Observational studyNeuropathology and applied neurobiology2026
Myofibre Density Reveals a Critical Threshold Around Age 6 in Steroid-Naïve Duchenne Muscular Dystrophy: A Retrospective Observational Study.
Observational study in Neuropathology and applied neurobiology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
aimsIn Duchenne muscular dystrophy (DMD), robust histological markers for assessing early disease progression remain elusive. We defined myofibre density (MFD) as the count of myofibres per square millimetre, which, in our preliminary survey of DMD muscle biopsies, steeply declined with age (Spearman's ρ: -0.85). We aimed to characterise age-dependent MFD dynamics in early-stage DMD.
methodsWe retrospectively assessed 46 archival muscle-biopsy slides (steroid-naïve; collected > 40 years ago) using semi-quantitative image analysis with digital restoration. MFD and classical histological variables were quantified. Age-MFD dynamics were modelled with segmented regression and validated using weakly informative Bayesian modelling. The primary measure was the MFD age-breakpoint. Secondary measures included breakpoint-detection power, age-predictive MFD cut-offs and behaviour of conventional variables across breakpoint-defined age bands.
resultsAfter quality and age-distribution screening, 35 slides (age 1-11 years) were analysed. Segmented regression identified a breakpoint at 6.25 years (95% confidence interval [CI]: 5.08-7.42); after which MFD plateaued at lower levels. Bayesian posterior estimate was 6.37 years (95% credible interval: 5.24-7.66). A 10,000-run Monte Carlo simulation (n = 35) showed approximately 80% power to recapture the breakpoint within ±1.25 years. MFD cut-offs > 596 and < 426 fibres/mm
conclusionsMFD, a simple metric, reveals a previously unrecognised phase of rapid myofibre loss lasting up to around age 6 in early-stage DMD.
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