Therapeutic efficacy of 1α,25-dihydroxyvitamin D3 and calcium in osteopenic ovariectomized rats:: Evidence for a direct anabolic effect of 1α,25-dihydroxyvitamin D3 on bone

被引:58
作者
Erben, RG [1 ]
Bromm, S [1 ]
Stangassinger, M [1 ]
机构
[1] Univ Munich, Inst Physiol Physiol Chem & Anim Nutr, D-80539 Munich, Germany
关键词
D O I
10.1210/en.139.10.4319
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
It is an important question for clinical therapy of osteoporosis with vitamin D metabolites whether these compounds exert their beneficial effects on the skeleton indirectly through an increase in intestinal calcium absorption or whether there is also a major direct component of action on bone. In this study, female 6-month-old Fischer rats were either ovariectomized (OVX) or sham operated. One month before surgery, all rats were placed on a diet containing 0.25% calcium and were kept on this diet throughout the study. Beginning 3 months post-OVX, groups of OVX rats orally received vehicle, a calcium supplement, low dose (0.025 mu g/kg.day) or high dose (0.1 mu g/kg.day) 1 alpha,25-dihydroxyvitamin D-3 [1,25-(OH)(2)D-3], or combinations of low and high dose 1,25-(OH)(2)D-3 with the calcium supplement. By 3 months postsurgery, pretreatment OVX controls had lost 74% and 37% of tibial and vertebral cancellous bone, respectively. Two-way factorial ANOVA showed that a 3-month treatment of osteopenic OVX rats with 1,25-(OH)(2)D-3 dose dependently increased vertebral and tibial cancellous bone mass (P < 0.001 and P = 0.021, respectively) and trabecular width (P < 0.001). Furthermore, 1,25-(OH)(2)D-3 increased serum calcium (P = 0.028) and urinary calcium excretion (P < 0.001) and reduced serum PTH levels (P < 0.001), osteoclast numbers (P < 0.001), and urinary collagen cross-links excretion (P < 0.001). Calcium supplementation alone was without therapeutic effect, and there was no significant two-way interaction between the individual treatment effects of 1,25-(OH)(2)D-3 and calcium on bone mass. These data indicate that the anabolic effects of 1,25-(OH)(2)D-3 in osteopenic OVX rats are mediated through a direct activity on bone.
引用
收藏
页码:4319 / 4328
页数:10
相关论文
共 33 条
[31]  
WALTERS MR, 1992, P SOC EXP BIOL MED, V199, P385, DOI 10.3181/00379727-199-43371B
[32]   BONE HISTOMORPHOMETRY IN VITAMIN-D-DEFICIENT RATS INFUSED WITH CALCIUM AND PHOSPHORUS [J].
WEINSTEIN, RS ;
UNDERWOOD, JL ;
HUTSON, MS ;
DELUCA, HF .
AMERICAN JOURNAL OF PHYSIOLOGY, 1984, 246 (06) :E499-E505
[33]   CHRONIC ADMINISTRATION OF 1,25-DIHYDROXYVITAMIN-D3 - INCREASED BONE BUT IMPAIRED MINERALIZATION [J].
WRONSKI, TJ ;
HALLORAN, BP ;
BIKLE, DD ;
GLOBUS, RK ;
MOREYHOLTON, ER .
ENDOCRINOLOGY, 1986, 119 (06) :2580-2585