We developed a computerized semiautomatic method allowing accurate measurement of bone remodeling activity of the cortico-endosteal envelope of iliac crest biopsies. Measurement of bone turnover of the cortico-endosteal and of the trabecular envelopes were performed in 33 untreated women with postmenopausal vertebral osteoporosis and in 8 age-matched normal women. In normal women, bone remodeling was not different in the trabecular and the cortico-endosteal envelopes. In contrast, osteoporotic women had a marked, significant increase of bone formation and resorption at the cortico-endosteal envelope when compared to trabecular bone. Despite this difference, bone turnover activities of both envelopes were related, as indicated by significant correlations for most parameters between both envelopes. Serum bone gla-protein, previously reported to reflect trabecular bone formation, was also highly correlated with static and dynamic assessment of bone formation of the cortico-endosteal envelope of osteoporotic women but did not reflect bone resorption. When trabecular and endosteal measurements were pooled, correlations between serum bone gla-protein and bone formation were similar or even improved. In conclusion, our data suggest that patients with postmenopausal osteoporosis have active bone turnover at the cortico-endosteal envelope which may contribute significantly to bone loss in this disease. Because the different bone envelopes react differently to various therapeutic regimens, bone turnover of the cortico-endosteal envelope should be considered when assessing the effect of new treatments.