The Effect of Pamidronate on Prevention of Osteoporosis in Ovariectomized Rats

Choi, Jang Seok; Seo, Seung Seok; Park, Jong Ho; Kong, Kyu Min

Abstract

Many agents for the treatment of osteoporosis are broadly classified as inhibitors of bone resorption and stimulators of bone formation. Many pharmacological derivatives of bisphosphonates are used in the treatment of osteoporosis by inhibiting osteoclast-mediated bone resorption. Although the pamidronate, derivative of bisphosphonates, has a potent antiresorptive activity, there are only a low reports about prevention and treatment of postmenopausal osteoporosis using it. The purpose of this study is to evaluate the changes of bone metabolism and bone mass after pamidronate administration during the early period of estrogen deficiency. Ninty-five Sprague-Dawley rats (weight 233-243 g) were divided into 3 groups. Group 1(n=28) was performed sham operation. Group 2 (n=25) was both ovariectomized and intravenously injected with 0.5 cc normal saline. Group 3 (n=42) was both ovariectomized and intravenously injected with 0.1 mg/kg pamidronate. During the first 8 weeks normal saline or pamidronate was intravenously injected twice a week(q 3 day or q 4 days). After 4 weeks of observation without injection the experiental animals were sacrificed at postoperative 12 weeks. There were statistically significant decrease in the body weight and the weight of uterus in group 1 compared with group 2, 3. There was statistically significant decrease in the bone mass of the spine, proximal femur, proximal tibia in the group 2 compared with group 1, 3. The difference of bone mass between group 1 and 3 was statistically insignificant. Serum osteocalcin and PICP concentration were significantly increased in group 2 and 3 compared with group 1. But there was no statistical significance between group 2 and 3 in serum osteocalcin and PICP concentration. Serum ICTP concentration was significantly decreased in group 1 and 3 compared with group 2, but the difference between group 1 and 3 was insignificant. These results suggests that the administration of the pamidronate during the early period of estrogen deficiency can inhibit bone resorption and prevent trabecular bone loss of the spine, proximal femur and proximal tibia metabolically.