Systemic administration of a novel octapeptide, amylin-(1-8), increases bone volume in male mice

Amylin increases bone mass when administered systemically to mice. However, because of its size, the full peptide is not an ideal candidate for the th erapy of osteoporosis. The fragment, amylin-(1-8), stimulates osteoblast pr oliferation in vitro, although it is without effect on carbohydrate metabol ism. The present study assessed the effects of daily administration of this peptide on sexually mature male mice for 4 wk. Amylin-(1-8) almost doubled histomorphometric indices of osteoblast activity but did not change measur es of bone resorption. Trabecular bone volume increased by 36% as a result of increases in both trabecular number and trabecular thickness, and tibial cortical width increased by 8%. On three-point bending tests of bone stren gth, displacement to fracture was increased by amylin( 1-8), from 0.302 +/- 0.013 to 0.351 +/- 0.017 mm (P +/- 0.02). In a separate experiment using d ynamic histomorphometry with bone-seeking fluorochrome labels, amylin-(1-8) was administered by local injection over the calvariae of female mice. Amy lin-(1-8) (40 nM) increased the double-labeled surface threefold. The effec t was dose dependent from 0.4 to 40 nM and was greater than that of an equi molar dose of human parathyroid hormone-(1-34) [hPTH-(1-34)]. Mineral appos ition rate was increased by 40 nM amylin-(1-8) but not by hPTH-(1-34). Amyl in-(1-8) thus has significant anabolic effects in vivo, suggesting that thi s peptide or analogs of it should be further evaluated as potential therapi es for osteoporosis.