottin (BM) is a natural compound derived from various citrus fruits and possesses multiple biological activities including anti-adipogenesis function. This study aimed to evaluate the effects of BM on osteoblast differentiation and its potential anti-osteoporosis capacity, as well as to explore the underlying mechanism. We demonstrated that BM, as a positive regulator for osteogenesis, significantly promoted osteoblast differentiation and bone formation. Mechanically, BM activated the Wnt/β-catenin signaling pathway and promoted the nuclear translocation of β-catenin. In addition, BM dramatically upregulated the expression of β-catenin, enhanced the transcriptional activation of T cell factor 7 (TCF7), and increased the expression of Runt-related transcription factor 2 (Runx2). Taken together, this study revealed that BM enhanced osteoblast differentiation and attenuated ovariectomy (OVX)-induced bone loss, possessing the potential to be developed into a food ingredient or supplement for preventing osteoporosis.

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

Purpose: This randomized controlled trial compared changes in bone mineral density (BMD) and bone turnover in postmenopausal women with low bone mass randomized to 12 months of either risedronate, exercise, or a control group., Methods: Two hundred seventy-six women with low bone mass, within 6 years of menopause, were included in analysis. Treatment groups were 12 months of (a) calcium and vitamin D supplements (CaD) (control), (b) risedronate + CaD (risedronate), or (c) bone-loading exercises + CaD (exercise). BMD and serum markers for bone formation (Alkphase B) and resorption (Serum Ntx) were analyzed at baseline, 6, and 12 months., Results: Using hierarchical linear modeling, a group by time interaction was found for BMD at the spine, indicating a greater improvement in the risedronate group compared to exercise (p ≤ .010) or control groups (p ≤ .001). At 12 months, for women prescribed risedronate, changes in BMD at the spine, hip, and femoral neck from baseline were + 1.9%, + 0.9%, and + .09%; in exercise group women, + 0.2%, + 0.5%, and - 0.4%; and in control group women, - 0.7%, + 0.5%, and - 0.5%. There were also significant differences in reductions in Alkphase B (RvsE, p < .001, RvsC, p < .001) and Serum Ntx (RvsE, p = .004, RvsC, p = .007) in risedronate women compared to exercise and control groups. For risedronate, 12-month changes in Alkphase B and Serum Ntx were - 20.3% and - 19.0%; for exercise, - 6.7% and - 7.0%; and for control, - 6.3% and - 9.0%., Conclusion: Postmenopausal women with low bone mass should obtain adequate calcium and vitamin D and participate in bone-loading exercises. Additional use of BPs will increase BMD, especially at the spine., (© 2021. International Osteoporosis Foundation and National Osteoporosis Foundation.)

Osteoporosis is a bone related disease that is characterised by bone loss that further increases the susceptibility to bone fractures and bone frailty due to disturbances in the micro-architecture of bone tissue. Fisetin (flavonoids) exhibited anti-inflammatory and antioxidative stress effects against various diseases. In this protocol, we make an effort to comfort the anti-osteoporosis effect of fisetin against ovariectomy (OVX) induced osteoporosis. A docking study of fisetin and alendronate on the estrogen (α and β) and vitamin D receptors was carried out. SaOS-2 (osteoblast like human) cells were used for the estimation of cell proliferation. The OVX induced OVX model was used and three doses of fisetin and alendronate was given to rats till 16 weeks. The hormone levels, bone turnover markers and biochemical parameters were estimated. Fisetin was docked into estrogen (α and β) and vitamin D receptors, resulting in stable complexes with lower binding scores. Fisetin significantly (p < 0.001) exhibited the induction of cell proliferation against the SaOS-2 cells. OVX induced osteoporosis rats exhibited a suppression of body weight and uterus index, after the Fisetin treatment. Fisetin treatment significantly (p < 0.001) improved the level of bone mineral content (BMC), bone mineral density (BMD) and biochemical parameters such as energy, maximum load, stiffness, young modules, maximum stress and reduced the level of 1,25(OH) 2 D 3 and E 2 . Fisetin treatment significantly (p < 0.001) declined the level of phosphorus (P), calcium (Ca) and boosted the level of VitD. Fisetin treatment significantly (p < 0.001) reduced the malonaldehyde (MDA) level and enhanced the glutathione (GSH), catalase (CAT), superoxide dismutase (SOD) level in the bone, intestine and hepatic tissue. Fisetin treatment suppressed the cytokines, RANKL/OPG ratio, receptor activator of nuclear factor-κB ligand (RANKL) and improved the level of osteoprotegerin (OPG). The findings suggest that fisetin could be a beneficial phytoconstituent for the treatment and prevention of postmenopausal osteoporotic complications.

Importance: The clinical decision to initiate bisphosphonate therapy for the treatment of osteoporosis requires balancing shorter-term harms and burdens (eg, gastroesophageal irritation or severe musculoskeletal pain) with longer-term benefits in reducing potential fractures., Objective: To assess the time to benefit (TTB) of bisphosphonate therapy for the prevention of nonvertebral and other fractures among postmenopausal women with osteoporosis., Data Sources: Randomized clinical trials (RCTs) were identified from systematic reviews commissioned by the US Preventive Services Task Force (1 review), the Agency for Healthcare Research and Quality (1 review), the Cochrane Library (2 reviews), and the Endocrine Society (1 review)., Study Selection: Studies selected were RCTs involving postmenopausal women with a diagnosis of osteoporosis based on existing vertebral fractures or bone mineral density T scores of -2.5 or lower. The selection process was focused on studies of alendronate, risedronate, and zoledronic acid because they are guideline-recommended first-line agents for reducing nonvertebral fractures. Studies were excluded if they did not focus on women with a primary diagnosis of osteoporosis, had no placebo arm, or had a lack of data on time to fracture., Data Extraction and Synthesis: Random-effects Weibull survival curves were fitted and Markov chain Monte Carlo methods were used to estimate the absolute risk reduction (ARR) and TTB for each study. These estimates were pooled using a random-effects meta-analysis model., Main Outcomes and Measures: The primary outcome was the time to 3 different ARR thresholds (0.002, 0.005, and 0.010) for the first nonvertebral fracture. Secondary outcomes included the time to 4 ARR thresholds (0.001, 0.002, 0.005, and 0.010) for hip fracture, any clinical fracture, and clinical vertebral fracture., Results: Of 67 full-text articles identified, 10 RCTs comprising 23 384 postmenopausal women with osteoporosis were included either as the original RCT or part of subsequently published pooled analyses. Among the studies, the number of participants ranged from 994 to 7765, with mean (SD) age ranging from 63 (7) years to 74 (3) years and follow-up duration ranging from 12 to 48 months. The pooled meta-analysis found that 12.4 months (95% CI, 6.3-18.4 months) were needed to avoid 1 nonvertebral fracture per 100 postmenopausal women receiving bisphosphonate therapy at an ARR of 0.010. To prevent 1 hip fracture, 200 postmenopausal women with osteoporosis would need to receive bisphosphonate therapy for 20.3 months (95% CI, 11.0-29.7 months) at an ARR of 0.005. In addition, 200 postmenopausal women with osteoporosis would need to receive bisphosphonate therapy for 12.1 months (95% CI, 6.4-17.8 months) to avoid 1 clinical vertebral fracture at an ARR of 0.005., Conclusions and Relevance: This meta-analysis found that the TTB of bisphosphonate therapy was 12.4 months to prevent 1 nonvertebral fracture per 100 postmenopausal women with osteoporosis. These results suggest that bisphosphonate therapy is most likely to benefit postmenopausal women with osteoporosis who have a life expectancy greater than 12.4 months.

Introduction: The aim of the study was to establish the influence of knowledge of osteoporosis and educational level on bone health., Material and Methods: The study group consisted of 351 women, aged 50-88 years (mean 66.3 ± 8.6). None of them had had any previous personal experience with osteoporosis diagnosis and treatment. They filled in a questionnaire consisting of 10 questions assessing their knowledge about osteoporosis. All of them underwent femoral neck densitometry (GE Lunar, USA)., Results: The mean score in the knowledge questionnaire was 7.4 ± 1.6 points (range 2-10). The lowest percentage of correct answers was observed in the sentences regarding the possibility of successful cure of osteoporosis and the role of physical activity in osteoporosis treatment. The mean score in the osteoporosis questionnaire correlated negatively with the age of the participants (r = -0.2, p < 0.05) and was better among patients with higher educational degree (8.2 vs. 6.4 points, p < 0.001). Both the educational degree and the level of knowledge of osteoporosis correlated with bone mineral density (BMD) and T-score., Conclusions: Elderly and less educated women showed lower levels of knowledge about osteoporosis and its consequences. The study suggests that bone health in postmenopausal women may be indirectly improved by education concerning osteoporosis and its prevention.

Mixed results have been reported regarding whether habitual tea intake affects bone health. This study investigated the relationship between green tea intake and bone mineral density (BMD) in postmenopausal Korean women. We used data from the Korean National Health and Nutrition Examination Surveys from 2008 to 2011 and divided the participants into three groups according to their frequency of green tea intake over the past 12 months. BMD of the lumbar spine, total femur, and femur neck was measured using dual-energy X-ray absorptiometry. The odds ratios (ORs) and 95% confidence intervals (CIs) of osteoporosis and osteopenia according to green tea consumption were analyzed. Participants who did not consume green tea or consumed less than one cup per day were more likely to have osteopenia of the lumbar spine or femur than those who consumed it once to three times a day (OR 1.81 and 1.85, 95% CI, 1.20-2.71; and 1.23-2.77). Moreover, ORs for osteoporosis were 1.91 (95% CI 1.13-3.23) and 1.82 (95% CI 1.09-3.05) in non-consumers and consumers who drank less than one cup per day, respectively, compared with the reference group. These results support that green tea consumption may have benefits on bone health.

Postmenopausal osteoporosis (PMOP) is a systemic chronic bone metabolic disease caused by the imbalance between bone formation and bone resorption mediated by estrogen deficiency. Both exercise and natural extracts are safe and effective means to prevent and control PMOP. The additive effect of exercise synergy extract against PMOP may be no less than that of traditional medicine. However, the mechanism of action of this method has not been clarified in detail. A large number of studies have shown that the pathogenesis of PMOP mainly involves the OPG-RANKL-RANK system, inflammation, and oxidative stress. Based on the abovementioned approaches, the present study reviews the anti-PMOP effects and mechanisms of exercise and natural extracts. Finally, it aims to explore the possibility of the target of the two combined anti-PMOP through this approach, thereby providing a new perspective for joint intervention research and providing a new direction for the treatment strategy of PMOP., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Tongxi Zhou et al.)

Postmenopausal women experience an increase in bone remodeling with the rate of bone resorption superseding the rate of bone formation. This results in a net bone loss with a subsequent increased risk for osteoporosis and fractures. High blood pressure (BP) has been associated with loss of bone mineral density and increased propensity to fractures. Strawberries are rich in polyphenols, which have been shown to have anti-hypertensive and bone-protective properties. Thus, we examined whether daily intake of strawberries would positively affect biomarkers of bone metabolism in postmenopausal women with pre- and stage 1-hypertension. Participants (age: 59 ± 6 years; body mass index: 31.5 ± 4.1 kg m -2 ; systolic BP: 140 ± 13 mmHg) were randomly assigned to consume (1) 50 g of freeze-dried strawberry powder (FDSP), (2) 25 g FDSP + 25 g of placebo powder, or (3) 50 g placebo powder for eight weeks. Results indicate a significant time-by-treatment interaction ( P = 0.04) for serum insulin-like growth factor (IGF)-1, a hormone that plays a major role in bone formation. Serum concentrations of bone-specific alkaline phosphatase, a marker of bone formation, and tartrate-resistant acid phosphatase-5b, a specific marker of bone resorption, were not affected by FDSP compared to placebo. Although not statistically significant, after eight weeks, osteocalcin increased in the 50 g FDSP group with a large effect size ( d = 0.6) when compared to the placebo-control group. Adiponectin increased by 5% and 6% in the 25 g and 50 g FDSP groups, respectively, while it declined in the placebo-control group by 25% ( P = 0.03 for time-by-treatment interaction). Our findings suggest that consumption of 25 g FDSP increases IGF-1 in postmenopausal women with pre- and stage 1-hypertension. However, further studies are needed to assert the effectiveness of a strawberry intervention for bone health.

Objective: To evaluate the efficacy and safety of intranasal salmon calcitonin in the treatment of osteoporosis., Methods: Eight Chinese and English databases were searched by electronic search (from the establishment of the database to October 2019). The literature was screened according to the inclusion criteria and exclusion criteria, the quality was evaluated according to Cochrane software, and the Review Manager 5.2 software was used for statistical analysis., Results: A total of 374 documents were retrieved and 12 (12 original studies) were included after the screening, with a total sample capacity of 1068 cases. Meta-analysis showed that the intranasal salmon calcitonin had obvious advantages in reducing blood calcium, improving the ratio of serum creatinine and alkaline phosphatase. In addition, the intranasal salmon calcitonin had no obvious advantages in other indicators. It cannot be illustrated that the combination of intranasal salmon calcitonin and other conventional drugs is more effective than the simple use of conventional drugs., Conclusion: The intranasal salmon calcitonin is superior to conventional drugs in reducing blood calcium, increasing creatinine ratio, and alkaline phosphatase, but its advantages in other indicators such as improving the bone mineral density (BMD) of lumbar vertebrae and hip have not been confirmed, and it is not clear that the combination of intranasal salmon calcitonin and other conventional drugs is better than the simple conventional drugs., (© 2021. The Author(s).)

Background: Evidences are beginning to accrue that flavonoids, particularly phytoestrogens, could have beneficial effects against several age-related diseases linked to estrogen deficiency including postmenopausal osteoporosis., Methods: In this study, the effect of chrysin on selected bone-remodeling markers in ovariectomized rats and its estrogen-like activity in silico were investigated., Results: The data indicated that administration of chrysin at 50 mg/kg and 100 mg/kg for 6 weeks to OVX rats significantly ( p < 0.05) prevented body weight gain and partially reverse uterine weight loss. In addition, treatment of OVX rats significantly ( p < 0.01) increased femur dry weight, femur ash weight, bone ash calcium, and phosphorous levels in a dose-dependent manner. However, there was significant ( p < 0.001) decline in serum estradiol level in all OVX rats compared to the sham-operated group. Interestingly, administration of chrysin significantly ( p < 0.05) reversed the reduction of estradiol induced by ovariectomy compared to untreated OVX rats. Moreover, administration of chrysin to OVX rats significantly ( p < 0.05) suppressed excessive elevation of bone-remodeling markers expression compared to untreated OVX rats. Similarly, molecular docking analysis revealed that chrysin interacts with both α and β estrogen receptors with exothermic binding energies of -229.83 kcal/Mol and -252.72 kcal/Mol, respectively, and also fits perfectly into the active site of both α and β estrogen receptors., Conclusion: This study demonstrated that chrysin exhibits potential antiosteoporotic effects against bone loss in OVX rats through enhanced bone mineral contents and preventing excessive elevation of bone-remodeling markers and bone-resorbing cytokine.

Postmenopausal osteoporosis is a frequent clinical condition which affects nearly 1 in 3 women. Estrogen deficiency leads to rapid bone loss which is maximal within the first 2-3 years after the menopause transition and can be prevented by menopause hormone therapy (MHT). Not only, MHT prevents bone loss and the degradation of the bone microarchitecture but it significantly reduces the risk of fracture at all bone sites by 20-40%. It is the only anti-osteoporotic therapy that has a proven efficacy regardless of basal level of risk, even in low-risk women for fracture. Following the publication of the WHI results, use of MHT has considerably declined due to safety concerns which raise the question as to whether it might still be used in the prevention of osteoporosis. Over the last years, subsequent re-analyses of the WHI and further trials have challenged the initial conclusions of the WHI. It is now clearer that the individual benefit-risk balance of MHT is dependent on the individual risk profile in each woman as well as whether estrogen is opposed or unopposed, the type of estrogens and progestogens or doses and routes of administration. It must be also reminded that to date osteoporosis is a chronic disease that cannot be cured. The choice of the 1st treatment option should thus always be made in the context of a more comprehensive long-term strategy. This is particular true in early postmenopausal women found to be at low/moderate risk of fragility fracture over the first 10 years after menopause but who may have a much greater lifetime risk. In the absence of contraindication, use of MHT should be considered as a 1st option for the maintenance of bone health in those women where specific bone active medications are not warranted. Subsequent reassessment of the individual benefit-risk balance of MHT is thereafter recommended, with the possibility of switching to another osteoporosis treatment if the balance is not considered as favourable as at the beginning of the menopause for women still at high risk of fracture., (Copyright © 2021. Published by Elsevier Ltd.)