Appendicular Lean Mass Index, Fat Mass Index Associated With Motor Function in DMD

In ambulatory patients with Duchenne muscular dystrophy (DMD), estimates of appendicular lean mass index (ALMI) and fat mass index (FMI) were associated with motor function and warrant further research to determine how they may be useful in clinical trial design, according to a recent study.¹ The findings were published in the journal Muscle & Nerve.

DMD, an inherited disorder characterized by progressive muscle weakness, typically manifests in childhood and currently has no cure. However, foundational therapies like glucocorticoids and novel therapies such as antisense oligonucleotides and gene therapies can help delay disease progression.² Authors of the current study aimed to determine whether estimates of ALMI derived from dual-energy x-ray absorptiometry (DXA) are associated with validated measures of motor function in patients with DMD.¹

“Long-term treatment of Duchenne muscular dystrophy with glucocorticoids slows disease progression, but results in side effects including decreased height growth and excessive weight gain, with fat mass accumulation,” the authors wrote. “Loss of muscle mass alongside fat mass accumulation in glucocorticoid-treated patients with DMD are thought to contribute to the deterioration of motor function with age.”

DXA is an imaging technique used to estimate body composition, while ALMI and FMI are both height-normalized surrogate measures of muscle mass and fat mass, respectively.

DMD, an inherited disorder characterized by progressive muscle weakness, typically manifests in childhood and currently has no cure. | image credit: OlegKachura - stock.adobe.com

While ALMI is known to be lower among patients with DMD vs age-matched peers without DMD, with a widening gap as the disease progresses, past research has not assessed the association between ALMI and motor function assessment outcomes while also accounting for relevant factors such as age and fat mass, according to the authors.

The current study included a total of 288 measurements from 137 patients in the UMass Medical School Duchenne Program clinical registry who were treated with glucocorticoids. The North Star Ambulatory Assessment (NSAA) and 10-meter walk/run test (10MWT) were used to evaluate motor function, and body composition was estimated with DXA. Four of the 288 total observations were missing information on NSAA, so the analyses included 284 NSAA measures and 288 10MWT measures.

In models of the association between ALMI and motor function, higher ALMI was associated with better motor function based on both NSAA and 10MWT observations. Conversely, higher FMI was associated with worse motor function based on NSAA and 10MWT measurements.

ALMI explained 16% of variance in NSAA score and 16% of the variance in 10MWT speed without controlling for other variables, while FMI explained 18% of the variance in NSAA score and 23% of the variance in 10MWT speed without controlling for other variables. Adding ALMI to a predictive model increased the proportion of explained NSAA score variance by 14% vs a model that only controlled for age.

A full model using the entire set of covariates—including age, age,2 ALMI, and FMI—explained 57% of the variance in NSAA scores and 63% of the variance in 10MWT speed. Controlling for age, age,² and AMI, each increase in ALMI of 1 kg/m² predicted an NSAA score 5.4 points higher (95% CI, 4.3-6.4; P < .001). When controlling for age, age,² and ALMI, each 1 kg/m² increase in FMI was predictive of a 1.5-point decrease in NSAA score (95% CI, −1.8 to −1.3; P < .001).

“Higher ALMI, a height-normalized estimate of skeletal muscle mass, was associated with better motor function on the NSAA and 10MWT,” the authors wrote. “Conversely, higher FMI, a height-normalized estimate of body fat mass, was associated with worse motor function. Both ALMI and FMI accounted for unique variance in motor function beyond that explained by age.”

The analyses did not control for a number of other factors associated with motor function variation, the authors noted. These included DMD genotypes, receipt of glucocorticoid treatment, and treatment with exon-skipping therapies. There was also little variation in pharmacologic interventions, with 94% of patients in the study receiving daily deflazacort. Therefore, larger cohort studies powered for subgroup analyses are warranted to determine whether the associations seen in the study are consistent across patient subgroups.

References

1. Kiefer M, Townsend E, Goncalves C, Shellenbarger KC, Gochyyev P, Wong BL. Appendicular lean mass index and motor function in ambulatory patients with Duchenne muscular dystrophy. Muscle Nerve. 2024;70(2):226-231. doi:10.1002/mus.28173

2. What are the new drugs for Duchenne muscular dystrophy? Drugs.com. Updated April 1, 2024. Accessed May 16, 2024. https://www.drugs.com/medical-answers/new-drugs-duchenne-muscular-dystrophy-3172658/