Controversy persists regarding the abnormality of bone turnover responsible for bone loss in women with postmenopausal osteoporosis. To evaluate this, we measured serum bone Gla-protein (BGP), a specific marker for bone turnover, in 62 untreated patients with postmenopausal osteoporosis. Results were compared with those in 142 normal women and were expressed as standard deviations from the age-adjusted predicted mean (Z score). Serum BGP was increased (+0.48 S.D., p = 0.002) in the osteoporotic patients; 9.7% of patients were greater than 2 S.D. above but none were greater than 2 S.D. below the normal mean. Moreover, when data from normal postmenopausal women (ages 51 to 75 years) and the osteoporotic patients were merged, significant negative correlation existed (r = -0.36, p less than 0.001) between serum BGP and bone density of the lumbar spine assessed by dual photon absorptiometry. Serum alkaline phosphatase, a less specific marker for bone formation, was also increased (+0.96 S.D., p less than 0.001) in the osteoporotic patients. The data suggest that overall bone turnover is increased in patients with postmenopausal osteoporosis and do not support the concept that an absolute decrease in bone formation is the major cause of the bone loss.