Updates in the skeletal and joint protective effects of tocotrienol: a mini review.

Osteoporosis and osteoarthritis continue to pose significant challenges to the aging population, with limited preventive options and pharmacological treatments often accompanied by side effects. Amidst ongoing efforts to discover new therapeutic agents, tocotrienols (TTs) have emerged as potential candidates. Derived from annatto bean and palm oil, TTs have demonstrated efficacy in improving skeletal and joint health in numerous animal models of bone loss and osteoarthritis. Mechanistic studies suggest that TTs exert their effects through antioxidant, anti-inflammatory, Wnt-suppressive, and mevalonate-modulating mechanisms in bone, as well as through self-repair mechanisms in chondrocytes. However, human clinical trials in this field remain scarce. In conclusion, TTs hold promise as agents for preventing osteoporosis and osteoarthritis, pending further evidence from human clinical trials.

Navigating the gut-bone axis: The pivotal role of Coprococcus3 in osteoporosis prevention through Mendelian randomization.

Osteoporosis (OP) constitutes a notable public health concern that significantly impacts the skeletal health of the global aging population. Its prevalence is steadily escalating, yet the intricacies of its diagnosis and treatment remain challenging. Recent investigations have illuminated a profound interlink between gut microbiota (GM) and bone metabolism, thereby opening new avenues for probing the causal relationship between GM and OP. Employing Mendelian randomization (MR) as the investigative tool, this study delves into the causal rapport between 211 varieties of GM and OP. The data are culled from genome-wide association studies (GWAS) conducted by the MiBioGen consortium, in tandem with OP genetic data gleaned from the UK Biobank, BioBank Japan Project, and the FinnGen database. A comprehensive repertoire of statistical methodologies, encompassing inverse-variance weighting, weighted median, Simple mode, Weighted mode, and MR-Egger regression techniques, was adroitly harnessed for meticulous analysis. The discernment emerged that the genus Coprococcus3 is inversely associated with OP, potentially serving as a deterrent against its onset. Additionally, 21 other gut microbial species exhibited a positive correlation with OP, potentially accentuating its proclivity and progression. Subsequent to rigorous scrutiny via heterogeneity and sensitivity analyses, these findings corroborate the causal nexus between GM and OP. Facilitated by MR, this study successfully elucidates the causal underpinning binding GM and OP, thereby endowing invaluable insights for deeper exploration into the pivotal role of GM in the pathogenesis of OP.

Exercise perspective: Benefits and mechanisms of gut microbiota on the body. / è¿åŠ¨è§’åº¦ï¼šè‚ é“èŒç¾¤å¯¹æœºä½“çš„ç›Šå¤„åŠå ¶æœºåˆ¶.

Gut microbiota refers to the vast and diverse community of microorganisms residing in the intestines. Factors such as genetics, environmental influences (e.g., exercise, diet), and early life experiences (e.g., infant feeding methods) can all affect the ecological balance of gut microbiota within the body. Dysbiosis of the gut microbiota is associated with extra-intestinal diseases such as Parkinson's syndrome, osteoporosis, and autoimmune diseases, suggesting that disturbances in gut microbiota may be one of the causes of these diseases. Exercise benefits various diseases, with gut microbiota playing a role in regulating the nervous, musculoskeletal, and immune systems. Gut microbiota can impact the body's health status through the gut-brain axis, gut-muscle axis, and immune pathways. Moderate-intensity aerobic exercise can increase the quantity of gut microbiota and change microbial abundance, although short-term exercise does not significantly affect the alpha diversity of the microbiota. Resistance exercise also does not have a significant regulatory effect on gut microbiota.

Pharmacist-initiated interventions to test quantitative bone mineral density and prescribe osteoporosis medications to prevent steroid-induced osteoporosis.

Fragility fractures associated with glucocorticoid-induced osteoporosis (GIO) can markedly impair quality of life. However, only 20% of patients are treated in compliance with the relevant management guidelines, and bone mineral density analysis with dual-energy X-ray absorptiometry (DXA) is only rarely performed. We report the intervention methods suggested by pharmacists and describe their efficacy. Patients who visited the outpatient clinic of the General Medicine Department of Ogaki Municipal Hospital and received steroids were enrolled. The rates of DXA implementation and compliance with GIO pharmacotherapy guidelines before and after pharmacist to physician-suggested interventions were compared. Guideline compliance was defined as prescription of osteoporosis drugs to patients with a score of ≥3. Administered prophylaxes and bone mineral density were subsequently assessed. The before and after intervention DXA rates were 1% (1/100 patients) and 96.0% (96/100 patients; P<0.01), respectively. Overall, 96.9% (93/96) of the patients met the GIO criteria for pharmacotherapy initiation (score ≥3), and the guideline compliance rates before and after the intervention were 39.8% (37/93) and 93.5% (87/93; P<0.01), respectively. Of the 56 patients who did not receive prophylaxis, 52 were recommended treatment, yielding an acceptance rate of 82.7% (43/52). Among the 37 patients receiving prophylaxis, 20 (54.1%) had a DXA-related young adult mean of ≤70%, of whom 11 (55.0%) agreed to drug therapy. The acceptance rate of pharmacotherapy recommendations for patients not receiving prophylaxis was higher than that for those receiving prophylaxis (P=0.03). Pharmacist-initiated interventions for GIO facilitates the administration of appropriate pharmacotherapy.

Nutraceuticals and Functional Foods: A Comprehensive Review of Their Role in Bone Health.

Bone health is the result of a tightly regulated balance between bone modeling and bone remodeling, and alterations of these processes have been observed in several diseases both in adult and pediatric populations. The imbalance in bone remodeling can ultimately lead to osteoporosis, which is most often associated with aging, but contributing factors can already act during the developmental age, when over a third of bone mass is accumulated. The maintenance of an adequate bone mass is influenced by genetic and environmental factors, such as physical activity and diet, and particularly by an adequate intake of calcium and vitamin D. In addition, it has been claimed that the integration of specific nutraceuticals such as resveratrol, anthocyanins, isoflavones, lycopene, curcumin, lutein, and ß-carotene and the intake of bioactive compounds from the diet such as honey, tea, dried plums, blueberry, and olive oil can be efficient strategies for bone loss prevention. Nutraceuticals and functional foods are largely used to provide medical or health benefits, but there is an urge to determine which products have adequate clinical evidence and a strong safety profile. The aim of this review is to explore the scientific and clinical evidence of the positive role of nutraceuticals and functional food in bone health, focusing both on molecular mechanisms and on real-world studies.

Synergistic Effects of Nutrients on Musculoskeletal Health in Gerontology: Understanding the Combined Impact of Macronutrients and Micronutrients.

With the global aging population, addressing prevalent age-related conditions such as osteoporosis and sarcopenia is crucial. Traditional nutritional strategies focusing on single nutrients like calcium, vitamin D, or protein have limitations, prompting a nuanced exploration of the relationship between aging, nutrition, and musculoskeletal health. This cross-sectional study examines the complex interplay between dietary intake of macronutrients, common micronutrients, and water, as well as their association with musculoskeletal health in adults aged 50 to 80 years, using U.S. National Health and Nutrition Examination Survey data (NHANES). Employing multiple linear regression, restricted cubic splines, weighted quantile sum (WQS), and quantile-based g-computation (QGC) regression models, our initial analysis using the WQS model revealed that a one-quartile increase in mixed macronutrient intake was associated with a significant 0.009 unit increase in bone mineral density (BMD) and a 0.670 unit increase in grip strength, while a similar increase in mixed micronutrient intake showed a 0.007 unit increase in BMD and a 0.442 unit increase in grip strength. Our findings highlight the importance of a balanced dietary approach in promoting musculoskeletal health in the elderly, offering holistic strategies for overall well-being.

Dietary Puerarin Translocates to Femur and Suppresses Osteoclast Differentiation in Ovariectomized Mice.

Osteoporosis is characterized by bone loss and deterioration in bone microstructure, leading to bone fragility. It is strongly correlated with menopause in women. Previously, we reported that diets supplemented with a kudzu (Pueraria lobata) vine extract suppressed bone resorption in ovariectomized (OVX) mice, a postmenopausal model. The main isoflavone in kudzu is puerarin (daidzein-8-C-glycoside). Puerarin (daidzein-8-C-glycoside), which is main isoflavone of kudzu, probably contributes to the beneficial effect. However, the underlying mechanism is unclear. Therefore, the nutrikinetics of puerarin and the comparison with the suppressive effects of kudzu isoflavones on osteoclast differentiation was examined in this study. We demonstrated that orally administered puerarin was absorbed from the gut and entered the circulation in an intact form. In addition, puerarin accumulated in RAW264.7 pre-osteoclast cells in a time-dependent manner. Tartrate-resistant acid phosphatase activity was decreased by puerarin treatment in a concentration-dependent manner in RAW264.7 cells stimulated with the receptor activator of nuclear factor kappa-B ligand. Ovariectomy-induced elevated bone resorption was suppressed, and the fragile bone strength was improved by puerarin ingestion in the diet. These findings suggested that orally administered puerarin was localized in bone tissue and suppressed bone resorption and osteoclastogenesis in ovariectomized mice.

New insights into dairy management and the prevention and treatment of osteoporosis: The shift from single nutrient to dairy matrix effects-A review.

Dairy is recognized as a good source of calcium, which is important for preventing osteoporosis. However, the relationship between milk and bone health is more complex than just calcium supplementation. It is unwise to focus solely on observing the effects of a single nutrient. Lactose, proteins, and vitamins in milk, as well as fatty acids, oligosaccharides, and exosomes, all work together with calcium to enhance its bioavailability and utilization efficiency through various mechanisms. We evaluate the roles of dairy nutrients and active ingredients in maintaining bone homeostasis from the perspective of the dairy matrix effects. Special attention is given to threshold effects, synergistic effects, and associations with the gut-bone axis. We also summarize the associations between probiotic/prebiotic milk, low-fat/high-fat milk, lactose-free milk, and fortified milk with a reduced risk of osteoporosis and discuss the potential benefits and controversies of these dairy products. Moreover, we examine the role of dairy products in increasing peak bone mass during adolescence and reducing bone loss in old age. It provides a theoretical reference for the use of dairy products in the accurate prevention and management of osteoporosis and related chronic diseases and offers personalized dietary recommendations for bone health in different populations.

Clinical Practice Guidelines of the Latin American Federation of Endocrinology for the use of vitamin D in the maintenance of bone health: recommendations for the Latin American context.

INTRODUCTION: These guidelines aim to provide evidence-based recommendations for the supplementation of Vitamin D in maintaining bone health. An unmet need persists in Latin American regarding the availability of clinical and real-world data for rationalizing the use of vitamin D supplementation. The objective of these guidelines is to establish clear and practical recommendations for healthcare practitioners from Latin American countries to address Vitamin D insufficiency in clinical practice. METHODS: The guidelines were developed according to the GRADE-ADOLOPMENT methodology for the adaptation or adoption of CPGs or evidence-based recommendations. A search for high quality CPGs was complemented through a comprehensive review of recent literature, including randomized controlled trials, observational studies, and systematic reviews evaluating the effects of Vitamin D supplementation on bone health. The evidence to decision framework proposed by the GRADE Working Group was implemented by a panel of experts in endocrinology, bone health, and clinical research. RESULTS: The guidelines recommend Vitamin D supplementation for individuals aged 18 and above, considering various populations, including healthy adults, individuals with osteopenia, osteoporosis patients, and institutionalized older adults. These recommendations offer dosing regimens depending on an individualized treatment plan, and monitoring intervals of serum 25-hydroxyvitamin D levels and adjustments based on individual results. DISCUSSION: The guidelines highlight the role of Vitamin D in bone health and propose a standardized approach for healthcare practitioners to address Vitamin D insufficiency across Latin America. The panel underscored the necessity for generating local data and stressed the importance of considering regional geography, social dynamics, and cultural specificities when implementing these guidelines.

[What to do to prevent osteoporosis ? Between myths and scientific reality]. / Que faire pour prévenir l'ostéoporose ? Entre mythes et réalité scientifique.

Osteoporosis is a skeletal disease characterized by low bone density and altered microarchitecture, exposing to bone fragility and an increased risk of fracture. Several therapeutic modalities can effectively reduce the risk of fractures both vertebral and non-vertebral. While a significant part of bone strength and structure is genetically determined, it should be recalled that the environment also plays a significant role in these parameters and the risk of fracture, thus offering preventive opportunities thanks to lifestyle. In this article, we review the common misconceptions and myths about the influence of diet and physical activity on bone mineral density and fracture risk.

L'ostéoporose est une maladie du squelette caractérisée par une densité osseuse basse et une microarchitecture altérée, exposant à une fragilité osseuse et à un risque accru de fracture. Plusieurs classes thérapeutiques existent, capables de réduire efficacement le risque de fracture à la fois vertébrale et non vertébrale. Si une partie importante de la force et de la structure osseuse est déterminée génétiquement, il faut garder en mémoire que l'environnement joue aussi un rôle non négligeable sur ces paramètres et le risque de fracture, offrant donc des opportunités de prévention grâce au style de vie. Dans cet article, nous passons en revue les idées préconçues et les mythes qui circulent à propos de l'influence de l'alimentation et de l'activité physique sur la densité minérale osseuse et le risque de fracture.

[Osteoporosis treatment for fracture prevention in elderly].

Fracture prevention in the elderly is an urgent issue at all levels: individual, family, and societal. Osteoporosis is the underlying cause of fractures in the elderly, and it is important to understand its pathogenesis and treatment. Diet, exercise, and pharmacotherapy are all important for fracture prevention. Particularly with regard to pharmacotherapy, it is important to understand the mechanism of action of each drug and its characteristics and problems from a clinical point of view. Appropriate treatment of osteoporosis has been proven to reduce fractures in the elderly, and its widespread implementation is desirable.

Developing and Investigating a Nanovibration Intervention for the Prevention/Reversal of Bone Loss Following Spinal Cord Injury.

Osteoporosis disrupts the fine-tuned balance between bone formation and resorption, leading to reductions in bone quantity and quality and ultimately increasing fracture risk. Prevention and treatment of osteoporotic fractures is essential for reductions in mortality, morbidity, and the economic burden, particularly considering the aging global population. Extreme bone loss that mimics time-accelerated osteoporosis develops in the paralyzed limbs following complete spinal cord injury (SCI). In vitro nanoscale vibration (1 kHz, 30 or 90 nm amplitude) has been shown to drive differentiation of mesenchymal stem cells toward osteoblast-like phenotypes, enhancing osteogenesis and inhibiting osteoclastogenesis simultaneously. Here, we develop and characterize a wearable device designed to deliver and monitor continuous nanoamplitude vibration to the hindlimb long bones of rats with complete SCI. We investigate whether a clinically feasible dose of nanovibration (two 2 h/day, 5 days/week for 6 weeks) is effective at reversing the established SCI-induced osteoporosis. Laser interferometry and finite element analysis confirmed transmission of nanovibration into the bone, and microcomputed tomography and serum bone formation and resorption markers assessed effectiveness. The intervention did not reverse SCI-induced osteoporosis. However, serum analysis indicated an elevated concentration of the bone formation marker procollagen type 1 N-terminal propeptide (P1NP) in rats receiving 40 nm amplitude nanovibration, suggesting increased synthesis of type 1 collagen, the major organic component of bone. Therefore, enhanced doses of nanovibrational stimulus may yet prove beneficial in attenuating/reversing osteoporosis, particularly in less severe forms of osteoporosis.

Endoplasmic reticulum protein of 57 kDa sulfhydration promotes intestinal calcium absorption to attenuate primary osteoporosis.

Endogenous hydrogen sulfide (H2S) plays an important role in bone metabolism. However, the exact role of H2S in intestinal calcium and phosphorus absorption and its potential in preventing and treating primary osteoporosis remains unknown. Therefore, this study aimed to investigate the potential of H2S in promoting intestinal calcium and phosphorus absorption and alleviating primary osteoporosis. We measured the apparent absorptivity of calcium, femoral bone density, expression and sulfhydration of the duodenal endoplasmic reticulum protein of 57 kDa (ERp57), duodenal cystathionine γ-lyase (CSE) expression, and serum H2S content in adult and old CSE-knockout and wild-type mice. We also assessed intracellular reactive oxygen species (ROS) and Ca2+ content in CSE-overexpressing or knockout intestinal epithelial cell (IEC)-6 cells. In senile mice, CSE knockout decreased endogenous H2S, ERp57 sulfhydration, and intestinal calcium absorption and worsened osteoporosis, which were partially reversed by GYY4137, an H2S donor. CSE overexpression in IEC-6 cells increased ERp57 sulfhydration, protein kinase A and C activity, and intracellular Ca2+, whereas CSE knockout exerted the opposite effects. Furthermore, hydrogen peroxide (H2O2) stimulation had similar effects as in CSE knockout, which were reversed by pretreatment with sodium hydrosulfide before H2O2 stimulation and restored by DL-dithiothreitol. These findings suggest that H2S attenuates primary osteoporosis by preventing ROS-induced ERp57 damage in intestinal epithelial cells by enhancing ERp57 activity and promoting intestinal calcium absorption, thereby aiding in developing therapeutic interventions to prevent osteoporosis.

Grape seed extract prevents oestrogen deficiency-induced bone loss by modulating the gut microbiota and metabolites.

Proanthocyanidin-rich grape seed extract (GSE) has been shown to have the potential to protect bones, although the underlying mechanism remains unknown. The current study aims to explore GSE's preventive and therapeutic impact on bone loss induced by oestrogen deficiency and the underlying mechanism through the gut microbiota (GM) and metabolomic responses. In oestrogen-deficient ovariectomized (OVX) mice, GSE ameliorated bone loss by inhibiting the expansion of bone marrow adipose tissue (BMAT), restoring BMAT lipolysis and promoting bone formation. GSE regulated OVX-induced GM dysbiosis by reducing the abundance of opportunistic pathogenic bacteria, such as Alistipes, Turicibacter and Romboutsia, while elevating the abundance of beneficial bacteria, such as Bifidobacterium. The modified GM primarily impacted lipid and amino acid metabolism. Furthermore, the serum metabolites of GSE exhibited a significant enrichment in lipid metabolism. In summary, GSE shows potential as a functional food for preventing oestrogen deficiency-induced bone loss by modulating GM and metabolite-mediated lipid metabolism.

Association between dietary folate intake and the risk of osteoporosis in adults: a cross-sectional study.

BACKGROUND: Increased intake of specific vitamins has been linked to a decreased prevalence of osteoporosis. However, the association between dietary folate intake and the risk of osteoporosis in the general population remains incompletely understood. Therefore, we aimed to determine the association between dietary folate intake and the risk of osteoporosis in the general population of the USA. METHODS: In this cross-sectional study, data from the National Health and Nutrition Examination Survey (2017-2020) were collected. Osteoporosis was considered to be indicated by a bone mineral density greater than 2.5 standard deviations below the mean of the young adult reference group. Dietary folate intake was measured by a 24-hour dietary recall. Multivariate logistic regression models and restricted cubic spline models were used. RESULTS: The study included 2297 participants (mean age: 63.69 ± 0.35 years), 49.92% of whom were female. In the general population, increased dietary folate intake was directly associated with a decreased risk of osteoporosis (P for trend = 0.005). In the age > 60 years and female subgroups, folate intake was inversely associated with the risk of osteoporosis (P for trend < 0.001). The dose‒response curve suggested that this association was nonlinear (P for nonlinearity = 0.015). CONCLUSIONS: Our cross-sectional study provides initial insights into the inverse association between dietary folate intake and the risk of osteoporosis in the general U.S. POPULATION: Further research is needed to confirm these associations.

[Update of the S3-guideline on diagnostics, prophylaxis and treatment of osteoporosis]. / Update der S3-Leitlinie Diagnostik, Prophylaxe und Therapie der Osteoporose.

With the aid of a new fracture risk model, the great treatment gap for osteoporosis should be closed. All patients older than 70 years should undergo a diagnostic procedure for osteoporosis. An additional risk threshold (≥ 10% per 3 years for femoral and vertebral fractures) should enable patients with a high risk of fracture to be treated with osteoanabolic agents. The use of osteoanabolic agents makes it necessary to administer antiresorptive drugs afterwards. Due to the low event rate of osteonecrosis of the jaw, the initiation of a specific osteoporosis treatment should not be delayed by prophylactic dental treatment. The adherence to the drug treatment should be improved by an individualized approach on the basis of a cooperation between patients, caregivers, and physicians. A regular assessment of falls, including the timed up and go test should be carried out in patients older than 70 years.

Norisoboldine, a Natural Alkaloid from Lindera aggregata (Sims) Kosterm, Promotes Osteogenic Differentiation via S6K1 Signaling Pathway and Prevents Bone Loss in OVX Mice.

SCOPE: Norisoboldine (NOR) is a major isoquinoline alkaloid component in the traditional Chinese herbal plant Lindera aggregata (Sims) Kosterm, with previously reported anti-osteoclast differentiation and antiarthritis properties. However, the roles of NOR on osteoblasts, bone marrow mesenchymal stem cells (BMSCs), and osteoporosis in vivo have never been well established. METHODS AND RESULTS: This study investigates the ability of NOR to improve bone formation in vitro and in vivo. Osteoblasts and BMSCs are used to study the effect of NOR on osteogenic and adipogenic differentiation. It finds that NOR promotes osteogenic differentiation of osteoblasts and BMSCs, while inhibiting adipogenic differentiation of BMSCs by reducing the relative expression of peroxisome proliferator-activated receptor Î³ (Ppar-γ) and adiponectin, C1Q and collagen domain containing (Adipoq). Mechanistic studies show that NOR increases osteoblast differentiation through the mechanistic target of rapamycin kinase (mTOR)/ribosomal protein S6 kinase; polypeptide 1 (S6K1) pathway, and treatment with an mTOR inhibitor rapamycin blocked the NOR-induced increase in mineral accumulation. Finally, the study evaluates the therapeutic potential of NOR in a mouse model of ovariectomy (OVX)-induced bone loss. NOR prevents bone loss in both trabecular and cortical bone by increasing osteoblast number and phospho-S6K1 (p-S6K1) expression in osteoblasts. CONCLUSION: NOR effects in enhancing osteoblast-induced bone formation via S6K1 pathway, suggesting the potential of NOR in osteoporosis treatment by increasing bone formation.

AN698/40746067 suppresses bone marrow adiposity to ameliorate hyperlipidemia-induced osteoporosis through targeted inhibition of ENTR1.

Hyperlipidemia-induced osteoporosis is marked by increased bone marrow adiposity, and treatment with statins for hyperlipidemia often leads to new-onset osteoporosis. Endosome-associated trafficking regulator 1 (ENTR1) has been found to interact with different proteins in pathophysiology, but its exact role in adipogenesis is not yet understood. This research aimed to explore the role of ENTR1 in adipogenesis and to discover a new small molecule that targets ENTR1 for evaluating its effectiveness in treating hyperlipidemia-induced osteoporosis. We found that ENTR1 expression increased during the adipogenesis of bone marrow mesenchymal cells (BMSCs). ENTR1 gain- and loss-of-function assays significantly enhanced lipid droplets formation. Mechanistically, ENTR1 binds peroxisome proliferator-activated receptor γ (PPARγ) and enhances its expression, thereby elevating adipogenic markers including C/EBPα and LDLR. Therapeutically, AN698/40746067 attenuated adipogenesis by targeting ENTR1 to suppress PPARγ. In vivo, AN698/40746067 reduced bone marrow adiposity and bone loss, as well as prevented lipogenesis-related obesity, inflammation, steatohepatitis, and abnormal serum lipid levels during hyperlipidemia. Together, these findings suggest that ENTR1 facilitates adipogenesis by PPARγ involved in BMSCs' differentiation, and targeted inhibition of ENTR1 by AN698/40746067 may offer a promising therapy for addressing lipogenesis-related challenges and alleviating osteoporosis following hyperlipidemia.