The cellular mechanisms for bone loss in type I (postmenopausal) osteoporosis are highly controversial. We attempted to resolve this by assessing rates of formation and resorption of iliac cancellous bone by a new histomorphometric method in 89 women with osteoporosis (mean age + SD, 66 + 6 years) and in 32 carefully selected normal postmenopausal women (64 + 6 years). In the osteoporotic women, bone resorption rate was increased by 39% (P <0.05) at the cellular level and by 67% (P <0.05) at the tissue level, whereas bone formation was unchanged at the tissue level but decreased by 14% (P <0.01) at the cellular (osteoblast) level. This pronounced remodeling imbalance (P <0.001) was probably exacerbated by a 45% increase (P < 0.1) in activation frequency of new remodeling foci. These abnormalities were associated with a high rate of cancellous bone loss (median, 5.8%/year versus 0.1%/year in controls). Thus, accelerated loss of cancellous bone in type I osteoporosis results from the combination of increased bone resorption and inadequate compensation by bone formation.