Search Results (430)

Aging is a complex physiological process that profoundly affects the functionality of the musculoskeletal system, contributing to an increase in the incidence of diseases such as osteoporosis, osteoarthritis, and sarcopenia. Cellular senescence plays a crucial role in these degenerative processes, promoting chronic inflammation and tissue dysfunction through the senescence-associated secretory phenotype (SASP). Recently, senotherapeutics have shown promising results in improving musculoskeletal health. Natural compounds such as resveratrol, rapamycin, quercetin, curcumin, vitamin E, genistein, fisetin, and epicatechin act on key signaling pathways, offering protective effects against musculoskeletal decline. On the other hand, molecules such as dasatinib, navitoclax, UBX0101, panobinostat, and metformin have been shown to be effective in eliminating or modulating senescent cells. However, understanding the mechanisms of action, long-term safety, and bioavailability remain areas for further investigation. In this context, physical exercise emerges as an effective non-pharmacological countermeasure, capable of directly modulating cellular senescence and promoting tissue regeneration, representing an integrated strategy to combat age-related diseases. Therefore, we have provided an overview of the main anti-aging compounds and examined the potential of physical exercise as a strategy in the management of age-related musculoskeletal disorders. Further studies should focus on identifying synergistic combinations of pharmacological and non-pharmacological interventions to optimize the effectiveness of anti-aging strategies and promoting healthier musculoskeletal aging. Full article

Vaccinium oldhamii, a blueberry species native to Korea, is a deciduous shrub in the Ericaceae family. Its fruit possesses various pharmacological properties, including anti-inflammatory effects and potential for treating osteoporosis. This study evaluated the effects of five fertilization concentration levels using Multifeed 20 (N:P:K = 20:20:20) on the growth and physiological characteristics of one-year-old V. oldhamii container seedlings. Treatments included 0 g·L⁻¹ (control), 0.5, 1.0, 1.5, and 2.0 g·L⁻¹. Increases in stem thickness, root length, and total dry weight were observed in the control, 0.5, 1.0, and 1.5 g·L⁻¹ treatments, whereas growth declined at 2.0 g·L⁻¹. Mortality rates exceeded 15% at concentrations above 1.0 g·L⁻¹. Photosynthetic capacity and chlorophyll content increased with fertilization. However, while growth improved with increasing fertilizer up to a certain level, it declined at the highest concentration. A fertilization rate of 0.5 g·L⁻¹ proved to be the most economically and environmentally efficient for producing healthy seedlings. This study provides the first fertilization threshold for V. oldhamii, offering practical guidance for nursery production and forming a foundation for future domestication strategies. Full article

Osteoclastogenesis—the activation and differentiation of osteoclasts—is one of the pivotal processes of bone remodeling and is regulated by RANKL/RANK signaling, the decoy function of osteoprotegerin (OPG), and a cascade of pro- and anti-inflammatory cytokines. The disruption of this balance leads to pathological bone loss in diseases such as osteoporosis and rheumatoid arthritis. FFAR4 (Free Fatty Acid Receptor 4), a G protein-coupled receptor for long-chain omega-3 fatty acids, has been confirmed as a key mediator of metabolic and anti-inflammatory effects. This review focuses on how FFAR4 acts as the selective receptor for the omega-3 fatty acid docosahexaenoic acid (DHA). It activates two divergent signaling pathways. The Gαq-dependent cascade facilitates intracellular calcium mobilization and ERK1/2 activation. Meanwhile, β-arrestin-2 recruitment inhibits NF-κB. These collective actions reshape the cytokine environment. In macrophages, DHA–FFAR4 signaling lowers the levels of TNF-α, interleukin-6 (IL-6), and IL-1β while increasing IL-10 secretion. Consequently, the activation of NFATc1 and NF-κB p65 is profoundly suppressed under TNF-α or RANKL stimulation. Additionally, DHA modulates the RANKL/OPG axis in osteoblastic cells by suppressing RANKL expression, thereby reducing osteoclast differentiation in an inflammatory mouse model. Full article

Background: Type 2 diabetes (T2D) has been placed among the risk factors for fragility (osteoporotic) fractures, particularly in menopausal women amid modern clinical practice. Objective: We aimed to analyze the bone status in terms of mineral metabolism assays, blood bone turnover markers (BTM), and bone mineral density (DXA-BMD), respectively, to assess the 10-year fracture probability of major osteoporotic fractures (MOF) and hip fracture (HF) upon using conventional FRAX without/with femoral neck BMD (MOF-FN/HF-FN and MOF+FN/HF+FN) and the novel model (FRAXplus) with adjustments for T2D (MOF+T2D/HF+T2D) and lumbar spine BMD (MOF+LS/HF+LS). Methods: This retrospective, cross-sectional, pilot study, from January 2023 until January 2024, in menopausal women (aged: 50–80 years) with/without T2D (group DM/nonDM). Inclusion criteria (group DM): prior T2D under diet ± oral medication or novel T2D (OGTT diagnostic). Exclusion criteria: previous anti-osteoporotic medication, prediabetes, insulin therapy, non-T2D. Results: The cohort (N = 136; mean age: 61.36 ± 8.2y) included T2D (22.06%). Groups DM vs. non-DM were age- and years since menopause (YSM)-matched; they had a similar osteoporosis rate (16.67% vs. 23.58%) and fracture prevalence (6.66% vs. 9.43%). In T2D, body mass index (BMI) was higher (31.80 ± 5.31 vs. 26.54 ± 4.87 kg/m²; p < 0.001), while osteocalcin and CrossLaps were lower (18.09 ± 8.35 vs. 25.62 ± 12.78 ng/mL, p = 0.002; 0.39 ± 0.18 vs. 0.48 ± 0.22 ng/mL, p = 0.048), as well as 25-hydroxyvitamin D (16.96 ± 6.76 vs. 21.29 ± 9.84, p = 0.013). FN-BMD and TH-BMD were increased in T2D (p = 0.007, p = 0.002). MOF+LS/HF+LS were statistically significant lower than MOF-FN/HF-FN, respectively, MOF+FN/HF+FN (N = 136). In T2D: MOF+T2D was higher (p < 0.05) than MOF-FN, respectively, MOF+FN [median(IQR) of 3.7(2.5, 5.6) vs. 3.4(2.1, 5.8), respectively, 3.1(2.3, 4.39)], but MOF+LS was lower [2.75(1.9, 3.25)]. HF+T2D was higher (p < 0.05) than HF-FN, respectively, HF+FN [0.8(0.2, 2.4) vs. 0.5(0.2, 1.5), respectively, 0.35(0.13, 0.8)] but HF+LS was lower [0.2(0.1, 0.45)]. Conclusion: Type 2 diabetic menopausal women when compared to age- and YSM-match controls had a lower 25OHD and BTM (osteocalcin, CrossLaps), increased TH-BMD and FN-BMD (with loss of significance upon BMI adjustment). When applying novel FRAX model, LS-BMD adjustment showed lower MOF and HF as estimated by the conventional FRAX (in either subgroup or entire cohort) or as found by T2D adjustment using FRAXplus (in diabetic subgroup). To date, all four types of 10-year fracture probabilities displayed a strong correlation, but taking into consideration the presence of T2D, statistically significant higher risks than calculated by the traditional FRAX were found, hence, the current model might underestimate the condition-related fracture risk. Addressing the practical aspects of fracture risk assessment in diabetic menopausal women might improve the bone health and further offers a prompt tailored strategy to reduce the fracture risk, thus, reducing the overall disease burden. Full article

Senescent cells secrete pro-inflammatory cytokines, collectively referred to as the senescence-associated secretory phenotype (SASP). Certain pro-inflammatory SASP factors are known to inhibit the differentiation of bone-forming osteoblast while promoting the differentiation of bone-resorbing osteoclasts, thereby causing osteoporosis. In this study, we screened cabozantinib, a tyrosine kinase inhibitor used to treat medullary thyroid cancer, for its ability to reduce doxorubicin-induced cellular senescence in both osteoblast and osteoclast progenitors. This non-cytotoxic agent suppressed the secretion of SASP factors (e.g., TNFα, IL1α, IL1β, IL6, and CCL2) from senescent osteoblast and osteoclast progenitors, resulting in enhanced osteoblast differentiation and reduced osteoclast differentiation. Furthermore, intraperitoneal administration of cabozantinib to age-related estrogen-deficient mice subjected to ovariectomy prevented bone loss without apparent side effects, increasing osteoblast numbers and reducing osteoclast numbers along the surface of the trabecular bone. In summary, our findings suggest that anti-aging cabozantinib has potential as a preventive anti-osteoporotic agent by promoting osteogenesis and inhibiting osteoclastogenesis through the repression of SASP. Full article

Tea is one of the most consumed beverages in the world, belonging to the category of compounds known as tannins and flavonoids. One of the polyphenols found in large amounts in green tea leaves (Camellia sinensis) is epigallocatechin-3-O-gallate (EGCG). Though EGCG has shown some pharmacological effects, to date, it has not been utilised as a therapeutic agent. This is attributed to the fact that EGCG lacks adequate stability, and it is known to degrade through epimerization or auto-oxidation processes, especially when it is exposed to light, temperature fluctuations, some pH values, or the presence of oxygen. Consuming green tea with EGCG can alleviate the effects of bone diseases, such as osteoporosis, and support faster bone regeneration in the case of fractures. Therefore, this review focuses on the current state of research, highlighting the effects of EGCG on bone biology, such as enhancing osteoblast differentiation, promoting bone mineralisation, improving bone microarchitecture, and inhibiting osteoclastogenesis through the modulation of the RANK/RANKL/OPG pathway. Additionally, EGCG exerts antioxidant, anti-inflammatory, and dose-dependent effects on bone cells. It also downregulates inflammatory markers (TNF-α, IL-1β, and COX-2) and reduces oxidative stress via the inhibition of reactive oxygen species generation and the activation of protective signalling pathways (e.g., MAPK and NF-κB). Studies in animal models confirm that EGCG supplementation leads to increased bone mass and strength. These findings collectively support the further exploration of EGCG as an adjunct in the treatment and prevention of metabolic bone diseases. The authors aim to present the relationship between EGCG and bone health, highlighting issues for future research and clinical applications. Full article

Secondary iron overload exacerbates osteoporosis by elevating reactive oxygen species (ROS), which suppress osteoblast function and enhance osteoclast activity, disrupting bone remodeling. Reducing iron overload and oxidative stress may improve bone health. Epigallocatechin-3-gallate (EGCG), the main bioactive compound in green tea extract (GTE), is recognized for its antioxidant and iron-chelating properties. This study examined the effect of GTE on bone formation and mineralization in iron-overloaded human osteoblast-like MG-63 cells. An iron-overloaded model was established using ferric ammonium citrate (FAC), followed by treatment with GTE, deferiprone (DFP), or their combination. GTE significantly reduced intracellular iron, ROS levels, and lipid peroxidation while upregulating the osteogenic marker BGLAP, the anti-resorptive marker OPG, and osteogenic mineralization, indicating restored bone health. These results suggest that EGCG-containing GTE mitigates iron-induced oxidative stress and promotes osteogenesis, highlighting its potential as a natural therapeutic supplement for managing iron-overload-associated osteoporosis. Full article

Tanshinones are a class of lipophilic diterpenoid quinones extracted from Salvia miltiorrhiza (Dan shen), a widely used herb in traditional Chinese medicine. These compounds, particularly tanshinone IIA (T-IIA) and sodium tanshinone sulfonate (STS), have been acknowledged for their broad spectrum of biological activities, including anti-inflammatory, antioxidant, anti-tumor, antiresorptive, and antimicrobial effects. Recent studies have highlighted the potential of tanshinones in the treatment of osteolytic diseases, characterized by excessive bone resorption, such as osteoporosis, rheumatoid arthritis, and periodontitis. The therapeutic effects of tanshinones in these diseases are primarily attributed to their ability to inhibit osteoclast differentiation and activity, suppress inflammatory cytokine production (e.g., tumor necrosis factor alpha (TNF-α), interleukin (IL)-1β, and IL-6), and modulate critical signaling pathways, including NF-kB, MAPK, PI3K/Akt, and the RANKL/RANK/OPG axis. Additionally, tanshinones promote osteoblast differentiation and mineralization by enhancing the expression of osteogenic markers such as Runx2, ALP, and OCN. Preclinical models have demonstrated that T-IIA and STS can significantly reduce bone destruction and inflammatory cell infiltration in arthritic joints and periodontal tissues while also enhancing bone microarchitecture in osteoporotic conditions. This review aims to provide a comprehensive overview of the pharmacological actions of tanshinones in osteolytic diseases, summarizing current experimental findings, elucidating underlying molecular mechanisms, and discussing the challenges and future directions for their clinical application as novel therapeutic agents in bone-related disorders, especially periodontitis. Despite promising in vitro and in vivo findings, clinical evidence remains limited, and further investigations are necessary to validate the efficacy, safety, and pharmacokinetics of tanshinones in human populations. Full article

Fracture risk is a serious yet underrecognized complication among patients with chronic kidney disease (CKD), especially in those with stages G3-G5D. The overlap between CKD-Mineral and Bone Disorder (CKD-MBD) and osteoporosis leads to complex bone changes that increase the likelihood of fragility fractures. Studies show that 18% to 32% of CKD patients also have osteoporosis, and these individuals are more than 2.5 times as likely to suffer from fractures compared to those without CKD. In the advanced stages of the disease, fracture risk is up to four times higher than in the general population, with the femur, forearm, and humerus being the most commonly affected sites. Hip fractures are of particular concern as they are linked to longer hospital stays and higher rates of morbidity and mortality. Furthermore, dialysis patients who experience hip fractures have a mortality rate 2.4 times higher than those in the general population with similar fractures. This increased risk underscores the need for proactive bone health maintenance in CKD patients to prevent fractures and related complications. This review explores the underlying pathophysiological mechanisms, diagnostic challenges, and treatment options related to bone fragility in CKD. Diagnostic tools, such as bone mineral density (BMD) assessments, the trabecular bone score (TBS), and biochemical markers, remain underused, especially in advanced CKD stages. Recent treatment strategies emphasize a multidisciplinary, stage-specific approach, incorporating calcium and vitamin D supplements, anti-resorptive agents like denosumab, and anabolic therapies such as teriparatide and romosozumab. Effective management needs to be tailored to the patient’s bone turnover status and stage of CKD. Despite progress in understanding bone fragility in CKD, significant gaps remain in both diagnosis and treatment. Personalized care, guided by updated KDIGO recommendations and based on an interdisciplinary approach, is essential to reduce fracture risk and improve outcomes in this vulnerable population. Further research is needed to validate risk assessment tools and refine therapeutic protocols. Full article

The genus Acmella has received growing attention for its pharmacological properties, including its potential applications in musculoskeletal disorders (MSDs). Plants in this genus, such as Spilanthes acmella, Blainvillea acmella, Acmella uliginosa, and Acmella oleracea contain various bioactive compounds which have demonstrated anti-inflammatory, analgesic, and anti-arthritic properties. This systematic review evaluates the clinical and preclinical evidence supporting the use of plants from Acmella genus for the treatment of MSD, such as arthritis, osteoporosis, muscle injuries, joint inflammation, and other related pathologies. The methodology used in this study involved a systematic literature review, following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, along with synthesis analysis and quality appraisal. The articles were retrieved from Scopus, Google Scholar, and PubMed databases. Eleven articles were further analyzed to determine the therapeutic potential of Acmella genus plants for musculoskeletal disorders. The plants included were Spilanthes acmella, Blainvillea acmella, Acmella uliginosa, and Acmella olerecia. The musculoskeletal disorders investigated were osteoporosis, osteoarthritis, and myopathies. The extracts from these plants were shown to decrease inflammation, enhance joint health, relieve pain, and stimulate osteogenic activity. These effects may be attributed to several active compounds found in these plants. The available evidence suggests that Spilanthes acmella and Blainvillea acmella have the potential to treat osteoporosis. Acmella oleracea and Acmella uliginosa have the potential to be used for the treatment of osteoarthritis, while Spilanthes acmella is used to treat myopathies. Further research is needed to establish the efficacy, optimal dosing, and safety of these plants. Full article

Background: Patients awaiting total hip arthroplasty (THA), particularly those with hip osteoarthritis (OA), face an elevated risk of osteoporosis due to age and gender-related factors. Osteoporosis, indicated by low bone mineral density (BMD), can affect implant osteointegration, long-term stability, and increase the likelihood of periprosthetic fractures. Despite these risks, osteoporosis is often underdiagnosed and undertreated in THA candidates. While several studies have addressed this issue in Northern populations, data on Southern European cohorts, particularly Italian patients, remain limited. This study aims to evaluate the prevalence of osteoporosis and vitamin D deficiency, as well as the rates of related treatments, in patients with hip osteoarthritis scheduled for THA. Methods: This single-center, retrospective study was conducted at Policlinico Universitario di TorVergata, Italy, involving 66 hip OA patients (35 men, 31 women; mean age 67.5 years). BMD was assessed at the femoral neck, total femur, and lumbar spine via DEXA, alongside vitamin D and PTH levels. Demographic data, ongoing anti-osteoporotic therapies, Harris Hip Score (HHS), and handgrip strength were recorded. Statistical analysis included t-tests and Pearson’s correlation. Osteoporosis was defined per WHO criteria, with significance set at p < 0.05. Results: In this study of 66 patients with hip osteoarthritis (35 men, 31 women; mean age 67.5 years), women exhibited significantly lower bone mineral density (BMD) at the total femur (−0.98 ± 1.42 vs. −0.08 ± 1.04; p < 0.05) and lumbar spine (−0.66 ± 1.74 vs. 0.67 ± 1.59; p < 0.05) compared to men. Handgrip strength was also significantly reduced in females (17.1 ± 8.2 kg) versus males (27.3 ± 10.3 kg; p < 0.05). Vitamin D levels were below 30 ng/mL in 89.4% of patients, and 63.6% had levels below 20 ng/mL; PTH levels were elevated (>65 pg/mL) in 54.5% of cases, indicating frequent secondary hyperparathyroidism. Only 9 patients were receiving vitamin D supplementation and none were on anti-osteoporotic treatment. Conclusions: These findings highlight the frequent coexistence of low BMD, vitamin D deficiency, and reduced muscle strength in THA candidates, suggesting a pattern of musculoskeletal vulnerability that warrants clinical attention. Full article

Background: Bisphosphonate-Related Osteonecrosis of the Jaw (BRONJ) is a severe complication associated with bisphosphonate therapy, commonly used in the treatment of osteoporosis and metastatic bone diseases. Low-Level Laser Therapy (LLLT) has been proposed as a potential treatment modality for BRONJ, with its anti-inflammatory, analgesic, and regenerative effects being of particular interest. This systematic review aims to critically assess the current evidence regarding the efficacy of LLLT in the management of BRONJ. Methods: This review was conducted following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A comprehensive search of electronic databases, including PubMed, Scopus, and Web of Science, was performed to identify relevant studies published up to September 2024. The systematic review protocol has been registered on the International Prospective Register of Systematic Reviews (PROSPERO) with the number 423003. All studies considered are observational. Studies were included if they investigated the application of LLLT in BRONJ treatment, reporting clinical outcomes such as pain reduction, lesion healing, and quality of life. The quality of the studies was assessed using the Cochrane Risk of Bias tool, and the data were synthesized descriptively. Results: A total of four studies met the inclusion criteria. The findings indicate that LLLT, particularly when used in conjunction with surgical debridement and pharmacological therapy, significantly may reduce pain and promote soft tissue healing in patients with BRONJ. However, the heterogeneity of study designs, laser parameters, and outcome measures limits the generalizability of these results. Furthermore, most studies were small-scale, with moderate to high risk of bias. Conclusions: The current evidence suggests that LLLT may be a beneficial adjunctive therapy in the treatment of BRONJ. However, conclusions are limited by the lack of randomized controlled trials and methodological heterogeneity, particularly for pain management and soft tissue regeneration. However, further high-quality randomized controlled trials with standardized laser protocols are necessary to establish its efficacy and optimize clinical application. Therefore, one of the limitations of this literature review with meta-analysis is that only four studies were considered and, moreover, they were observational. The results of the meta-analysis showed that there is not enough evidence to declare a statistical correlation; this result will surely be due to the small number of studies and heterogeneity. Full article

Stauntonia hexaphylla (Thunb.) Decne (SH) is known for its anti-inflammatory, analgesic, antioxidant, and anti-osteoporotic properties. This study investigated the composition of SH leaves and fruits and assessed their individual and combined effects in an in vitro osteoporosis model. Extracts with varying leaf-to-fruit ratios (SH82, SH55, SH28) were evaluated in MC3T3-E1 and RAW264.7 cells to examine osteogenesis and bone resorption biomarkers. SH leaves were rich in chlorogenic acids (CGAs) and flavonoids, while fruits contained phenolic acids with minimal flavonoids. Leaf extracts exhibited superior antioxidant activity and ROS suppression. Both leaf and fruit extracts enhanced ALP activity, calcium deposition, and collagen formation in MC3T3-E1 cells, with leaf extracts demonstrating greater efficacy. Additionally, osteoblastogenesis-related genes were upregulated, while TRAP activity and osteoclast-related gene expression were significantly inhibited. The combined extract exerted a synergistic effect, with SH28 showing the most pronounced osteogenic enhancement and TRAP inhibition. Key components, including neo-CGA, CGA, rutin, and luteolin-7-O-glucoside, positively influenced ALP and TRAP activities. These findings highlight the potential of SH, particularly at a high leaf-to-fruit ratio, as a promising natural agent for osteoporosis prevention. Full article

Every year, millions of people worldwide suffer from bone tissue damage caused by bone trauma and surgical operations, as well as diseases such as osteoporosis, osteoarthritis, osteomyelitis, and periodontitis. Bone defect repair is one of the major challenges in the field of regenerative medicine. Although bone grafts are the gold standard for treating bone defects, factors such as donor sources and immune responses limit their application. Functionalized nanomaterials have become an effective means of treating bone diseases due to their good biocompatibility and osteoinductivity, anti-inflammatory, and antibacterial properties. Metal–organic frameworks (MOFs) are porous coordination polymers composed of metal ions and organic ligands, featuring unique physical properties, including a high surface area–volume ratio and porosity. In regenerative medicine, MOFs function as the functions of drug carriers, metal ion donors, nanozymes, and photosensitizers. When combined with other functional materials, they regulate cellular reactive oxygen species, macrophage phenotypic transformation, bone resorption, osteogenesis, and mineralization, providing a new paradigm for bone tissue engineering. This study reviews the classification of functionalized MOF composites in biomedicine and the application of their synthesis techniques in bone diseases. The unique in vivo and in vitro applications of MOFs in bone diseases, including osteoarthritis, osteoporosis, bone tumors, osteomyelitis, and periodontitis, are explored. Their properties include excellent drug loading and sustained release abilities, high antibacterial activity, and bone induction abilities. This review enables readers to better understand the cutting-edge progress of MOFs in bone regeneration applications, which is crucial for the design of and functional research on MOF-related nanomaterials. Full article

Ginseng phytochemicals have attracted considerable attention for their potential therapeutic applications in bone-related diseases including osteosarcoma, osteoporosis, and osteoarthritis. Recent research has highlighted the promising effects of ginsenosides and polysaccharides from ginseng by studying multi-target effects and combination therapies in osteosarcoma progression. Beyond osteosarcoma, ginseng phytochemicals have been explored for their effects on osteoporosis. Various ginsenosides and ginseng extract were shown to regulate signaling pathways involved in activating osteoblast and inhibiting osteoclast in vitro and in vivo models. Ginseng ginsenosides have also demonstrated potential anti-osteoarthritic properties. Recent studies discussed how ginsenoside reduced inflammation and cartilage degradation as a therapeutic candidate for osteoarthritis management. In this review, we examine the anti-osteosarcoma, anti-osteoporotic, and anti-osteoarthritic activities of ginseng-derived phytochemicals reported in studies published between 2014 and 2024. This review also provides a comprehensive overview of the working mechanisms of these compounds in various model systems. Furthermore, we address the limitations of current research approaches and outline future directions to maximize the therapeutic application of ginseng phytochemicals in the management of bone-related diseases. Full article