DOSE-RESPONSE EFFECT OF SHORT-TERM CALCITRIOL TREATMENT ON BONE AND MINERAL METABOLISM IN NORMAL MALES

To evaluate the effects of short-term treatment with calcitriol on bio chemical markers of calcium and bone metabolism, 36 normal male volunt eers (aged 21-54 years) were randomized to oral treatment for 7 days w ith either (A) calcitriol, 1 mu g twice daily, (B) calcitrol, 0.5 mu g twice daily, or (C) placebo twice daily, Serum calcium increased slig htly in a dose-dependent manner (maximal increase 2.5%, p < 0.05) foll owed by a heavy increase in both 24 h (max, 156.1%, p < 0.001) and fas ting urinary calcium excretion (max, 123.1%, p < 0.001), and a strikin g reduction in serum PTH (max, -43.1%, p < 0.001). Biochemical markers of osteoblast activity and bone formation increased immediately in a dose-dependent manner [serum osteocalcin (max, 37.8%, p < 0.03) and se rum procollagen type I C-terminal propeptide (PICP) (max, 26.0%, p < 0 .05)], whereas there was no effect on serum bone alkaline phosphatase, Calcitriol treatment had no effect on biochemical markers of bone res orption [serum C-terminal telopeptide of type I collagen (ICTP) and fa sting urinary excretion of hydroxyproline/creatinine (OHP)]. Extraosse ous collagen matrix synthesis was not affected evaluated by serum proc ollagen type III N-terminal propeptide (PIIINP). In the follow-up peri od (15 weeks) no unequivocal changes were observed, The fast and protr acted increase in biochemical markers of osteoblast activity and bone formation, without affecting bone resorption and extraosseous connecti ve tissue metabolism points toward a selective effect of calcitriol on bone matrix formation.