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Serum Bone Gla Protein and the Vitamin D Endocrine System in the Oophorectomized Rat

Albert Einstein Medical Center and Temple University School of Medicine Philadelphia, Pennsylvania 19141
The University of Pennsylvania Philadelphia, Pennsylvania 19104
The National Animal Disease Center Ames, Iowa 50010

Address requests for reprints to: Sol Epstein, M.D., Division of Endocrinology and Metabolism, Albert Einstein Medical Center, York and Taber Roads, Philadelphia, Pennsylvania 19141.

Abstract

Because of the importance of estrogen in osteoporosis, the effects of decreased estrogen production using sensitive measurements of bone mineral metabolism were studied in oophorectomized rats. Serum levels of ionized calcium, bone gla protein (BGP), vitamin D metabolites (25-hydroxyvitamin D and 1,25-dihydroxyvitamin D), and estradiol were measured before and serially for 6 weeks after oophorectomy in the rat. In addition, static and dynamic indices of bone histomorphometry were determined after double tetracycline labeling. Fifty Sprague- Dawley female rats (-250 g) were studied. Twenty-five rats underwent oophorectomy (0), while the remaining rats were sham operated. Estrogen deficiency was noted in the O group within a week after surgery (estradiol, 2.45 ± 0.78 vs. 27.9 ± 4.15 pg/ml; P < 0.05). Serum ionized calcium levels, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, and PTH levels did not differ between the two groups during the length of the study. Serum BGP levels were the same in both groups until the second week postoophorectomy, after which BGP remained significantly elevated in the 0 animals (121.7 ± 5.95 us. 76.7 ± 3.87; P < 0.001). Bone histomorphometry revealed increased osteoid volume (4.4 ± 0.9% vs. 2.3 ± 0.7%), osteoblast surface (26.5 ± 2.4% vs. 3.2 ± 1.2%), tetracycline surface (18.9 ± 4.1% vs. 6.8 ± 2.2%), as well as osteoclast surface (8.2 ± 1.4% vs. 2.5 ± 2%) in all O animals compared with those in the sham-operated group. These data indicate that oophorectomy and decreased estrogen result in increased bone turnover with elevated BGP levels. The marked BGP elevation within 2 weeks postoophorectomy suggests that estrogen withdrawal results in rapid altered bone mineral metabolism. The lack of concomitant increase in circulating PTH levels suggests that other factors may be mediating the bone loss following surgical oophorectomy. (Endocrinology 122: 624–630,1988)

Received February 17, 1987.

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