Age‐related changes in appendicular lean mass in males with Duchenne muscular dystrophy: A retrospective review

Abstract

Background Appendicular lean mass (ALM) trajectory in males with Duchenne muscular dystrophy (DMD) has potential applicability for treatment and research and has not been characterized. Methods This chart review included longitudinal data on 499 males with DMD receiving glucocorticoids and 693 controls, ages 5 to 22.9 y. ALM (kg) was measured by dual energy x‐ray absorptiometry (DXA). Appendicular lean mass index (ALMI, kg/m2) was calculated for height adjustment. Reference centiles were generated using data from healthy controls, and ALM and ALMI Z‐scores were calculated for patients with DMD. Generalized linear models were used to estimate median Z‐scores by age and functional mobility status (FMS) score. ALM velocity by age was modeled using superimposition, translation and rotation (SITAR). Results Compared to controls, males with DMD had lower ALM from an early age. ALMI Z‐scores dropped below 0 at age 8 y or FMS of 2, and below −2.0 at age 13 y or FMS of 3 (P < .05). Age at peak ALM velocity was similar in both groups, but the magnitude was higher in controls (3.5 vs. 0.7 kg/y, P < .0001). Patients with DMD had a transient loss of ALM around age 12 y, an increase at age 14 y, then a further decline at age 16 y, remaining low thereafter. Conclusions Males with DMD have progressive decline in lean mass with age and worsening functional mobility. DXA measurement of ALM may be useful for monitoring lean mass status in patients with DMD, providing valuable information for individual treatment plans and research endeavors.

Dual-energy X-ray absorptiometry measures of lean body mass as a biomarker for progression in boys with Duchenne muscular dystrophy

“…Inclusion of a whole-body scan into this annual examination would present minimal additional burden for the patient. Furthermore, several studies have demonstrated a relationship between DXA-derived lean body mass measures and muscle strength in patients with DMD, in addition to demonstrating that males with DMD have lower lean body mass as compared with heathy males 13 – 15 , 27 – 29 .…”

“…DXA has also been used to assess fat mass and lean body mass in patients with DMD, demonstrating that DXA measures of lean body mass correlate with function and strength 13 , 14 , and is also routinely used to assess bone health in patients with DMD. Patients with DMD receiving glucocorticoids consistently had lower DXA-measured appendicular lean body mass compared with age-matched healthy controls 15 . A separate study showed DXA-measured increases in lean body mass in patients with DMD following 2 years of steroid treatment compared with steroid-naïve patients, with no concomitant changes in body fat 16 .…”

Bone Mineral Density Assessment by Quantitative Computed Tomography in Glucocorticoid-Treated Boys With Duchenne Muscular Dystrophy: A Linear Mixed-Effects Modeling Approach

“…Summer et al. ( 31 ) observed that the age of appendicular lean mass loss in DMD children was approximately 12 years. However, their results may not be applicable to all DMD patients because their studies were not investigating the effects of GC exposure.…”

Low‐Intensity Vibration Protects the Weight‐Bearing Skeleton and Suppresses Fracture Incidence in Boys With Duchenne Muscular Dystrophy: A Prospective, Randomized, Double‐Blind, Placebo‐Controlled Clinical Trial

“…(19) Although the decline in bone status in DMD parallels deterioration of muscle phenotype, it does not appear to be directly caused by the disease itself but instead as a secondary consequence of the reduced loading that parallels muscle weakness. (1,20) Exercise regimens as a strategy to preserve muscle function and bone accrual in DMD children shows some promise; however, it is still unclear if this can protect from skeletal decline or if instead can lead to an increased risk of fractures. (21) As a surrogate for exercise, low-magnitude mechanical signals, delivered using low-intensity vibration (LIV), have been demonstrated to have an anabolic effect on bone in animal models, (22) driven by some degree by biasing bone marrow mesenchymal stem cells away from adipogenesis and towards osteoblastogenesis.…”