Walking Prolonged with Corticosteroids in DMD, at the Cost of Fractures

Susan Jeffrey

May 11, 2007

May 10, 2007 — A chart review of 143 boys with Duchenne muscular dystrophy (DMD) shows long-term treatment with corticosteroids prolonged independent ambulation by more than 3 years and decreased scoliosis risk, although this benefit came at the cost of more vertebral and lower limb fractures.


"To make an informed decision, patients and parents have to balance the benefits and risks of steroid treatment," the researchers, with first author Wendy M. King, from Ohio State University (OSU) and Columbus Children's Research Institute, conclude.

Their findings are published in the May 8 issue of Neurology.

Orthopedic Effects

Corticosteroids are the only medications shown to alter the natural course of DMD, the authors write. Previous studies have confirmed corticosteroids such as prednisone and deflazacort improve strength and function and prolong ambulation for up to 3 years, and the adverse effects of chronic corticosteroid use are well documented, they note.

However, few studies have examined the long-term orthopedic effects of corticosteroid treatment in DMD, the authors write. OSU has been involved in DMD trials as part of the Clinical Investigation of Duchene Dystrophy group since 1983 and has a tertiary neuromuscular clinic with a large population of both steroid- and nonsteroid-treated DMD patients.

For this study, they reviewed charts of 159 boys with genetically confirmed dystrophinopathies followed between 2000 and 2003 at their clinic. Of these, 16 with Becker dystrophy were subsequently excluded, leaving 143 boys for the present analysis. Of the patients, 75 had received steroids for at least 1 year; 68 had never been treated or had received only a brief submaximal dose. The mean duration of treatment was about 8 years.

Boys receiving treatment had independent ambulation for 3.3 years longer than untreated boys and had a lower prevalence of scoliosis. For those who did develop scoliosis, the scoliotic curve was milder with treatment.

Outcomes in DMD Patients With and Without Long-Term Corticosteroid Treatment

End Point
Steroids
No Steroids
P
Age ceased independent ambulation (y)
12.52
9.21
< .0001
Prevalence of scoliosis (%)
31
91
< .0001
Scoliotic curve (º)
11.6
33.2
< .0001

However, vertebral compression fractures occurred in 32 of the treated patients, compared with no fractures in the untreated group ( P = .0012). Long bone fractures also occurred 2.6 times more often in treated boys.

Further Study of Osteoporosis in DMD Needed

"Because of the orthopedic implications of steroid therapy in this population, aggressive prophylactic measures are indicated as soon as therapy is initiated," the authors write. At the time of the study, boys begun on treatment were prescribed calcium supplements, either as calcium carbonate 350 mg three times daily or a calcium tablet with vitamin D supplement of 750 to 1200 mg daily. "Currently, all boys who begin corticosteroid treatment at OSU have dietary counseling and a consult to the bone mineral metabolism laboratory for baseline [dual energy X-ray absorptiometry] DEXA scanning," with scanning repeated every 6 months to 2 years.

The role of bisphosphonates in this population remains to be determined, they add, and further studies are needed looking into how best to prevent or treat osteoporosis.

To define steroid bone complications in DMD, data should be comparative for factors such as age, calcium and vitamin D supplementation, age at initiation of treatment, and standardization of methodology, particularly the inclusion of bone-mineral content corrected for area, height for age, and bone area for height, they note.

"Meeting this type of data collection head on requires cooperation between centers and collaborations with experts in bone mineralization," they conclude. "In the absence of such data, it is impossible to interpret the recommendations of dose regimens attempting to combat the potential complications of steroid-induced osteoporosis in a disease with reduced muscle mass and small (narrow) bone area for height."

The study was supported by the General Clinical Research Center at Ohio State University and the National Center of Research Resources at the National Institutes of Health.

Neurology . 2007;68:1607-1613. Abstract

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