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 biochemical markers of calcium and bone metabolism, 36 normal male volunteers (aged 21-54 years) were randomized to oral treatment for 7 days with either (A) calcitriol, 1 microgram twice daily, (B) calcitriol, 0.5 microgram twice daily, or (C) placebo twice daily. Serum calcium increased slightly in a dose-dependent manner (maximal increase 2.5%, p < 0.05) followed by a heavy increase in both 24 h (max. 156.1%, p < 0.001) and fasting urinary calcium excretion (max. 123.1%, p < 0.001), and a striking 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 serum 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 resorption [serum C-terminal telopeptide of type I collagen (ICTP) and fasting urinary excretion of hydroxyproline/creatinine (OHP)]. Extraosseous collagen matrix synthesis was not affected evaluated by serum procollagen type III N-terminal propeptide (PIIINP). In the follow-up period (15 weeks) no unequivocal changes were observed. The fast and protracted increase in biochemical markers of osteoblast activity and bone formation, without affecting bone resorption and extraosseous connective tissue metabolism points toward a selective effect of calcitriol on bone matrix formation.
Gram
J
J
Department of Endocrinology, Odense University Hospital, Denmark.
Junker
P
P
Nielsen
H K
HK
Bollerslev
J
J
D000284:Administration, Oral; D000328:Adult; D000704:Analysis of Variance; D015415:Biomarkers / Q000097:blood; D015519:Bone Density / Q000187:drug effects*; D001846:Bone Development / Q000187:drug effects; D001862:Bone Resorption / Q000097:blood; D002117:Calcitriol / Q000008:administration & dosage / Q000494:pharmacology*; D002118:Calcium / Q000097:blood / Q000652:urine; D003094:Collagen / Q000097:blood; D024042:Collagen Type I; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005500:Follow-Up Studies; D006801:Humans; D006909:Hydroxyproline / Q000652:urine; D008297:Male; D008875:Middle Aged; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects; D015675:Osteocalcin / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D010455:Peptides / Q000097:blood; D011347:Procollagen / Q000097:blood
D015415:Biomarkers; D024042:Collagen Type I; D010446:Peptide Fragments; D010455:Peptides; D011347:Procollagen; C052929:collagen type I trimeric cross-linked peptide; C041876:procollagen Type III-N-terminal peptide; C042813:procollagen type I carboxy terminal peptide; D015675:Osteocalcin; D003094:Collagen; D002117:Calcitriol; D006909:Hydroxyproline; D002118:Calcium