Skeletal effects of amylin and related peptides

Amylin and adrenomedullin are related peptides with some homology to both c alcitonin and calcitonin gene related peptide. Both amylin and adrenomedull in recently have been found to stimulate the proliferation of osteoblasts i n vitro and to increase indices of bone formation when administered either locally or systemically in vivo. Amylin also has been found to act on chond rocytes, stimulating their proliferation in culture and increasing tibial g rowth plate width and tibial length when administered systemically to adult mice. Systemic administration of amylin also is associated with increased fat mass, consistent with its known effects on fuel metabolism. However, we recently have established that the osteotropic effects of amylin are retai ned in an octapeptide fragment of the molecule, which has no activity on ca rbohydrate metabolism. Thus, this small peptide, or analogues of it, are po tential candidates as anabolic therapies for osteoporosis. Similar fragment s of adrenomedullin, which retain activity on bone but lack the parent pept ide's vasodilator properties, also are being defined. In addition to a pote ntial therapeutic role, these peptides may play a part in normal bone physi ology. Amylin is secreted after eating and may direct calcium and protein a bsorbed from the meal into new bone synthesis. Amylin circulates in high co ncentrations in obese individuals and might contribute to the association b etween bone mass and fat mass. Finally, adrenomedullin and its receptor are easily detectable during rodent embryogenesis, suggesting that these pepti des also might act as autocrine or paracrine regulators of bone growth. Fur ther research is necessary to confirm these interesting possibilities.