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Ovariectomized Murine Model of Postmenopausal Calcium Malabsorption
Author(s) -
Kalu Dike N.,
Chen Cang
Publication year - 1999
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1359/jbmr.1999.14.4.593
Subject(s) - ovariectomized rat , calcium , endocrinology , medicine , calcium metabolism , osteoporosis , chemistry , malabsorption , feces , in vivo , absorption (acoustics) , estrogen , biology , paleontology , microbiology and biotechnology , physics , acoustics
Two experiments were carried out to examine whether the ovariectomized mouse is a potential in vivo model of intestinal calcium malabsorption as occurs in postmenopausal osteoporosis. In the first experiment, we compared the effects of ovariectomy and 17β‐estradiol (E 2 ) therapy on calcium absorption in C3H/HeJ (C3H) and C57BL/6J (C57BL) mice, which have high and low peak bone mass, respectively. For each strain of mice, three groups were studied: sham operated, ovariectomized, (OVX), and OVX + E 2 (60 μg/kg of body weight [bw]/day). Therapy was continued for 35 days and calcium absorption measured. In the C3H mice, ovariectomy caused an increase in fecal calcium (17.6%), and a decrease in the amount (12.8%) and percentage (12.5%) of calcium absorbed. The decrease was prevented by E 2 therapy, but the differences in the calcium absorption parameters among the groups were not statistically significant. In contrast, in the C57BL mice, ovariectomy caused a marked increase in fecal calcium (84.5%, p < 0.01), and a marked decrease in the amount (55%, p < 0.01) and percentage (34.8%, p < 0.001) of calcium absorbed, and the decrease in the percentage of calcium absorbed was partially prevented by E 2 therapy ( p < 0.05). In experiment 2, a dose‐response study of the effects of E 2 therapy on calcium absorption in OVX C57BL mice was carried out. Five groups of mice were studied: Group 1, sham operated; Group 2, OVX; Group 3, OVX + 60 μg of E 2 /kg of bw/day; Group 4, OVX + 120 μg of E 2 /kg of bw/day; Group 5, OVX + 240 μg of E 2 /kg of bw/day. Therapy was continued for 28 days and calcium absorption measured. Ovariectomy caused a marked increase in fecal calcium (50%, p < 0.0001) and urinary calcium (31%, p < 0.0001) and a marked decrease in calcium absorption (44.9%, p < 0.0001), and these changes were prevented by E 2 therapy. The highest level of calcium absorption (109%, p < 0.0001, vs. OVX) was observed in the 120 μg of E 2 group. Ovariectomy and E 2 slightly increased plasma 1,25‐dihydroxyvitamin D (1,25(OH) 2 D) levels but there was no significant correlation between 1,25(OH) 2 D levels and calcium absorption. The findings in the C57BL mice suggest that estrogen is a physiological regulator of calcium absorption in this strain of mice. Furthermore, these findings share many characteristics with intestinal calcium malabsorption and its reversal by estrogen therapy in hypoestrogenic women. We propose that the OVX C57BL mice warrants further characterization as a potential animal model for investigating issues related to calcium malabsorption in postmenopausal women.