Musculoskeletal disorders related to chronic liver and biliary diseases are garnering increasing attention, and numerous observational studies have explored the risk of these disorders in patients with chronic liver and biliary disease(19). In this study involving 1,683 participants, a significant association between gallstones and sarcopenia was identified. Participants with gallstones had a notably higher likelihood of developing sarcopenia, with adjusted odds ratios of 2.15 in Model 1 and 2.71 in Model 2, indicating a robust relationship even after controlling for various sociodemographic and health-related factors. Furthermore, the analysis revealed that appendicular skeletal muscle mass (ASM) was inversely related to the likelihood of gallstone occurrence, suggesting a potential interplay between these two conditions. Subgroup analyses highlighted that the increased risk of sarcopenia associated with gallstones was particularly pronounced in females, where the odds were 2.756 times higher compared to their counterparts without gallstones. Notably, individuals with diabetes exhibited a markedly elevated risk of sarcopenia, with an odds ratio of 8.576, underscoring the compounded effects of metabolic conditions on muscle health. While trends indicating increased risk were observed in other subgroups, such as those with hypertension and younger adults, these associations did not achieve statistical significance. Overall, the findings emphasize the complex interrelationship between gallstone disease and sarcopenia, warranting further investigation to clarify the underlying mechanisms and potential clinical implications.
The underlying mechanisms linking sarcopenia and gallstone disease warrant further exploration. Chronic inflammation and metabolic dysfunction, which are common in both conditions, may play a pivotal role in their interrelationship(20). Chronic inflammation is a significant contributor to both malnutrition and sarcopenia, impacting metabolism through mechanisms such as elevated resting energy expenditure and increased muscle catabolism(21, 22). Inflammatory bowel disease (IBD) patients, for instance, often experience malnutrition, with prevalence rates as high as 65–75% for Crohn's disease and 18–62% for ulcerative colitis, primarily due to malabsorption, dietary restrictions, and increased energy demands associated with their inflammatory state(23). Notably, malnutrition is closely linked to alterations in body composition, including weight loss and reduced skeletal muscle mass, which could exacerbate the risk of developing sarcopenia(24). Furthermore, micronutrient deficiencies common in IBD, such as those in iron, zinc, and vitamins, along with insufficient protein intake, can further drive the onset of sarcopenia. This relationship highlights how disruptions in nutrient intake and gut health may contribute to the etiology of both sarcopenia and gallstones, as poor nutrition can lead to metabolic dysfunction and inflammatory responses that promote gallstone formation. Additionally, vitamin D deficiency plays a crucial role in IBD-related sarcopenia, with lower serum levels linked to decreased vitamin D receptor expression, which is essential for muscle health(25). Therefore, addressing malnutrition and monitoring micronutrient levels, particularly vitamin D, may provide therapeutic opportunities to mitigate both sarcopenia and gallstone disease through improved metabolic health. Additionally, emerging evidence highlights the intricate relationship between skeletal muscle mass, glucose homeostasis, and gut microbiota(26), suggesting potential mechanisms that may link sarcopenia with gallstone disease. Decreased skeletal muscle mass, characteristic of sarcopenia, can impair glucose regulation, which in turn may contribute to metabolic dysfunction and the formation of gallstones. The gut microbiota plays a crucial role in this interplay by modulating lipopolysaccharide (LPS) production and short-chain fatty acids (SCFA), which influence host metabolism, including that of skeletal muscle(27, 28).
The findings highlight significant clinical implications regarding the association between sarcopenia and gallstones. This connection underscores the importance of incorporating metabolic and nutritional considerations into the management of gallstone disease, particularly in the aging population, where both conditions are prevalent. Early identification of individuals at risk for sarcopenia could enhance preventive strategies and therapeutic outcomes. For example, integrating nutritional evaluations and personalized exercise programs into the care of gallstone patients may help prevent muscle loss and improve overall health. Physical activity and nutrition interventions are crucial treatments for sarcopenia, with compelling evidence supporting the benefits of adequate protein and nutrient intake, as well as exercise, in maintaining muscle mass and strength(29). Additionally, vitamin D has been shown to promote the proliferation and differentiation of myogenic cells, directly increasing muscle mass. Recent studies indicate that vitamin D supplementation can enhance strength and physical performance in patients with lower baseline levels(30). The elevated risk of gallstones in females further emphasizes the need for gender-specific screening and intervention strategies, highlighting the value of tailored approaches in clinical practice.
To our knowledge, this study is among the first to explore the relationship between sarcopenia and gallstone disease. The potential implications of sarcopenia could include increased risk of functional impairment, disability, and higher rates of comorbidities, which may negatively impact patients' quality of life. Our findings suggest the need to consider not only pharmacological treatments for gallstones but also the roles of exercise and nutrition in managing patients who may be at risk for sarcopenia. Given the rising incidence of gallstones and the prevalence of sarcopenia among older adults, these insights may help inform more comprehensive management strategies. By emphasizing nutritional interventions and encouraging physical activity, healthcare providers could potentially enhance outcomes for patients with gallstones and address the risks associated with sarcopenia.
Despite the study’s strengths, this study has several limitations that should be acknowledged. Firstly, the cross-sectional design restricts the ability to establish causal relationships between sarcopenia and gallstone disease, highlighting the need for longitudinal studies to explore the temporal dynamics between these conditions. Additionally, the assessment of gallstones relied on self-reported data, which may introduce reporting bias, as participants might not accurately recall or disclose their medical history. Lastly, while utilizing data from the NHANES database, the findings may not be generalizable to all populations, as the sample may not fully represent individuals with gallstone disease or sarcopenia outside the demographic characteristics captured in the dataset. Therefore, a large-scale, prospective, multi-center study is necessary to thoroughly explore the relationship between gallstone disease and sarcopenia, as well as to identify potential underlying mechanisms and effective management strategies.