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.