In Duchenne muscular dystrophy (DMD) osteoporosis and fragility fractures present significant comorbidities, resulting from progressive myopathy reduced weight-bearing and osteotoxic effects of prolonged glucocorticoid (GC) use. This systematic literature review (SLR) assessed the natural course of bone mineral density (BMD) in individuals with DMD and the factors associated with its natural progression. A systematic literature review was conducted to evaluate BMD in individuals with DMD. Searches were performed in PubMed® and Embase® for peer-reviewed articles published between 2000 and 2023, focusing on DMD patients aged 5-15 years receiving GC treatment. Statistical analyses employed an initial correlation analyses followed by generalized linear mixed models (GLMMs) to investigate relationships between bone health biomarkers and clinical factors. Strong associations were observed between lumbar spine (LS) BMD Z-scores, age and GC treatment duration. LS areal BMD (aBMD) Z-scores declined with age (-0.25 SDS/year, p < 0.001, n = 1527) and with longer GC use (-0.24 SDS/year, p < 0.001, n = 817). Total body less head (TBLH) and lateral distal femur (LDF) BMD Z-scores also decreased with age at a rate of -0.26 SDS/year and - 0.41 SDS/year, respectively. The percentage of individuals with fractures increased by 21% (p < 0.01, n = 1066) for every 1-SDS decrease in LS aBMD Z-score. Reductions in LS aBMD Z-scores significantly accelerated after 11 years of age, with older versus younger individuals experiencing a faster decline. Understanding the natural history of BMD and disease progression relating to bone fragility will help to support clinical trial design to assess and improve bone strength in DMD. To our knowledge, this is the first SLR investigating BMD Z-score trajectories in individuals with DMD receiving GCs and highlights associations between age and GC treatment duration with declining LS aBMD, TBLH, and LDF Z-scores.
Ford et al. (Fri,) studied this question.