We recently established that the dependence of bone mineral density (BMD) on body weight in women is mainly attributable to a close relationship between total body fat mass and BMD. The present study assesses whether this latter relationship might be contributed to by the hormones insulin or amylin, both of which may influence fat mass and calcium metabolism. Fifty-three normal postmenopausal women underwent a 75-g glucose tolerance test with measurement of plasma insulin and amylin concentrations every 30 min for 2 h. Body composition and BMD/height (to provide a quantity with the dimensions of volumetric density that is independent of body size) were measured by dual-energy X-ray absorptiometry, and volumetric density of the third lumbar vertebral body was calculated. Circulating insulin concentrations correlated with BMD/height and volumetric density of the third lumbar vertebral body (r = 0.28-0.52). They also were related to body weight (r = 0.34-0.56) and fat mass (r = 0.38-0.56) but were not independently related to lean mass on multiple regression. There were no consistent relationships between amylin levels and these variables. Multiple-regression analyses with fat mass and insulin levels as independent variables indicated that BMD/height of total body and femoral trochanter were primarily related to fat mass, whereas, in femoral neck, the significant relationship was with insulin. Volumetric density of the third lumbar vertebral body was related to insulin levels alone on this analysis.(ABSTRACT TRUNCATED AT 250 WORDS)