The causal association of sarcopenia with osteoporosis and obesity: a Mendelian randomization analysis

Ran, Shu; Zhao, Min-Fei; Liu, Baolin

doi:10.1007/s00198-022-06628-z

Cited by 4 publications

(3 citation statements)

References 2 publications

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“…In addition, several studies have indicated causal relationships between HGS and various markers of adiposity. 15,16,46 Similar to muscle weakness, excess adiposity is associated with an increased risk of metabolic and cardiovascular complications. 47 Based on these findings, we can confirm that skeletal muscle strength is fundamental in preventing cardiovascular events and helps sustain a longer and healthy life.…”

Section: Discussionmentioning

confidence: 99%

Genetic Liability to Higher Muscle Strength Associates with a Lower Risk of Cardiovascular Disease Mortality in Men Irrespective of Physical Activity in Adulthood: A Longitudinal Cohort Study

Herranen,

Waller,

Joensuu

et al. 2024

Preprint

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BackgroundLow muscle strength predicts premature mortality. We determined whether genetic liability to muscle strength is associated with mortality and whether this association is influenced by long-term leisure-time physical activity (PA).Methods and ResultsWe estimated the effects of a polygenic score for hand grip strength (PGS HGS) on all-cause and cardiovascular disease (CVD) mortality risk in the older Finnish Twin Cohort (N=8815, 53% women). National registries provided dates and causes of death. PA volume was assessed longitudinally in 1975, 1981, and 1990 using validated questionnaires. During the 16.9-year median follow-up time (143,723 person-years), 2896 deaths occurred, of which 1089 were due to CVD. We found a significant interaction between sex and PGS HGS (P=0.016) for predicting all-cause mortality. In men, one standard deviation increase in the PGS HGS was associated with a decreased risk both of all-cause (hazard ratio, HR [95% confidence interval, CI]): 0.93 [0.89–0.98] and CVD mortality (HR 0.88 [0.81–0.96]). Associations persisted after adjusting for PA, but only with CVD mortality after adjusting for other lifestyle covariates (HR 0.85 [0.76–0.96]). The cumulative incidence rates by age 75 years were 4.3% lower for all-cause mortality and 2.1% lower for CVD mortality in the highest PGS HGS quintile compared to the lowest quintile. No PGS HGS×PA interactions were found. PGS HGS was not associated with mortality in women.ConclusionsHigher PGS HGS was associated with a decreased risk of all-cause and CVD mortality in men; however, long-term PA in adulthood did not potentiate this association.Clinical PerspectiveWhat Is New?To the best of our knowledge, this is the first study to use a genome-wide polygenic score for hand grip strength to investigate whether the association between genetic liability to muscle strength and lifespan is affected by physical activity.Our results suggest that individuals with a genetic predisposition for higher muscle strength have a modest decreased risk of cardiovascular disease mortality, independent of their lifestyle.What Are the Clinical Implications?Polygenic scores for muscle strength require further development but may help identify individuals who represent extreme ends of genetic predisposition and vulnerability to premature death.

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Section: Discussionmentioning

confidence: 99%

Genetic Liability to Higher Muscle Strength Associates with a Lower Risk of Cardiovascular Disease Mortality in Men Irrespective of Physical Activity in Adulthood: A Longitudinal Cohort Study

Herranen,

Waller,

Joensuu

et al. 2024

Preprint

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“…For example, MR analyses, while reducing the in uence of confounding factors in observational studies, cannot completely exclude the co-mingling of genetic background and environmental factors. In addition, this study relied primarily on data from a European population, and its results may not be fully applicable to other ethnicities or populations (35). Therefore, future studies need to further validate these ndings in a wider range of populations and explore the role of different immune cell pro les in different types of osteomyelitis to ensure wider applicability and relevance of our ndings.…”

Section: Discussionmentioning

confidence: 99%

Osteomyelitis and immune cell phenotypes: a study based on a Mendelian randomisation approach

Long,

Dong,

et al. 2023

Preprint

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Background: Osteomyelitis is a severe bone marrow infection, whose pathogenesis is not fully understood. This study aims to explore the causal relationship between immune cell characteristics and osteomyelitis, in hopes of providing new insights for the prevention and treatment of osteomyelitis. Methods: Based on two independent samples, this study employed a two-sample Mendelian randomization (MR) analysis to assess the causal relationship between 731 immune cell characteristics (divided into 7 groups) and osteomyelitis. Genetic variants were used as proxies for risk factors to ensure the selected instrumental variables meet the three key assumptions of MR analysis. GWAS data for immune characteristics came from the public GWAS catalog, while data for osteomyelitis was sourced from the Finnish database. Results: At a significance level of 0.05, 21 immune phenotypes were identified as having a causal relationship with the development of osteomyelitis. In the B cell group, phenotypes such as Memory B cell %B cell, CD20- %B cell, and Memory B cell %lymphocyte showed a positive causal relationship with osteomyelitis, while Naive-mature B cell %B cell and IgD- CD38- AC phenotypes showed a negative causal relationship. In addition, specific immune phenotypes in the cDC cell group, Myeloid cell group, TBNK cell group, T cell maturation stage, and Treg cell group also showed significant associations with osteomyelitis. Through reverse MR analysis, it was found that osteomyelitis had no significant causal impact on these immune phenotypes, suggesting that the occurrence of osteomyelitis might not in turn affect these immune cell phenotypes. Conclusion: This study reveals for the first time the causal relationship between specific immune cell characteristics and the development of osteomyelitis, providing a new perspective for understanding the immune mechanism of osteomyelitis. These findings are significant for formulating targeted prevention and treatment strategies, and hold promise for improving the clinical treatment outcomes of patients’ osteomyelitis.

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“…Bone marrow adipose tissue increases, inflammatory adipokines, and adipocyte-derived extracellular vesicles together with a sedentary behavior, associated with obesity, appear to play a pivotal role for the development of the composition alterations leading to sarcopenia, but also to osteoporosis [6,7], in addition to the aforementioned chronic diseases. The cross-talk between fat, skeletal muscle and the skeleton represents an important homoeostatic feedback system in which adipokines, myokines and molecules secreted by osteoblasts represent the link of an active bone-adipose-muscle axis [8].…”

Section: Interplay Of Adipose Tissue Skeletal Muscle and Bonesmentioning

confidence: 99%

Sarcopenic obesity and the impact on bone health

Migliaccio,

Mocini,

Minnetti

et al. 2024

Current Opinion in Clinical Nutrition &Amp; Metabolic Care

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Purpose of the review Sarcopenic obesity is a newly identified pathological entity defined by an increase in body fat mass with an associated sarcopenia, characterized by loss of muscle mass, strength, and function. Recently, the concomitant presence of skeletal alteration with sarcopenic obesity has been described leading to a new clinical entity defined osteosarcopenic obesity (OSO). Many studies have tried to unravel the metabolic complex mechanism leading to this clinical entity in order to understand the pathophysiology of this complex condition with the aim of posing an early diagnosis to improve the therapeutic approaches. The purpose of this narrative review is to highlight and revise recent studies on this issue. Recent findings Recent research in the field of OSO has highlighted the role of nutrition and physical activity in the development and management of these conditions. While molecular and cellular pathways remain partially understood, there is a growing focus on lifestyle interventions as key factors in reducing the impact of OSO. These studies emphasize the need for early diagnosis and appropriate therapeutic strategies to improve quality of life and decrease morbidity and mortality associated with OSO. Summary Although the pathophysiological pathways underlying OSO are not fully understood, the clinical implications underscore the need for expanded research in this field. This research is crucial for enabling early diagnosis and implementing effective therapeutic interventions, with the goal of reducing morbidity and mortality and enhancing quality of life.

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The causal association of sarcopenia with osteoporosis and obesity: a Mendelian randomization analysis

Cited by 4 publications

References 2 publications

Genetic Liability to Higher Muscle Strength Associates with a Lower Risk of Cardiovascular Disease Mortality in Men Irrespective of Physical Activity in Adulthood: A Longitudinal Cohort Study

Genetic Liability to Higher Muscle Strength Associates with a Lower Risk of Cardiovascular Disease Mortality in Men Irrespective of Physical Activity in Adulthood: A Longitudinal Cohort Study

Osteomyelitis and immune cell phenotypes: a study based on a Mendelian randomisation approach

Sarcopenic obesity and the impact on bone health

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