Antiosteoporosis Effect and Possible Mechanisms of the Ingredients of Fructus Psoraleae in Animal Models of Osteoporosis: A Preclinical Systematic Review and Meta-Analysis.

OBJECTIVE: Fructus Psoraleae (FP) and its ingredients (IFP) have a variety of biological activities and are widely used to treat osteoporosis (OP). Herein, we conducted a systematic review to evaluate the efficacy of IFP for an animal model of OP from the current literatures. Potential mechanisms of IFP in the treatment of OP were also summarized. MATERIALS AND METHODS: We carried out a search for electronic literature in the PubMed, Chinese National Knowledge Infrastructure, EMBASE, Wanfang, Web of Science, Chinese Biomedical Literature Database, and Cochrane Library, as well as Chinese VIP databases targeting articles published from inception to June 2021. The inclusion criteria were animal studies that assessed the efficacy and safety of IFP for OP, regardless of publication status or language. The exclusion criteria included (1) other types of studies (in vitro studies, case reports, clinical trials, reviews, abstracts, comments, and editorials), (2) combination with other compounds, (3) compared with other traditional Chinese medicine, (4) not osteoporosis or bone loss model, (5) studies with insufficient data, (6) lack of a control group, and (7) duplicate publications. The modified Collaborative Approach to Meta-Analysis and Review of Animal Data from Experimental Stroke (CAMARADES) 10-item quality checklist was used to evaluate the risk of bias of included studies. We computed the relative risk (RR) and the standard mean difference (SMD) for dichotomous outcomes and continuous outcomes, respectively. When heterogeneity was detected or there was significant statistical heterogeneity (P < 0.05 or I 2 > 50%), a random-effects model was employed, followed by further subgroup analysis and metaregression estimations to ascertain the origins of heterogeneity. Otherwise, we used a fixed-effects model (P ≥ 0.05 or I 2 ≤ 50%). The primary outcome measures were bone mineral density (BMD), serum osteocalcin(S-OCN), bone volume over total volume (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th), trabecular separation (Tb.Sp), bone maximum load, and elasticity modulus. The secondary outcome measure was the antiosteoporosis mechanisms of IFP. The STATA 12.0 software was used to analyze the data. RESULTS: Overall, 16 studies focusing on 379 animals were enrolled into the study. The risk of bias score of included studies ranged from 4 to 7 with an average score of 5.25. The present study provided the preliminary preclinical evidence that administration of IFP could significantly increase the S-OCN, BMD, BV/TV, and Tb.N while Tb.Th and Tb.Sp were remarkably decreased by IFP in OP model animals (P < 0.05). Moreover, IFP could significantly improve the bone biomechanical indicator bone maximum load and elasticity modulus (P < 0.05). In terms of the possible mechanisms of treatment of OP, IFP exerts anti-OP effects in animal models probably through osteoprotegerin/receptor activator of the nuclear factor-κB ligand/receptor activator of nuclear factor-κB (OPG/RANKL/RANK), peroxisome proliferator activated receptor γ (PPAR-γ)/Axin2/Wnt, antioxidative stress via forkhead box O3a (FoxO3a)/Axin2/Wnt, phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR), estrogen-like effect, and gamma-aminobutyric acid/gamma-aminobutyric acid receptor (GABA/GABABRI) signaling pathway. CONCLUSION: Taken together, the findings suggest the possibility of developing IFP as a drug or an ingredient in diet for the clinical treatment of OP. We recommend that rigorous, as well as high-quality, trials involving large sample sizes should be conducted to confirm our findings.

Effect of dietary sources of calcium and protein on hip fractures and falls in older adults in residential care: cluster randomised controlled trial.

OBJECTIVE: To assess the antifracture efficacy and safety of a nutritional intervention in institutionalised older adults replete in vitamin D but with mean intakes of 600 mg/day calcium and <1 g/kg body weight protein/day. DESIGN: Two year cluster randomised controlled trial. SETTING: 60 accredited residential aged care facilities in Australia housing predominantly ambulant residents. PARTICIPANTS: 7195 permanent residents (4920 (68%) female; mean age 86.0 (SD 8.2) years). INTERVENTION: Facilities were stratified by location and organisation, with 30 facilities randomised to provide residents with additional milk, yoghurt, and cheese that contained 562 (166) mg/day calcium and 12 (6) g/day protein achieving a total intake of 1142 (353) mg calcium/day and 69 (15) g/day protein (1.1 g/kg body weight). The 30 control facilities maintained their usual menus, with residents consuming 700 (247) mg/day calcium and 58 (14) g/day protein (0.9 g/kg body weight). MAIN OUTCOME MEASURES: Group differences in incidence of fractures, falls, and all cause mortality. RESULTS: Data from 27 intervention facilities and 29 control facilities were analysed. A total of 324 fractures (135 hip fractures), 4302 falls, and 1974 deaths were observed. The intervention was associated with risk reductions of 33% for all fractures (121 v 203; hazard ratio 0.67, 95% confidence interval 0.48 to 0.93; P=0.02), 46% for hip fractures (42 v 93; 0.54, 0.35 to 0.83; P=0.005), and 11% for falls (1879 v 2423; 0.89, 0.78 to 0.98; P=0.04). The risk reduction for hip fractures and falls achieved significance at five months (P=0.02) and three months (P=0.004), respectively. Mortality was unchanged (900 v 1074; hazard ratio 1.01, 0.43 to 3.08). CONCLUSIONS: Improving calcium and protein intakes by using dairy foods is a readily accessible intervention that reduces the risk of falls and fractures commonly occurring in aged care residents. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12613000228785.

Nutritional intake and bone health.

Osteoporotic or fragility fractures affect one in two women and one in five men who are older than 50. These events are associated with substantial morbidity, increased mortality, and an impaired quality of life. Recommended general measures for fragility fracture prevention include a balanced diet with an optimal protein and calcium intake and vitamin D sufficiency, together with regular weight-bearing physical exercise. In this narrative Review, we discuss the role of nutrients, foods, and dietary patterns in maintaining bone health. Much of this information comes from observational studies. Bone mineral density, microstructure-estimated bone strength, and trabecular and cortical microstructure are positively associated with total protein intake. Several studies indicate that fracture risk might be lower with a higher dietary protein intake, provided that the calcium supply is sufficient. Dairy products are a valuable source of these two nutrients. Hip fracture risk appears to be lower in consumers of dairy products, particularly fermented dairy products. Consuming less than five servings per day of fruit and vegetables is associated with a higher hip fracture risk. Adherence to a Mediterranean diet or to a prudent diet is associated with a lower fracture risk. These various nutrients and dietary patterns influence gut microbiota composition or function, or both. The conclusions of this Review emphasise the importance of a balanced diet including minerals, protein, and fruit and vegetables for bone health and in the prevention of fragility fractures.

Modulation of gut microbiota by chondroitin sulfate calcium complex during alleviation of osteoporosis in ovariectomized rats.

Although chondroitin sulfate calcium complex (CSCa) was claimed to have the bioactivity for bone care in vitro, its anti-osteoporosis bioactivity was little reported in vivo. Here, the effects of CSCa on osteoporosis rats were investigated. Results showed that, compared with the osteoporosis rats, CSCa could improve the bone mineral density and microstructure of femur, and change the bone turnover markers level in serum. 16S rRNA sequencing and metabolomics analysis indicated CSCa intervention altered the composition of gut microbiota along with metabolite profiles in ovariectomized rat faeces. The correlation analysis showed some gut microbiota taxa were significantly correlated with osteoporosis phenotypes and the enriched metabolites. Taken together, dietary CSCa intervention has the potential to alleviate the osteoporosis and related symptoms probably involving gut microbiota or the metabolite profiles as demonstrated in rats. This study provides some scientific evidence for the potential effects of CSCa as the food supplement on the osteoporosis.

Osteosarcopenic adiposity syndrome update and the role of associated minerals and vitamins.

The objectives are to present an updated synopsis on osteosarcopenic adiposity (OSA) syndrome and evaluate the roles of selected micronutrients in its prevention and management. OSA refers to the concurrent deterioration of bone (osteopenia/osteoporosis), muscle (sarcopenia) and adipose tissue expansion. It portrays the most advanced stage in a continuum of body composition disorders. Although OSA has been widely studied involving the populations of different backgrounds, its prevalence is hard to collate because different methodologies and criteria were used for its diagnosis. Another critical health aspect is the presence of low-grade chronic inflammation (LGCI) which contributes to OSA and vice versa. Nutrition is important in the prevention and management of both OSA and LGCI. Although micronutrients act in numerous metabolic and physiological processes, their roles here are presented in relation to OSA (and its components) and LGCI in general and relevant to the COVID-19 pandemic. These include calcium, magnesium, phosphorus, potassium, sodium and vitamins D and K; their interactions, physiological ratios and synergism/antagonism are discussed as well. In conclusion, calcium, magnesium and vitamin D have a profound impact on OSA and its components, and the latter two also on LGCI. Potassium and vitamin K are vital in bone, muscle functioning and possibly adipose tissue modification. Both, but particularly vitamin D, surfaced as important modulators of immune system with application in COVID-19 infections. While both phosphorus and sodium have important roles in bone, muscle and can impact adiposity, due to their abundance in food, their intake should be curbed to prevent possible damaging effects.

[Nutrition in the prevention and control of osteoporosis]. / Nutrición en la prevención y el control de la osteoporosis.

INTRODUCTION: Objective: although osteoporosis develops in advanced stages of life, it must be prevented and stopped from the pediatric age, acting on modifiable factors, especially diet and lifestyle. The objective of this work is to review the latest evidence on nutritional improvements that can help in the prevention and control of the disease. Methods: bibliographic search related to the topic. Results: it is advisable to avoid energy restrictions, especially in postmenopausal women and particularly if they have osteopenia/osteoporosis since, in relation to these pathologies, excess weight may be preferable, rather than underweight. Protein intake higher than the recommended one is beneficial for the bone, provided that the calcium intake is adequate. Excessive intake of sugar and saturated fat should be avoided, but attempts should be made to achieve the nutritional goals set for ω-3 polyunsaturated fatty acids and fiber. It is important to monitor vitamin D status and calcium intake, which is inadequate in high percentages of individuals, as well as improving the contribution of vitamins K, C and group B, and also magnesium, potassium, iron, zinc, copper, fluorine, manganese, silicon and boron, and avoiding the excessive contribution of phosphorus and sodium. Conclusions: osteoporosis is an underdiagnosed pathology and of increasing prevalence. Due to its high morbidity and mortality, prevention is important and, from a nutritional point of view, it is convenient to bring the diet closer to the theoretical ideal. In general, increasing the consumption of dairy products, fish, vegetables and fruits, as well as reducing the consumption of salt, during childhood and throughout life, seems convenient for the bone improvement of most of the population.

INTRODUCCIÓN: Introducción y objetivos: la osteoporosis, aunque se manifiesta en etapas avanzadas de la vida, se debe prevenir y frenar desde la edad pediátrica, actuando sobre los factores modificables, especialmente la alimentación y el estilo de vida. El objetivo del presente trabajo es revisar las últimas evidencias sobre las mejoras nutricionales que pueden ayudar en la prevención y el control de la enfermedad. Métodos: búsqueda bibliográfica en relación con el tema. Resultados: conviene evitar las restricciones energéticas, especialmente en mujeres posmenopáusicas, sobre todo si tienen osteopenia/osteoporosis dado que, en relación con estas patologías, puede ser preferible un exceso de peso frente a un peso insuficiente. Una ingesta proteica superior a la recomendada es beneficiosa para el hueso siempre que la ingesta de calcio sea adecuada. Se debe evitar una ingesta excesiva de azúcar y de grasa saturada, pero se deben intentar alcanzar los objetivos nutricionales marcados para los ácidos grasos poliinsaturados ω-3 y la fibra. Es importante vigilar la situación en vitamina D y la ingesta de calcio, que es inadecuada en elevados porcentajes de individuos. También conviene mejorar el aporte de vitaminas K, C y del grupo B, así como de magnesio, potasio, hierro, zinc, cobre, flúor, manganeso, silicio y boro, y evitar el aporte excesivo de fósforo y sodio. Conclusiones: la osteoporosis es una patología infradiagnosticada y de prevalencia creciente. Por su elevada morbilidad y mortalidad es importante la prevención y desde el punto de vista nutricional conviene aproximar la dieta al ideal teórico. En general, el incremento en el consumo de lácteos, pescado, verduras, hortalizas y frutas, así como la reducción del consumo de sal, durante la infancia y a lo largo de la vida parecen convenientes para la mejora ósea de la mayor parte de la población.

Short communication: Dietary bovine milk-derived exosomes improve bone health in an osteoporosis-induced mouse model.

Osteoporosis is a systemic skeletal disease characterized by low bone mass and micro-architectural deterioration of bone tissue, with a consequent increase in bone fragility and fracture susceptibility. In an aged society with increased life expectancy, the incidence rate of osteoporosis is also rapidly increasing. Inadequate nutrition may negatively influence bone metabolism. Recently, many studies have investigated the functionality of milk-derived exosomes, which play important roles in cell-to-cell communication. However, there are few reports of how milk-derived exosomes influence osteoblast proliferation and differentiation. Here, we determined whether bovine colostrum-derived exosomes promote anti-osteoporosis in vitro and in vivo. Tartrate-resistant acid phosphatase-stained cells were significantly inhibited in Raw264.7 cells treated with exosomes, indicating reduced osteoclast differentiation. We induced osteoporosis in mice using glucocorticoid pellets after orally administering exosomes for 2 mo. Interestingly, the bone mineral density of exosome-fed mouse groups was significantly improved compared with the glucocorticoid-induced osteoporosis group without exosome treatment. In addition, Lactobacillus were decreased in the gut microbiota community of osteoporosis-induced mice, but the gut microbiota community composition was effectively restored by exosome intake. Taken together, we propose that exosomes isolated from bovine colostrum could be a potential candidate for osteoporosis prevention, bone remodeling improvement, and inhibition of bone resorption. To our knowledge, this is the first time that a protective effect of milk exosomes against osteoporosis has been demonstrated in vivo. Our results strongly suggest that bovine colostrum exosomes might be used as a prophylaxis to prevent the onset of osteoporosis. Indeed, our results offer promising alternative strategies in the nutritional management of age-related bone complications.

Is a 'healthy diet' and a 'calcium-rich diet' the same thing? Qualitative study examining perceptions of a calcium-rich diet in individuals who have received bone health education.

BACKGROUND: In the present study, we aimed to (i) examine perceptions of achieving calcium and vitamin D recommended dietary allowance (RDA) and (ii) determine how participants talked about food in relation to RDA recommendations. METHODS: Participants aged ≥50 years who were prescribed osteoporosis medication and received two modes of bone health education were eligible. Relying on a qualitative description design, we interviewed participants 1 month after they had attended an education session and received a self-management booklet. Calcium and vitamin D intakes were estimated by in-depth questions about diet and supplements and compared with perceptions of achieved RDA levels. Interview transcripts were analysed based on an analytic hierarchical process. RESULTS: Forty-five participants (29 reporting previous fragility fractures) were included. Calcium and vitamin D RDA appeared to be potentially achieved by 64% and 93% of participants, respectively, primarily because of reliance on supplements. Few participants talked about vitamin D in relation to food intake and 49% of participants were unclear about the calcium content of food. Most considered that a healthy diet was equivalent to a calcium-rich diet. We noted no differences in our findings in the subset of individuals with fragility fractures. CONCLUSIONS: Despite reporting a prescription for osteoporosis medication and receiving bone health education, a substantial number of individuals appeared to have sub-optimal calcium levels. This may be attributed to the challenge of achieving RDA with diet alone and the misconception of a healthy diet as a calcium-rich diet.

The association of calcium intake with osteoporotic vertebral fractures in a large Chinese cohort.

The effect of calcium on prevention of osteoporosis and related fracture which are aging issues is unclear. The aim of this study is to explore the association of calcium intake with vertebral fracture. This study enrolled 3,457 participants from China Action on Spine and Hip Status (CASH) study from 2013 and 2017. Dietary calcium intake was collected using validated food frequency questionnaires (FFQ). Vertebral fracture of CT images was defined as the primary outcome. The mean calcium intake of men and women were 522.75mg/day and 507.21mg/day, respectively. 6% reduction in the odds of fracture risk was observed per 100 unit increase of calcium intake from food among females (OR, 0.94; 95% CI, 0.89-0.99), but results among males were not significant. We divided calcium intake into quintiles when modelling its associations with fracture risk, negative associations of fracture risk with calcium intake were found among females. In a population with low usual calcium intake, higher dietary calcium intake was associated with fewer vertebral fracture in women and that no such association was seen in men.

Canadian recommendations for vitamin D intake for persons affected by multiple sclerosis.

In 2016, the Multiple Sclerosis (MS) Society of Canada convened a panel of expert scientists, clinicians and patient advocate to review the evidence for an association between vitamin D status and MS prevention and/or disease modification. The goal was to develop clear and accurate recommendations on optimal vitamin D intake and status for people affected by MS for use in clinical practice and public health policy. The final consensus report was based on a review and grading of existing published papers combined with expert opinions of panel members. The report led to recommendations published in November of 2018 on the website of the MS Society of Canada, one in a format for use by health professionals and another in a question and answer format that was targeted to persons affected by MS and the general public. For people at risk of developing MS, the vitamin D recommendations are similar to those for the general public following the Dietary Reference Intakes (DRI) for Canada and the United States. Adults should achieve and maintain a normal vitamin D status with monitoring by physicians (serum 25-hydroxyvitamin D (25(OH)D) = 50-125 nmol/L, requiring 600-4000 IU vitamin D/d intake). For pregnant women, newborn infants, and all youth at risk of MS, vitamin D intakes should also follow DRI recommendations but additionally their serum 25-(OH)D should be monitored. For persons living with MS, existing evidence did not allow prediction of a vitamin D intake that might modify MS disease course. For this group the recommendations included: (1) serum 25-(OH)D should be maintained in the range of 50-125 nmol/L (600-4000 IU/d intake).; and (2) vitamin D should not be used as a standalone treatment for MS. For children and adolescents, serum 25OHD status was recommended to be measured upon diagnosis of a first clinical demyelinating event, and monitored every 6 months to achieve a target of 75 nmol/L Since people living with MS are at increased risk of osteoporosis, falls, and bone fractures, it was recommended to achieve a minimum serum 25OHD concentration that is protective for bone health in the general population. The revision of the MS Society recommendations on vitamin D awaits future clinical trial evidence.

Tuna Bone Powder Alleviates Glucocorticoid-Induced Osteoporosis via Coregulation of the NF-κB and Wnt/ß-Catenin Signaling Pathways and Modulation of Gut Microbiota Composition and Metabolism.

SCOPE: The effects and mechanism of tuna bone powder (TBP) on glucocorticoid-induced osteoporosis (GIOP) alleviation in terms of signaling pathway coregulation and gut microbiota modulation are investigated. METHODS AND RESULTS: The powder size distribution and composition of TBP are measured. The GIOP female mice induced by dexamethasone intramuscular injection are used to examine the anti-osteoporosis effects of TBP in a 10 week experiment, and improved bone mineral density and bone microarchitecture are observed via micro-CT. In addition, qRT-PCR results show that the NF-κB pathway is inhibited to reduce bone resorption, whereas the Wnt/ß-catenin pathway is activated to enhance bone formation after treatment. Moreover, TBP treatments suppress the release of pro-inflammatory cytokines, repair dysfunction of the intestinal epithelial barrier, and prevent aggravated systemic inflammation in mRNA levels. Additionally, 16S rRNA gene sequencing indicate that TBP treatments enhance the abundance of anti-inflammatory bacteria and short-chain fatty acid (SCFA) producers, which is consistent with increased SCFA contents in feces measured via GC-MS. CONCLUSION: These data show that TBP ameliorates GIOP in mice through four aspects, including coregulating signaling pathways, blocking proinflammatory cytokines, repairing the intestinal epithelial barrier, and modulating gut microbiota. Therefore, TBP may be a potential prebiotic agent to alleviate osteoporosis in humans.

Osteoporosis and osteoarthritis are two sides of the same coin paid for obesity.

Obesity is characterized by adipose tissue expansion and chronic low-grade inflammation. Among the inflammatory mediators related to obesity development are the adipokines. These cytokines are released from fatty tissues and act in an autocrine, paracrine, or endocrine manner. Adipocytes influence the comorbidities of obesity such as osteoporosis (OP) and osteoarthritis (OA). It is still controversial as to whether OP is associated with either a low or high body mass index, but it is quite clear that the latter condition increases the risk for OA development. Bone marrow adipocytes (BMAs) have the same precursors of osteoblasts, which are the primary cells involved in bone formation, and the amount of BMAs appears to be inversely related to bone mineral density. Although adipokines released by these adipocytes influence bone loss progress, their exact role remains controversial. Differently, the infrapatellar fat pad (IPFP) is indicated to protect the function of joint regarding OA. However, there is relatively limited information about the secretion of adipokines and other inflammatory mediators by the IPFP. Despite some inconsistencies, nutritional interventions targeting obesity may also benefit patients with OP and OA. The association among obesity, OP, and OA is quite complex, and many factors need to be explored that are mainly related to the role of adipokines derived locally rather than from visceral and subcutaneous adipose tissue. Also, nutritional intervention may affect fatty tissue mass and secretion of inflammatory mediators that may, at least in part, influence other tissues in the organism such as bone and articular cartilage. The aim of this review was to present the latest knowledge about the interrelationship between obesity and OA or OP and to discuss whether a dietary intervention for obesity will hold promise for patients with OA or OP.

Pisidium coreanum Inhibits Multinucleated Osteoclast Formation and Prevents Estrogen-Deficient Osteoporosis.

Mollusks have served as important sources of human food and medicine for a long time. Raw Pisidium coreanum, a freshwater bivalve of the phylum Mollusca, is used in traditional therapies in parts of Asia. However, the therapeutic effects of Pisidium coreanum on bone diseases are not known. We investigated the functional roles of Pisidium coreanum in osteoporotic bone diseases. Pisidium coreanum inhibited the differentiation of bone marrow-derived monocytic cells into mature osteoclasts in vitro. The ovariectomized mice that received oral administration of Pisidium coreanum showed improvements in both trabecular and cortical bones. This preventive activity of Pisidium coreanum against bone loss was due to limited osteoclast maturation with reduced osteoclast surface extent in trabecular bone tissue. The formation of large multinucleated osteoclasts in vitro was significantly decreased in response to Pisidium coreanum, consistent with the reduced expression levels of osteoclast markers and fusion-related genes, such as NFATc1, p65, integrin αvß3, DC-STAMP, OC-STAMP, Atp6v0d2, FAK, CD44, and MFR. These data suggest that Pisidium coreanum inhibits osteoclast differentiation by negatively regulating the fusion of mononuclear osteoclast precursors. Thus, our data demonstrate the ability of Pisidium coreanum to effectively prevent estrogen-deficient osteoporosis through inhibition of multinucleated osteoclast formation.

A diet containing high- versus low-daidzein does not affect bone density and osteogenic gene expression in the obese Zucker rat model.

Phytoestrogens are nonsteroidal plant compounds with similar chemical structures to mammalian estrogen capable of mimicking the effect of estrogen in selective tissues. A diet rich in phytoestrogens is associated with a variety of health benefits including decreased risks for heart disease, breast cancer, and osteoporosis. Obesity has long thought to be associated with improved bone density due to increased mechanical loading, but recent literature suggests obesity may actually decrease bone health. Daidzein, a soy-derived phytoestrogen, has been shown to improve parameters of bone health in lean animal models of osteoporosis but has not been tested in obese animals. Following a one-week acclimation to a standard AIN-93G diet, 19 five-week-old female obese Zucker rats (OZR) were randomly assigned to a modified AIN-93G diet containing either high daidzein (HD, 0.121 g kg-1 feed) or low daidzein (LD, 0.01 g kg-1 feed). After 8 weeks, tibias and femurs were removed to assess true density (Archimedes principal), mechanical strength (three-point bending test), and femoral osteogenic gene expression. Serum was collected to assess osteocalcin and deoxypyridinoline. Our results indicated that there were no significant differences between the measures for tibial or femoral true density or mechanical strength for the rats in the HD and LD diet groups. Similarly, there were no significant differences in gene expressions related to osteogenic pathways, or serum biomarkers of bone formation and resorption. Overall, an increased dose of daidzein from soy protein supplementation does not elicit an improvement in markers of bone health in obese Zucker rats.

The effects of dietary fatty acids on bone, hematopoietic marrow and marrow adipose tissue in a murine model of senile osteoporosis.

Purpose: Marrow adipose tissue (MAT) expansion and associated lipotoxicity are important drivers of age-related bone loss and hematopoietic bone marrow (HBM) atrophy. Fish oil and borage oil (rich in ω3 fatty acids) can partially prevent aged-related bone loss in SAMP8 mice. However, whether preservation of bone mass in this progeria model is associated with MAT volumes remains unknown.Results: MAT volume fraction (MAT%) showed a negative association with hematopoietic bone marrow (HBM%;r=-0.836, p<0.001) and bone (bone%;r=-0.344, p=0.013) volume fractions.Adjusting for multiple comparisons, bone% was higher and MAT% was lower in Fish oil (FO)-supplemented groups vs. controls (p<0.001). HBM% did not differ significantly between the four groups. However, in the group supplemented with FO, HBM comprised higher fractions and MAT constituted lower fractions of total marrow vs. controls (p<0.001).Conclusion: Feeding FO-enriched diet prevented age-related bone and HBM loss, by reducing MAT expansion. Our results further emphasize on the role(s) of MAT expansion in bone and HBM atrophy.Methods: SAMP8 mice (n>9 /group) were allocated into 4 categories and fed a control ration, FO-, sunflower oil (SFO)- and borage oil-enriched diets for lifetime. Femurs were scanned using microcomputed tomography (µCT) and bone, MAT, and HBM volumes were determined using an image analysis software.

Tanshinone prevents alveolar bone loss in ovariectomized osteoporosis rats by up-regulating phosphoglycerate dehydrogenase.

Osteoporosis is manifested by reduced bone mass. Tanshinone has been shown to affect osteoclast differentiation, but its role in osteoporosis remains less clear. This study aimed to investigate the effects and molecular mechanisms of tanshinone on osteoporosis. Osteoporosis was induced by bilateral ovariectomy (OVX) in adult female rats treated with or without tanshinone. Trabecular bone structure was assessed by micro-computed tomography (micro-CT). Bone marrow stromal cells (BMSCs) were isolated for analysis of stemness and senescence. mRNA levels of age related genes were examined and the role of the gene that was upregulated by tanshinone treatment was suppressed to determine its involvement in tanshinone mediated effects. Finally, the mechanism underlying tanshinone induced gene upregulation was explored. We found that tanshinone treatment restored alveolar bone structure in OVX rats as well as the stemness and senescence status of BMSCs isolated from OVX rats. Tanshinone upregulated Phgdh mRNA levels and inhibition of phosphoglycerate dehydrogenase Phgdh, the protein encoded by the Phgdh gene, abolished the effects of tanshinone on BMSC stemness and senescence. Finally, we found that OVX lead to hypermethylation of the promoter region of Phgdh which was suppressed by tanshinone treatment. Our study shows that tanshinone potently suppress OVX induced osteoporosis and BMSC senescence through upregulation of PHGDH.

Biofunctional soyasaponin Bb in peanut (Arachis hypogaea L.) sprouts enhances bone morphogenetic protein-2-dependent osteogenic differentiation via activation of runt-related transcription factor 2 in C2C12 cells.

Improvement of bone formation is necessary for successful treatment of the bone defects associated with osteoporosis. In this study, we sought to elucidate the osteogenic activity of peanut sprouts and their bioactive components. We found that peanut sprout water extract (PSWE) enhanced bone morphogenetic protein-2-mediated osteoblast differentiation in a dose-dependent manner by stimulating expression of runt-related transcription factor 2 (Runx2) via activation of AKT/MAP kinases. We identified a major component of PSWE, soyasaponin Bb, as the bioactive compound responsible for improvement of anabolic activity. Soyasaponin Bb from PSWE enhanced expression of the osteogenic transcription factor Runx2 and alkaline phosphatase. The soyasaponin Bb content depended on sprouting time of peanut, and the anabolic action of PSWE was dependent on soyasaponin Bb content. Thus, PSWE and soyasaponin Bb have the potential to protect against bone disorders, including osteoporosis.

Dietary strategies for mitigating osteosarcopenia in older adults: a narrative review.

The synchronic loss of bone mineral density and decrease in muscle mass, strength, and function defines the scenario of osteosarcopenia, which is associated with an increased risk of falls and fractures in older adults. An important role in preventing muscle and bone loss is played by nutritional factors, in particular the intake of proteins, calcium, magnesium and vitamin D. This review summarizes the available literature concerning the influence of protein intake and supplementation (vitamin D, Ca, Mg, branched-chain amino acids) on the decline of musculoskeletal integrity in healthy older adults. Furthermore, in this paper, we attempted to give some suggestions to build up adequate nutritional and dietary strategies against the age-related loss of muscle and bone mass.

Effects of Isolated Isoflavones Intake on Health.

BACKGROUND: Isoflavones are naturally occurring flavonoids, commonly found in the food consumed for centuries in the East-Asian population, characterized by a structure able to exert nonsteroidal estrogen-like activity on human cells. They have attracted researcher interest all around the word, following the results obtained in epidemiological and clinical studies. The involvement of isoflavones and their metabolites in various biological processes suggests that they can influence several metabolic pathways and can influence the gene expression at epigenetic level, involving effects that probably are due to early life exposure. They show positive health effects on several diseases, especially in the prevention of coronary heart and neurological diseases, hormone-related cancers, osteoporosis, and postmenopausal symptoms. METHODS: We have performed a critical evaluation of available literature trough a structured search of bibliographic databases about isoflavones health promoting properties, risk assessment and mechanisms of action. In addition, we supplied useful information on their biochemical properties, sources and bioavailability. RESULTS: Although these molecules have been the subjects of numerous researches, their role for the wellness of the human organism remains controversial. Moreover, there are substantial inconsistencies between the results obtained by epidemiologic studies conducted on Eastern population, which found high health promoting properties, and Western clinical trials, which found much less positive effects. CONCLUSION: Further epidemiologic studies and well-designed prospective human studies are to determine the beneficial effects of isoflavones exposure, as well as establishing its safe therapeutic.

Dihydrodaidzein and 6-hydroxydaidzein mediate the fermentation-induced increase of antiosteoporotic effect of soybeans in ovariectomized mice.

The consumption of soybeans is known to have beneficial effects on osteoporosis in postmenopausal women. However, the effects of soybean fermentation on the bioavailability and the antiosteoporotic effect have not yet been elucidated. To address this question, we fed ovariectomized C57BL/6J mice with a 5% nonfermented raw soybean (RS)- or fermented soybean (FS)-supplemented diet. After 18 wk of treatment, microcomputed tomography showed that FSs significantly increased bone mineral density compared with RSs. This was because of the up-regulation of bone morphogenic protein 2 (Bmp2) and its downstream target osteopontin in bone tissues. We analyzed isoflavone metabolite profiles in the sera of RS- or FS-fed mice and observed that the levels of 19 isoflavone metabolites were significantly increased in the sera of FS-fed mice. Among these metabolites, we observed that both dihydrodaidzein (DHD) and 6-hydroxydaidzein (6-HD) increased osteogenesis via Bmp2 signaling pathway in MC3T3-E1 cells and reduced receptor activator of nuclear factor κ-B ligand-induced osteoclastogenesis in RAW264.7 cells through the inhibition of NF-κB activation and MAPK phosphorylation. These data suggest that improved bioavailability of FSs resulted from the production of active metabolites such as DHD and 6-HD after consumption. DHD and 6-HD can be used as potential therapeutics for the amelioration of osteoporotic bone loss.-Kim, J.-S., Lee, H., Nirmala, F. S., Jung, C. H., Kim, M. J., Jang, Y.-J., Ha, T. Y., Ahn, J. Dihydrodaidzein and 6-hydroxydaidzein mediate the fermentation-induced increase of anti-osteoporotic effect of soybeans in ovariectomized mice.