The role of bile acid metabolism in bone and muscle: from analytics to mechanisms.

Osteoporosis and sarcopenia are both common age-related disorders that are associated with increased morbidity and mortality. Bone and muscle are metabolically very active tissues that require large amounts of energy. Bile acids (BAs), a group of liver-derived steroid compounds, are primarily known as emulsifiers that facilitate the resorption of dietary fat and lipids. In addition, they have pleiotropic metabolic functions in lipoprotein and glucose metabolism, inflammation, and intestinal bacterial growth. Through these effects, they are related to metabolic diseases, such as diabetes, hypertriglyceridemia, atherosclerosis, and nonalcoholic steatohepatitis. BAs mediate their metabolic effects through receptor dependent and receptor-independent mechanisms. Emerging evidence suggests that BAs are also involved in bone and muscle metabolism. Under normal circumstances, BAs support bone health by shifting the delicate equilibrium of bone turnover toward bone formation. In contrast, low or excessive amounts of BAs promote bone resorption. In cholestatic liver disease, BAs accumulate in the liver, reach toxic concentrations in the circulation, and thus may contribute to bone loss and muscle wasting. In addition, the measurement of BAs is in rapid evolution with modern mass spectrometry techniques that allow for the detection of a continuously growing number of BAs. This review provides a comprehensive overview of the biochemistry, physiology and measurement of bile acids. Furthermore, it summarizes the existing literature regarding their role in bone and muscle.

Osteosarcopenia: Prevalence and 10-Year Fracture and Mortality Risk - A Longitudinal, Population-Based Study of 75-Year-Old Women.

Osteosarcopenia is the coexistence of low bone mass and sarcopenia. In older women, its prevalence is not well described, and it is unknown if sarcopenia is additive to low bone mass for fracture and mortality risk. The study investigated prevalence of osteosarcopenia and if osteosarcopenia is associated with higher fracture and mortality risk than low bone mass alone in older community-dwelling women. The longitudinal, population-based OPRA Cohort (n = 1044), all aged 75 at inclusion, followed for 10 years. Using WHO and EWGSOP2 definitions for low bone mass (T-score < -1.0 femoral neck) and sarcopenia (knee strength; appendicular lean muscle mass) women were categorized (1) Normal, (2) Low bone mass (LBM), and 3) Osteosarcopenia (probable; confirmed). Risk of hip, major osteoporotic fracture, and mortality were estimated. Osteosarcopeniaconfirmed prevalence increased from age 75 to 80 and 85 from 3.0% (29/970) to 4.9% (32/656) to 9.2% (33/358) but prevalence is potentially 2-4 times higher (11.8%, 13.4%, 20.3%) based on osteosarcopeniaprobable. Having osteosarcopeniaprobable significantly increased 10-year risk of hip fracture (HRadj 2.67 [1.34-5.32]), major osteoporotic fracture (HRadj 2.04 [1.27-3.27]), and mortality (HRadj 1.91 [1.21-3.04]). In contrast, LBM increased osteoporotic fracture risk (HRadj 2.08 [1.46-2.97], but not hip fracture (HRadj 1.62 [0.92-2.85]) or mortality (HRadj 0.94 [0.64-1.38]). Median time-to-hip fracture was 7.6 years (normal), 6.0 years (LBM), and 5.7 years (osteosarcopeniaprobable). Prevalence of confirmed osteosarcopenia is almost 10% at age 85. Probable osteosarcopenia significantly increased risk of hip and major osteoporotic fractures and mortality more so than low bone mass alone.

The Interconnection Between Muscle and Bone: A Common Clinical Management Pathway.

Often observed with aging, the loss of skeletal muscle (sarcopenia) and bone (osteoporosis) mass, strength, and quality, is associated with reduced physical function contributing to falls and fractures. Such events can lead to a loss of independence and poorer quality of life. Physical inactivity (mechanical unloading), especially in older adults, has detrimental effects on the mass and quality of bone as well as muscle, while increases in activity (mechanical loading) have positive effects. Emerging evidence suggests that the relationship between bone and muscle is driven, at least in part, by bone-muscle crosstalk. Bone and muscle are closely linked anatomically, mechanically, and biochemically, and both have the capacity to function with paracrine and endocrine-like action. However, the exact mechanisms involved in this crosstalk remain only partially explored. Given older adults with lower bone mass are more likely to present with impaired muscle function, and vice versa, strategies capable of targeting both bone and muscle are critical. Exercise is the primary evidence-based prevention strategy capable of simultaneously improving muscle and bone health. Unfortunately, holistic treatment plans including exercise in conjunction with other allied health services to prevent or treat musculoskeletal disease remain underutilized. With a focus on sarcopenia and osteoporosis, the aim of this review is to (i) briefly describe the mechanical and biochemical interactions between bone and muscle; (ii) provide a summary of therapeutic strategies, specifically exercise, nutrition and pharmacological approaches; and (iii) highlight a holistic clinical pathway for the assessment and management of sarcopenia and osteoporosis.

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.

Prevalence of osteosarcopenia and its association with mortality and fractures among patients undergoing hemodialysis.

INTRODUCTION: Osteosarcopenia is an age-related syndrome characterized by the coexistence of osteoporosis and sarcopenia. Little is known about the clinical implications of osteosarcopenia among patients undergoing hemodialysis. This study investigated the prevalence of osteosarcopenia and its association with all-cause mortality and fractures in this population. MATERIALS AND METHODS: This retrospective cohort study included outpatients undergoing hemodialysis in Japan. Sarcopenia was defined according to the recommendations of the Asian Working Group for Sarcopenia 2019. Osteoporosis was defined as a T-score of the calcaneus bone < - 2.5. We divided patients into three groups: robust (no osteoporosis or sarcopenia), osteoporosis or sarcopenia alone (osteoporosis without sarcopenia or sarcopenia without osteoporosis), and osteosarcopenia (osteoporosis and sarcopenia). Cox proportional-hazard and negative binomial regression models were used to estimate the associations between osteosarcopenia and all-cause mortality and fractures. RESULTS: Among the 328 patients (mean age, 65.5 ± 11.3 years; men, 59.1%), the prevalence of osteosarcopenia was 22.9%. During the follow-up period (1972 person-years), 131 deaths and 113 fractures occurred. Patients with osteoporosis or sarcopenia alone (hazard ratio 1.36; 95% confidence interval 0.85-2.18) and osteosarcopenia (hazard ratio 2.13; 95% confidence interval, 1.23-3.68) showed a higher risk of all-cause mortality than the robust group. Similar results were observed for the risk of fractures in patients with osteosarcopenia. CONCLUSIONS: Patients undergoing hemodialysis showed a high prevalence of osteosarcopenia, and osteosarcopenia was associated with a poor prognosis in this patient population. Assessing osteosarcopenia may be useful for accurate prognostic stratification of patients undergoing hemodialysis.

Association of chronic liver disease with bone diseases and muscle weakness.

The liver is a vital organ involved in nutrient metabolism, hormone regulation, immunity, cytokine production, and gut homeostasis. Impairment in liver function can result in malnutrition, chronic inflammation, decreased anabolic hormone levels, and dysbiosis. These conditions eventually cause an imbalance in osteoblast and osteoclast activities, resulting in bone loss. Osteoporosis is a frequent complication of chronic liver disease (CLD) that adversely affects quality of life and increases early mortality. Sarcopenia is another common complication of CLD characterized by progressive loss of skeletal muscle mass and function. Assessment criteria for sarcopenia specific to liver disease have been established, and sarcopenia has been reported to be associated with an increase in the risk of liver disease-related events and mortality in patients with CLD. Owing to their similar risk factors and underlying pathophysiological mechanisms, osteoporosis and sarcopenia often coexist (termed osteosarcopenia), progress in parallel, and further exacerbate the conditions mentioned above. Therefore, comprehensive management of these musculoskeletal disorders is imperative. This review summarizes the clinical implications and characteristics of osteoporosis, extending to sarcopenia and osteosarcopenia, in patients with CLD caused by different etiologies.

Fat as a Friend or Foe of the Bone.

PURPOSE OF REVIEW: The objective of this review is to summarize the literature on the prevalence and diagnosis of obesity and its metabolic profile, including bone metabolism, focusing on the main inflammatory and turnover bone mediators that better characterize metabolically healthy obesity phenotype, and to summarize the therapeutic interventions for obesity with their effects on bone health. RECENT FINDINGS: Osteoporosis and fracture risk not only increase with age and menopause but also with metabolic diseases, such as diabetes mellitus. Thus, patients with high BMI may have a higher bone fragility and fracture risk. However, some obese individuals with healthy metabolic profiles seem to be less at risk of bone fracture. Obesity has become an alarming disease with growing prevalence and multiple metabolic comorbidities, resulting in a significant burden on healthcare and increased mortality. The imbalance between increased food ingestion and decreased energy expenditure leads to pathological adipose tissue distribution and function, with increased secretion of proinflammatory markers and harmful consequences for body tissues, including bone tissue. However, some obese individuals seem to have a healthy metabolic profile and may not develop cardiometabolic disease during their lives. This healthy metabolic profile also benefits bone turnover and is associated with lower fracture risk.

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.

Nonalcoholic Fatty Liver Disease, Bone and Muscle Quality in Prolactinoma: A Pilot Study.

OBJECTIVE: Hyperprolactinemia has negative impacts on metabolism and musculoskeletal health. In this study, individuals with active prolactinoma were evaluated for nonalcoholic fatty liver disease (NAFLD) and musculoskeletal health, which are underemphasized in the literature. METHODS: Twelve active prolactinoma patients and twelve healthy controls matched by age, gender, and BMI were included. Magnetic resonance imaging-proton density fat fraction (MRI-PDFF) was used to evaluate hepatic steatosis and magnetic resonance elastography (MRE) to evaluate liver stiffness measurement (LSM). Abdominal muscle mass, and vertebral MRI-PDFF was also evaluated with MRI. Body compositions were evaluated by dual energy X-ray absorptiometry (DXA). The skeletal muscle quality (SMQ) was classified as normal, low and weak by using "handgrip strength/appendicular skeletal muscle mass (HGS/ASM)" ratio based on the cut-off values previously stated in the literature. RESULTS: Prolactin, HbA1c and CRP levels were higher in prolactinoma patients (p<0.001, p=0.033 and p=0.035, respectively). The median MRI-PDFF and MRE-LSM were 3.0% (2.01-15.20) and 2.22 kPa (2.0-2.5) in the prolactinoma group and 2.5% (1.65-10.00) and 2.19 kPa (1.92-2.54) in the control group, respectively and similiar between groups. In prolactinoma patients, liver MRI-PDFF showed a positive and strong correlation with the duration of disease and traditional risk factors for NAFLD. Total, vertebral and pelvic bone mineral density was similar between groups, while vertebral MRI-PDFF tended to be higher in prolactinoma patients (p=0.075). Muscle mass and strength parameters were similar between groups, but HGS/ASM tended to be higher in prolactinoma patients (p=0.057). Muscle mass was low in 33.3% of prolactinoma patients and 66.6 of controls. According to SMQ, all prolactinoma patients had normal SMQ, whereas 66.6% of the controls had normal SMQ. CONCLUSION: Prolactinoma patients demonstrated similar liver MRI-PDFF and MRE-LSM to controls despite their impaired metabolic profile and lower gonadal hormone levels. Hyperprolactinemia may improve muscle quality in prolactinoma patients despite hypogonadism.

Prognostic impact of osteosarcopenia in patients undergoing pancreatic resection for pancreatic ductal adenocarcinoma.

BACKGROUND: We investigated the prognostic impact of osteosarcopenia, defined as the combination of osteopenia and sarcopenia, in patients undergoing pancreatic resection for pancreatic ductal adenocarcinoma (PDAC). METHODS: The relationship of osteosarcopenia with disease-free survival and overall survival was analyzed in 183 patients who underwent elective pancreatic resection for PDAC. Computed tomography was used to measure the pixel density in the midvertebral core of the 11th thoracic vertebra for evaluation of osteopenia and in the psoas muscle area of the 3rd lumbar vertebra for evaluation of sarcopenia. Osteosarcopenia was defined as the simultaneous presence of both osteopenia and sarcopenia. The study employed a retrospective design to examine the relationship between osteosarcopenia and survival outcomes. RESULTS: Osteosarcopenia was identified in 61 (33%) patients. In the univariate analysis, disease-free survival was significantly worse in patients with male sex (p = 0.031), pathological stage ≥ III PDAC (p = 0.001), NLR, ≥ 2.71 (p = 0.041), sarcopenia (p = 0.027), osteopenia (p = 0.001), and osteosarcopenia (p < 0.001), and overall survival was significantly worse in patients with male sex (p = 0.001), pathological stage ≥ III PDAC (p = 0.001), distal pancreatectomy (p = 0.025), sarcopenia (p = 0.003), osteopenia (p < 0.001), and osteosarcopenia (p < 0.001). In the multivariate analysis, the independent predictors of disease-free survival were osteosarcopenia (p < 0.001) and pathological stage ≥ III PDAC (p = 0.002), and the independent predictors of overall survival were osteosarcopenia (p < 0.001), male sex (p = 0.006) and pathological stage ≥ III PDAC (p = 0.001). CONCLUSION: Osteosarcopenia has an adverse prognostic impact on long-term outcomes in patients undergoing pancreatic resection for PDAC.

Effects of high-intensity training on fatty infiltration in paraspinal muscles in elderly males with osteosarcopenia - the randomized controlled FrOST study.

BACKGROUND: Osteosarcopenia is a common geriatric syndrome with an increasing prevalence with age, leading to secondary diseases and complex consequences such as falls and fractures, as well as higher mortality and frailty rates. There is a great need for prevention and treatment strategies. METHODS: In this analysis, we used magnetic resonance imaging (MRI) data from the randomised controlled FrOST trial, which enrolled community-dwelling osteosarcopenic men aged > 72 years randomly allocated to 16 months of twice-weekly high-intensity resistance training (HIRT) or a non-training control group. MR Dixon imaging was used to quantify the effects of HIRT on muscle fat infiltration in the paraspinal muscles, determined as changes in muscle tissue, fat faction and intermuscular adipose tissue (IMAT) in the erector spinae and psoas major muscles. Intention-to-treat analysis with multiple imputation was used to analyse the data set. RESULTS: After 16 months of intervention, 15 men from the HIRT and 16 men from the CG were included in the MRI analysis. In summary, no positive effects on the fat infiltration of the erector spinae and psoas major muscles were observed. CONCLUSIONS: The previously reported positive effects on lumbar spine bone mineral density (BMD) suggest that mechanotransduction induces tropic effects on bone, but that fat infiltration of the erector spinae and psoas major muscles are either irreversible or, for some unknown reason, resistant to exercise. Because of the beneficial effects on spinal BMD, HIRT is still recommended in osteosarcopenic older men, but further research is needed to confirm appropriate age-specific training exercises for the paraspinal muscles. The potential of different MRI sequences to quantify degenerative and metabolic changes in various muscle groups must be better characterized. TRIAL REGISTRATIONS: FrOST was approved by the University Ethics Committee of the Friedrich-Alexander University of Erlangen-Nürnberg (number 67_15b and 4464b) and the Federal Office for Radiation Projection (BfS, number Z 5-2,246,212 - 2017-002). Furthermore, it fully complies with the Declaration of Helsinki and is registered at ClinicalTrials.gov: NCT03453463 (05/03/2018). JAMA 310:2191-2194, 2013.

Effects of resistance training and nutritional support on osteosarcopenia in older, community-dwelling postmenopausal Korean females (ERTO-K study): a study protocol.

BACKGROUND: Osteosarcopenia is geriatric syndrome defined as the concomitant occurrence of osteopenia/osteoporosis, and sarcopenia. Osteosarcopenia is a relatively new concept in geriatric medicine; however, it may increase the risk of fragility fractures, several morbidities and mortalities, and socioeconomic costs. Although resistance exercises and nutritional support-including protein, calcium, and vitamin D-are potential non-pharmacological management procedures, evidence is still lacking. The objective of this study was therefore to evaluate the effect of combined resistance exercise and nutritional support on the quality and quantity of bone and muscle in postmenopausal females with osteosarcopenia. METHODS: This research proposal presents the protocol for a prospective, single-center, single-blinded, two-armed randomized controlled trial. Thirty-four participants with osteosarcopenia will be recruited and randomly divided into intervention and control groups; both groups will receive nutritional supplements (protein, 40 g; vitamin D, 1600 IU; calcium, 600 mg) daily. The intervention group will undergo 24 weeks of resistance exercise of increasing intensity, achieved through a three-phase step-up process. The primary outcomes will be the changes in skeletal muscle index and bone marrow density of the lumbar spine and femoral neck between the baseline and end of intervention (24 weeks). The secondary outcomes will be the body composition, whole body phase angle, physical function assessment, quality of life, psychological assessment, and bone turnover markers of participants, surveyed at multiple time points. DISCUSSION: This randomized controlled trial may reveal the effect of resistance exercise and nutritional support on older postmenopausal women with osteosarcopenia. The results will provide evidence for developing proper non-pharmacological management guidelines for postmenopausal women. TRIAL REGISTRATION: Clinical Research Information Service of Republic of Korea, KCT0008291, Registered on 16 March 2023, https://cris.nih.go.kr/cris/search/detailSearch.do/25262 .

Lacto-ovo-vegetarian diet is inversely associated with the osteosarcopenia in older adults.

OBJECTIVE: Osteosarcopenia adversely affects the quality of life and physical health of older adults. We sought to explore the association between dietary patterns and osteosarcopenia in community-dwelling older adults. METHODS: This is a cross-sectional study from Northeast China, in which, we included older community adults aged 60 and above. Through face-to-face interviews, we collected dietary information from participants using a food frequency questionnaire. Subsequently, principal component analysis (PCA) was used to obtain the dietary patterns of the participants. Through physical examination, we obtained the participants' information on osteosarcopenia, which was defined by the coexist of osteopenia and sarcopenia. We analysed the association between dietary patterns and dietary compositions with ostesarcopenia. RESULTS: In this study, a total of 9429 participants were included, and the prevalence of osteosarcopenia in community-dwelling older adults was 6.2%. PCA identified three main dietary patterns, and the lacto-ovo-vegetarian dietary pattern was inversely associated with osteosarcopenia. Compared to the lowest lacto-ovo-vegetarian quartile (Q1), the Q4 group (OR = 0.64, 95% CI:0.49-0.83) was inversely associated with osteosarcopenia. Through the weighted quantile sum regression model, we also found that the overall effect of the lacto-ovo-vegetarian dietary components was inversely associated with osteosarcopenia (OR = 0.58, 95% CI: 0.37-0.92); the largest contributors were vegetables, fresh milk, eggs, and dairy products. CONCLUSION: Overall, we found that a lacto-ovo-vegetarian dietary pattern, particularly the consumption of vegetables, fresh milk, eggs, and dairy products, was inversely associated with osteosarcopenia in older adults. And this might provide new insights for the prevention and treatment of osteosarcopenia.

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.

Analysis of related factors for sarco-osteoporosis in middle-aged and elderly inpatients and development and validation of a nomogram.

BACKGROUND: Sarco-osteoporosis is a skeletal muscle disease associated with aging and complex pathological factors. At present, there are few studies on the analysis of its related factors, and a nomogram to estimate the risk of sarco-osteoporosis in middle-aged and elderly patients is not available. METHODS: A total of 386 patients admitted to our hospital from October 2021 to October 2022 were collected, and the general demographic data and clinical data of the patients were collected.386 subjects were enrolled in the study and randomly divided into training set and validation set at a ratio of 7:3. In the training set, the Least absolute shrinkage and selection operator(LASSO)regression technique was used to select the optimal predictive features, and multivariate logistic regression was used to screen the factors associated with sarco-osteoporosis, and a nomogram was constructed using meaningful variables from multivariate analysis. The performance of the nomograms was assessed and validated by Area Under Curve (AUC) and calibration curves. RESULTS: There were no significant differences in baseline characteristic of individuals in training set and validation set, six variables with non-zero coefficients were screened based on LASSO regression in the training set. Multivariate logistic regression analysis showed that the related factors for sarco-osteoporosis in middle-aged and elderly inpatients included age (OR = 1.08, 95%CI 1.03 ∼ 1.14), regular exercise (OR = 0.29, 95%CI 0.15 ∼ 0.56), albumin (OR = 0.9, 95%CI 0.82 ∼ 0.98), height (OR = 0.93, 95%CI 0.88 ∼ 0.99) and lean mass index (OR = 0.66, 95%CI 0.52 ∼ 0.85), and a nomogram was constructed based on the above factors. AUC of nomogram were 0.868(95%CI 0.825 ∼ 0.912) in the training set and 0.737(95%CI 0.646 ∼ 0.828) in the validation set. Calibration curve analysis showed that the predicted probability of sarco-osteoporosis had high consistency with the actual probability, and the absolute error of the training set and verification set was 0.018 and 0.03, respectively. CONCLUSIONS: Our research showed that the occurrence of sarco-osteoporosis was associated with age, regular exercise, albumin, height and lean mass index, and we have developed a nomogram that can be effectively used in the preliminary and in-depth risk prediction of sarco-osteoporosis in middle-aged and elderly hospitalized patients.

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.

Osteosarcopenia is a significant predictor of recurrence and the prognosis after resection for extrahepatic bile duct cancer.

PURPOSE: This study examined the impact of osteosarcopenia on recurrence and the prognosis after resection for extrahepatic biliary tract cancer (EBTC). METHODS: We retrospectively analyzed 138 patients after resection for perihilar cholangiocarcinoma (11), distal cholangiocarcinoma (54), gallbladder carcinoma (30), or ampullary carcinoma (43). Osteosarcopenia is defined as the concomitant occurrence of osteopenia and sarcopenia. We investigated the relationship between osteosarcopenia and the overall survival (OS) and disease-free survival (DFS) in univariate and multivariate analyses. RESULTS: Osteosarcopenia was identified in 38 patients (27.5%) before propensity score (PS) matching. In the multivariate analysis, the independent recurrence factors were the prognostic nutrition index (p = 0.015), osteosarcopenia (p < 0.001), poorly differentiated adenocarcinoma (p = 0.004), perineural invasion (p = 0.002), and non-curability (p = 0.008), whereas the independent prognostic factors were prognostic nutrition index (p = 0.030), osteosarcopenia (p < 0.001), poorly differentiated adenocarcinoma (p = 0.007), lymphatic invasion (p = 0.018), and non-curability (p = 0.004). After PS matching, there was no significant difference in the variables between the patients with and without osteosarcopenia (n = 34 each). The 5-year DFS and OS after PS matching in patients with osteosarcopenia were significantly worse than in patients without osteosarcopenia (17.6% vs. 38.8%, p = 0.013 and 20.6% vs. 57.4%, p = 0.0005, respectively). CONCLUSIONS: Preoperative osteosarcopenia could predict the DFS and OS of patients after resection for EBTC.

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.

The Association of Cardiovascular Diseases Risk Scores and Osteosarcopenia Among Older Adult Populations: The Results of Bushehr Elderly Health (BEH) Program.

Considering the association of cardiovascular disease (CVD) with both osteoporosis and sarcopenia, this study aimed to explore the association between a newly developed CVD risk score and osteosarcopenia in the elderly population. Participants in the second phase of the Bushehr Elderly Health (BEH) program were included. Osteosarcopenia was defined as having both osteopenia/osteoporosis and sarcopenia. The 10-year CVD risk score was estimated using the WHO lab-based model. The participants were considered as high-risk if the CVD risk was ≥ 20%. The estimated risks were compared in individuals with and without osteosarcopenia. The association of CVD risk and osteosarcopenia was investigated using a logistic regression model, adjusted by potential confounders. In all, 2392 participants (1161 men) with a mean age of 69.3 (± 6.3) years were studied and 532 [242 (45.5%) men] individuals were diagnosed with osteosarcopenia. The median (IQR) CVD risks were 0.340 (0.214) and 0.229 (0.128) in men with and without osteosarcopenia, respectively (P < 0.001); In women, the corresponding values were 0.260 (0.147) and 0.207 (0.128), respectively (P < 0.001). Adjusted by confounders, CVD risk ≥ 20% in women, increased the odds of osteosarcopenia by 72%. Body mass index showed an inverse association with osteosarcopenia in both men (0.81, 95%CI: 0.78-0.85) and women (0.66, 95%CI: 0.62-0.70). Considering the area under the ROC curve, the models showed a discriminative ability of 82% in men and 89% in women. This study displayed a significant association between WHO CVD risk score and osteosarcopenia. Due to the difficult diagnosis of osteosarcopenia, the high association of cardiovascular risk score with this disease can help identify high-risk individuals and refer them for further diagnostic procedures. Considering the high prevalence of osteosarcopenia and its complications in the older population, comprehensive strategies are needed to find high-risk populations.

Coexistence of Low Muscle Mass and Osteoporosis as a Predictor of Fragility Fractures in Long-Term Kidney Transplant Recipients.

INTRODUCTION: Sarcopenia and osteoporosis are highly prevalent among kidney transplant recipients (KTRs). Although osteoporosis is known to increase fracture risk in KTRs, it is unclear whether sarcopenia or osteosarcopenia is associated with this increased risk. Thus, we aimed to investigate the association of the coexistence of low muscle mass (LMM) and osteoporosis with the risk of fracture in long-term KTRs. METHODS: Exactly 342 stable KTRs underwent dual-energy X-ray absorptiometry and skeletal muscle mass index (SMI) measurement using bioelectrical impedance analysis. RESULTS: LMM and osteoporosis were observed in 109 (31.9%) and 93 patients (27.2%), respectively. During a follow-up period of 5.1 years, 48 (14.0%) fractures occurred. KTRs with LMM had a higher fracture risk, but this was not significant (adjusted hazard ratio [aHR] 1.82, 95% confidence interval [CI] 0.94-3.50, p = 0.073). Similar results were obtained in KTRs with osteoporosis (aHR 1.84, 95% CI 0.96-3.47, p = 0.063). We divided the KTRs into four groups according to the presence of LMM and/or osteoporosis. The cumulative incidence rates of fractures were 13.0%, 11.1%, 10.5%, and 31.3% in the KTRs without both LMM and osteoporosis, those with LMM alone, those with osteoporosis alone, and those with both, respectively. The KTRs with both LMM and osteoporosis had a 2.92fold higher risk of fractures (95% CI 1.29-6.49; p = 0.010) than those without both LMM and osteoporosis. CONCLUSION: Long-term KTRs with the coexistence of LMM and osteoporosis had an independently higher risk of fragility fractures than those without both LMM and osteoporosis. The combination of SMI and osteoporosis definitions can be used to identify KTRs with a high fracture risk.