Skeletal site-related differences in trabecular bone composition have been studied in autopsy samples from 63 individuals (age range 23-92 years). From each individual, bone samples were excised from the iliac crest, lumbar spine, femoral neck, and calcaneus. Samples were analyzed for their-content of ash, calcium, collagen, extractable proteins, osteocalcin, and IGF-I. Significant differences were found between the skeletal sites, the lumbar spine being the least mineralized site and the femur the most. The femur and lumbar spine had a higher osteocalcin and IGF-I content compared with the other skeletal sites, suggesting a higher bone turnover rate. The intercorrelations between the anatomical sites were low for minerals and collagen but high for osteocalcin and IGF-I. The latter might indicate that the presence of these proteins in the bone matrix is mainly controlled by endocrine mechanisms which may influence the osteoblast function. Finally, regression analysis showed a significant age-related decrease of skeletal IGF-I at all sites examined. This finding supports the hypothesis of an IGF-I-mediated pathogenesis of senile osteoporosis. In summary, our data imply that a global assessment of skeletal function and bone quality, based upon analyses at one anatomical site, should be applied with caution.