Dermatosis in magnesium-deficient hairless rats has been described as a reproducible model of skin inflammation. It was therefore felt of interest to search for the effects of various anti-inflammatory compounds on this model. Results showed that 1) Dexamethasone acetate completely abolished the rash, 2) Indomethacin, a Non-Steroidal Anti-Inflammatory Drug (NSAID), inhibitor of the cyclooxygenase pathway was quite inactive, 3) Benoxaprofen, a NSAID inhibitor of both cyclooxygenase and lipoxygenase pathways only slightly modified the development of the pathology. Activity of steroidal anti-inflammatory drugs on this model may be related to their immunosuppressive effects.

In order to study the action of tiludronate on the changes in intraosseous vascularization induced by ovariectomy, and to link these effects to those observed in bone remodelling, 30 female Sprague-Dawley rats (age 40 weeks) were studied. Ten rats were shamoperated and treated by vehicle, 10 rats were ovariectomized and treated by vehicle, and 10 rats were ovariectomized and treated orally with tiludronate, 0.16 mmol/kg/per day, 3 days a week for 16 weeks, from the day following ovariectomy. The rats were killed after 4 months, and a histomorphometric study and quantification of intraosseous vessels carried out on the sixth lumbar vertebra. The area of the intraosseous sinusoidal capillaries increased after ovariectomy, which also induced a moderate increase in resorption surfaces and osteoid surfaces leading to a decrease of 40% in the trabecular bone volume at the lumbar spine level. This bone mineral loss was completely prevented by tiludronate, which normalized the bone turnover. However, tiludronate was without any effect on intraosseous vascularization. These results indicate that the surface area of the intraosseous sinusoidal capillaries was correlated positively with resorption surfaces and negatively with trabecular bone volume and the number of bone trabeculae. In these experimental conditions, an inhibitor of bone resorption can exert its positive effect on bone mass without normalization of vascularization.

Hairless rats with dermatosis induced with a poor magnesium diet were previously shown to bear biochemical and immunological abnormalities. It was therefore felt of interest to investigate the spleen cells proliferative responses from these rats, both in the rash and the remission phases, when testosterone and parathormone plasma levels were also determined. Results showed that proliferative responses to mitogens and PTH levels were inversely related to the intensity of the dermatosis, whereas testosterone levels were more or less decreased. The role of 1.25 dihydroxyvitamin D3 in these modifications is questionable.

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...