Acute effect of oral, intraperitoneal, and intravenous 1 alpha-hydroxycholecalciferol on markers of bone metabolism.
OBJECTIVE
To study the acute effect of 1 alpha-hydroxycholecalciferol (1 alpha-OHD3) on serum levels of alkaline phosphatase, Ca2+, osteocalcin, parathyroid hormone (PTH), phosphate and type I and III procollagens (PICP and PIIINP respectively) in patients undergoing peritoneal dialysis. Also, 1,25-(OH)2D3 was measured.


METHODS
Single doses of 1 alpha-OHD3 (80 ng/kg body wt) were given in randomized cross-over fashion, orally, intraperitoneally (i.p.) and intravenously (i.v.) on three occasions. Blood was sampled at 0, 1, 6, 12, and 24 h after administration of 1 alpha-OHD3.


RESULTS
Following oral administration of 1 alpha-OHD3, a decrease in serum alkaline phosphatase was seen when levels at 1 and 6 h were compared to baseline (P < 0.05). Oral and i.v. drug administrations resulted in an increasing trend in serum Ca2+ throughout the study (P < 0.05). Moreover, a difference in serum Ca2+ was found when 24-h levels after oral 1 alpha-OHD3 dose was compared to baseline (P < 0.05). Serum osteocalcin at 12 and 24 h after oral 1 alpha-OHD3 compared to baseline were increased (P < 0.05). Intact PTH followed a circadian rhythm after all three routes of drug delivery. After 24 h, significant decreases of intact PTH were observed in the oral and i.v. group. No changes in serum phosphate and serum PICP levels were observed over time after oral, i.p., and i.v. delivery of 1 alpha-OHD3. However, serum PIIINP following oral and i.p. administration of 1 alpha-OHD3 decreased at 1 and 6 h (P < 0.05).


CONCLUSIONS
Oral and i.v. administration of 1 alpha-OHD3 does influence serum levels of osteocalcin, PTH, and PIIINP: Noticeable is the significant increase in serum osteocalcin after oral administration of 1 alpha-OHD3, the remarkable increase (22.6%) in osteocalcin 24 h after i.v. 1 alpha-OHD3, though not statistically significant, the increase in serum PTH levels 12 h following oral and i.v. doses of 1 alpha-OHD3 and the moderate effect on serum Ca2+ levels.
Joffe
P
P
Department of Nephrology, Herlev County Hospital, University of Copenhagen, Denmark.
Ladefoged
S D
SD
Cintin
C
C
Jensen
L T
LT
Hyldstrup
L
L
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000469:Alkaline Phosphatase / Q000097:blood; D015415:Biomarkers; D001842:Bone and Bones / Q000378:metabolism*; D002118:Calcium / Q000097:blood; D005260:Female; D006801:Humans; D006887:Hydroxycholecalciferols / Q000008:administration & dosage / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D007676:Kidney Failure, Chronic / Q000097:blood / Q000628:therapy; D008297:Male; D008875:Middle Aged; D015675:Osteocalcin / Q000097:blood; D010281:Parathyroid Hormone / Q000097:blood; D010530:Peritoneal Dialysis; D011347:Procollagen / Q000097:blood
D015415:Biomarkers; D006887:Hydroxycholecalciferols; D010281:Parathyroid Hormone; D011347:Procollagen; D015675:Osteocalcin; D000469:Alkaline Phosphatase; D002118:Calcium