Monitoring Bone Micro-architecture with a Special Focus on Bone Strength
Introduction. Osteoporosis is a chronic disease characterized by the loss of bone mass and the deterioration of bone micro-architecture leading to a subsequent increase in fracture risk. High-resolution peripheral quantitative computed tomography (HR-pQCT) provides non-invasive measures of bone micro-architecture and strength in live humans but its ability to monitor small skeletal changes is yet poorly understood. The objectives of this thesis were to 1) determine HR-pQCT precision for volumetric density, geometry, cortical and trabecular micro-architecture, as well as estimates of bone strength; 2) determine the monitoring time interval (MTI) and least significant change (LSC) metrics; and 3) to characterize annual changes in bone area, density, and micro-architecture at the distal radius and tibia using HR-pQCT in postmenopausal women. Methods. To determine precision error as well as monitoring and change metrics of the distal radius and tibia, 34 postmenopausal women (mean age 74, SD±7 years) from the Saskatoon cohort of the Canadian Multicentre Osteoporosis Study (CaMos) were measured using HR-pQCT. To characterize the annual change in bone outcomes of this same cohort, 51 women (mean age±SD: 77±7 years) were measuring at baseline and again 1 year later. Precision errors were calculated as coefficient of variation (CV% and CV%RMS). The LSC was determined from precision errors and then divided by the median annual percent changes to define MTIs for bone area, density, and micro-architecture. Repeated measures analysis of variance (ANOVA) with Bonferroni adjustment for multiple comparisons were used to characterize the mean annual change in total density, cortical perimeter, trabecular and cortical bone area, density, content, and micro-architecture. Significant changes were accepted at P<0.05. Results and Discussion. HR-pQCT precision errors were <10% for bone densitometric, geometric, and mechanical properties; while precision errors were <16% for cortical and trabecular micro-architectural outcomes. Further, the use of either automatic or modified contour methods for the dual-threshold technique for cortical micro-architectural analysis provided similar precision. Densitometric and geometric outcomes had longer monitoring times (>3 years), while micro-architecture had monitoring times of ~2 years. The observed annual changes were statistically significant for several outcomes; however, only cortical and trabecular area, as well as cortical density at the distal tibia changed beyond the LSC. Overall, thesis findings will assist design and interpretation of prospective HR-pQCT studies in postmenopausal women.
DegreeDoctor of Philosophy (Ph.D.)
SupervisorKontulainen, Saija A.
CommitteeJohnston, James D.; Lanovaz, Joel L.; Cooper, Dave M.
Copyright DateAugust 2015
Monitoring Bone Changes, Bone Micro-architecture, Bone Strength, Precision