Associations between low muscle mass and high intramuscular fat infiltration and frailty, bone mineral density, trabecular bone score, and risk of falls, fractures, and hospitalizations

• Grant number: 25/14828-8
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: November 01, 2025
• End date: October 31, 2028
• Field of knowledge: Health Sciences - Physiotherapy and Occupational Therapy
• Principal Investigator: Tiago da Silva Alexandre
• Grantee: Roberta de Oliveira Máximo
• Host Institution: Centro de Ciências Biológicas e da Saúde (CCBS). Universidade Federal de São Carlos (UFSCAR). São Carlos , SP, Brazil
• Associated research grant: 24/01918-6 - Brain, muscle, bone and adipose tissue interplay: unveiling mechanisms to prevent frailty and promote healthy ageing, AP.TEM

Abstract

The impairment of muscle composition, characterized by the simultaneous presence of low muscle mass and high intramuscular fat infiltration, has been associated with negative outcomes in older adults. However, there are still gaps in understanding the combined role of these conditions in determining frailty, the compromise of bone health, and the occurrence of adverse events such as falls, fractures, and hospitalizations.This work plan is linked to the FAPESP Thematic Project entitled "Interaction between brain, muscle, bone, and adipose tissue: revealing mechanisms to prevent frailty and promote healthy aging", and aims to analyze the association between muscle composition, assessed by magnetic resonance imaging (MRI), and multiple clinical and bone-related outcomes in older adults. The study will use data from the UK Biobank and the Hospital Episodes Statistics (HES) database, which provide large-scale, high-resolution imaging, clinical information, and sociodemographic data, enabling robust analyses across various subgroups.The study will be structured around three specific objectives:1.To evaluate the association between low muscle mass and high intramuscular fat infiltration with the Fried frailty phenotype.2.To evaluate the association between low muscle mass and high intramuscular fat infiltration with bone mineral density (BMD) and trabecular bone score (TBS).3.To analyze whether the combination of low muscle mass, high intramuscular fat infiltration, low BMD, and low TBS constitutes a risk factor for the incidence of falls, fractures, and hospitalizations.The statistical analyses will involve: multinomial regression models for the first objective, multiple linear regression for the second, and Poisson regression models for the third. Exposure will be categorized according to four muscle composition profiles, and all outcomes will be analyzed with adjustment for sociodemographic, clinical, behavioral, and hormonal covariates. All analyses will follow strict criteria for consistency, bias control, and statistical significance (p < 0.05), ensuring robustness and precision of the findings.The proposal also includes the future validation and adaptation of predictive models (Machine Learning), initially developed using the UK Biobank data, with the goal of applying them to Brazilian cohorts such as ELSI-Brazil. This will strengthen the national applicability of the results. The project will be carried out over a 48-month period, with well-defined phases for literature review, statistical analysis, and scientific writing. The findings will be disseminated through high-impact journals, international conferences, and communication channels with Primary Health Care professionals and the general public.