Effect of mithramycin on hydroxyproline metabolism in Paget's disease

Hydroxyproline was measured in the plasma and urine of six patients with symptomatic osseous Paget's disease before and after parenteral mithramycin treatment. The plasma profile data included free, peptide, and protein hydroxyproline values. Corresponding urine samples were analyzed for total hydroxyproline content and, in some instances, for free hydroxyproline. Plasma values of free and peptide hydroxyproline fell promptly toward the range of normal within 24 hr after the first intravenous injection of mithramycin. Protein hydroxyproline in the plasma was slightly but significantly lower than in the 15 normal control subjects, and this value did not change appreciably over the 4-day period during which the patients were treated. The urine excretion rate of total hydroxyproline decreased precipitously. Our results support the hypothesis that mithramycin rapidly reduces the accelerated rate of "collagenolytic" activity of osteocytes and osteoclasts in this disorder, presumably by an inhibiting effect on these bone-modeling cells. The major degradative lesion, as reflected in the plasma and urine, is characterized by the production of non-TCA-precipitable peptides containing hydroxyproline, which rapidly fell to normal levels after the administration of mithramycin.