Leukocyte telomere length is associated with MRI-thigh fat-free muscle volume: data from 16 356 UK Biobank adults.

BACKGROUND: Telomere attrition may share common biological mechanisms with bone and muscle loss with aging. Here, we investigated the association between these hallmarks of aging using data from UK Biobank, a large observational study. METHODS: Leukocyte telomere length (LTL as T/S ratio) was measured using a multiplex qPCR assay at baseline (2006-2010). Bone mineral density (whole body and regional; via dual-energy X-ray absorptiometry), trabecular bone score (via lumbar-spine dual-energy X-ray absorptiometry images), fat-free muscle volume (thighs; via magnetic resonance imaging), and muscle fat infiltration (thighs; via magnetic resonance imaging) were measured during the imaging visit (2014-2018). Regression models were used to model LTL against a muscle or bone outcome, unadjusted and adjusted for covariates. RESULTS: A total of 16 356 adults (mean age: 62.8 ± 7.5 years, 50.5% women) were included. In the fully adjusted model, thigh fat-free muscle volume was associated with LTL in the overall sample (adjusted standardized ß (aß) = 0.017, 95% CI 0.009 to 0.026, P < 0.001, per SD increase in LTL), with stronger associations in men (aß = 0.022, 95% CI 0.010 to 0.034, P < 0.001) than in women (aß = 0.013, 95% CI 0.000 to 0.025, P = 0.041) (sex-LTL P = 0.028). The adjusted odds ratio (aOR) for low thigh fat-free muscle volume (body mass index-adjusted, sex-specific bottom 20%) was 0.93 per SD increase in LTL (95% CI 0.89 to 0.96, P < 0.001) in the overall sample, with stronger associations in men (aOR = 0.92, 95% CI 0.87 to 0.99, P = 0.008) than women (aOR = 0.93, 95% CI 0.88 to 0.98, P = 0.009), although the sex difference was not statistically significant in this model (sex-LTL P = 0.37). LTL was not associated with bone mineral density, trabecular bone score, or muscle fat infiltration in the overall or subgroup analyses (P > 0.05). CONCLUSIONS: LTL was consistently associated with thigh fat-free muscle volume in men and women. Future research should investigate moderating effects of lifestyle factors (e.g., physical activity, nutrition, or chronic diseases) in the association between LTL and muscle volume.

Challenges in Delivering Effective Care for Older Persons with Fragility Fractures.

Fragility fractures occur because of low-impact trauma or even spontaneously in individuals with osteoporosis. Caring for older persons with fragility fractures can present several challenges due to the unique needs and vulnerabilities of this population. Older individuals commonly have multiple medical conditions, such as osteoporosis, arthritis, cardiovascular diseases, and diabetes. These comorbidities can complicate fracture management and increase the risk of complications. Fracture repair through surgery may be more complex in older patients due to poor bone quality, decreased tissue elasticity, and higher chances of anesthesia complications. In addition, mobility and functional limitations post-fracture are highly prevalent in this population, affecting their independence and increasing their risk of institutionalization. Addressing these challenges requires a multidisciplinary approach involving orthopedic surgeons, geriatricians, physical and rehabilitation physicians, physiotherapists, occupational therapists, dieticians, social workers, and caregivers. Preventive measures, such as fall prevention strategies and osteoporosis management, can also play a vital role in reducing the incidence of fragility fractures in older persons.

Using magnetic resonance imaging to measure head muscles: An innovative method to opportunistically determine muscle mass and detect sarcopenia.

BACKGROUND: Sarcopenia is associated with multiple adverse outcomes. Traditional methods to determine low muscle mass for the diagnosis of sarcopenia are mainly based on dual-energy X-ray absorptiometry (DXA), whole-body magnetic resonance imaging (MRI) and bioelectrical impedance analysis. These tests are not always available and are rather time consuming and expensive. However, many brain and head diseases require a head MRI. In this study, we aim to provide a more accessible way to detect sarcopenia by comparing the traditional method of DXA lean mass estimation versus the tongue and masseter muscle mass assessed in a standard brain MRI. METHODS: The H70 study is a longitudinal study of older people living in Gothenburg, Sweden. In this cross-sectional analysis, from 1203 participants aged 70 years at baseline, we included 495 with clinical data and MRI images available. We used the appendicular lean soft tissue index (ALSTI) in DXA images as our reference measure of lean mass. Images from the masseter and tongue were analysed and segmented using 3D Slicer. For the statistical analysis, the Spearman correlation coefficient was used, and concordance was estimated with the Kappa coefficient. RESULTS: The final sample consisted of 495 participants, of which 52.3% were females. We found a significant correlation coefficient between both tongue (0.26) and masseter (0.33) with ALSTI (P < 0.001). The sarcopenia prevalence confirmed using the alternative muscle measure in MRI was calculated using the ALSTI (tongue = 2.0%, masseter = 2.2%, ALSTI = 2.4%). Concordance between sarcopenia with masseter and tongue versus sarcopenia with ALSTI as reference has a Kappa of 0.989 (P < 0.001) for masseter and a Kappa of 1 for the tongue muscle (P < 0.001). Comorbidities evaluated with the Cumulative Illness Rating Scale were significantly associated with all the muscle measurements: ALSTI (odds ratio [OR] 1.16, 95% confidence interval [CI] 1.07-1.26, P < 0.001), masseter (OR 1.16, 95% CI 1.07-1.26, P < 0.001) and tongue (OR 1.13, 95% CI 1.04-1.22, P = 0.002); the higher the comorbidities, the higher the probability of having abnormal muscle mass. CONCLUSIONS: ALSTI was significantly correlated with tongue and masseter muscle mass. When performing the sarcopenia diagnostic algorithm, the prevalence of sarcopenia calculated with head muscles did not differ from sarcopenia calculated using DXA, and almost all participants were correctly classified using both methods.

The Impact of Interventional Weight Loss on Bone Marrow Adipose Tissue in People Living with Obesity and Its Connection to Bone Metabolism.

This review focuses on providing physicians with insights into the complex relationship between bone marrow adipose tissue (BMAT) and bone health, in the context of weight loss through caloric restriction or metabolic and bariatric surgery (MBS), in people living with obesity (PwO). We summarize the complex relationship between BMAT and bone health, provide an overview of noninvasive imaging techniques to quantify human BMAT, and discuss clinical studies measuring BMAT in PwO before and after weight loss. The relationship between BMAT and bone is subject to variations based on factors such as age, sex, menopausal status, skeletal sites, nutritional status, and metabolic conditions. The Bone Marrow Adiposity Society (BMAS) recommends standardizing imaging protocols to increase comparability across studies and sites, they have identified both water-fat imaging (WFI) and spectroscopy (1H-MRS) as accepted standards for in vivo quantification of BMAT. Clinical studies measuring BMAT in PwO are limited and have shown contradictory results. However, BMAT tends to be higher in patients with the highest visceral adiposity, and inverse associations between BMAT and bone mineral density (BMD) have been consistently found in PwO. Furthermore, BMAT levels tend to decrease after caloric restriction-induced weight loss. Although weight loss was associated with overall fat loss, a reduction in BMAT did not always follow the changes in fat volume in other tissues. The effects of MBS on BMAT are not consistent among the studies, which is at least partly related to the differences in the study population, skeletal site, and duration of the follow-up. Overall, gastric bypass appears to decrease BMAT, particularly in patients with diabetes and postmenopausal women, whereas sleeve gastrectomy appears to increase BMAT. More research is necessary to evaluate changes in BMAT and its connection to bone metabolism, either in PwO or in cases of weight loss through caloric restriction or MBS, to better understand the role of BMAT in this context and determine the local or systemic factors involved.

Circulating Osteoprogenitor Cells Have a Mixed Immune and Mesenchymal Progenitor Function in Humans.

BACKGROUND: Circulating osteoprogenitors (COP) are a population of cells in the peripheral circulation that possess functional and phenotypical characteristics of multipotent stromal cells (MSCs). This population has a solid potential to become an abundant, accessible, and replenishable source of MSCs with multiple potential clinical applications. However, a comprehensive functional characterization of COP cells is still required to test and fully develop their use in clinical settings. METHODS: This study characterized COP cells by comparing them to bone marrow-derived MSCs (BM-MSCs) and adipose-derived MSCs (ASCs) through detailed transcriptomic and proteomic analyses. RESULTS: We demonstrate that COP cells have a distinct gene and protein expression pattern with a significantly stronger immune footprint, likely owing to their hematopoietic lineage. In addition, regarding progenitor cell differentiation and proliferation pathways, COP cells have a similar expression pattern to BM-MSCs and ASCs. CONCLUSION: COP cells are a unique but functionally similar population to BM-MSCs and ASCs, sharing their proliferation and differentiation capacity, thus presenting an accessible source of MSCs with strong potential for translational regenerative medicine strategies.

Sarcopenic obesity definitions and their associations with physical frailty in older Brazilian adults: data from the SARCOS study

ABSTRACT Objective: To identify the obesity diagnosis with the highest association with physical frailty associated with sarcopenia EWGSOP II (sarcopenic obesity). Subjects and methods: We performed a cross-sectional analysis of 371 community-dwelling older adults. Appendicular skeletal lean mass and total body fat (TBF) were assessed using dual-energy x-ray absorptiometry, and physical frailty was defined using Fried's criteria. The phenotypes were identified according to the presence of sarcopenia by EWGSOP II and obesity, which was diagnosed using two concepts: BMI obesity (BMI ≥ 30 kg/m2) and TBF obesity (percentage of TBF ≥ 35% for women and ≥ 25% for men). Finally, the association of each group with physical frailty was evaluated. Results: The mean age was 78.15 ± 7.22 years. Sarcopenia EWGSOP II was diagnosed in 19.8% (n = 73), body mass index obesity was identified in 21.8% (n = 81), TBF obesity was identified in 67.7% (n = 251), and physical frailty was identified in 38.5% (n = 142). In a regression analysis for frailty, sarcopenic TBF obesity presented an odds ratio of 6.88 (95% confidence interval 2.60-18.24; p < 0.001). Conclusion: In older Brazilian adults, sarcopenic obesity diagnosed by TBF obesity has a robust association with frailty and is independent of body mass index.

GDF-15 Is Associated with Poor Physical Function in Prefrail Older Adults with Diabetes.

Introduction: Growth differentiation factor 15 (GDF-15) has been shown to be a metabolic and appetite regulator in diabetes mellitus (DM) and obesity. We aimed to investigate (i) the association between GDF-15 and DM with and without poor physical function independent of inflammation and (ii) the prediction model for poor physical function in prefrail older adults. Methods: A cross-sectional study of 108-prefrail participants ≥60 years recruited for multidomain interventions. Data was collected for demographics, cognition, function, frailty, nutrition, handgrip strength (HGS), short physical performance battery (SPPB), and gait speed. Serum concentrations of GDF-15, IL-6, and TNF-α were measured. GDF-15 was classified into tertiles (T1, T2, and T3), and its association was studied with DM and physical function (DM poor physical function, DM no poor physical function, no DM poor physical function, and no DM no poor physical function). Results: Compared with T1, participants in T3 were significantly older, had a lower education level, had almost three times higher prevalence of DM, slower gait speed, longer chair-stand time, and lower SPPB scores. On multivariate analysis, the odds of having both DM and poor physical performance compared to having no DM and no poor physical performance were significantly higher in GDF-15 T3 vs. GDF-15 T1 (aOR 9.7, 95% CI 1.4-67.7; p = 0.021), and the odds of having DM no poor physical function compared to having no DM and no poor physical performance were significantly higher in GDF-15 T2 (aOR 12.7, 95% CI 1.1-143.7; p = 0.040) independent of BMI, IL-6, TNF-α, nutrition, physical function, education, age, and gender. Conclusion: The association of GDF-15 with DM-associated poor physical function is independent of inflammation in prefrail older adults. Its causal-association link needs to be determined in longitudinal studies.

Very Low and High Levels of Vitamin D Are Associated with Shorter Leukocyte Telomere Length in 148,321 UK Biobank Participants.

Background: Shorter leukocyte telomere length (LTL) is observed in multiple age-related diseases, which are also associated with vitamin D deficiency (i.e., osteosarcopenia, neurocognitive disorders, cancer, osteoarthritis, etc.), suggesting a close association between vitamin D and LTL. In this study, we examined the relationship between vitamin D levels and LTL in older participants of the UK Biobank. Methods: Data were collected from the UK Biobank. Participants aged 60 and older (n = 148,321) were included. Baseline LTL was measured using a multiplex qPCR technique and expressed as the ratio of the telomere amplification product (T) to that of a single-copy gene (S) (T/S ratio). Serum 25-hydroxyvitamin D (25OHD) was stratified by z score and linked to LTL in a linear regression model adjusting for covariates. Results: Compared to the medium level, a low (in the range of 16.6 nmol/L, 29.7 nmol/L) or extremely low (≤16.6 nmol/L) level of serum 25OHD was associated with shorter LTL: 0.018 SD (standardized ß = -0.018, 95% CI -0.033 to -0.003, p = 0.022) and 0.048 SD (standardized ß = -0.048, 95% CI -0.083 to -0.014, p = 0.006), respectively. Additionally, the high serum 25OHD groups (>95.9 nmol/L) had 0.038 SD (standardized ß = -0.038, 95% CI -0.072 to -0.004, p = 0.030) shorter mean LTL than the group with medium 25OHD levels. The associations above were adjusted for multiple variables. Conclusions: In this population-based study, we identified an inverted U-shape relationship between LTL and vitamin D status. Our findings could be affected by unmeasured confounders. Whether high or low vitamin D-associated shorter LTL is mechanistically related to age-related conditions remains to be elucidated.

Undercarboxylated osteocalcin and ibandronate combination ameliorates hindlimb immobilization-induced muscle wasting.

Immobilization leads to muscle wasting and insulin resistance, particularly during ageing. It has been suggested that undercarboxylated osteocalcin (ucOC) improves muscle mass and glucose metabolism. Bisphosphonates, an anti-osteoporosis treatment, might protect muscle wasting independent of ucOC. We hypothesize that the combination of ucOC and ibandronate (IBN) treatments has superior protective effects against immobilization-induced muscle wasting and insulin resistance than either treatment alone. C57BL/6J mice were hindlimb-immobilized for two weeks, with injections of vehicle, ucOC (90 ng/g daily) and/or IBN (2 µg/g weekly). Insulin/oral glucose tolerance tests (ITT/OGTT) were performed. Immediately after immobilization, muscles (extensor digitorum longus (EDL), soleus, tibialis anterior, gastrocnemius and quadriceps) were isolated and measured for muscle mass. Insulin-stimulated glucose uptake (EDL and soleus) was examined. Phosphorylation/expression of proteins in anabolic/catabolic pathways were examined in quadriceps. Primary human myotubes derived from older adult muscle biopsies were treated with ucOC and/or IBN, then signalling proteins were analysed. Combined treatment, but not individual treatments, significantly increased the muscle weight/body weight ratio in immobilized soleus (31.7%; P = 0.013) and quadriceps (20.0%; P = 0.0008) muscles, concomitant with elevated p-Akt (S473)/Akt ratio (P = 0.0047). Combined treatment also enhanced whole-body glucose tolerance (16.6%; P = 0.0011). In human myotubes, combined treatment stimulated greater activation of ERK1/2 (P = 0.0067 and 0.0072) and mTOR (P = 0.036), and led to a lesser expression of Fbx32 (P = 0.049) and MuRF1 (P = 0.048) than individual treatments. These findings suggest a potential therapeutic role for the ucOC and bisphosphonates combination in protecting against muscle wasting induced by immobilization and ageing. KEY POINTS: It has been suggested that undercarboxylated osteocalcin (ucOC) improves muscle mass and glucose metabolism. Bisphosphonates, an anti-osteoporosis treatment, might protect against muscle wasting independent of ucOC. The combination treatment of ucOC and ibandronate was shown to exert a greater therapeutic effect against immobilization-induced muscle wasting, and led to greater activation of anabolic pathway and less expression of catabolic signalling proteins in myotubes derived from older adults, compared with individual treatments. The combination treatment was found to improve whole-body glucose tolerance. Our findings suggest a potential therapeutic role for the ucOC and bisphosphonates combination in protecting against muscle wasting induced by immobilization and ageing.

Osteoporosis and Bone Marrow Adipose Tissue.

PURPOSE OF REVIEW: This review focuses on the recent findings regarding bone marrow adipose tissue (BMAT) concerning bone health. We summarize the variations in BMAT in relation to age, sex, and skeletal sites, and provide an update on noninvasive imaging techniques to quantify human BMAT. Next, we discuss the role of BMAT in patients with osteoporosis and interventions that affect BMAT. RECENT FINDINGS: There are wide individual variations with region-specific fluctuation and age- and gender-specific differences in BMAT content and composition. The Bone Marrow Adiposity Society (BMAS) recommendations aim to standardize imaging protocols to increase comparability across studies and sites. Water-fat imaging (WFI) seems an accurate and efficient alternative for spectroscopy (1H-MRS). Most studies indicate that greater BMAT is associated with lower bone mineral density (BMD) and a higher prevalence of vertebral fractures. The proton density fat fraction (PDFF) and changes in lipid composition have been associated with an increased risk of fractures independently of BMD. Therefore, PDFF and lipid composition could potentially be future imaging biomarkers for assessing fracture risk. Evidence of the inhibitory effect of osteoporosis treatments on BMAT is still limited to a few randomized controlled trials. Moreover, results from the FRAME biopsy sub-study highlight contradictory findings on the effect of the sclerostin antibody romosozumab on BMAT. Further understanding of the role(s) of BMAT will provide insight into the pathogenesis of osteoporosis and may lead to targeted preventive and therapeutic strategies.

Bone-muscle crosstalk following exercise plus Ursolic acid by myomiR-133a/Cx43-Runx2 axis in aged type 2 diabetes rat models.

Natural bioactive compound, Ursolic acid (UA), plus different types of exercise may exert the action on glycemic control, leading to clinical benefits in the prevention and treatment of aging/diabetes-associated complications. So, this study examined the effects of eight weeks combination of 250 mg of UA per day per kilogram of body weight of rat as well as resistance/endurance training on miR-133a expression across serum, bone marrow, skeletal muscle, and Connexin 43 (Cx43)-Runt-related transcription factor 2 (Runx2) signaling axis in high-fat diet and low-dose streptozotocin-induced T2D (here, HFD/STZ-induced T2D). The study was conducted on 56 male Wistar rats (427 ± 44 g, 21 months old), having HFD/STZ-induced T2D randomly assigned into 7 groups of 8 including (1) sedentary non-diabetic old rats (C); (2) sedentary type 2 diabetes animal model (D); (3) sedentary type 2 diabetes animal model + UA (DU); (4) endurance-trained type 2 diabetes animal model (DE); (5) resistance-trained type 2 diabetes animal model (DR); (6) endurance-trained type 2 diabetes animal model + UA (DEU); and (7) resistance-trained type 2 diabetes animal model + UA (DRU). Resistance training included a model of eight weeks of ladder resistance training at 60-80% maximal voluntary carrying capacity (MVCC) for five days/week. Treadmill endurance exercise protocol included eight weeks of repetitive bouts of low-/high-intensity training with 30%-40% and 60%-75% maximal running speed for five days/week, respectively. UA Supplementary groups were treated with 500 mg of UA per kg of high-fat diet per day. The results revealed significant supplement and exercise interaction effects for the BM miR-133a (p = 0.001), the bone marrow Runx2 (p = 0.002), but not the serum miR-133a (p = 0.517), the skeletal muscle miR-133a (p = 0.097) and the Cx43 (p = 0.632). In conclusion, only eight weeks of resistance-type exercise could affect miR-133a profile in muscles and osteoblast differentiation biomarker RUNX2 in aged T2D model of rats. 250 mg of UA per kilogram of body weight rat per day was administered orally, less than the sufficient dose for biological and physiological impacts on osteoblast differentiation biomarkers in aged T2D model of rats following eight weeks.

Relationship Between Plasma Homocysteine and Bone Density, Lean Mass, Muscle Strength and Physical Function in 1480 Middle-Aged and Older Adults: Data from NHANES.

Hyperhomocysteinemia induces oxidative stress and chronic inflammation (both of which are catabolic to bone and muscle); thus, we examined the association between homocysteine and body composition and physical function in middle-aged and older adults. Data from the National Health and Nutrition Examination Survey was used to build regression models. Plasma homocysteine (fluorescence immunoassay) was used as the exposure and bone mineral density (BMD; dual-energy X-ray absorptiometry; DXA), lean mass (DXA), knee extensor strength (isokinetic dynamometer; newtons) and gait speed (m/s) were used as outcomes. Regression models were adjusted for confounders (age, sex, race/Hispanic origin, height, fat mass %, physical activity, smoking status, alcohol intakes, cardiovascular disease, diabetes, cancer and vitamin B12). All models accounted for complex survey design by using sampling weights provided by NHANES. 1480 adults (median age: 64 years [IQR: 56, 73]; 50.3% men) were included. In multivariable models, homocysteine was inversely associated with knee extensor strength (ß = 0.98, 95% CI 0.96, 0.99, p = 0.012) and gait speed (ß = 0.85, 95% CI 0.78, 0.94, p = 0.003) and borderline inversely associated with femur BMD (ß = 0.84, 95% CI 0.69, 1.03, p = 0.086). In the sub-group analysis of older adults (≥ 65 years), homocysteine was inversely associated with gait speed and femur BMD (p < 0.05) and the slope for knee extensor strength and whole-body BMD were in the same direction. No significant associations were observed between homocysteine and total or appendicular lean mass in the full or sub-group analysis. We found inverse associations between plasma homocysteine and muscle strength/physical function, and borderline significant inverse associations for femur BMD.

Consensus guidelines for sarcopenia prevention, diagnosis and management in Australia and New Zealand.

BACKGROUND: Sarcopenia is an age-associated skeletal muscle condition characterized by low muscle mass, strength, and physical performance. There is no international consensus on a sarcopenia definition and no contemporaneous clinical and research guidelines specific to Australia and New Zealand. The Australian and New Zealand Society for Sarcopenia and Frailty Research (ANZSSFR) Sarcopenia Diagnosis and Management Task Force aimed to develop consensus guidelines for sarcopenia prevention, assessment, management and research, informed by evidence, consumer opinion, and expert consensus, for use by health professionals and researchers in Australia and New Zealand. METHODS: A four-phase modified Delphi process involving topic experts and informed by consumers, was undertaken between July 2020 and August 2021. Phase 1 involved a structured meeting of 29 Task Force members and a systematic literature search from which the Phase 2 online survey was developed (Qualtrics). Topic experts responded to 18 statements, using 11-point Likert scales with agreement threshold set a priori at >80%, and five multiple-choice questions. Statements with moderate agreement (70%-80%) were revised and re-introduced in Phase 3, and statements with low agreement (<70%) were rejected. In Phase 3, topic experts responded to six revised statements and three additional questions, incorporating results from a parallel Consumer Expert Delphi study. Phase 4 involved finalization of consensus statements. RESULTS: Topic experts from Australia (n = 62, 92.5%) and New Zealand (n = 5, 7.5%) with a mean ± SD age of 45.7 ± 11.8 years participated in Phase 2; 38 (56.7%) were women, 38 (56.7%) were health professionals and 27 (40.3%) were researchers/academics. In Phase 2, 15 of 18 (83.3%) statements on sarcopenia prevention, screening, assessment, management and future research were accepted with strong agreement. The strongest agreement related to encouraging a healthy lifestyle (100%) and offering tailored resistance training to people with sarcopenia (92.5%). Forty-seven experts participated in Phase 3; 5/6 (83.3%) revised statements on prevention, assessment and management were accepted with strong agreement. A majority of experts (87.9%) preferred the revised European Working Group for Sarcopenia in Older Persons (EWGSOP2) definition. Seventeen statements with strong agreement (>80%) were confirmed by the Task Force in Phase 4. CONCLUSIONS: The ANZSSFR Task Force present 17 sarcopenia management and research recommendations for use by health professionals and researchers which includes the recommendation to adopt the EWGSOP2 sarcopenia definition in Australia and New Zealand. This rigorous Delphi process that combined evidence, consumer expert opinion and topic expert consensus can inform similar initiatives in countries/regions lacking consensus on sarcopenia.

Comparing the Fracture Profile of Osteosarcopenic Older Adults with Osteopenia/Osteoporosis Alone.

PURPOSE: To determine whether osteosarcopenia is associated with a greater likelihood of recurrent fractures, as well as type of fracture, than osteopenia/osteoporosis or sarcopenia alone. METHODS: Anthropometry (height/weight; scales and stadiometer), body composition (bone mineral density [BMD] and appendicular lean mass; dual-energy x-ray absorptiometry), grip strength (hydraulic dynamometer), and gait speed (4 m) were measured in an outpatient clinic. WHO definition for osteopenia/osteoporosis (BMD T-score below -1 SDs) while sarcopenia was defined by SDOC or EWGSOP2. Number and location of fractures within the past 5 years were self-reported and verified by medical records (unverified fractures excluded). Univariable and multivariable regressions were used to examine the association between the exposure and outcome while adjusting for confounders. RESULTS: 481 community-dwelling older adults (median age: 78, IQR: 72, 83; 75.9% women) were included. Prevalence of osteosarcopenia depended on the definition (SDOC: 179 (37.2%); EWGSOP2: 123 (25.6%)). In multivariable analysis adjusting for age, sex, alcohol, smoking, BMI, lowest BMD T-score, physical activity, and comorbidities, the likelihood of recurrent fractures (≥ 2 vs 0-1) was significantly higher in those with osteosarcopenia versus osteopenia/osteoporosis irrespective of the definition (SDOC: odds ratio [OR]: 1.63, 95% CI: 1.03, 2.59, p = 0.037; EWGSOP2: OR: 1.83, 95% CI: 1.12, 3.01, p = 0.016]. Associations with sarcopenia alone (SDOC: 10; EWGSOP2: 7) were not possible due to the extremely low prevalence of this condition in those with normal BMD. CONCLUSION: Our data suggest osteosarcopenia is associated with a greater likelihood of recurrent fractures versus osteopenia/osteoporosis alone. Further studies are needed to evaluate the relationship with sarcopenia alone.

One-year mortality after hip fracture surgery: urban-rural differences in the Colombian Andes.

To determine urban-rural differences influencing mortality in patients with hip fracture in Colombian Andes Mountains over a 1-year period. PURPOSE: To identify the urban-rural differences of sociodemographic variables, fracture-related characteristics, and preoperative and postoperative clinical factors associated with 1-year mortality in patients over 60 years old who underwent hip fracture surgery in the Andes Mountains. METHODS: A total of 126 patients with a fragility hip fracture during 2019-2020 were admitted to a tertiary care hospital. They were evaluated preoperatively and followed up until discharge. Those who survived were contacted by telephone at 1, 3, and 12 months. Univariate, bivariate, and Kaplan-Meier analyses with survival curves were performed. Relative risk was calculated with a 95% confidence interval. RESULTS: A total of 32.5% of the patients died within 1 year after surgery, with a significant difference between those who resided in rural areas (43.1%) and those who resided in urban areas (23.5%) (RR 1.70; 95% CI, 1.03 to 2.80, p = 0.036). In the multivariate analysis, anemia (hemoglobin level ≤ 9.0 g/dL during hospitalization) (RR 6.61; 95% CI, 1.49-29.37, p = 0.003), a blood transfusion requirement (RR 1.47; 95% CI, 1.07 to 2.01, p = 0.015), the type of fracture (subtrochanteric fracture (RR = 4.9, 95% CI = 1.418-16.943, p = 0.005)), and postoperative acute decompensation of chronic disease (RR 1.60; 95% CI, 1.01 to 2.53, p = 0.043) were found to be independent predictive factors of 1-year mortality after surgery. CONCLUSIONS: There was a difference in 1-year mortality between patients from rural and urban areas. More studies must be conducted to determine whether rurality behaves as an independent risk factor or is related to other variables, such as the burden of comorbidities and in-hospital complications.

Comparative analysis of fat composition in marrow, serum, and muscle from aging C57BL6 mice.

Osteosarcopenia is an age-related condition characterized by fragile bone and low muscle mass and function. Fat infiltration concomitantly contributes to age-related bone and muscle decline. Fat-secreted factors could be locally secreted in the muscle and bone marrow milieu affecting cell function and survival. However, the specific fat-related secretory factors that may simultaneously affect those tissues remain unknown. Using targeted-lipidomics approach, we comprehensively quantified fat composition (lipid mediators [LMs]) in bone marrow flush, gastrocnemius and serum obtained from 6-, 24- and 42-week-old C57BL6 mice. Compared to young mice (6wks), all tissues in older mice showed significantly higher levels of arachidonic acid (AA) and AA-derived eicosanoids, PGA 2, TXB 2, and 11,12-EET, which are known to affect muscle and bone function. Moreover, Lipoxin B4, another AA product and an enhancer of bone turnover and negative regulator for muscle, showed significantly lower values in older mice compared to young mice in both genders. Furthermore, eicosapentaenoic acid and docosahexaenoic acid autoxidation products (20-HDoHE, 11-HDoHE, 7-HDoHE and 4-HDoHE), and omega-3 fatty acids that negatively regulate bone and muscle health, were significantly higher in older mice. In conclusion, these results suggest that LMs could play a role in modulating musculoskeletal function during aging.

Associations between leukocyte telomere length and osteosarcopenia in 20,400 adults aged 60 years and over: Data from the UK Biobank.

PURPOSE: Two mechanisms implicated in telomere shortening are oxidative stress and inflammation, both of which are linked to bone and muscle loss suggesting a pathological link between telomere attrition and osteosarcopenia. Using older adults aged 60 years and over in the UK Biobank, we examined the association between leukocyte telomere length and osteosarcopenia. METHODS: Baseline leukocyte telomere length was measured using a multiplex qPCR technique and expressed as the amount of the telomere amplification product (T) to that of a single-copy gene (S) (T/S ratio). Osteosarcopenia data was from the first imaging visit and defined by WHO criteria (femoral neck bone density T score ≤ -1) for osteopenia/osteoporosis plus either the EWGSOP2 (low appendicular lean mass/height2 and low grip strength) or SDOC (low grip strength and slow walking pace) criteria for sarcopenia. Binary or multinomial logistic regression models were used to associate telomere length and osteosarcopenia or its components, adjusting for the covariates: age, sex, race, education, Townsend deprivation index, alcohol, smoking, BMI/weight, physical activity levels. RESULTS: Among 20,400 older adults (mean age: 67.79 ± 4.9 years, 53% men), the prevalence of osteosarcopenia by EWGSOP2 (n = 96, 0.47%) or SDOC (n = 205, 1%) criteria was low at the first imaging visit (mean 8.82 years after baseline). Baseline telomere length was not associated with osteosarcopenia by EWGSOP2 (Relative Risk (RR): 1.00, 95% CI: 0.82-1.23 comparing osteosarcopenia to normal (non-osteopenic, non-osteoporotic, and non-sarcopenic) per Standard Deviation (SD) increase in telomere length) or SDOC (RR: 0.95, 95% CI: 0.83-1.09) criteria. Longer telomere length was associated with a lower risk of slow walking pace (Odds Ratio: 0.92, 95% CI: 0.87-0.99 per SD increase in telomere length, p = 0.021). Telomere length, however, was not associated with low grip strength, low bone density or low appendicular lean mass/height2 (p > 0.05). CONCLUSIONS: In this population-based study, telomere length was not associated with osteosarcopenia; however, slow walking pace was. Further studies are needed to reexamine this relationship, including a greater number of the oldest-old (≥75 years) where osteosarcopenia is more prevalent.

Roles of nutrition in muscle health of community-dwelling older adults: evidence-based expert consensus from Asian Working Group for Sarcopenia.

General muscle health declines with age, and in particular, sarcopenia-defined as progressive loss of muscle mass and strength/physical performance-is a growing issue in Asia with a rising population of community-dwelling older adults. Several guidelines have addressed early identification of sarcopenia and management, and although nutrition is central to treatment of sarcopenia, there are currently few guidelines that have examined this specifically in the Asian population. Therefore, the Asian Working Group for Sarcopenia established a special interest group (SIG) comprising seven experts across Asia and one from Australia, to develop an evidence-based expert consensus. A systematic literature search was conducted using MEDLINE on the topic of muscle health, from 2016 (inclusive) to July 2021, in Asia or with relevance to healthy, Asian community-dwelling older adults (≥60 years old). Several key topics were identified: (1) nutritional status: malnutrition and screening; (2) diet and dietary factors; (3) nutritional supplementation; (4) lifestyle interventions plus nutrition; and (5) outcomes and assessment. Clinical questions were developed around these topics, leading to 14 consensus statements. Consensus was achieved using the modified Delphi method with two rounds of voting. Moreover, the consensus addressed the impacts of COVID-19 on nutrition, muscle health, and sarcopenia in Asia. These statements encompass clinical expertise and knowledge across Asia and are aligned with findings in the current literature, to provide a practical framework for addressing muscle health in the community, with the overall aim to encourage and facilitate broader access to equitable care for this target population.

Creatinine to Cystatin C Ratio, a Biomarker of Sarcopenia Measures and Falls Risk in Community-Dwelling Older Women.

BACKGROUND: The ratio of creatinine to cystatin C (Cr:Cyc) has been proposed as a biomarker of sarcopenia, as greater Cr:Cyc is typically associated with greater muscle mass. We examined the relationship between Cr:Cyc with individual sarcopenia measures, 5-year self-reported falls, and 12-year fall-related hospitalizations in a prospective cohort study of 1 118 community-dwelling older women (mean age 75.2 ± 2.7 years). METHODS: Serum Cr:Cyc, hand grip strength, and timed-up-and-go performance were assessed at baseline (1998), while dual-energy x-ray absorptiometry-derived appendicular lean mass (ALM)/height2 (m) was obtained in a subset of women at baseline and 1 year (n = 334). Incident 5-year self-reported falls and 12-year falls-related hospitalizations were considered. RESULTS: In a multivariable-adjusted model, women with the lowest Cr:Cyc (Quartile [Q] 1) had 5% (1.0 kg) weaker grip strength, as well as 3.7% (0.22 kg/m2) and 5.5% (0.031) lower ALM adjusted for height2 or body mass index, respectively, compared to women in Q4 (all p < .05). 329 women reported an incident fall over 5 years, and 326 fall-related hospitalizations were recorded over 12 years. Women in Q1 of Cr:Cyc had a greater relative hazard for a fall over 5 years (hazard ratio [HR] 1.50; 95% confidence interval [CI] 1.11-2.01) and fall-related hospitalization over 12 years (HR 1.53; 95% CI 1.13-2.07) compared to Q4 in the multivariable-adjusted model. CONCLUSION: These findings support further investigation into the use of Cr:Cyc as a muscle biomarker to help clinicians identify individuals at risk of falls for early inclusion into evidence-based primary prevention programs targeting improvements to diet and exercise.

Validation of a Semiautomatic Image Analysis Software for the Quantification of Musculoskeletal Tissues.

Accurate quantification of bone, muscle, and their components is still an unmet need in the musculoskeletal field. Current methods to quantify tissue volumes in 3D images are expensive, labor-intensive, and time-consuming; thus, a reliable, valid, and quick application is highly needed. Tissue Compass is a standalone software for semiautomatic segmentation and automatic quantification of musculoskeletal organs. To validate the software, cross-sectional micro-CT scans images of rat femur (n = 19), and CT images of hip and abdomen (n = 100) from the Osteoporotic Fractures in Men (MrOS) Study were used to quantify bone, hematopoietic marrow (HBM), and marrow adipose tissue (MAT) using commercial manual software as a comparator. Also, abdominal CT scans (n = 100) were used to quantify psoas muscle volumes and intermuscular adipose tissue (IMAT) using the same software. We calculated Pearson's correlation coefficients, individual intra-class correlation coefficients (ICC), and Bland-Altman limits of agreement together with Bland-Altman plots to show the inter- and intra-observer agreement between Tissue Compass and commercially available software. In the animal study, the agreement between Tissue Compass and commercial software was r > 0.93 and ICC > 0.93 for rat femur measurements. Bland-Altman limits of agreement was - 720.89 (- 1.5e+04, 13,074.00) for MAT, 4421.11 (- 1.8e+04, 27,149.73) for HBM and - 6073.32 (- 2.9e+04, 16,388.37) for bone. The inter-observer agreement for QCT human study between two observers was r > 0.99 and ICC > 0.99. Bland-Altman limits of agreement was 0.01 (- 0.07, 0.10) for MAT in hip, 0.02 (- 0.08, 0.12) for HBM in hip, 0.05 (- 0.15, 0.25) for bone in hip, 0.02 (- 0.18, 0.22) for MAT in L1, 0.00 (- 0.16, 0.16) for HBM in L1, and 0.02 (- 0.23, 0.27) for bone in L1. The intra-observer agreement for QCT human study between the two applications was r > 0.997 and ICC > 0.99. Bland-Altman limits of agreement was 0.03 (- 0.13, 0.20) for MAT in hip, 0.05 (- 0.08, 0.18) for HBM in hip, 0.05 (- 0.24, 0.34) for bone in hip, - 0.02 (- 0.34, 0.31) for MAT in L1, - 0.14 (- 0.44, 0.17) for HBM in L1, - 0.29 (- 0.62, 0.05) for bone in L1, 0.03 (- 0.08, 0.15) for IMAT in psoas, and 0.02 (- 0.35, 0.38) for muscle in psoas. Compared to a conventional application, Tissue Compass demonstrated high accuracy and non-inferiority while also facilitating easier analyses. Tissue Compass could become the tool of choice to diagnose tissue loss/gain syndromes in the future by requiring a small number of CT sections to detect tissue volumes and fat infiltration.