The Skeletal Phenotype in Becker Muscular Dystrophy: The Under-Studied Cousin of Duchenne

Topic:

Clinical Trials

Poster Number: P12

Author(s):

Rana Halloun, MD, Children's Hospital of Eastern Ontario, Ottawa, Canada, Stefan Jackowski, PhD, Children's Hospital of Eastern Ontario, Ottawa, Canada, Maya Scharke, Children's Hospital of Eastern Ontario, Ottawa, Canada, Jinhui Ma, PhD, McMaster University, Hamilton, Ontario, Canada, Ken Gaither, PhD, Clario, Philadelphia, Pennsylvania, USA, Thomas Fuerst, PhD, Clario, Philadelphia, Pennsylvania, USA, Hugh McMillan, MD, Children's Hospital of Eastern Ontario, Ottawa, Canada, James MacDougall, PhD, Edgewise Therapeutics, Joanne Donovan, MD, PhD, Edgewise Therapeutics, Leanne Ward, MD, FRCPC, Children’s Hospital of Eastern Ontario

Background: Becker muscular dystrophy (BeckerMD) is a progressive myopathy caused by pathogenic variants in the dystrophin gene. Contraction-induced injury leads to replacement of muscle by fat and fibrosis, with progressive loss of function, including ambulation. To date, information on the skeletal phenotype in BeckerMD is scarce. Objectives: To describe the multi-site bone mineral density (“bone density”) phenotype and to determine factors associated with bone density reduction in BeckerMD. Methods: Cross-sectional analysis of 66 ambulatory, corticosteroid-naive individuals with BeckerMD at baseline (pre-treatment) enrolled in a multicenter phase 2 clinical trial (NCT05291091) was conducted. Participants underwent areal bone density at the lumbar spine (L1-4), proximal (total) hip, and total body less head (TBLH); TB lean mass was also captured. Bone density results were converted to age- and sex-matched Z-scores; lean mass was expressed as lean mass index (LMI, weight (kg)/height [m2]). LMI and muscle function tests, including the North Star Ambulatory Assessment (NSAA), were studied for their independent relationships with bone density Z-scores. Results: Mean (±SD) age was 24.6±11 years (range 12 to 50). Bone density Z-scores were lowest at the total hip (mean -1.7±1.1), followed by TBLH (-1.5±SD 1.2), and highest at L1-4 (-0.3±1.3). A multiple linear regression model showed low LMI was associated with low total hip bone density Z-score (β=0.2, 95% CI 0.04-0.33). A similar model showed higher LMI was highly associated with better NSAA scores (β=3.66, 95% CI 2.66 to 4.66). Conclusions: In this cohort of individuals with BeckerMD, reductions in multi-site bone density Z-scores were present despite retained ambulation, and LMI was independently associated with low total hip bone density Z-scores (the most affected skeletal site). Additionally, LMI was highly associated with NSAA, supporting LMI as a surrogate for muscle strength. These findings underscore the importance of routine bone health surveillance in BeckerMD despite preserved ambulation.