Assessing biomarkers of bone metabolism and the role of the interleukin-6 signaling pathway in patients with Duchenne muscular dystrophy

Duchenne muscular dystrophy (DMD), a genetic disorder from lack of dystrophin, leads to osteoporosis and increased bone fragility. This study performed biomarker analyses to understand bone health in people living with DMD. Demographic data and total body less head (TBLH) bone mineral density (BMD) Z-scores were collected from 160 boys with DMD aged 6-11 years receiving corticosteroid therapy (prednisone, prednisolone, or deflazacort) who participated in the SPITFIRE trial (NCT03039686). Serum samples from 45 boys treated with placebo were compared with 50 age-matched healthy volunteers. Lower levels of dickkopf-1, osteoprotegerin (OPG), procollagen type 1 N-terminal propeptide (P1NP), and C-terminal telopeptide (CTX-1) were reported in boys with DMD. Sclerostin, receptor activator of nuclear factor kappa-Β ligand (RANKL), and soluble interleukin-6 receptor (IL-6R) levels were higher. IL-6 levels were unchanged and correlated positively with P1NP, CTX-1, and OPG levels. TBLH BMD Z-scores decreased over 6 (-0.15 [n = 139]) and 12 months (-0.29 [n = 80]), while age and BMD Z-scores at baseline were clinical parameters associated with BMD Z-score longitudinal progression. TBLH BMD Z-scores associated with circulating IL-6R levels at baseline. Treatments to prevent osteoporotic fragility fractures in DMD are needed. Results suggest IL-6 signaling as a key mediator of bone fragility in DMD, serving as a potential new therapeutic approach.