Boys with Duchenne muscular dystrophy (DMD) on a long-term daily regimen of glucocorticoids are more likely to develop spinal fractures, have poorer growth and gain more body fat, than do those on intermittent use, a two-year study reports.
But study findings also suggest that those taking oral glucocorticoids each day tend to prolong their ability to walk. The researchers stress that children with DMD should be routinely screened for bone health and vertebral fractures using appropriate imaging techniques.
The study, “Growth, bone health & ambulatory status of boys with DMD treated with daily vs. intermittent oral glucocorticoid regimen” was published in the journal Bone.
Oral glucocorticoids (GCs), such as prednisolone and Emflaza (deflazacort), are the standard of care for children with DMD, due to their ability to slow muscle deterioration and preserve an ability to walk.
Treatment with GCs usually starts between ages 4 and 6, when the motor capacities of these patients peak and stop improving.
However, long-term GC use has consequences. Several reports show that long-term treatment significantly increases the risk of spinal fractures, deepens bone fragility, and leads to growth deficits and obesity among DMD boys.
One study, based on eight years of data covering 79 DMD patients, reported that 37 of these boys who never were treated with Emflaza also never developed any spinal fractures, while these fractures that were found in treated patients. However, the untreated group also had poorer cardiac function and more severe scoliosis, among other findings.
Studies are lacking into whether different GC regimens might lessen the risk of bone fractures in DMD patients.
Based on clinical observations suggesting a daily regimen worsens the risk for spine fractures more than an intermittent regimen does, a group of researchers in the U.K. conducted a retrospective study to compare growth, body mass, bone mineral density, vertebral fractures, and walking ability in DMD children on daily or intermittent GC regimens.
The study included 25 boys using GCs daily who were being treated at the Royal Manchester Children’s Hospital, and 25 boys on an intermittent regimen — 10 days on and 10 days off — treated at Birmingham Children’s Hospital. Boys in both groups had a mean age of 8 and had been treated with GCs for a mean of two years.
Clinical reports on bone health (vertebral and long bone fractures, and bone mineral density), height, weight, and walking ability were analyzed for a period of two years.
At the study’s start, or baseline, boys on daily GCs already showed a significantly shorter stature, and their height progressively decreased over 2.5 years. By contrast, the stature of boys receiving intermittent GCs remained unchanged.
Despite their reduced growth, boys on daily GCs increased their body mass index to significantly higher levels than those on an intermittent regimen, suggesting these children gained more fat mass or adiposity.
Most bone measurements showed that bone mineral density, a measure of bone strength, dropped significantly over the study’s two years, but the rate of bone mineral density loss was similar between the treatment groups.
However, significantly more boys on daily GC use, 10 out of 25 (40%), developed vertebral fractures than did those on intermittent GC treatment, 2 out of 25 (8%).
No significant differences were seen in the number of long bone fractures, which were rare.
There was a trend for daily GC treatment to prolong a patient’s ability to walk, the researchers reported. At the final assessment at two years of follow-up, 10 boys on the intermittent regimen and five on the daily use had lost this ability.
“In conclusion, there was a trend for more boys on daily GCs to remain ambulant [able to walk] but at the cost of more VFs [vertebral fractures], greater adiposity and markedly diminished growth,” the researchers wrote.
Researchers also suggest that quantitative computed tomography (QCT) imaging of the spine, rather than dual-energy x-ray absorptiometry — the imaging technique generally used to measure bone density — may be more useful to assess bone health and predict vertebral fracture in children with DMD.
The high prevalence of vertebral fractures and the limited value of X-ray absorptiometry in assessing vertebral fractures “suggests the need for VF screening as part of the boys routine bone health assessments,” the researchers stressed.
“The decline in volumetric bone density as measured by peripheral QCT may be a more sensitive measure of bone loss and vertebral fracture risk,” they added.