Thigh Muscle Fat Fraction and 1-2 year NSAD decline in Ambulatory men with Becker Muscular Dystrophy

Topic:

Other

Poster Number: 11 S

Author(s):

Kelly Rock, PT, DPT, PhD, University Of Florida, Donovan Lott, PhD, University of Florida, Rebecca Wilcocks, PhD, University of Florida, Alison Barnard, PhD, University of Florida, Sean Forbes, PhD, University of Florida, Claudia Senesac, PhD, University of Florida, Prathyusha Bellam, PT, University of Florida, Shakeel Ahmed, PhD, University of Florida, Pratiksha Awale, PT, University of Florida, Eric Baetscher, Oregon Health & Science University, William D Rooney, PhD, Oregan Health and Science University, Glenn Walter, PhD, University of Florida, Krista H Elvire Vandenborne, PhD, University of Florida

Background: Becker muscular dystrophy (BMD) leads to the replacement of skeletal muscle by fat and to impaired functional performance. Quantitative magnetic resonance (qMR) imaging measurements of muscle fat fraction (FF) have been used as a biomarker of muscle deterioration. The North Star Assessment for Limb Girdle Type Muscular Dystrophies (NSAD) is a clinical-reported outcome measure aimed to assess a wide range of functional abilities. Biomarker enrichment strategies are needed in BMD clinical trial design to stratify participants by their likelihood of disease and functional progression.
Objectives: To assess how baseline qMR FF of thigh muscles relates to NSAD scores and longitudinal changes in ambulatory men with BMD.
Methods: Thirty-one ambulatory men with BMD (18-62 years) completed a 2-year natural history study including 3-point Dixon qMR whole body imaging (WBI) and NSAD assessments. Thigh muscle FF was calculated as the average FF from the the quadriceps and hamstrings muscle groups. Participants were stratified into four groups based on baseline thigh muscle FF: FF<20, FF20-40, FF40-60, and FF60-80. Spearman’s rho assessed correlations and longitudinal NSAD changes over 1-2 years were reported. Longitudinal data points after a serious injury or fracture were excluded from the analysis. Results: Thigh muscle FF ranged from 3 to 69% (median: 40%), and baseline NSAD scores ranged from 5 to 54 (median: 33). FF was strongly negatively correlated with baseline NSAD score (rs=-0.88; p<0.001), indicating that higher thigh FF is associated with poorer motor function. NSAD scores declined over time in individuals with thigh FF greater than 20%. At 1 year follow-up, the average NSAD decline was approximately 2 points in the FF40-60 and FF60-80 groups. At 2 years, average NSAD declines of 4 to 5 points were observed for the FF20-40, FF40-60, and FF60-80 groups. Those with FF<20 had stable NSAD scores. Three men with BMD lost the ability to ambulate ≥10 m during follow-up (two by year 1, one by year 2). Conclusion: Thigh muscle FF, measured by qMR WBI, is associated with NSAD performance in ambulatory men with BMD. Muscle FF corresponds with baseline NSAD scores and longitudinal decline, particularly in individuals with thigh muscle FF greater than 20%. Stratifying participants by muscle FF may improve clinical trial design by providing insight to which participants are likely to show functional decline.