Effect of the vitamin D analogues paricalcitol and calcitriol on bone mineral in vitro

被引:35
作者
Balint, E
Marshall, CF
Sprague, SM
机构
[1] Northwestern Univ, Sch Med, Evanston NW Healthcare, Res Inst,Div Nephrol, Evanston, IL 60201 USA
[2] Northwestern Univ, Sch Med, Evanston NW Healthcare, Dept Med, Evanston, IL 60201 USA
关键词
paricalcitol; calcitriol; bone; calcium; calvariae;
D O I
10.1053/ajkd.2000.17667
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
Paricalcitol (19-nor-1,25-dihydroxyvitamin D-2), a new vitamin D analogue, recently became available for the treatment of hyperparathyroidism in patients with end-stage renal disease. It is safe and effective in suppressing parathyroid hormone, with apparently less propensity for hypercalcemia than calcitriol (1,25-dihydroxyvitamin D-3) However, the mechanism of action on bone has not been fully elucidated. This study compares the effects of paricalcitol and calcitriol on the bone mineral. Neonatal (5- to 7-day-old) mouse calvariae were incubated in the absence or presence of either paricalcitol or calcitriol for 48 hours, and calcium flux, osteocalcin and acid and alkaline phosphatase activity, and interleukin-6 (IL-6) release were determined. Increasing concentrations of both calcitriol and paricalcitol increased calcium efflux. At lower concentrations, paricalcitol had no effect on acid phosphatase activity; however, at 10(-8) mol/L, paricalcitol caused a significant increase similar to that of calcitriol at 10(-9) mol/L, Increasing concentrations of paricalcitol had no effect ion alkaline phosphatase activity, whereas calcitriol (10(-8) mol/L) caused significant inhibition. At low concentrations, paricalcitol had no effect on osteocalcin release; however, at 10(-8) mol/L, both compounds significantly increased osteocalcin production, Neither compound had an effect on IL-6 release. These data show that: (1) at low concentrations, both compounds induce a similar calcium efflux from cultured bone; (2) at low concentrations, paricalcitol has no effect on osteocalcin or acid and alkaline phosphatase activity; (3) at greater concentrations, paricalcitol and calcitriol have similar effects on acid phosphatase and osteocalcin activity; (4) calcitriol, but not paricalcitol, inhibits alkaline phosphatase release; and (5) the bone-resorbing effect of both compounds is independent of IL-6 release. Thus, although both compounds have similar effects on calcium efflux from bone, at therapeutic concentrations, paricalcitol does not seem to inhibit osteoblast activity. This may explain, in part, the lower calcemic effect of paricalcitol. (C) 2000 by the National Kidney Foundation, Inc.
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页码:789 / 796
页数:8
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