Endocrine Abstracts

Background: Recent evidence highlights the dramatic loss of trabecular bone following loss of ambulation in people with DMD. An opportunity to introduce osteoporosis therapy without fractures is when loss of ambulation is imminent. There is a need to explore biomarkers to predict loss of ambulation, that can be assessed in the clinic, to guide such discussions.

Methods: A retrospective study was conducted in 26 boys with DMD treated with daily glucocorticoid. Lean mass and fat mass from DXA, performed during routine bone monitoring, was obtained at three timepoints. Thirteen remained ambulant through-out follow-up and thirteen others were non-ambulant at the third DXA scan. Lean mass index (LMI) and fat mass index (FMI) were converted into Z-scores. Descriptive data presented as median (range). Statistical significance was noted at P < 0.05.

Results: Median glucocorticoid dose (prednisolone equivalent in mg/kg/day) in the group that remained ambulant were 0.5 mg/kg/day (0.5, 0.8), 0.5 mg/kg/day (0.3, 0.8) and 0.6 mg/kg/day (0.3, 0.7), respectively [P = 0.37]. Median glucocorticoid dose (prednisolone equivalent in mg/kg/day) in the group that lost ambulation was 0.7 mg/kg/day (0.5, 0.8), 0.5 mg/kg/day (0.3, 0.8) and 0.3 mg/kg/day (0.2, 0.8), respectively [P < 0.001]. Median LMI Z-scores in those that continued to be ambulant were low, but remained stable at -1.9 (-3.8, +3.1), -1.5 (-4.4, +1.9) and -2.1 (-4.5, -0.3), respectively [P = 0.72]. Median LMI Z-scores in those that lost ambulation by the third DXA declined with follow-up and were -3.0 (-4.1, -1.2), -4.3 (-5.7, -0.1) and -4.6 (-6.9, -3.3), respectively [P < 0.001]. Median LMI Z-scores were significantly lower at 2nd DXA in this group [P < 0.001]. Logistic regression analysis with LMI Z scores at 2nd DXA and duration of glucocorticoid as co-variates identified LMI Z-scores as a significant independent factor [P = 0.025, Exp(B) 0.4, 95%CI for Exp(B) 0.1, 0.9] that predicts loss of ambulation.

Conclusion: In boys with DMD, DXA LMI Z-scores declined significantly with follow-up in those that lose ambulation. Our study provides the first evidence of the potential utility for DXA LMI Z-scores to predict loss of ambulation, thus extending the clinical utility of DXA in DMD to identify those where bone protective therapy can be considered without fractures.