Long-term oral tiludronate prevents decrease in bone mineral density in rats with ovariectomy-induced osteopenia

Abstract

This study evaluated the effect of long-term oral administration of tiludronate on ovariectomy (OVX)-induced osteopenia in the aged rat. Bone mineral density (BMD) measurements, using dual energy X-ray absorptiometry, were performed on lumbar vertebrae and the right femur of adult anaesthetized rats; before OVX, 3 months after the operation, 6 months after the beginning of treatment and at the end of the study, afier 12 months of treatment. Treatment with tiludronate began only after bone loss (statistically significant reduction in BMD at lumbar vertebrae level) had been demonstrated. The rats received tiludronate dissolved in distilled water by the oral route, which is the route used in man. The intermittent schedule in man (1 week eanh month) was adjusted for rats (2 days per week) so that it reflected an equivalent treatment sequence relative to the shorter bone resorption/formation cycle. Tiludronate was administered at an optimally effective dose in the rat and at a dose approximately five times greater. Control animals (sham and OVX) received distilled water only. The BMD of the lumbar vertebrae in control OVX rats was significantly less than that in sham operated rats from 3 months after the operation and the femoral BMD decreased from 9 months postovariectomy. Under these study conditions, the decrease in the BMD of lumbar vertebrae was prevented by optimum doses of tiludionate. Furthermore, the difference in femoral BMD induced by OVX (as compared to sham), was futiy prevented by tiludronate. Conclusions: Long-term treatment with oral tiludronate prevents or reverses OVXinduced losses in BMD. This study in the rat was equivalent to a four-year study in man and the benefits of treatment with tiludronate increased continuously throughout the study. 40 patients with postmenopausal osteoporosis were enrolled in the study. The first group (n=20) was treated with salmon calcitonin nasal spray (200 IU/day) and oral calcium (I000 mg/day) for 24 weeks. The second group (n=20) was treated with oral etidronate (400 mg/day) for 2 weeks, after that this group was given oral calcium (i000 mg/day) for 10 weeks. This treatment regiment for the second group was repeated once again.Serum alkali phosphatase, calcium and phosphorus, urinary calcium / creatin!n, hydroxiproline / creatinin ratio and spinal bone mineral density (BMD) were statistically evaluated at the beginning and at the end of the treatment. In both group, serum alkali phosphatase, calcium and phosphorus, urinary calcium / creatinin and hydroxiproline / creatinin ratio changes before and after treatment have not showed statistically significant results. Although BMD was increasefl 7.1% in the calcitonin treatment group (p<0.05) and 4.9% in the etidronate group (p<0.05), the difference between groups was not statistically significant for BMD (p>0.05). Our study suggests that both etidronate and calcitonin increase BMD in postmenopausal osteoporosis. TUESDAY MAY 21, 1996CONTINUOUS AMINOBISFHOSPHONATE (PAMIDRONATE) TREATMENT OF OSTEOPOROSIS; MAINTAINED BENEFI...