The purpose of this study was to determine which longitudinal analysis technique (no registration (NR), slice-match (SM) registration, or three-dimensional registration (3DR)) produced the most realistic longitudinal changes in a 3-year study of bone density and structure using high-resolution peripheral quantitative computed tomography (HR-pQCT). We assessed HR-pQCT scans of the distal radius and tibia for men and women (N = 40) aged 55-70years at baseline and 6, 12, 24, and 36months. To evaluate which longitudinal analysis technique (NR, SM, or 3DR) best captured physiologically reasonable 3-year changes, we calculated the standard deviation of the absolute rate of change in each bone parameter. The data were compared between longitudinal analysis techniques using repeated measures ANOVA and post hoc analysis. As expected, both SM and 3DR better captured physiological longitudinal changes than NR. At the tibia, there were no differences between SM and 3DR; however, at the radius where precision was lower, 3DR produced better results for total bone mineral density. At least SM or 3DR should be implemented in longitudinal studies using HR-pQCT. 3DR is preferable, particularly at the radius, to ensure that physiological changes in bone density are observed.
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