It is well established that chronic excess of glucocorticoids has negative effects on bone and collagen turnover, and that secondary osteoporosis is a known clinical complication of endogenous Cushing's syndrome (CS). The aim of the present study was to evaluate bone dimension and bone mineral content in relation to biochemical markers of bone and collagen turnover, in a consecutive series of 23 patients with endogenous CS (18 with pituitary adenoma and 5 with adrenal tumor; 17 women, 6 men; mean age 39.7+/-2.8 (S.E. M.) and 44.3+/-3.1 years respectively), compared with 23 age-, sex- and body mass index-matched healthy controls. Bone mineral densities were uniformly reduced in the different regions analyzed: lumbar spine (16.1%, P<0.001), femoral neck (15.2%, P<0.001), total body (11.5%, P<0.001), and the subregions of arms (8.4%, P<0.05), legs (10.1%, P<0.05) and trunk (15.8%, P<0.001). Similar results were observed for bone mineral content, although these were less prominent. The calculated area was significantly decreased in trunk (13.8%, P<0.01) and total body (11.6%, P<0.05). Serum levels of osteocalcin were significantly decreased (28%, P<0.03) in patients with CS. No significant differences were observed for the formative markers carboxyterminal propeptide of type I procollagen and aminoterminal propeptide of type I procollagen. Markers of bone resorption, serum Crosslaps and carboxyterminal cross-linked telopeptide of type I collagen were increased in patients compared with controls, although only significantly for Crosslaps (P<0.02). No correlations between formative and resorptive markers were found in the patients, but in controls, the formative markers were positively correlated with resorptive markers. In conclusion, bone dimension and bone mineral content of the entire skeleton are found to be decreased in endogenous CS. As judged by biochemical markers of bone remodeling, this is caused by decreased bone formation and an increased bone resorption.