Osteosarcopenia predicts greater risk of functional disability than sarcopenia: a longitudinal analysis of FraDySMex cohort study.

OBJECTIVES: Aging involves significant changes in body composition, marked by declines in muscle mass and bone mineral density alongside an increase in fat mass. Sarcopenia is characterized by low strength and muscle mass, and osteosarcopenia is the coexistence of sarcopenia and osteopenia/osteoporosis. Physiologically, there is a crosstalk between muscle and bone tissues mediated by several pathways. Both, sarcopenia and osteosarcopenia, have been related with adverse outcomes such as functional disability. However, there is a lack of longitudinal studies. Therefore, this study aimed to assess whether sarcopenia and osteosarcopenia phenotypes increased the risk of functional disability in a longitudinal cohort of community-dwelling adults. DESIGN: This study constitutes a secondary longitudinal analysis of data derived from the prospective cohort FraDySMex (Frailty, Dynapenia, and Sarcopenia in Mexican adults). SETTING AND PARTICIPANTS: FraDySMex is conducted in community-dwelling adults aged 50 years or older living in Mexico City. Data from 2014 to 2015 was considered as baseline evaluation, and the 2019 wave was the follow-up evaluation. Individuals with complete baseline and follow-up evaluations were included in the analysis. MEASUREMENTS: Sarcopenia diagnosis adhered to the FNIH criteria, while osteopenia/osteoporosis classification followed WHO guidelines. Osteosarcopenia was defined as the concurrent presence of sarcopenia and osteopenia/osteoporosis. Functional disability was identified by the Lawton Instrumental Activities of Daily Living (IADL) Scale. Adjusted mixed-effects logistic regression models were estimated to evaluate the effect of body composition phenotype on the risk of functional disability. RESULTS: The final sample included 320 adults with complete longitudinal data. The majority of were women (83.4%) and had 7-12 years of education (48.4%). At the baseline evaluation, 50.9% aged 50-70. The osteosarcopenia phenotype was associated with a higher risk of functional disability (OR: 2.17, p = 0.042) compared with the no osteopenia/sarcopenia group. Conversely, sarcopenia (OR: 1.50, p = 0.448) and osteopenia/osteoporosis (OR: 1.50, p = 0.185) phenotypes were not associated with functional disability. CONCLUSIONS: Our study underscores that osteosarcopenia significantly increased the risk of functional disability, particularly in terms of Instrumental Activities of Daily Living (IADL). These results emphasize the importance of screening for sarcopenia, osteopenia/osteoporosis, and osteosarcopenia across various clinical settings. Early detection and intervention hold promise for averting functional disability and mitigating associated adverse outcomes in adults.

Strontium zinc silicate simultaneously alleviates osteoporosis and sarcopenia in tail-suspended rats via Piezo1-mediated Ca2+ signaling.

Background: Long-term physical inactivity probably leads to a co-existence of osteoporosis and sarcopenia which result in a high risk of falls, fractures, disability and even mortality. However, universally applicable and feasible approaches are lacking in the concurrent treatment of osteoporosis and sarcopenia. In this study, we evaluated the effect of strontium zinc silicate bioceramic (SZS) extract on osteoporosis and sarcopenia and explored its underlying mechanisms. Methods: Hindlimb osteoporosis and sarcopenia were established in a tail-suspended rat model. The bones were conducted µCT scanning, histological examination, and gene expression analysis, and the muscles were conducted histological examination and gene expression analysis. In vitro, the effect of SZS extract on osteoblasts was determined by alizarin red S staining, immunofluorescence and qPCR. Similarly, the effect of SZS extract on myoblasts was determined by immunofluorescence and qPCR.. At last, the role of Piezo1 and the change of intracellular calcium ion (Ca2+) were explored through blockading the Piezo1 by GsMTx4 in MC3T3-E1 and C2C12 cells, respectively. Results: We found that SZS extract could concurrently and efficiently prevent bone structure deterioration, muscle atrophy and fibrosis in hind limbs of the tail-suspended rats. The in vivo study also showed that SZS extract could upregulate the mRNA expression of Piezo1, thereby maintaining the homeostasis of bones and muscles. In vitro study demonstrated that SZS extract could promote the proliferation and differentiation of MC3T3-E1 and C2C12 cells by increasing the intracellular Ca2+ in a Piezo1-dependent manner. Conclusion: This study demonstrated that SZS extract could increase Piezo1-mediated intracellular Ca2+, and facilitate osteogenic differentiation of osteoblast and myogenic differentiation of myoblasts, contributing to alleviation of osteoporosis and sarcopenia in a tail-suspended rat model. The translational potential of this article: The current study might provide a universally applicable and efficient strategy to treat musculoskeletal disorders based on bioactive ceramics. The verification of the role of Piezo1-modulated intracellular Ca2+ during osteogenesis and myogenesis provided a possible therapeutic target against mechanical related diseases.

MicroRNAs and their Modulatory Effect on the Hallmarks of Osteosarcopenia.

PURPOSE OF THE REVIEW: Osteosarcopenia is a geriatric syndrome associated with disability and mortality. This review summarizes the key microRNAs that regulate the hallmarks of sarcopenia and osteoporosis. Our objective was to identify components similarly regulated in the pathology and have therapeutic potential by influencing crucial cellular processes in both bone and skeletal muscle. RECENT FINDINGS: The simultaneous decline in bone and muscle in osteosarcopenia involves a complex crosstalk between these tissues. Recent studies have uncovered several key mechanisms underlying this condition, including the disruption of cellular signaling pathways that regulate bone remodeling and muscle function and regeneration. Accordingly, emerging evidence reveals that dysregulation of microRNAs plays a significant role in the development of each of these hallmarks of osteosarcopenia. Although the recent recognition of osteosarcopenia as a single diagnosis of bone and muscle deterioration has provided new insights into the mechanisms of these underlying age-related diseases, several knowledge gaps have emerged, and a deeper understanding of the role of common microRNAs is still required. In this study, we summarize current evidence on the roles of microRNAs in the pathogenesis of osteosarcopenia and identify potential microRNA targets for treating this condition. Among these, microRNAs-29b and -128 are upregulated in the disease and exert adverse effects by inhibiting IGF-1 and SIRT1, making them potential targets for developing inhibitors of their activity. MicroRNA-21 is closely associated with the occurrence of muscle and bone loss. Conversely, microRNA-199b is downregulated in the disease, and its reduced activity may be related to increased myostatin and GSK3ß activity, presenting it as a target for developing analogues that restore its function. Finally, microRNA-672 stands out for its ability to protect skeletal muscle and bone when expressed in the disease, highlighting its potential as a possible therapy for osteosarcopenia.

Impact of Fat Mass on Osteoporosis, Sarcopenia, and Osteosarcopenia in Peritoneal Dialysis Patients.

INTRODUCTION: The relationship between fat mass and osteoporosis, sarcopenia, and osteosarcopenia is complex. While higher fat mass generally has a negative impact on bone and muscle health in the general population, the impact in peritoneal dialysis (PD) patients is less well understood. METHODS: In this study of 359 PD patients, sarcopenia was identified using appendicular skeletal muscle per square meter (ASM/m2), with cut-off values of <7.0 kg/m2 for men and <5.5 kg/m2 for women. Fat tissue index (FTI) and lean tissue index (LTI) were determined using body composition monitoring, with the lowest tertile classified as low FTI and low LTI. Bone mineral density was measured, with a T-score below -2.5 indicating osteoporosis. RESULTS: The prevalence of osteoporosis, sarcopenia, and osteosarcopenia was 25%, 32%, and 15%, respectively. Notably, 60% of osteoporotic patients had sarcopenia, and about 45% of sarcopenic patients had osteoporosis. Patients with osteoporosis were older and had significantly lower LTI (15.3 vs. 12.7 kg/m2, p < 0.001) and ASM (7.3 vs. 5.8 kg/m2, p < 0.001). Osteoporotic patients also had lower FTI, but this was more pronounced in men than in women. Patients with both sarcopenia and osteoporosis had the lowest LTI and FTI compared to those with only one or neither condition. Low FTI was a significant determinant for osteoporosis (OR, 2.34; 95% CI, 1.43-3.85; p = 0.001), sarcopenia (OR, 2.91; 95% CI, 1.82-4.64; p < 0.001), and osteosarcopenia (OR, 2.34; 95% CI, 1.30-4.24; p = 0.005) in univariate analysis, and these associations remained significant after adjustment for age and body mass index. CONCLUSION: Osteoporosis and sarcopenia are common and interrelated in PD patients. Low fat mass, but not normal/high fat mass, was significantly associated with these conditions, suggesting the importance of maintaining adequate fat mass in PD patients.

Prevalence and risk factors of osteosarcopenia in elderly patients with uncontrolled type 2 diabetes.

PURPOSE: To assess the prevalence of osteosarcopenia (OS) in elderly patients with type 2 diabetes mellitus (T2DM) and explore the related risk factors for developing this condition. METHODS: This cross-sectional study enrolled hospitalized T2DM patients aged 60 years and older. Patients underwent assessments of total hip bone mineral density (BMD), grip strength, the Short Physical Performance Battery (SPPB), and body composition. Based on the 2019 Asian Working Group for Sarcopenia (AWGS) criteria, appendicular skeletal muscle mass (ASM), grip strength, and SPPB were measured to diagnose sarcopenia. BMD and T values of the lumbar spine and hip were measured using dual-energy X-ray absorptiometry (DXA). Osteosarcopenia was defined when both sarcopenia and osteoporosis criteria were met. Statistical analysis included binary logistic regression to identify significant risk factors. RESULTS: A total of 254 hospitalized T2DM patients (80 males and 174 females) were included. They were divided into T2DM-OS (n = 58) and T2DM-NOS (n = 196) groups based on the presence of osteosarcopenia. The average ages were 72.724 ± 6.463 and 69.265 ± 6.035 years, respectively. The prevalence of osteosarcopenia in T2DM patients was 22.8%, with 20.7% (12 males) and 79.3% (46 females) in the T2DM-OS group. After adjusting for confounding factors, it was found that male gender (OR: 5.738, 95% CI: 1.602-20.551, P = 0.007), fasting plasma glucose (OR: 0.904, 95% CI: 0.821-0.995, P = 0.038), and ASMI (OR: 0.049, 95% CI: 0.013-0.184, P < 0.001) were major influencing factors for the development of osteosarcopenia in elderly T2DM patients. CONCLUSIONS: The prevalence of T2DM-OS is relatively high, with male gender, low fasting plasma glucose, and low ASMI identified as risk factors.

Sarcopenia and self-reported markers of physical frailty in patients with osteoporosis.

Bone and muscle impairment, named osteoporosis and sarcopenia, may co-occur with age, and patients with both disorders might exhibit physical frailty. One-hundred sixty-three patients were included. 14.2% had both disorders and presented more frequent with previous fall, reduced daily activity level, walk/balance challenges, and need of walking aid, indicating overall frailty. PURPOSE: In older adults, sarcopenia (muscle impairment) and physical frailty may accompany osteoporosis (bone brittleness), yet osteoporosis is typically assessed without evaluating these conditions, even though coexistence may contribute to exacerbated negative health outcomes. We aimed at evaluating the prevalence of sarcopenia and impaired muscle domains in osteoporotic patients and explore the risk of osteosarcopenia from markers of physical frailty. METHODS: In Copenhagen, Denmark, osteoporotic patients aged 65 + were assessed cross-sectionally in 2018-2019. Evaluations included muscle mass, strength, and function; bone mineral density; and self-reported physical activity, fall, balance challenges, dizziness, and the need of walking aid. Low bone mass, low-energy fracture, or treatment with anti-osteoporotic medication defined patient with osteoporosis, and sarcopenia was defined by low muscle strength and mass. Osteosarcopenia was defined from the coexistence of both conditions. RESULTS: One-hundred sixty-three patients with osteoporosis were included. Of those, 23 (14.2%) exhibited sarcopenia, hence osteosarcopenia. Hand-grip-strength, 30-s-chair-stand-test, relative-appendicular-lean-muscle-mass, and gait-speed were below cut-off levels in 21.0%, 30.9%, 28.8%, and 23.6% of the patients, respectively. Previous fall, activity level, walk and balance challenges, and need of walking aid were statistically (or borderline) significantly more often affected in the osteosarcopenic group compared with the solely osteoporotic. Logistic regression analysis, however, revealed that only the need for walking aid significantly increased the risk of an osteosarcopenia diagnosis (odds ratio 5.54, 95% CI (1.95-15.76), p < 0.01). CONCLUSIONS: Sarcopenia and impaired muscle domains were frequent in osteoporotic patients, as were markers of physical frailty, indicating the need of thorough examination of osteoporotic patients.

Exploring neuronal mechanisms of osteosarcopenia in older adults.

Until recently, research on the pathogenesis and treatment of osteoporosis and sarcopenia has primarily focused on local and systemic humoral mechanisms, often overlooking neuronal mechanisms. However, there is a growing body of literature on the neuronal regulation of bone and skeletal muscle structure and function, which may provide insights into the pathogenesis of osteosarcopenia. This review aims to integrate these neuronal regulatory mechanisms to form a comprehensive understanding and inspire future research that could uncover novel strategies for preventing and treating osteosarcopenia. Specifically, the review explores the functional adaptation of weight-bearing bone to mechanical loading throughout evolutionary development, from Wolff's law and Frost's mechanostat theory to the mosaic hypothesis, which emphasizes neuronal regulation. The recently introduced bone osteoregulation reflex points to the importance of the osteocytic mechanoreceptive network as a receptor in this neuronal regulation mechanism. Finally, the review focuses on the bone myoregulation reflex, which is known as a mechanism by which bone loading regulates muscle functions neuronally. Considering the ageing-related regressive changes in the nerve fibres that provide both structural and functional regulation in bone and skeletal muscle tissue and the bone and muscle tissues they innervate, it is suggested that neuronal mechanisms might play a central role in explaining osteosarcopenia in older adults.

Osteosarcopenia in Finland: prevalence and associated factors.

This cross-sectional study investigated osteosarcopenia prevalence and its correlates among 2142 adults aged 55 and older in Finland. Findings show 3.9% had osteosarcopenia, while 13.8% and 11.1% had probable sarcopenia only or osteoporosis only, respectively. Osteosarcopenia was associated with low BMI, impaired mobility, ADL limitations and depression. Sarcopenia appeared to drive these associations more than osteoporosis. Osteosarcopenia may be a risk factor for functional decline, hospitalization, and institutionalization, warranting further research. PURPOSE: Osteosarcopenia is a disorder consisting of concurrent osteoporosis and sarcopenia. This cross-sectional study using nationally representative data from Finland in 2000 aimed to determine the prevalence of osteosarcopenia in Finland. In addition, associations of sociodemographic, lifestyle, anthropometric, physical and mental function indicators, chronic conditions and various biomarkers with osteosarcopenia were examined. METHODS: The study included 2142 subjects aged 55 and over (mean age 68.0 years, SD 9.0). Probable sarcopenia was defined as grip strength < 27 kg for men and < 16 kg for women. Osteoporosis was defined as either ultrasound-based bone density measurement of T < -2.5, or self-reported, pre-existing diagnosis of osteoporosis. Participants were categorized into 4 groups: no sarcopenia and no osteoporosis, probable sarcopenia only, osteoporosis only, and osteosarcopenia. Information on sociodemographic, lifestyle, anthropometric, physical and mental function indicators, chronic conditions and various biomarkers were collected via structured interview, questionnaires, clinical examination, and blood and urine samples. RESULTS: The prevalence of probable sarcopenia, osteoporosis and osteosarcopenia was 13.8%, 11.1%, and 3.9%, respectively. Osteosarcopenia was associated with low BMI, slow gait speed, impaired mobility, impaired ability in the activities of daily living and depression. Of the two components, probable sarcopenia appeared to contribute to these associations more than osteoporosis. CONCLUSION: According to representative population-based study, about every fifth person with probable sarcopenia also has osteoporosis. Mobility and ADL limitations were more common among people with osteosarcopenia than those with osteoporosis or probable sarcopenia alone. Future studies are needed to examine osteosarcopenia as an independent risk factor for functional decline, hospitalization, and institutionalization.

Impact of osteopenia and osteosarcopenia on the outcomes after surgery of hepatobiliary-pancreatic cancers.

Objective: The purpose of this study is to investigate potential associations between osteopenia, osteosarcopenia, and postoperative outcomes in patients with hepatobiliary-pancreatic cancer (HBPC). Methods: Three online databases, including Embase, PubMed, and the Cochrane Library, were thoroughly searched for literature describing the relationship between osteopenia, osteosarcopenia, and outcomes of surgical treatment of HBPC patients from the start of each database to September 29, 2023. The Newcastle-Ottawa Scale was used to rate the quality of the studies. Results: This analysis included a total of 16 articles with a combined patient cohort of 2,599 individuals. The results demonstrated that HBPC patients with osteopenia had significantly inferior OS (HR: 2.27, 95% CI: 1.70-3.03, p < 0.001) and RFS (HR: 1.96, 95% CI: 1.42-2.71, p < 0.001) compared to those without osteopenia. Subgroup analysis demonstrated that these findings were consistent across univariate and multivariate analyses, as well as hepatocellular carcinoma, biliary tract cancer, and pancreatic cancer. The risk of postoperative major complications was significantly higher in patients with osteopenia compared to those without osteopenia (OR: 1.66, 95% CI: 1.19-2.33, p < 0.001). Besides, we also found that the presence of osteosarcopenia in HBPC patients was significantly related to poorer OS (HR: 3.31, 95% CI: 2.00-5.48, p < 0.001) and PFS (HR: 2.50, 95% CI: 1.62-3.84, p < 0.001) in comparison to those without osteosarcopenia. Conclusion: Preoperative osteopenia and osteosarcopenia can predict poorer OS and RFS with HBPC after surgery.

Impact of Preoperative Osteosarcopenia and Postoperative Administration of Pancrelipase on the Prognosis of Borderline Resectable and Unresectable Locally Advanced Pancreatic Cancer.

BACKGROUND: This study aimed to identify postoperative recurrence and prognostic factors, including osteosarcopenia for borderline resectable (BR) and unresectable locally advanced (UR-LA) pancreatic cancer and to examine the impact of postoperative pancreatic enzyme replacement therapy (PERT). METHODS: We retrospectively examined 32 resected patients with BR and UR-LA pancreatic cancer. We investigated independent factors in the disease-free survival and overall survival. The relation of osteosarcopenia with the clinicopathological factors was investigated. Additionally, the association of the administration of a standard dose of pancrelipase, the amount of lipase required for patients with pancreatic exocrine insufficiency, for ≥6 months postoperatively with improvement of sarcopenia, osteopenia, and osteosarcopenia and completion rate of adjuvant chemotherapy was investigated. RESULTS: Multivariate analyses identified osteosarcopenia (P = 0.049) and lymph node metastasis (P = 0.01) as independent recurrence predictors, and osteosarcopenia (P = 0.002), maximum tumor diameter ≥40 mm (P = 0.006), and no adjuvant therapy (P = 0.01) as independent prognostic predictors. In the osteosarcopenia group, serum CA19-9 levels were higher (P = 0.03). The administration of a standard dose of pancrelipase for ≥6 months postoperatively was none in the osteosarcopenia group (0% vs 42.9%, P = 0.01), while significantly improved postoperative sarcopenia (33% vs 0%, P = 0.004), increased number of cycles of adjuvant chemotherapy (n = 6 vs n = 3, P = 0.03), and the completion rate of adjuvant chemotherapy in excluding cases interrupted because of recurrence (86% vs 25%, P = 0.007). CONCLUSIONS: Osteosarcopenia was an independent recurrent and prognostic factor in patients after pancreatectomy for locally advanced pancreatic cancer. Appropriate postoperative PERT may contribute to a better prognosis by improving sarcopenia and increasing the completion rate of adjuvant chemotherapy.

Aromatase inhibitor-induced bone loss osteosarcopenia in older patients with breast cancer: effects of the RANK/RANKL system's inhibitor denosumab vs. bisphosphonates.

The raising number of older patients who are diagnosed with breast cancer represents a significant medical and societal challenge. Aromatase inhibitors (AI), which are commonly utilized to treat this condition in these patients have significant adverse events on bone and muscle health. Falling estrogen production leads to an increase in RANKL secretion by osteoblasts with accelerated bone remodeling due to osteoclast activity. Furthermore, estrogen deficiency reduces skeletal muscle strength and mass. The humanized monoclonal antibody, denosumab, neutralizes RANKL, thereby inhibiting osteoclast formation, function and survival and ultimately exerting powerful anti-resorptive effects.. In this study, we report on the efficacy of denosumab in mitigating aromatase inhibitor-induced bone loss (AIBL) and sarcopenia in older women with breast cancer. From January 2022 to January 2023, we enrolled 30 patients (female sex, ≥ 65 years) diagnosed with non-metastatic breast cancer undergoing adjuvant endocrine therapy; patients received, as per clinical practice, primary bone prophylaxis with denosumab (60 mg via subcutaneous injection every 6 months) according to oncologic guidelines. This group was matched with 30 patients with non-metastatic breast cancer, who were treated with biphosphonates (BF) therapy (oral alendronate 70 mg/week). For each patient bone mineral density (BMD) and bone quality in terms of trabecular bone score (TBS) in addition to body composition and Relative Skeletal Muscle Index (RSMI) was assessed by bone densitometry at baseline and after one year of treatment. Significant improvements in TBS at the lumbar spine, RSMI and whole-body composition (arms, legs, and trunk) were observed in the denosumab group compared with the BF group. These findings underscore the role of denosumab as an effective strategy in managing AIBL and osteosarcopenia in older women with breast cancer and undergoing adjuvant endocrine therapy, which is crucial for improving quality of life, preventing functional decline, and optimizing treatment outcomes.

A Novel MRI-Based Paravertebral Muscle Quality (PVMQ) Score for Evaluating Muscle Quality and Bone Quality: A Comparative Study with the VBQ Score.

Purpose: This study aims to develop a novel MRI-based paravertebral muscle quality (PVMQ) score for assessing muscle quality and to investigate its correlation with the degree of fat infiltration (DFF) and the vertebral bone quality (VBQ) score of paravertebral muscles. Additionally, the study compares the effectiveness of the PVMQ score and the VBQ score in assessing muscle quality and bone quality. Methods: PVMQ scores were derived from the ratio of paravertebral muscle signal intensity (SI) to L3 cerebrospinal fluid SI on T2-weighted MRI. Image J software assessed paravertebral muscle cross-sectional area (CSA) and DFF. Spearman rank correlation analyses explored associations between PVMQ, VBQ scores, DFF, and T-scores in both genders. Receiver operating characteristic (ROC) curves compared PVMQ and VBQ scores' effectiveness in distinguishing osteopenia/osteoporosis and high paraspinal muscle DFF. Results: In this study of 144 patients (94 females), PVMQ scores were significantly higher in osteoporosis and osteopenia groups compared to normals, with variations observed between genders (P < 0.05). PVMQ showed stronger positive correlation with VBQ scores and DFF in females than males (0.584 vs 0.445, 0.579 vs 0.528; P < 0.01). ROC analysis favored PVMQ over VBQ for low muscle mass in both genders (AUC = 0.767 vs 0.718, 0.793 vs 0.718). VBQ was better for bone mass in males (0.737/0.865 vs 0.691/0.858), whereas PVMQ excelled for females (0.808/0.764 vs 0.721/0.718). Conclusion: The novel PVMQ score provides a reliable assessment of paravertebral muscle quality and shows a strong correlation with VBQ scores and DFF, particularly in females. It outperforms VBQ scores in evaluating muscle mass and offers valuable insights for assessing bone mass in females. These findings underscore the potential of the PVMQ score as a dual-purpose tool for evaluating both muscle and bone health, informing future research and clinical practice.

The association between computed tomography-based osteosarcopenia and osteoporotic vertebral fractures: a longitudinal study.

PURPOSE: Osteoporosis and sarcopenia usually coexist in older population. The concept of osteosarcopenia has been proposed in recent years. However, studies on the relationship between osteosarcopenia and the risk of fracture are rare, and the association is unclear at present. This study aimed to investigate the association between osteosarcopenia evaluated based on chest computed tomography (CT) and osteoporotic vertebral fracture (OVF). METHODS: This study recruited 7906 individuals aged 50 years and older who did not have OVFs and underwent chest CT for physical examination between July 2016 and September 2019. Subjects were followed up annually until June 2023. Osteosarcopenia was defined by a low muscle area of the erector spinae (< 25.4 cm2) and the bone attenuation (Hounsfield unit, HU < 135). Genant's grades were used to define OVFs. Control subjects were selected by Propensity Score Matching at a ratio 20:1. Cox proportional hazards models were used to assess the associations between osteosarcopenia and OVFs. RESULTS: Of the 7906 participants included, 95 had a new OVF within a median follow-up of 3 years. A total of 1900 control subjects were matched. Individuals in the osteosarcopenia group had a higher prevalence of spinal fractures than those in normal group (16.4% vs. 0.4%, P < 0.001). Osteosarcopenia was independently associated with OVF (adjusted hazard ratio (aHR): 12.67, 95% confidence interval (CI) 3.79-42.40) and severe OVF (aHR = 14.07, 95% CI 1.84-107.66). Similar trends were observed in males, females and those subjects aged older than 60 years. Osteosarcopenia had good predictive efficacy for OVF (area under the curve = 0.836). A nomogram was also developed for clinical application. CONCLUSION: Osteosarcopenia assessed based on chest CT was associated with OVF, and osteosarcopenia has good performance for vertebral fracture prediction.

A Pilot Study on Circulating, Cellular, and Tissue Biomarkers in Osteosarcopenic Patients.

Aging comes with the loss of muscle and bone mass, leading to a condition known as osteosarcopenia. Circulating, cellular, and tissue biomarkers research for osteosarcopenia is relatively scarce and, currently, no established biomarkers exist. Here we find that osteosarcopenic patients exhibited elevated basophils and TNFα levels, along with decreased aPPT, PT/INR, IL15, alpha-Klotho, DHEA-S, and FGF-2 expression and distinctive bone and muscle tissue micro-architecture and biomarker expressions. They also displayed an increase in osteoclast precursors with a concomitant imbalance towards spontaneous osteoclastogenesis. Similarities were noted with osteopenic and sarcopenic patients, including a lower neutrophil percentage and altered cytokine expression. A linear discriminant analysis (LDA) on models based on selected biomarkers showed a classification accuracy in the range of 61-78%. Collectively, our data provide compelling evidence for novel biomarkers for osteosarcopenia that may hold potential as diagnostic tools to promote healthy aging.

Osteosarcopenia increases the risk of mortality: a systematic review and meta-analysis of prospective observational studies.

BACKGROUND & AIMS: Osteosarcopenia is a recently recognized geriatric syndrome. The association between osteosarcopenia and mortality risk is still largely underexplored. In this systematic review with meta-analysis of prospective cohort studies, we aimed to explore whether osteosarcopenia could be associated with a higher mortality risk. METHODS: Several databases were searched from the inception to 16th February 2024 for prospective cohort studies dealing with osteosarcopenia and mortality. We calculated the mortality risk in osteosarcopenia vs. controls using the most adjusted estimate available and summarized the data as risk ratios (RRs) with their 95% confidence intervals (CIs). A random-effect model was considered for all analyses. RESULTS: Among 231 studies initially considered, nine articles were included after exclusions for a total of 14,429 participants (mean age: 70 years; 64.5% females). The weighted prevalence of osteosarcopenia was 12.72%. Over a mean follow-up of 6.6 years and after adjusting for a mean of four covariates, osteosarcopenia was associated with approximately 53% increased risk of mortality (RR: 1.53; 95% CI: 1.28-1.78). After accounting for publication bias, the re-calculated RR was 1.48 (95%CI: 1.23-1.72). The quality of the studies was generally good, as determined by the Newcastle Ottawa Scale. CONCLUSIONS: Osteosarcopenia was significantly linked with an increased risk of mortality in older people, indicating the need to consider the presence of osteoporosis in patients with sarcopenia, and vice versa, since the combination of these two conditions typical of older people may lead to further complications, such as mortality.

Osteosarcopenia: the coexistence of sarcopenia and osteopenia is predictive of prognosis and postoperative complications after curative resection for colorectal cancer.

PURPOSE: To establish if osteosarcopenia is related to postoperative complications, prognosis, and recurrence of colorectal cancer (CRC) after curative surgery. METHODS: The clinical data of 594 patients who underwent curative resection for CRC between January, 2013 and December, 2018 were analyzed retrospectively to examine the relationship between clinicopathological data and osteosarcopenia. The following definitions were used: sarcopenia, low skeletal muscle mass index; osteopenia, low bone mineral density on computed tomography at the level of the 11th thoracic vertebra; and osteosarcopenia, sarcopenia with osteopenia. RESULTS: Osteosarcopenia was identified in 98 patients (16.5%) and found to be a significant risk factor for postoperative complications (odds ratio 2.53; p = 0.011). The 5-year overall survival (OS) and recurrence-free survival (RFS) rates of the patients with osteosarcopenia were significantly lower than those of the patients without osteosarcopenia (OS: 72.5% and 93.9%, respectively, p < 0.0001; RFS: 70.8% and 92.4%, respectively, p < 0.0001). Multivariate analysis identified osteosarcopenia as an independent prognostic factor associated with OS (hazard ratio 3.31; p < 0.0001) and RFS (hazard ratio 3.67; p < 0.0001). CONCLUSION: Osteosarcopenia may serve as a predictor of postoperative complications and prognosis after curative surgery for CRC.

Bidirectional crosstalk between bone and muscle: the role of RANKL pathway in osteosarcopenia.

Osteosarcopenia, which refers to the concomitant presence of osteoporosis and sarcopenia, is expected to increase in the rapidly progressive aging world, with serious clinical implications. However, the pathophysiology of osteosarcopenia has not been fully elucidated, and no optimal treatment specific to osteosarcopenia is available. The RANKL-RANK pathway is widely used as a therapeutic target for osteoporosis. Growing evidence supports the importance of the RANKL-RANK pathway, not only in bone, but also in muscle, and the therapeutic potential of targeting this pathway in muscle diseases has been noted. The muscles and bones closely communicate with each other through various secretory factors called myokines and osteokines. This review covers the roles of the RANKL-RANK pathway in the bone and muscle and their reciprocal interactions. Moreover, we will suggest future directions to move forward for the treatment of osteosarcopenia to prepare for an upcoming aging society.

Integrating transcriptomic and proteomic data for a comprehensive molecular perspective on the association between sarcopenia and osteoporosis.

BACKGROUND: Osteoporosis and sarcopenia are common age-related conditions characterized by the progressive loss of bone density and muscle mass, respectively. Their co-occurrence, often referred to as osteosarcopenia, presents significant challenges in elderly care due to increased fragility and functional impairment. Existing studies have identified shared pathological mechanisms between these conditions, including inflammation, hormonal imbalances, and metabolic dysregulation, but a comprehensive understanding of their molecular interplay remains incomplete. OBJECTIVE: This study aims to deepen our understanding of the molecular interactions between sarcopenia and osteoporosis through an integrated omics approach, revealing potential therapeutic targets and biomarkers. METHODS: Employing a combination of proteomics and transcriptomics analyses, this study analyzed bone and muscle tissue samples from patients diagnosed with osteoporosis and osteosarcopenia. Techniques included high-throughput sequencing and label-free proteomics, supported by advanced bioinformatics tools for data analysis and functional annotation of genes and proteins. RESULTS: The study found marked differences in gene and protein expressions between osteoporosis and osteosarcopenia tissues. Specifically, genes like PDIA5, TUBB1, and CYFIP2 in bone, along with MYH7 and NCAM1 in muscle, exhibited differential expression at both mRNA and protein levels. Pathway analyses revealed the significance of oxidative-reduction balance, cellular metabolism, and immune response in the progression of these conditions. Importantly, the study pinpointed osteoclast differentiation and NF-kappa B signaling pathways as critical in the molecular dynamics of osteosarcopenia, suggesting potential targets for therapy. CONCLUSIONS: This study utilized transcriptomics and proteomics to identify key genes and proteins impacting sarcopenia and osteoporosis, employing advanced network tools to delineate interaction networks and crucial signaling pathways. It highlighted genes like PDIA5 and TUBB1, consistently expressed in both analyses, involved in pathways such as osteoclast differentiation and cytokine interactions. These insights enhance understanding of the molecular interplay in bone and muscle degeneration with aging, suggesting directions for future research into therapeutic interventions and prevention strategies for age-related degenerative diseases.

The Impact of Combination of Aerobic and Resistive Exercise on Activities of Daily Living and Risk of Fall in Osteosarcopenic Patients.

Objectives: It is aimed to explain the impact of the combination of aerobic and resistive exercise on activities of daily living and the risk of falls in osteosarcopenic patients. Methods: Female and male patients over 70 years of age followed up from the osteoporosis outpatient clinic were screened. Appropriate patients were evaluated for sarcopenia gait speed, grip strength and skeletal muscle mass. Patients with sarcopenia who did not have the exclusion criteria were included in the 3-month aerobic and resistive exercise program. Changes in skeletal muscle mass measurements, physical performance and balance tests were evaluated at 1 month and 3 months. Results: Sarcopenia was screened in 91 patients with osteoporosis and osteopenia. Sarcopenia was detected in 27 patients and 23 completed the 3-month study. The mean age of the patients was 78.4±5.7 years and the number of female patients was 16 (69.6%). There was no significant change in skeletal muscle mass measurements and Katz Activities of Daily Living Scale performed at 1 and 3 months (p>0.05). Short Physical Performance Battery (SPPB), Timed Up and Go Test (TUGT) and Berg Balance Test (BBT) were found to improve significantly in the first month, and it continued to develop in the third month (p<0.05). Conclusion: Although the combination of aerobic and resistive exercise in osteosarcopenic patients did not lead to a significant increase in skeletal muscle mass, It has a significant effect on physical performance and balance. It can be foreseen that this will increase the independence of the person while reducing the risk of falling.

The efficacy of nutritional screening indexes in predicting the incidence of osteosarcopenia and major osteoporotic fracture in the elderly.

INTRODUCTION: The effect of nutritional status on osteosarcopenia (OS) and major osteoporotic fracture (MOF) among the elderly is still unclear. So we aimed to compare the efficacy of the Mini-Nutrition Assessment-Short Form (MNA-sf), the Geriatric Nutritional Risk Index (GNRI) and Controlling Nutritional Status (CONUT) for predicting OS and MOF among the elderly. MATERIALS AND METHODS: A total of 409 participants were enrolled in this prospective study. Blood biochemical indexes, nutritional status, and bone- and muscle-related examinations were assessed at initial visit to the outpatient. Participants were divided into 4 groups: (1) control; (2) osteopenia/osteoporosis; (3) sarcopenia; (4) osteosarcopenia, and then followed for 5 years, recording the occurrence time of MOF. RESULTS: The frequency values of osteopenia/osteoporosis, sarcopenia, and OS, at baseline, were respectively 13.4, 16.1, and 12% among the study samples. Correlation analysis showed that nutritional status scores were associated with body mass index, handgrip strength, albumin, bone mineral density, and physical functions. According to multivariate models, poor nutritional status was significantly associated with a higher risk of OS and MOF (P < 0.05). Survival analysis showed that the MOF rate in malnutrition group was significantly higher than normal nutrition group (P < 0.05). The receiver operator characteristic curve shows that the value of MNA-sf to diagnose OS and MOF is greater (P < 0.05). CONCLUSION: The poor nutritional status was associated with a higher risk of both OS and MOF. MNA-sf showed a superior diagnostic power for OS and MOF among the elderly. Early nutrition assessments and interventions may be key strategies to prevent OS and fractures.