The effects of acute pharmacologic steroid treatment on skeletal and mineral metabolism were assessed in 56 multiple sclerosis patients who were to receive 1 g intravenous methylprednisolone for 10 days, followed by a 4 day intravenous and 28 day oral glucocorticoid taper. Serum and urine samples were obtained at baseline and then within 3 days, 1, 2, and 3 weeks after beginning steroids. A subset of patients (n = 11) had sampling throughout the 6 weeks of steroid administration and up to 8 weeks afterward. All mean basal biochemistries were normal except 25(OH)D, which was in the "insufficient" range (25-50 nM) at 10 nM. During and after steroid administration, there were no changes in ionized calcium, 25(OH)D, urinary hydroxyproline, or pyridinoline. There was an increase in 1,25(OH)2D and a decrease in serum phosphorus, accompanied by an increase in urinary phosphate clearance, within 3 days of administration (p < 0.006). Serum osteocalcin (BGP) decreased to below assay sensitivity limits within 3 days of steroid administration (p < 0.0002), increasing thereafter but remaining at 50% of baseline by the third week. PTH(1-84) increased to a peak at week 2 (p < 0.02), after both the 1,25(OH)2D peak and the serum phosphorus nadir. Tartrate-resistant acid phosphatase, urinary calcium, and urinary cyclic AMP all increased above baseline (p < 0.05) with a pattern similar to that of PTH. To investigate further the immediate effects of steroid administration, serum samples were obtained at the same four times on both the day before and the day after the first intravenous methylprednisolone dose in a randomly chosen subset of patients (n = 9).(ABSTRACT TRUNCATED AT 250 WORDS)