Background: DMD is an X-linked recessive disorder, due to mutations of the DMD gene on Xp21, encoding dystrophin, characterized by high cytokines and progressive muscle degeneration, with loss of ambulation, increasing immobility and complicated by late cardio-respiratory failure. Use of high dose corticosteroid aims to prolong mobility, delay/reduce complications and to increase lifespan but adverse effects on bone health include bone loss and increased vertebral and long bone fracture risk.Corticosteroids also suppress DHEAS and the hypothalamic pituitary testicular axis, resulting in near universal profound pubertal delay. Bisphosphonates harden bone and are used in DMD to try to reduce fracture frequency. Normal progress through puberty has a major impact upon bone mass accrual, with increased cortical thickness and trabecular mineralization.
Aims: To assess the effect of pubertal induction with testosterone (T) on rate of change of bone mineral density (BMD), as a measure of bone mass accrual, in a cohort of adolescent boys with DMD most of whom were concurrently treated with bisphosphonate as zoledronic acid (ZA). Methods: Boys with DMD aged 14 and above (N=16), who were prepubertal, were commenced on HRT. Zoledronic acid was continued at 6 monthly intervals. Graduated increases of oral T undecanoate were made, with transition to long acting parenteral T as intramuscular T undecanoate, over 24 months, to mimic normal pubertal progress. Rate of change of BMD was calculated for the year prior to and for 12 and 24.months after onset of T.
Results: IM testosterone undecanoate group (N=11): Median age at start of androgen 14.5yr Median age at start of IM T 16.3 y. Mean % change of BMD before androgen +2.15% Mean % change of BMD 1 year after androgen +10.15%, Mean % change of BMD 2 year after androgen +25.4%.10 of 11 were on ZA prior to androgen, 8 of 11 have 2 year data. Oral testosterone undecanoate group (N=4): Median age at start of oral T 14.5yr, Mean latest dose of oral T 109mg/ day. Mean % change of BMD before androgens −3.6%, Mean % change of BMD in first year of androgen 19.48%, Mean % change of BMD after 618 months of oral T 19.48%. 4/4 were on ZA prior to androgen.
Conclusion: Pubertal induction and ongoing use of T in adolescent boys with DMD has a major positive effect on bone mass accrual, that is likely to reduce current and future fracture risk.
27 - 29 Sep 2018
European Society for Paediatric Endocrinology