Duchenne muscular dystrophy (DMD) is a rare genetic disorder caused by lack of dystrophin, a protein vital for muscle strength. DMD is associated with osteoporosis and increased bone fragility due to progressive muscle weakness, reduced ambulation and osteotoxic effects of prolonged, high-dose glucocorticoids. Biomarker analyses were performed to enhance understanding of DMD bone health.
Analysis of serum samples from 45 patients with DMD aged 6−11 years who received placebo in the SPITFIRE trial (NCT03039686) and 50 age-matched donor samples from healthy individuals showed that circulating DKK1 and OPG (bone turnover regulators), P1NP (bone formation marker) and CTX-1 (bone resorption marker) levels were significantly reduced in patients with DMD. Sclerostin and RANKL (bone turnover regulators) and soluble IL-6 receptor (IL-6R; bone metabolism) levels were significantly increased. While circulating IL-6 levels were similar in both groups, IL-6 levels correlated positively and significantly with P1NP, CTX-1 and OPG levels. In patients with DMD, total body less head bone mineral density (TBLH BMD; imaging biomarker of bone loss and fracture risk) Z-scores decreased significantly over 6 and 12 months (change from baseline −0.15 [n=139] and −0.29 [n=80], respectively); baseline TBLH BMD Z-scores correlated significantly with circulating IL-6R levels.
Treatments to prevent the development and progression of osteoporotic fragility fractures in DMD are needed. Results suggest IL-6 signaling could be a key systemic mediator of bone fragility in DMD. Inhibiting IL-6R could serve as a new therapeutic approach.