AMYLIN INCREASES BONE VOLUME BUT CANNOT AMELIORATE DIABETIC OSTEOPENIA

Amylin normally secreted in a regulated fashion by the pancreatic beta-cells in parallel with insulin and has been reported to have bone-conserving properties. Type I diabetes mellitus results in a low-turnover osteopenia in the presence of decreased amylin, which is in contrast to type II diabetes where less bone loss, in the presence of high amylin levels, occurs. We investigated the effects of amylin on bone mineral metabolism in normal and diabetic (streptozotocin-induced) rats, in order to ascertain whether amylin would modify the streptozotocin-induced diabetic osteopenia. Ten-week-old male Sprague-Dawley rats were randomized as follows: group A (n = 18) received normal saline; group B (n = 18) received amylin; group C, diabetic rats (n = 23), received normal saline; and group D, diabetic rats (n = 23), received amylin. Amylin (100 pmol/100 g b.w.) was administered by a daily subcutaneous injection. Double calcein-labeled tibiae were removed for histomorphometric analysis followed sacrifice on day 19. Results showed no difference in blood ionized calcium between groups. Blood glucose remained above 600 mg/dl in the diabetic animals and was not affected by the administration of amylin. Serum osteocalcin, insulin-like growth factor-1 (IGF-1), parathyroid hormone (PTH), and 1,25 dihydroxyvitamin D [1,25(OH)(2)D] were significantly lower in the diabetic rats compared with control group A by day 19. Amylin produced higher levels of serum osteocalcin in group B on day 9 (P < 0.05) compared with controls but returned to control values (group A) by day 19; no such change occurred in the diabetic group. Amylin administration did not influence IGF-1, 1,25(OH)(2)D or PTH levels compared with the untreated animals. Analysis of the bone histomorphometry showed a low-turnover osteopenia in the diabetic animals. Amylin administration resulted in a significant increase in bone volume in the normal rats, group B (P < 0.05), but was unable to significantly alter this parameter in the diabetic animals. In conclusion, amylin has a beneficial effect on the bone metabolism of the rat in vivo by increasing bone volume. It is, however, unable to overcome the osteopenia caused by streptozotocin-induced diabetes mellitus at the doses used in this study.