NEW RESEARCH has revealed that prednisone, but not the alternative corticosteroid vamorolone, disrupts key bone and cartilage biomarkers in children with Duchenne muscular dystrophy, offering fresh insight into how the drug drives growth failure in this population.
Corticosteroids have remained a mainstay of Duchenne muscular dystrophy management, despite their well-documented tendency to cause osteopenia and growth failure in children. Vamorolone, a newer bone-sparing corticosteroid, has shown efficacy comparable to prednisone without the associated growth deceleration, though the biological mechanisms behind this difference have remained unclear. Researchers have sought biomarkers that distinguish prednisone’s effects on bone and cartilage metabolism from vamorolone’s.
The study analysed longitudinal serum samples from a double-blind, placebo- and prednisone-controlled trial of vamorolone in boys aged 4 to under 7 years with Duchenne muscular dystrophy, using proteomic assay methods. Participants were randomised to Period 1, a 24-week phase comprising placebo, prednisone (0.75 mg/kg/day), or vamorolone (6 mg/kg/day) arms.
In Period 2, a further 24-week phase, the placebo and vamorolone groups crossed over to vamorolone treatment. Bone turnover markers, including ALP, osteocalcin, P1NP, and CTX1, were assessed alongside proteomic screening for serum proteins uniquely regulated by prednisone.
ALP, osteocalcin, P1NP, and CTX1 levels fell significantly with prednisone treatment but remained unchanged with vamorolone or placebo. Proteomic analysis identified 10 serum proteins that were reduced specifically by prednisone, each corresponding to genes implicated in genetic disorders of cartilage or bone, including collagens (COL2A1, chondrocalcin, COL6A1, COL9A1, COL10A1, COL11A2), aggrecan core protein (ACAN), biglycan (BGN), osteopetrosis-associated transmembrane protein 1 (OSTM1), and noggin (NOG).
When participants crossed over from prednisone to vamorolone, all 10 biomarkers returned to baseline levels. Change in height z-scores correlated most strongly with change in ALP among corticosteroid-treated boys.
These findings have suggested that the novel biomarkers reflect prednisone-driven apoptosis of hypertrophic chondrocytes and osteoblasts, a process from which vamorolone appears to spare growth plate cells.
The results have reinforced growing clinical interest in vamorolone as a bone-sparing alternative to prednisone for children with Duchenne muscular dystrophy who require chronic corticosteroid treatment.
Clinicians may use these biomarkers, particularly ALP and COL10A1, to monitor growth plate activity and guide corticosteroid choice in affected children, pending further validation.
Tobin RA et al. Prednisone, not vamorolone, suppresses novel serum bone and cartilage biomarkers associated with growth failure in children with Duchenne muscular dystrophy. Sci Rep. 2026;16:21839.
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