Background: Bone loss and increased bone turnover are reported in patients taking antiepileptic drugs (AEDs), especially enzyme- inducing AEDs including carbamazepine (CBZ). We sought to determine whether postmenopausal women on long-term treatment with CBZ-monotherapy are at a higher risk of osteoporosis than individually matched controls.Subjects and methods: Thirteen postmenopausal women with epilepsy on CBZ monotherapy for at least four years and 13 age-matched control subjects consisting of the patients close female friends were studied. Blood samples were drawn and serum was analyzed for indices of changes in bone metabolism including calcium, phosphate, vitamin D (25OHD), parathyroid hormone (PTH) and FT4. In addition, bone formation markers including alkaline phosphatase (ALP), bone-specific alkaline phosphatase (BAP) and osteocalcin, and CrossLaps (CTX-1) as a marker for bone resorption were analyzed. Bone mineral density was measured in lumbar spine, femoral neck, proximal and distal forearm and total body bone mineral density by dual-energy x-ray absorptiometry. Bone mineral content and density was determined as T- and Z-scores in each region. Results: The main finding in the study is increased frequency of osteoporosis in the CBZ group compared with the control group. Among patients on CBZ, 10 had T-scores below -2.5 SD in one or more region (77%), demonstrating osteoporosis and 2 had T-scores between -1 and -2.5 SD (15%) demonstrating osteopenia. In the control group, the figures were 6 (46%) and 3 (23%), respectively. Reduced BMD in the patients was most obvious for proximal forearm and femoral neck compared with the controls (p< 0.046). The difference in Z-score for femoral neck was also significant (p<0.038). Significantly increased ALP and BAP levels (p<0.005 and p<0.009) were seen in the patients. There was also an increase in Osteocalcin and Crosslaps, but the differences were not statistically significant. On the other hand, there was a significant reduction in vitamin D, p=0.038. Conclusion: Long-term CBZ monotherapy increase bone turnover by increasing the activity of both bone formation and degradation markers, leading to decreased BMD and osteoporosis. The negative effect on bone is strengthened by a decrease in vitamin D after CBZ treatment.