#apaperaday: Relationship between growth and ambulation loss in Duchenne muscular dystrophy boys on steroids

In today’s #apaperaday, Prof. Aartsma-Rus reads and comments on the paper titled: Relationship between growth and ambulation loss in Duchenne muscular dystrophy boys on steroids

Today I’m travelling to @Radboud_Uni to teach and the pick is from European Journal of Neurology by Stimpson et al on the relationship between growth and loss of ambulation in Duchenne patients who use steroids. DOI: 10.1111/ene.16415

Chronic corticosteroid use is part of the standards of care for Duchenne patients. It slows down disease progression but also leads to side effects. Daily and intermittent regimen (usually 10 days on 10 days off) are used and both prednisone and deflazacort are used.

There have been reports deflazacort may delay loss of ambulation more than prednisone. Authors argue, that deflazacort also leads to more growth stunting than prednisone and that a shorter stature may be protective for loss of ambulation. Here they studied this in a large cohort.

They use data in the North Star database, which has long term follow up for patients in the UK, who mostly were monitored every 6 months. 2228 observations were available of 648 patients. 66% used prednisone, 22% deflazacort and 11% used no steroids.

Loss of ambulation was 10 for patients off steroids, 12.9 for deflazacort and 12.7 for prednisone (on/off regimen); and 15.8 for daily deflazacort and 14.9 for daily prednisone. Weight gain was increased for patients on daily prednisone and deflazacort after initiation

Weight gain influenced loss of ambulation (more weight gain, earlier loss of ambulation), but this was still later than patients not on steroids. Height was reduced for patients on daily steroids and influenced loss of ambulation too (less height LATER loss of ambulation).

Authors discuss their hypothesis that shorter stature is protective for loss of ambulation seems to hold true. They did not see significant differences between daily deflazacort & prednisone. They also did not see a difference between intermittent deflazacort & prednisone.

They also cite a case report of a Duchenne patient who had no growth hormones and who had a mild course. Weight gain, rather than weight is a risk. So maintaining weight – even when overweight is important (i.e. avoiding further weight gain)

Authors discuss it is possible  the later loss of ambulation with shorter stature is a direct effect (less muscle strain) but can also be an indirect effect. Vamorolone does not lead to growth stunting and longer term studies are needed to study loss of ambulation there.

Thus more work is needed. Finally authors discuss that short stature also impacts quality of life and self confidence and that this impact has to be studied as well. For some patients maintaining the ability to walk may be very important, while for others stature may be preferred

I appreciate the authors making this comment because in the end the patients have to make this decision and different people will see this differently. With more information patients will be able to make a more informed decision.

For vamorolone: I know some families worry that the fact that patients will be taller may lead to earlier loss of ambulation. For now we do not know if this will be the case. However, it is of course more complex than only height, vamorolone also seems to improve bone mass