Key Takeaways & Executive Findings
- •• Bidirectional causal relationship exists between whole-body fat-free mass and bone mineral density. • Higher whole-body fat-free mass increases lumbar spine BMD but decreases forearm BMD. • Lower BMD at various sites (forearm, lumbar spine, femoral neck) leads to reduced whole-body fat-free mass. • Findings provide genetic evidence for the muscle-bone interaction and potential intervention targets.
Abstract
BACKGROUND: Sarcopenia and osteoporosis have attracted significant attention in the academic community due to their high prevalence and severe adverse outcomes. Although existing studies have suggested a potential causal relationship between sarcopenia and osteoporosis, the evidence remains insufficient. OBJECTIVE: Based on large-scale genome-wide data, to explore the causal relationship between genetically predicted sarcopenia and osteoporosis through a bidirectional Mendelian randomization approach. METHODS: Genome-wide significant loci (P < 5×10-8) associated with sarcopenia-related traits were selected from the UK Biobank database (an open database jointly developed by the UK government, the Medical Research Council, and the Wellcome Trust), followed by linkage disequilibrium analysis. Osteoporosis data were obtained from the GEnetic Factors for OSteoporosis Consortium (GEFOS; an open database funded by the EU Framework Program for Research and Development, jointly led by Erasmus University Medical Center in the Netherlands), including 28,498 European ancestry subjects, with a focus on data from osteoporosis-prone fracture sites. The study used inverse variance weighting as the primary analysis method, supplemented by MR-Egger regression, weighted median method, and MR-RAPS for multiple validation. To ensure the reliability of the results, multiple sensitivity analyses were performed. RESULTS AND CONCLUSION: Inverse variance weighting analysis showed a bidirectional causal relationship between whole-body fat-free mass and bone mineral density (P < 0.05). Forward causal analysis indicated that whole-body fat-free mass was positively associated with lumbar spine bone mineral density (OR=1.124, 95%CI: 1.008-1.253, P=0.035) and negatively associated with forearm bone mineral density (OR=0.821, 95%CI: 0.699-0.966, P=0.017). Reverse causal analysis showed that forearm bone mineral density (OR=1.033, 95%CI: 1.002-1.066, P=0.036), lumbar spine bone mineral density (OR=1.054, 95%CI: 1.025-1.084, P < 0.001), and femoral neck bone mineral density (OR=1.059, 95%CI: 1.008-1.113, P=0.021) were all positively associated with whole-body fat-free mass. A reduction in whole-body fat-free mass can lead to decreased lumbar spine bone mineral density, and a decrease in bone mineral density at various sites further exacerbates the loss of whole-body fat-free mass. Although the data in this study mainly come from European populations, due to the universality of genome-wide association analysis methods and the commonality of genetic backgrounds, the results still have important reference value for exploring the pathogenesis of sarcopenia and osteoporosis in the Chinese population, formulating clinical intervention strategies, and assessing genetic risk.
1. Introduction
Population aging is a major challenge to global public health, with the incidence and disability rates of musculoskeletal diseases becoming increasingly prominent. Sarcopenia and osteoporosis have become important diseases that seriously threaten the health and quality of life of the elderly [1-2]. These two diseases not only significantly increase the risk of falls and fractures in the elderly but also lead to progressive decline in physiological function, imposing a huge economic burden on the healthcare system.
Sarcopenia is a geriatric syndrome characterized by progressive loss of skeletal muscle mass and function, with global epidemiological data showing significant regional differences, with prevalence ranging from 5.0% to 49.8% in people over 65 years [3]. Clinical studies have confirmed that sarcopenia not only significantly increases the risk of adverse outcomes in the elderly but is also closely related to the occurrence and progression of various chronic diseases [4]. Osteoporosis is characterized by reduced bone mass and deterioration of bone microarchitecture [5]. According to the Global Burden of Disease study, the overall prevalence of osteoporosis in adults is 18.3%, with a significantly higher prevalence in women (23.1%) than in men (11.7%) [6]. Osteoporosis clinically manifests as bone pain, height loss, and fatigue, and severe cases can lead to osteoporotic fractures and other serious consequences [7]. Notably, sarcopenia and osteoporosis often coexist in the same patient, giving rise to the new clinical concept of 'osteosarcopenia' [8].
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Yin Xingxiao, Jiang Yang, Song Yanping, Yao Na, Shen Zhen, Li Yanqi, Song Yueyu, Peng Hao, Chen Qigang (2026). Association between sarcopenia and osteoporosis: a genome-wide data analysis in European populations. Chinese Journal of Tissue Engineering Research. https://doi.org/10.12307/2026.21267
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Frequently Asked Questions
What is the main objective of this study?
The main objective is to explore the causal relationship between genetically predicted sarcopenia and osteoporosis using a bidirectional Mendelian randomization approach based on large-scale genome-wide data.
What data sources were used?
Sarcopenia-related traits data were from the UK Biobank, and osteoporosis data were from the GEFOS consortium, including 28,498 European ancestry subjects.
What were the key findings?
The study found a bidirectional causal relationship between whole-body fat-free mass and bone mineral density. Specifically, higher whole-body fat-free mass increased lumbar spine BMD but decreased forearm BMD, and lower BMD at various sites led to reduced whole-body fat-free mass.
What methods were used for analysis?
The primary analysis used inverse variance weighting, supplemented by MR-Egger regression, weighted median method, and MR-RAPS, along with multiple sensitivity analyses.
What is the clinical significance of this study?
The findings provide genetic evidence for the muscle-bone interaction, suggesting that interventions targeting muscle mass may also benefit bone health, and vice versa, which could inform clinical strategies for preventing and managing sarcopenia and osteoporosis.
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