ACUTE EFFECT OF ORAL, INTRAPERITONEAL, AND INTRAVENOUS 1-ALPHA-HYDROXYCHOLECALCIFEROL ON MARKERS OF BONE METABOLISM

Objective. To study the acute effect of 1alpha-hydoxycholecalciferol (1alpha-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. Design. Single doses of 1alpha-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 1alpha-OHD3. Main results. Following oral administration of 1alpha-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 1alpha-OHD3 dose was compared to baseline (P < 0.05). Serum osteocalcin at 12 and 24 h after oral 1alpha-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 1alpha-OHD3. However, serum PIIINP following oral and i.p. administration of 1alpha-OHD3 decreased at 1 and 6 h (P < 0.05). Conclusion. Oral and i.v. administration of 1alpha-OHD3 does influence serum levels of osteocalcin, PTH, and PIIINP. Noticeable is the significant increase in serum osteocalcin after oral administration of 1alpha-OHD3, the remarkable increase (22.6/o) in osteocalcin 24 h after i.v. 1alpha-OHD3, though not statistically significant, the increase in serum PTH levels 12 h following oral and i.v. doses of 1alpha-OHD3 and the moderate effect on serum Ca2+ levels.