OBJECTIVE: The objective of this study was to prospectively investigate the effect of pregnancy on biochemical markers of bone turnover in healthy pregnant women. METHODS: During the course of our longitudinal study, biochemical markers of bone remodeling were measured in all three trimester of pregnancy (first trimester: 12.5+/-1.8 SD, second trimester: 21.6+/-1 SD, third trimester: 34.8+/-1.6 SD weeks of gestation). Serum type I collagen C-telopeptides (CTX) and a crosslinked peptide of the carboxy-terminal telopeptide of type I collagen (ICTP) were used as markers of bone resorption. Bone alkaline phosphatase (BAP) and the N-terminal propeptides of type I collagen (PINP) were used as biochemical markers of bone formation. Blood samples for the analysis of all 4 biochemical markers according to each trimester of pregnancy were available in 49 patients. RESULTS: The main changes for all biochemical markers were seen between the second and the third trimester. According to the markers of bone resorption, both serum CTX and ICTP showed a significant increase from the first to the third and from the second to the third trimester (p<0.001; median percentage change: CTX=101.5% and ICTP=40%). Concerning markers of bone formation, PINP showed a significant decrease from the first to the second trimester (p=0.001) followed by a significant increase from the second to the third trimester (p<0.001, 63.8%) and an overall increase from the first to the third trimester (p<0.001). BAP also showed a significant increase from the second to the third trimester (p<0.001; 51.7%) and an overall increase from the first to the third trimester (p<0.001). CONCLUSION: Markers of bone resorption were significantly increased during pregnancy. In contrast to bone resorption, markers of bone formation showed an increase as well as a decrease during pregnancy indicating a state of high bone turnover. This might coincide with the change in bone mineral density that was observed in some, but not all, studies using "dual-energy x-ray absorptiometry" (DXA) as well as "quantitative ultrasonometry" (QUS).