EFFECT OF PREDNISONE ON PROTEIN-METABOLISM IN DUCHENNE DYSTROPHY

Prednisone improves strength in Duchenne dystrophy and changes the nat ural history of the disease. We studied the in vivo effects of prednis one (0.75 mg.kg(-1).day(-1)) on muscle and whole body protein metaboli sm in six patients with Duchenne dystrophy and three patients with Pec ker dystrophy. Patients were admitted to the Clinical Research Center for study and consumed a constant flesh-free diet. Strength was measur ed by manual and quantitative muscle testing. Fractional muscle protei n breakdown was estimated by the ratio of 3-methylhistidine to creatin ine excretion determined in three consecutive 24-h urine collections. Whole body protein kinetics were studied in the postabsorptive state u sing a primed continuous infusion of L-[1-C-13]leucine. Fractional mus cle protein synthesis was determined from tracer incorporation into no ncollagen muscle protein obtained by needle biopsy. After 6-8 wk of pr ednisone treatment, average muscle strength increased by 15% (P < 0.04 ), and 24-h creatinine excretion (an index of muscle mass) increased b y 21% (P = 0.002). 3-Methylhistidine excretion decreased by 10%, but t he change was not statistically significant. The ratio of 3-methylhist idine to creatinine excretion decreased by 26% (P < 0.04). Fractional muscle protein synthesis and whole body protein synthesis and breakdow n did not change significantly. We conclude that the beneficial effect of prednisone on strength in Duchenne dystrophy appears to be associa ted with an increase in muscle mass, which may be mediated by inhibiti on of muscle proteolysis rather than stimulation of muscle protein syn thesis.