Skeletal muscles (SKM) and bones form a morpho-functional unit, interconnected throughout life primarily through biomechanical coupling. This relationship serves as a key reciprocal stimulus, but they also interact via various hormones, such as sex steroids, growth hormone-insulin-like growth factor 1 (GH-IGF1) axis hormones, and adipokines like leptin and adiponectin. Additionally, myokines (released by muscles) and osteokines (released by bones) facilitate dense crosstalk, influencing each other's activity. Key myokines include interleukin (IL)-6, IL-7, IL-15, and myostatin, while osteocalcin (OC) and sclerostin are crucial bone-derived mediators affecting SKM cells. Moreover, miRNAs act as endocrine-like regulators, contributing to a complex network. This review covers the current understanding of bone-muscle crosstalk, which is essential for grasping the musculoskeletal apparatus's role in disease pathogenesis and may inform therapeutic development.

Osteoporosis, a multifaceted metabolic bone disease, is becoming increasingly prevalent and poses a significant burden on global healthcare systems. Given the limitations of traditional treatments such as pharmacotherapy, tissue engineering has emerged as a promising alternative for osteoporosis management. This review begins by exploring the pathogenesis of osteoporosis, with a focus on the abnormal metabolic, cellular, and molecular signalling microenvironments that drive the disease. We also examine commonly used clinical diagnostic techniques, discussing their strengths and limitations. Notably, this review evaluates various advanced tissue engineering strategies for osteoporosis treatment. Delivery systems, including injectable hydrogels and nanomaterials, are detailed alongside bone tissue engineering materials such as bioactive ceramics, bone cements, and polymers. Additionally, biologically active substances, including exosomes and cytokines, and emerging therapies that leverage small-molecule drugs are explored. Through a comprehensive analysis of the advantages and limitations of current biomaterials and therapeutic approaches, this review provides insights into future directions for tissue engineering-based solutions. By synthesizing current advancements, it aims to inspire innovative perspectives for the clinical management of osteoporosis.

In this study, four thermal damage assessment methods were used to investigate the thermal damage caused by femtosecond lasers on skin tissues. Collagen volume and texture characteristic parameters of the skin microstructure were calculated and analyzed by Masson staining of skin samples and grayscale covariance matrix. The skin thermal damage parameters and the degree of skin protein denaturation were analyzed by the Arrhenius equation and Raman spectroscopy. The results show that as the laser power increases or the scanning speed decreases, the collagen volume of skin tissue decreases, the angular second-order moments and correlations increase, the entropy value and contrast decrease, the parameters of thermal damage of skin tissue increase, the intensity of the characteristic peak spectral bands of the Raman spectrum of skin tissue in regions 1 and 4 decreases, and the degree of protein denaturation increases, which indicates that the degree of thermal damage of skin tissue increases.

The aim of this study was to investigate the predictive value of lumbar local fat parameters for osteoporotic vertebral compression re-fracture (OVCRF) after percutaneous kyphoplasty (PKP) and to develop a nomogram that could provide novel strategies for the prevention of OVCRF.

We included patients who underwent PKP at Zhongda Hospital between January 2012 and December 2021. The cohort was randomly divided into training and validation cohorts in a 7:3 ratio. Data collection encompassed general patient information, lumbar local fat parameters, and additional imaging data. Lumbar local fat parameters included intramuscular fat, subcutaneous fat, and epidural fat. Patients were classified into re-fracture and non-re-fracture groups based on the occurrence of OVCRF within two years post-PKP. A nomogram was developed utilizing LASSO-logistic regression, and model evaluation was performed through receiver operating characteristic curves, calibration curves, and decision curve analysis.

A total of 452 patients were included in this study. LASSO-logistic regression analysis identified age, bone mineral density (BMD), alkaline phosphatase (ALP), the fat infiltration ratio of paravertebral muscle (PVM-FIR), subcutaneous fat thickness (SFT), and the difference in local kyphotic angle (dLKA) between preoperative and postoperative periods as independent predictive factors for OVCRF. The evaluation curves demonstrated that the model exhibited strong predictive ability and clinical utility.

This study established a nomogram for predicting the occurrence of OVCRF following PKP based on lumbar local fat parameters. The model offers a valuable reference for the prediction and prevention of OVCRF.

According to World Health Organization, one in six people will be older than 60 by 2030. The rising life expectancy is anticipated to contribute to a subsequent increase of geriatric fractures worldwide. Osteosarcopenia, which is the coexistence of osteoporosis and sarcopenia, greatly affects older people. Recent studies have tried to identify the prevalence of osteosarcopenia in older populations as well as its correlation with fragility fractures such as hip fractures. The latter pose a major burden on both health loss and costs worldwide. Increasing amount of evidence suggests that osteosarcopenia in patients with hip fractures contributes to higher rates of mortality and complications. At the same time, research focuses on the molecular basis of the interplay between osteoporosis and sarcopenia by utilizing genomic or proteomic approaches. These promising studies could reveal potential preventive or diagnostic biomarkers to optimize the management of osteosarcopenia in hip fractures patients. The fact that bones and muscle can also function as endocrine organs further highlights the complex relationship between osteoporosis and sarcopenia, underscoring the need for a better understanding of the role of myokines and osteokines in osteosarcopenia. Finally, the impact of osteosarcopenia on pain management and rehabilitation after hip fracture surgery, requires further assessment.

Disturbances in lipid metabolism are closely related to intervertebral disc degeneration (IDD). However, the lipid metabolism characteristics of nucleus pulposus (NP) cells during IDD are unclear. Exercise protects against IDD and acts as a potent mediator of organ metabolism, in which muscle-secreted myokines actively participate. However, whether exercise-induced myokines alleviate IDD by regulating lipid metabolism in NP cells remains unknown. The present study revealed that lipid accumulation is the metabolic reprogramming phenotype in NP cells during IDD, which was attributed to an imbalance between increased fatty acid/triglyceride synthesis and diminished utilization, and was further associated with extracellular matrix (ECM) degradation and cell senescence. To explore the interaction between exercise and IDD, Sprague-Dawley rats were subjected to five weeks of treadmill running exercise, and rats in the exercise group exhibited less severe IDD than did those in the sedentary group. The expression of meteorin-like protein (Metrnl), a newly-discovered myokine that participates in lipid metabolism regulation, was observed to increase in muscle, serum and NP tissue after exercise. Moreover, Metrnl ameliorated lipid accumulation in NP cells and further alleviated ECM degradation and cell senescence. Mechanistically, Metrnl activated the fatty acid β-oxidation rate-limiting enzyme carnitine palmitoyltransferase 1A (CPT1A) via peroxisome proliferator-activated receptor α (PPARα) to increase lipid utilization in NP cells. This study provides insight into the lipid metabolic features of NP cells in IDD and reveals the intrinsic connections among exercise, metabolism and IDD, with the myokine Metrnl emerging as a pivotal mediator with therapeutic potential.

Bone aging is linked to changes in the lineage differentiation of bone marrow stem cells (BMSCs), which show a heightened tendency to differentiate into adipocytes instead of osteoblasts. The therapeutic potential of irisin in addressing age-related diseases has garnered significant attention. More significantly, irisin has the capacity to enhance bone mass recovery and sustain overall bone health. Its mechanism of action in preventing osteoporosis has generated considerable interest within the research community. Nonetheless, the targeting effect of irisin on age-related osteoporosis and its underlying molecular biological mechanisms remain unclear.

The specific role of irisin in osteogenic-adipogenic differentiation in young or aging BMSCs was evaluated by multiple cells staining and quantitative real-time PCR (RT-qPCR) analysis. RNA-seq and protein Western blotting excavated and validated the key pathway by which irisin influences the fate determination of aging BMSCs. The macroscopic and microscopic changes of bone tissue in aging mice were examined using Micro-computed tomography (Micro-CT) and morphological staining.

It was noted that irisin affected the multilineage differentiation of BMSCs in a manner dependent on the dosage. Simultaneously, the Wnt signaling pathway might be a crucial mechanism through which irisin sustains the bone-fat balance in aging BMSCs and mitigates the decline in pluripotency. In vivo, irisin reduced bone marrow fat deposition in aging mice and effectively alleviating the occurrence of bone loss.

Irisin mediates the Wnt signaling pathway, thereby influencing the fate determination of BMSCs. In addition, it is essential for preserving metabolic equilibrium in the bone marrow microenvironment and significantly contributes to overall bone health. The findings provide new evidence for the use of iris extract in the treatment of age-related osteoporosis.

Osteosarcopenia is a geriatric syndrome associated with an increased risk of frailty, falls, fractures, disability, and death. Calf circumference (CC) has been used as a simple and practical skeletal muscle marker to diagnose sarcopenia. This study aimed to explore the relationship of calf circumference and osteoporosis (OP) and hip fractures (HF) in middle-aged and older adults. This is important for screening OP and HF in the community and improving the quality of life of older adults.

This study was based on the National Health and Nutrition Examination Survey (NHANES) 1999-2006. Logistic regression analysis and restricted cubic spline were used to investigate the correlation of CC with OP and HF. The receiver operating characteristic (ROC) curve was utilized to determine the optimal cut-off value for CC. Finally, logistic regression model analysis was applied to test the predictive efficacy of CC.

Among 4575 individuals with a mean age of 63.0 ± 11.5 years, the OP group had higher proportions of females (P < 0.001) and non-Hispanic whites (P < 0.001). Logistic regression and RCS demonstrated that lower CC was associated with a greater risk of OP and HF in the female group (P < 0.001). ROC curves showed that CC of 33.65 cm and 33.85 cm were the best cut-off values for predicting OP and HF in middle-aged and older females. Logistic regression analyses found good predictive efficacy for cut-off values of CC in females.

In middle-aged and older women, low CC is associated with a higher risk of OP and HF. These findings have important implications for managing osteosarcopenia and associated fractures in older adults.

Not applicable.

Objective: Osteoporosis is prevalent in patients with chronic kidney disease (CKD), with risk increasing as CKD progresses, subsequently elevating fracture risk. While previous studies have shown a link between low skeletal muscle mass and osteoporosis in the general population, there is limited research exploring this relationship in patients with advanced CKD (stages 3-5D). This study aimed to evaluate whether skeletal muscle area (SMA), as measured by abdominal CT, is correlated with bone mineral density (BMD) in advanced CKD patients beginning hemodialysis. Methods: This single-center, retrospective cohort study included patients who started maintenance hemodialysis at Daejeon St. Mary's Hospital from January 2018 to September 2021. Patients who underwent abdominal CT and BMD assessments within three months of dialysis initiation were enrolled, resulting in a sample of 87 individuals. Baseline characteristics were analyzed, with patients stratified by sex and SMA quartiles. Pearson's correlation and multivariate regression analyses were conducted to the relationship between SMA and BMD T-scores. Results: The study cohort had an average age of 65.4 years, with 52.9% of participants being male. Male patients exhibited significantly higher SMA and BMD T-scores in both the lumbar spine and femur compared to female patients. SMA showed the strongest positive correlation with BMD at both sites (lumbar spine, r = 0.424; femur, r = 0.514; p < 0.001). Multivariate analysis identified SMA as an independent positive predictor of BMD, while alkaline phosphatase (ALP) was independently associated with lower femur BMD. In the SMA-based subgroup analysis, patients with lower SMA had significantly lower BMD T-scores and a higher risk of osteoporosis. Logistic regression indicated that patients in the lowest SMA quartile had substantially increased odds of osteoporosis compared to those in the highest quartile, with an adjusted odds ratio of 30.59 (p = 0.008). Conclusions: Lower skeletal muscle mass is significantly associated with lower bone density and a higher risk of osteoporosis in advanced CKD patients initiating hemodialysis. SMA, as measured by abdominal CT, may serve as a useful marker for identifying patients at elevated osteoporosis risk in this population.

Bilateral communication between bones and muscles is essential for healing composite bone-muscle injuries from orthopedic surgeries and trauma. However, these injuries are often characterized by exaggerated inflammation, which can disrupt bone-muscle crosstalk, thereby seriously delaying the healing of either tissue. Existing approaches are largely effective at healing single tissues. However, simultaneous healing of multiple tissues remains challenging, with little research conducted to date. Here we introduce collagen patches that overcome this overlooked issue by harnessing the plasticity of macrophage phenotypes. Phosphatidylserine liposomes (PSLs) capable of shifting the macrophage phenotype from inflammatory M1 into anti-inflammatory/prohealing M2 were coated on collagen patches via a layer-by-layer method. Original collagen patches failed to improve tissue healing under inflammatory conditions coordinated by M1 macrophages. In contrast, PSL-coated collagen patches succeeded in accelerating bone and muscle healing by inducing a microenvironment dominated by M2 macrophages. In cell experiments, differentiation of preosteoblasts and myoblasts was completely inhibited by secretions of M1 macrophages but unaffected by those of M2 macrophages. RNA-seq analysis revealed that type I interferon and interleukin-6 signaling pathways were commonly upregulated in preosteoblasts and myoblasts upon stimulation with M1 macrophage secretions, thereby compromising their differentiation. This study demonstrates the benefit of PSL-mediated M1-to-M2 macrophage polarization for simultaneous bone and muscle healing, offering a potential strategy toward simultaneous regeneration of multiple tissues. STATEMENT OF SIGNIFICANCE: Existing approaches for tissue regeneration, which primarily utilize growth factors, have been largely effective at healing single tissues. However, simultaneous healing of multiple tissues remains challenging and has been little studied. Here we demonstrate that collagen patches releasing phosphatidylserine liposomes (PSLs) promote M1-to-M2 macrophage polarization and are effective for simultaneous healing of bone and muscle. Transcriptome analysis using next-generation sequencing reveals that differentiation of preosteoblasts and myoblasts is inhibited by the secretions of M1 macrophages but promoted by those of M2 macrophages, highlighting the importance of timely regulation of M1-to-M2 polarization in tissue regeneration. These findings provide new insight to tissue healing of multiple tissues.

Osteo-sarcopenia (OS) has become a global public health problem and a frontier research problem, as a combination of sarcopenia (SP) and osteoporosis (OP) diseases. The clinical performances include muscle weakness, systemic bone pain, standing difficulty, even falls and fractures, etc., which seriously affect the patient's life and work. The pathological mechanism of the OS may be the abnormal metabolism which disrupts the equilibrium stability of the musculoskeletal system. Therefore, this study combined vitamin D (Vit. D) and whole-body vibration training (WBVT) to intervene in subjects of OS, aiming to evaluate the effectiveness and safety of the diagnosis and treatment protocol and to explore the efficacy mechanism.

We propose a multicenter, parallel-group clinical trial to evaluate the efficacy and safety of Vit. D combined with WBVT intervention in OS. Subjects who met the inclusion or exclusion criteria and signed the informed consent form would be randomly assigned to the WBVT group, Vit. D group, or WBVT+ Vit. D group. All subjects will be treated for 1 month and followed up after 3 and 6 months. The primary outcomes are lumbar bone mineral density (BMD) and appendicular skeletal muscle mass (ASM) measured by dual-energy X-ray absorptiometry (DXA) and handgrip strength measured by grip strength meter. Secondary outcomes include serum markers of myostatin (MSTN), irisin and bone turnover markers (BTM), SARC-CalF questionnaire, 1-min test question of osteoporosis risk, patient health status (evaluated by the SF-36 health survey), physical performance measurement that includes 5-time chair stand test, 6-m walk, and the short physical performance battery (SPPB).

If Vit. D combined with WBVT can well relieve OS symptoms without adverse effects, this protocol may be a new treatment strategy for OS. After therapeutic intervention, if the serum marker MSTN/irisin is significant, both have the potential to become sensitive indicators for screening OS effective drugs and treatments, which also indicates that WBVT combined with Vit. D plays a role in improving OS by regulating MSTN/irisin.

Chinese Clinical Trial Registry ChiCTR2400082269 . Registered on March 26, 2024.

Inflammaging, an immune status characterized by a sustained increase in pro-inflammatory markers and a decline in anti-inflammatory mechanisms, is a critical risk factor in the development of sarcopenia. Landscapes of the causal relationships between immunity and sarcopenia are needed to understand the mechanism of sarcopenia and provide novel treatments comprehensively.

We used Mendelian Randomization (MR) as the basic method in this study. By setting immune proteins, immune cells, and sarcopenia as exposures and outcomes alternatively, and then combining them in different directions, we potentially estimated their causal relationships and directions and subsequently mapped the comprehensive causal landscape based on this information efficiently. To further understand the network, we developed a method based on rank-sums to integrate multiple algorithms and identify the key immune cells and proteins.

More than 1,000 causal relationships were identified between immune cell phenotypes, proteins, and sarcopenia traits (p < 0.05), and the causal maps of these linkages were established. In the threshold of FDR < 0.05, hundreds of causal linkages were still significant. The final comprehensive map included 13 immune cell phenotypes and 8 immune proteins. The star factors in the final map included EM CD8br %CD8br, EM DN (CD4- CD8-) %DN, SIRT2, and so on.

By reading the landscapes in this study, we may not only find the factors and the pathways that have been reported and proven but also identify multiple novel immunity cell phenotypes and proteins with enriched upstream and downstream pathways.

Disorders of the musculoskeletal system are the major contributors to the global burden of disease and current treatments show limited efficacy. Patients often suffer chronic pain and might eventually have to undergo end-stage surgery. Therefore, future treatments should focus on early detection and intervention of regional lesions. Microrobots have been gradually used in organisms due to their advantages of intelligent, precise and minimally invasive targeted delivery. Through the combination of control and imaging systems, microrobots with good biosafety can be delivered to the desired area for treatment. In the musculoskeletal system, microrobots are mainly utilized to transport stem cells/drugs or to remove hazardous substances from the body. Compared to traditional biomaterial and tissue engineering strategies, active motion improves the efficiency and penetration of local targeting of cells/drugs. This review discusses the frontier applications of microrobotic systems in different tissues of the musculoskeletal system. We summarize the challenges and barriers that hinder clinical translation by evaluating the characteristics of different microrobots and finally point out the future direction of microrobots in the musculoskeletal system.

Menopause, an extremely delicate phase in a woman's life, is characterized by a drop in estrogen levels. This decrease has been associated with the onset of several diseases, including postmenopausal osteoporosis and sarcopenia, which often coexist in the same person, leading to an increased risk of fractures, morbidity, and mortality. To date, there are no approved pharmacological treatments for sarcopenia, while not all of those approved for postmenopausal osteoporosis are beneficial to muscles. In recent years, research has focused on the field of myokines, cytokines, or peptides secreted by skeletal muscle fibers following exercise. Among these, irisin has attracted great interest as it possesses myogenic properties but at the same time exerts anabolic effects on bone and could therefore represent the link between muscle and bone. Therefore, irisin could represent a new therapeutic strategy for the treatment of osteoporosis and also serve as a new biomarker of sarcopenia, thus facilitating diagnosis and pharmacological intervention. The purpose of this review is to provide an updated summary of what we know about the role of irisin in postmenopausal osteoporosis and sarcopenia.

The present review will highlight recent reports supporting the relevance of extracellular vesicles to the musculoskeletal system in health and disease.

Preserving the health of the musculoskeletal system is important to maintain a good quality of life, and the bone-muscle crosstalk is crucial in this regard. This latter is largely mediated by extracellular vesicles released by the different cell populations residing in muscle and bone, which deliver cargoes, microRNAs, and proteins being the most relevant ones, to target cells. Extracellular vesicles could be exploited as therapeutic tools, in view of their resistance to destruction in the biological fluid and of the possibility to be functionalized according to the need. Extracellular vesicles are recognized as crucial players in the bone-muscle cross-talk. Additional studies however are required to refine their use as biomarkers of early alterations of the musculoskeletal system, and as potential therapeutic tools.

Skeletal muscle diseases, a broad category encompassing a myriad of afflictions such as acute muscle injury and muscular dystrophies, pose a significant health burden globally. These conditions often lead to muscle weakness, compromised mobility, and a diminished quality of life. In light of this, innovative and effective therapeutic strategies are fervently sought after. Exosomes, naturally extracellular vesicles with a diameter of 30-150 nm, pervade biological fluids. These microscopic entities harbor a host of biological molecules, including proteins, nucleic acids, and lipids, bearing a significant resemblance to their parent cells. The roles they play in the biological theater are manifold, influencing crucial physiological and pathological processes within the organism. In the context of skeletal muscle diseases, their potential extends beyond these roles, as they present a promising therapeutic target and a vehicle for targeted drug delivery. This potentially paves the way for significant clinical applications. This review aims to elucidate the mechanisms underpinning exosome action, their myriad biological functions, and the strides made in exosome research and application. A comprehensive exploration of the part played by exosomes in skeletal muscle repair and regeneration is undertaken. In addition, we delve into the use of exosomes in the therapeutic landscape of skeletal muscle diseases, providing a valuable reference for a deeper understanding of exosome applications in this realm. The concluding section encapsulates the prospective avenues for exosome research and the promising future they hold, underscoring the tremendous potential these diminutive vesicles possess in the field of skeletal muscle diseases. The Translational Potential of this Article. The comprehensive exploration of exosome's diverse biological functions and translational potential in the context of skeletal muscle diseases presented in this review underscores their promising future as a therapeutic target with significant clinical applications, thus paving the way for innovative and effective therapeutic strategies in this realm.