骨质疏松性少肌性肥胖综合征的诊断、治疗及相关影响因素

文题释义： 骨质疏松性少肌性肥胖：是一种复杂的全身性疾病,往往对机体的活动能力造成负面影响,其发病机制可能与衰老或其他疾病有关,且多发生于老年群体。其包括3种反映体成分异常的症状：骨质疏松症、少肌症和肥胖。 少肌症：是一个较传统的术语,用来描述与年龄相关的肌肉质量和力量的广泛性丧失。据报道,少肌症的发生发展常伴随一些并发症的发生,如身体功能下降、障碍和生活质量差等。 背景：研究表明,骨质疏松症、少肌症和肥胖是影响骨折、高血压和血脂异常等代谢性疾病的重要影响因素。 目的：阐述骨质疏松性少肌性肥胖的患病现况、影响因素,及其对骨折、血脂异常的影响,探讨饮食和运动在预防骨质疏松性少肌性肥胖发生中的作用,为骨质疏松性少肌性肥胖的防治提供理论依据。 方法：通过关键词“osteosarcopenic obesity,sarcopenic obesity,osteoporosis,sarcopenia,obesity,fracture,dyslipidemia,骨质疏松性少肌性肥胖综合征,血脂异常”检索PubMed、WANFANG DATA数据库1990年至2018年发表的相关文章,限定语言为“English”或“中文”。共纳入71篇文献进行分析探讨。 结果与结论：①骨质疏松性少肌性肥胖患病率存在显著的年龄、性别、民族或种族差异;②目前骨质疏松性少肌性肥胖的诊断虽尚未有国际统一标准,但欧洲、亚洲、美国等大洲或国家已出现相应的诊断标准;③骨质疏松性少肌性肥胖的发生发展不仅受生活、饮食习惯的影响,还受基因、细胞因子和代谢性激素等因素的作用;④骨质疏松性少肌性肥胖对骨折、血脂异常的影响远大于单纯性骨质疏松症、少肌症和肥胖对二者的作用。 ORCID: 0000-0003-1898-651X(陈兴才);0000-0001-6717-8231(孔存青) 中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程     

Sarcopenic obesity or obese sarcopenia: A cross talk between age-associated adipose tissue and skeletal muscle inflammation as a main mechanism of the pathogenesis

Sarcopenia, an age-associated decline in skeletal muscle mass coupled with functional deterioration, may be exacerbated by obesity leading to higher disability, frailty, morbidity and mortality rates. In the combination of sarcopenia and obesity, the state called sarcopenic obesity (SOB), some key age- and obesity-mediated factors and pathways may aggravate sarcopenia. This review will analyze the mechanisms underlying the pathogenesis of SOB. In obese adipose tissue (AT), adipocytes undergo hypertrophy, hyperplasia and activation resulted in accumulation of pro-inflammatory macrophages and other immune cells as well as dysregulated production of various adipokines that together with senescent cells and the immune cell-released cytokines and chemokines create a local pro-inflammatory status. In addition, obese AT is characterized by excessive production and disturbed capacity to store lipids, which accumulate ectopically in skeletal muscle. These intramuscular lipids and their derivatives induce mitochondrial dysfunction characterized by impaired β-oxidation capacity and increased reactive oxygen species formation providing lipotoxic environment and insulin resistance as well as enhanced secretion of some pro-inflammatory myokines capable of inducing muscle dysfunction by auto/paracrine manner. In turn, by endocrine manner, these myokines may exacerbate AT inflammation and also support chronic low grade systemic inflammation (inflammaging), overall establishing a detrimental vicious circle maintaining AT and skeletal muscle inflammation, thus triggering and supporting SOB development. Under these circumstances, we believe that AT inflammation dominates over skeletal muscle inflammation. Thus, in essence, it redirects the vector of processes from “sarcopenia → obesity” to “obesity → sarcopenia”. We therefore propose that this condition be defined as “obese sarcopenia”, to reflect the direction of the pathological pathway.     

Association between ?308 G/A TNF-α Polymorphism and Appendicular Skeletal Muscle Mass Index as a Marker of Sarcopenia in Normal Weight Obese Syndrome

Background and Aim. Normal weight obese (NWO) syndrome is characterized by normal body mass index (BMI), but high amount of fat mass and reduced lean mass. We evaluated allelic frequency of the G/A −308 TNF-α polymorphism and prevalence of sarcopenia in NWO. Methods. We enrolled 120 Italian healthy women, distinguished into 3 groups: normal weight (NW); NWO, and preobese-obese (PreOB/OB) and evaluated anthropometric parameters, body composition by dual X-ray absorptiometry, blood tests, and genotyping of G/A −308 TNF-α polymorphism. Results. We found a positive association between sarcopenic obesity and −308 TNF-α polymorphism. All obese women were sarcopenic and were no carrier of mutation (G/G). Among all G/G, NWO showed significant differences in lean mass and total body lean mass (TBLean) with respect to NW and PreOB/OB (P < 0.001). Regarding appendicular skeletal muscle mass index values, 4.21% of NW were sarcopenic (50% G/G and 50% G/A); the same percentage was observed in NWO subjects (100% G/G). Moreover, 2.10% of PreOB/OB were sarcopenic and all were G/G. Conclusion. Our study suggests that TNF-α polymorphism contributes to sarcopenic obesity susceptibility, in association with body composition. This is the first study that shows the importance of TNF-α polymorphism to determine TBLean variation in NWO syndrome.     

Relationship between Sarcopenic Obesity and Cardiovascular Disease Risk as Estimated by the Framingham Risk Score

This study was conducted to assess the association between sarcopenic obesity and cardiovascular disease (CVD) risk in Korean adults (n=3,320; ≥40 yr) who participated in the 5th Korean National Health and Nutrition Examination Survey in 2010. The appendicular skeletal muscle mass divided by body weight was calculated for each participant; participants with values <1 standard deviation below the mean reference value (i.e., aged 20-39 yr) were considered sarcopenic. Subjects were further classified into 4 groups according to their obesity (i.e., body mass index ≥25 kg/m²) and sarcopenic status. Individuals'' 10-yr CVD risk was determined using the Framingham risk model. The sarcopenic obese group had more participants (43.8% men, 14.6% women) with a high risk of CVD (≥20%). The sarcopenic obese group was associated with an increased 10-yr CVD risk than the non-sarcopenic, non-obese group (odds ratio [OR], 2.49; 95% confidence interval [CI], 1.53-4.06, P<0.001 in men; OR, 1.87; 95% CI, 1.02-3.41, P=0.041 in women). Sarcopenic non-obese and non-sarcopenic obese subjects were not associated with an increased 10-yr CVD risk. Sarcopenic obesity, but not non-sarcopenic obesity, was closely associated with an increased CVD risk in Korean adults.

Graphical Abstract

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Chronology of age-related disease definitions: osteoporosis and sarcopenia

Low muscle mass at older age has been associated with functional impairments, cognitive decline and mortality. The term sarcopenia, coined in 1988, has been used interchangeably to describe low muscle mass, strength, and function. Without a well defined definition, results of studies using the term sarcopenia cannot be compared. Difficulties in defining sarcopenia parallel the history of defining osteoporosis. To understand critical steps that are needed to reach consensus in defining age-related diseases, we have identified milestones in the history of defining osteoporosis and compared these to sarcopenia. As a result, the main missing steps in the process of defining sarcopenia are: specific treatment options, pharmaceutical interest, and public awareness. Similar to osteoporosis being defined as 'low bone mineral density', the term sarcopenia should be reserved for 'low muscle mass'. Consensus must be reached regarding the diagnostic criteria to quantify muscle mass, correction factors, and reference populations used to define cut-off values of muscle mass.     

Do Bone Density,Bone Microarchitecture,and Body Composition Differ in Recipients of Allogeneic Hematopoietic Stem Cell Transplant? A Cross-Sectional Study from Southern India

The significant advancements made in the field of allogeneic hematopoietic stem cell transplantation (allo-HSCT) have ensured increased longevity in transplant recipients. However, they do have late effects that may adversely affect the endocrine system, bone health, and body composition. This study was undertaken to evaluate bone mineral density (BMD), trabecular bone score, and body composition in recipients of allo-HSCT and compare them with age, sex, and body mass index (BMI) matched controls. This was a cross-sectional study done in 63 cases and 65 matched controls. The mean femoral neck BMD was found to be lower in cases than in controls (0.777 [0.119] versus 0.846 [0.122] g/cm², P =  .002). Among cases, the mean BMD at the neck of femur was lower in patients who had received myeloablative conditioning compared with those who had received the nonmyeloablative regimen (0.731 [0.090] versus 0.802 [0.126] g/cm², P = .014]. The mean (SD) bone density at the lumbar spine was significantly lower in the group that had received total body irradiation compared with the group that did not (0.930 [0.111] versus 0.993 [0.127], P = .044). Trabecular bone score did not differ between cases and controls (1.383 [0.877] versus 1.389 [0.750], P = .670). The lean mass was significantly lower (15.9 [2.4] versus 18.6 [4.8] kg/m², P < .001) and the prevalence of sarcopenia (42% versus 11%, P < .001) significantly higher in cases than in controls. Normal-weight obesity was also noted to be higher among those with sarcopenia than in those without (12/26 versus 5/36; P = .009). The procedure of allo-HSCT may thus cause an impairment of bone health and alterations in body composition well after the cure of the primary disease.     

Sarcopenia is associated with increased severe postoperative complications after colon cancer surgery

IntroductionStudies have shown that sarcopenia is associated with poor outcomes in patients with gastrointestinal cancer undergoing surgery. We aimed to investigate the relationship between postoperative complications of sarcopenic patients who had been operated on for colon cancer and the effects on short-term mortality.Material and methodsIn this study, patients who had undergone colon cancer surgery between January 2013 and December 2018 were collected retrospectively. Sarcopenia was diagnosed by the skeletal muscle index (SMI) derived from a preoperative computed tomography scan. Multiple logistic regression analysis was performed to determine whether sarcopenia is associated with postoperative major complications (POMC).ResultsThe study included 160 patients with a mean age of 62.4 ±12.6 years. Clavien-Dindo grade 1–2 (minor) complications were not significantly different between the groups (p = 0.896). However, grade ≥ 3 (major) complications were detected in 13 (17.8%) patients in the sarcopenic group (SG) and in 5 patients in the non-sarcopenic group (NSG) (5.7%) (p = 0.016). Length of intensive care unit (ICU) stay was longer in SG (p = 0.002) and there was no difference between 1-month and 6-month mortality rates (p = 0.273 and p = 0.402, respectively). According to univariate analyses, sarcopenia and age over 65 years were related to POMC. In multivariate analyses, sarcopenia (odds ratio = 3.039; 95% confidence interval 1.008–9.174; p = 0.048) and advanced age (odds ratio = 3.246; 95% confidence interval 1.078–9.803; p = 0.036) were found to be independent risk factors for POMC.ConclusionsThis study showed that while sarcopenia is a risk factor for POMC, sarcopenia also prolongs the duration of ICU stay. Also sarcopenia has no effect on short-term mortality.     

Mitochondrial DNA deletion and sarcopenia

PurposeAccumulation of mitochondrial DNA deletions and the resultant impaired oxidative phosphorylation may play a pathogenic role in the mediation of age-related sarcopenia.MethodsTwenty four participants of the New Mexico Aging Process Study were classified as normal lean (n = 15) or sarcopenic (n = 9) based on body composition determined by Dual Energy x-ray Absorptiometry. Complex I and Complex IV activities were measured in the skeletal muscle samples obtained from gastrocnemius muscle. A two-stage nested polymerase chain reaction strategy was used to identify the mitochondrial DNA deletions in the entire mitochondrial genome in the skeletal muscle samples.ResultsAlthough Complex I activity was not significantly different (5.5 ± 0.9 vs. 4.6 ± 0.7 mU/mg protein, P > 0.05), Complex IV activity was higher in sarcopenic subjects (1.4 ± 0.3 vs. 1.0 ± 0.1 mU/mg protein, P < 0.05). Mitochondrial DNA deletions were mostly located in the region of Complex I and spanned from nicotinamide adenine dinucleotide dehydrogenase 1 to nicotinamide adenine dinucleotide dehydrogenase 6. Deletions in the 8,577–10,407 bp and 10,233–11,249 bp regions were associated with a significant decrease in Complex I activity (P < 0.05 and P = 0.02, respectively). Total cumulative deletion, defined as the sum of individual length of deletions in a subject, was comparable in subjects with and without sarcopenia (1760 ± 726 vs. 1782 ± 888 bp, P > 0.05). The magnitude of mitochondrial DNA deletion, however, correlated positively with lean body mass (r = 0.43, P < 0.05).ConclusionThus, mitochondrial DNA deletions are common in elderly subjects and are negatively related to Complex I activity. The positive association between mitochondrial DNA deletions and lean body mass needs to be confirmed by studies in a larger study population.     

Relationship between postmenopausal osteoporosis and the components of clinical sarcopenia

Purpose

The aim of the study was to determine the relationship between the components of clinical sarcopenia and osteoporosis in postmenopausal women.

Methods

A population-based cohort of 590 Finnish postmenopausal women (mean age 67.9; range 65–72) was selected from the Osteoporosis Fracture Prevention (OSTPRE-FPS) study in 2002. Bone mineral density (BMD) and lean tissue mass were assessed by dual X-ray absorptiometry (DXA). The study sample was divided into three categories according to the WHO BMD classification: normal, osteopenia and osteoporosis. The study sample was divided into non-sarcopenic, presarcopenic, sarcopenic and non-classified groups according to quartiles of RSMI i.e. relative skeletal muscle index (appendicular muscle mass (kg)/square of height (m)), hand grip strength (kPa) and walking speed.

Results

In logistic regression analysis sarcopenic women had 12.9 times higher odds of having osteoporosis (p ≤ 0.001, OR = 12.9; 95% CI = 3.1–53.5) in comparison to non-sarcopenic women. In comparison to women in the highest grip strength quartile, women within the lowest quartile had 11.7 times higher odds of having osteoporosis (p = 0.001, OR = 11.7; 2.6–53.4). Sarcopenic women had 2.7 times higher odds of having fractures than their non-sarcopenic counterparts (p = 0.005, OR = 2.732; 1.4–5.5). Sarcopenic women had also 2.1 times higher risk of falls during the preceding 12 months compared to non-sarcopenic women (p = 0.021, OR = 2.1; 1.1–3.9). Adjustment for age, body mass index (BMI), physical activity and hormone therapy (HT) did not significantly alter these results.

Conclusions

The components of clinical sarcopenia are strongly associated with osteoporosis. Grip strength is the most significant measurement to reveal the association between sarcopenia and osteoporosis, falls and fractures.     

Impact of frailty and ultrasonography-based sarcopenia on the development of postoperative complications in gastrointestinal cancer patients

Background/aim Gastrointestinal (GI) system cancers are frequent among older adults and it is still difficult to predict which are at increased risk for postoperative complications. Frailty and sarcopenia are increasing problems of older population and may be associated with adverse outcomes. In this study we aimed to examine the effect of sarcopenia and frailty on postoperative complications in older patients undergoing surgery for GI cancers.Materials and methods Forty-nine patients admitted to general surgery clinic with the diagnosis of gastrointestinal system cancers were included in this cross-sectional study. Frailty status was assessed using the Edmonton Frail Scale (EFS). Sarcopenia was defined due to the EWGSOP2 criteria and ultrasonography was used to evaluate muscle mass.Results The median age of the patients was 70 (min-max: 65–87). Fourteen (28.6%) patients were found to be sarcopenic and 16 (32.7%) patients were frail, and 6 (37.5%) of these patients were also severe sarcopenic (p = 0.04). When the postoperative complications were assessed, time to oral intake, time to enough oral intake, length of hospital stay in the postoperative period were found to be longer in frail patients (p = 0.02, p = 0.03, p = 0.04 respectively). Postoperative complications were not different due to the sarcopenia.Conclusion Frailty, but not sarcopenia was associated with adverse outcomes in older adults undergoing GI cancer surgery. Comprehensive geriatric assessment before surgical intervention may help to identify patients who are at risk.     

The Association between the Low Muscle Mass and Osteoporosis in Elderly Korean People

The purpose of this study was to predict osteoporosis risk as decreasing muscle mass and to declare the cut-off value of low muscle mass in an elderly Korean population. This study was based on data from the 2008-2010 Korea National Health and Nutritional Examination Surveys (KNHANES). The subjects included 1,308 men and 1,171 women over 65 yr. Bone mineral density (BMD) and appendicular skeletal muscle (ASM) were measured by dual energy X-ray absorptiometry (DXA), and appendicular skeletal muscle was adjusted by height as a marker of sarcopenia. After confirming the correlation between low muscle mass and BMD, the best cut-off value of muscle mass to estimate osteoporosis was suggested through the receiver operating characteristic (ROC) curve. For both men and women, BMD correlated positively with low muscle mass when ASM/Ht² was used as a marker for sarcopenia. The ROC curve showed that ASM/Ht² was the best marker for osteoporosis at a cut-off value of 6.85 kg/m² for men and 5.96 kg/m² for women. When these cut-off values were used to determine sarcopenia, the risk of osteoporosis increased 4.14 times in men and 1.88 times in women. In particular, men (OR 2.12) with sarcopenia were more greatly affected than women (OR 1.15), even after adjusting for osteoporosis risk factors. In elderly Korean people, sarcopenia is positively correlated with BMD and there is a strong correlation between sarcopenia and osteoporosis with risk of bone fracture.     

High Prevalence of Sarcopenia in Korean Patients after Hip Fracture: a Case-Control Study

Sarcopenia-related falls and fractures are increasing worldwide due to the aging population. The purpose of this study was to 1) evaluate anthropometric characteristics related to hip fracture in Korean patients, 2) investigate sarcopenia prevalence in hip fracture (HF) and non-hip fracture (NF) groups, and 3) investigate the correlation between sarcopenia and osteoporosis. This case-control study examined 359 HF and 1,614 NF normal populations using Korea National Health and Nutrition Examination Survey data. We performed whole-body dual energy X-ray absorptiometry to analyze body composition using the skeletal muscle mass index (SMI: lean mass/height²) and bone mineral density (BMD). In the HF group, using the AWGS definition, the prevalence of sarcopenia in women and men was 44.3% and 68.2%, respectively; in the NF group, it was 7.1% and 16.1%, respectively. Lower appendicular SMI (P < 0.001), leg muscle mass (P < 0.001), and higher prevalence of sarcopenia (P < 0.001) were observed in the HF group after adjustment for age and gender. In multivariate analysis, sarcopenia (OR = 6.52; 95% CI = 4.67-9.09), age (OR = 1.15; 95% CI = 1.13-1.17), and osteoporosis (OR = 1.87; 95% CI = 1.35-2.58) were associated with the occurrence of a hip fracture. This study showed a higher prevalence of sarcopenia in patients with hip fractures compared with a normal population, and higher prevalence of sarcopenia in men.     

Sarcopenia definition: Does it really matter? Implications for resistance training

The loss of muscle mass, strength and function, known as sarcopenia, is common in older adults, and is associated with falls, fractures, cardiometabolic diseases, and lower quality of life. Sarcopenia can also occur secondarily to chronic diseases. Recently, sarcopenia was recognized as a disease with an International Classification of Disease (ICD) code, yet, at least five definitions for its clinical identification exist. Most definitions include three themes: low muscle mass, strength and physical performance. However, the definitions vary by the number of themes needed to diagnose sarcopenia and, within each theme various parameters and cut-off levels exist. The lack of consensus on what constitutes a diagnosis can create confusion and hesitation in sarcopenia diagnosis. Currently, no pharmacological treatment exists for sarcopenia. Resistance training (RT) is safe and effective to improve muscle mass, strength and physical performance in older adults and clinical populations. Based on current guidelines, whether an individual is defined as “sarcopenic”, or not, does not change the way RT is prescribed. Here, we present evidence and the inconsistencies in sarcopenia definitions and recommend that focus should be on optimizing ways to prescribe RT and increase long-term adherence, rather than on slight modifications to sarcopenia definitions.     

Next-generation sequencing of 12 obesity genes in a Portuguese cohort of patients with overweight and obesity

We examined 12 monogenic obesity genes in 72 Portuguese individuals with overweight and obesity (class 1 and class 2), some of which with suspected genetic obesity, to identify known or unknown potential obesity variants. Genomic DNA was analyzed for variants in genes LEP, LEPR, MC4R, POMC, PCSK1, BDNF, NTRK2, SIM1, SH2B1, UCP3, GCG and ADCY3 through next generation sequencing (NGS). The impact of the rare variants was investigated in the ClinVar database and using in silico tools for prediction of pathogenicity. Four potential pathogenic missense variants were detected at the heterozygous state in five individuals: two in the ADCY3 gene, NM_004036.5:c.1153G > A (p.Val385Ile) (rs756783003) and NM_004036.5:c.1222G > A (p.Gly408Arg) (rs201606553), one in gene SH2B1, NM_001145795.1:c.127C > A (p.Arg43Ser) (rs547678855), and the fourth in gene POMC NM_000939.4:c.706C > G (p.Arg236Gly) (rs28932472), which was found in two individuals. Moreover, six rare variants near splicing sites were also identified, as well as eight rare synonymous variants. In summary, some potential pathogenic rare missense variants were identified, two of them in ADCY3 gene, the most recently identified gene as having a role in monogenic obesity. Further analysis should be performed to confirm the clinical relevance of these variants.     

Prevalence rate and associated factors of sarcopenic obesity in korean elderly population

This study was conducted to estimate the prevalence rates and to explore associated factors of sarcopenic obesity (SO) in 2,221 Koreans over 60 yr-of age from the Fourth Korea National Health and Nutrition Examination Survey (2009). Participants were assessed by dual energy X-ray absorptiometry. Appendicular skeletal muscle mass divided by body weight was used to define sarcopenia and waist circumference was used to define obesity. We estimated the prevalence rates of SO according to age-groups, sex and region. In addition, each group was compared by demographic characteristics, metabolic status, nutrition, and physical activity. The prevalence rates of SO were 6.1% (95% confidential interval [CI] = 6.1-6.2) for men and 7.3% (95% CI = 7.3-7.3) for women, respectively. SO was positively associated with no current working and the number of combined medical conditions. High serum insulin level was positively associated with SO, whereas vitamin D was negatively associated with SO in both men and women. In conclusion, the prevalence rates of SO are 6.1% in men and 7.3% in women. SO is associated with insulin resistance, inappropriate nutrition, and low physical activity.     

Brain-derived neurotrophic factor in relation to central obesity in children with sleep disordered breathing

IntroductionSleep disordered breathing (SDB) represents common comorbidities of childhood obesity leading to interrupted sleep and sleep deprivation. Sleep deprivation alters secretion of brain-derived neurotrophic factor (BDNF), which is an appetite regulator. However, little is known about the relation between BDNF and central obesity in children with SDB. The aim of the study was to evaluate BDNF level and anthropometric indices in relation to SDB in children with obesityMaterial and methodsA prospective case-control study was conducted on 30 children with obesity (BMI > 95^th percentile) and 30 healthy lean children (BMI 5^th-85^th percentile). Polysomnographic, anthropometric data and BDNF serum level were obtained from all included children. Serum level of BDNF and anthropometric indices of obesity were assessed in relation to SDB in children with obesity. Regression analysis was done to determine predictors for SDB in children with obesity.ResultsIn comparison to healthy controls, anthropometric indices of central obesity were significantly higher while BDNF was significantly lower in obese children, especially those with SDB. Respiratory disturbance index has a significant positive correlation with anthropometric indices of central obesity and a significant negative correlation with BDNF level. Central obesity and decreased BDNF were associated with 2-fold increased risk for SDB. Waist circumference/height ratio and neck circumference/height ratio have 89.5%, 75% sensitivity and 81.23%, 84.62% specificity at a cutoff point > 0.62, > 0.24 respectively for prediction of SDB in children with obesity.ConclusionsCentral obesity and decreased BDNF represent independent predictors for SDB in children with obesity. Anthropometric indices adjusted to height are a simple screening tool for SDB in obese children.     

Markers of inflammation and their association with muscle strength and mass: A systematic review and meta-analysis

BackgroundChronic inflammation has been associated with sarcopenia and its components skeletal muscle strength and muscle mass. The aim of this systematic review and meta-analysis was to determine the relationship between systemic inflammation, muscle strength and/or muscle mass in adults.MethodsAn electronic search using keywords such as ‘acute phase proteins, cytokines and sarcopenia, muscle mass, muscle strength’ was conducted via Pubmed, Web of Science and Embase from inception until the 30th of June 2020. A meta-analysis using correlation data was performed to determine the overall relationship between inflammation and muscle strength and muscle mass in adults.ResultsOverall, 168 articles; 149 cross-sectional articles (n = 76,899 participants, 47.0 % male) and 19 longitudinal articles (n = 12,295 participants, 31.9 % male) met inclusion criteria. Independent of disease state, higher levels of C reactive protein (CRP), Interleukin (IL)-6 and Tumor necrosis factor (TNF)α were associated with lower handgrip and knee extension strength (CRP; r = −0.10, p < 0.001, IL-6; r = −0.13, p < 0.001, TNFα; r = −0.08, p < 0.001 and CRP; r = −0.18, p < 0.001, IL-6; r = −0.11, p < 0.001, TNFα; r = −0.13, p < 0.001 respectively) and muscle mass (CRP; r = −0.12, p < 0.001, IL-6; r = −0.09, p < 0.001, TNFα; r = −0.15, p < 0.001). Furthermore, higher levels of systemic inflammatory markers appeared to be associated with lower muscle strength and muscle mass over time.ConclusionHigher levels of circulating inflammatory markers are significantly associated with lower skeletal muscle strength and muscle mass.     

Muscle and bone,two interconnected tissues

As bones are levers for skeletal muscle to exert forces, both are complementary and essential for locomotion and individual autonomy. In the past decades, the idea of a bone–muscle unit has emerged. Numerous studies have confirmed this hypothesis from in utero to aging works. Space flight, bed rest as well as osteoporosis and sarcopenia experimentations have allowed to accumulate considerable evidence. Mechanical loading is a key mechanism linking both tissues with a central promoting role of physical activity. Moreover, the skeletal muscle secretome accounts various molecules that affect bone including insulin-like growth factor-1 (IGF-1), basic fibroblast growth factor (FGF-2), interleukin-6 (IL-6), IL-15, myostatin, osteoglycin (OGN), FAM5C, Tmem119 and osteoactivin. Even though studies on the potential effects of bone on muscle metabolism are sparse, few osteokines have been identified. Prostaglandin E2 (PGE2) and Wnt3a, which are secreted by osteocytes, osteocalcin (OCN) and IGF-1, which are produced by osteoblasts and sclerostin which is secreted by both cell types, might impact skeletal muscle cells. Cartilage and adipose tissue are also likely to participate to this control loop and should not be set aside. Indeed, chondrocytes are known to secrete Dickkopf-1 (DKK-1) and Indian hedgehog (Ihh) and adipocytes produce leptin, adiponectin and IL-6, which potentially modulate bone and muscle metabolisms. The understanding of this system will enable to define new levers to prevent/treat sarcopenia and osteoporosis at the same time. These strategies might include nutritional interventions and physical exercise.