Individual trabecula segmentation (ITS)-based morphological analyses and microfinite element analysis of HR-pQCT images discriminate postmenopausal fragility fractures independent of DXA measurements

Abstract

Osteoporosis is typically diagnosed by dual energy x-ray absorptiometry (DXA) measurements of areal bone mineral density (aBMD). Emerging technologies, such as high-resolution peripheral quantitative computed tomography (HR-pQCT), may increase the diagnostic accuracy of DXA and enhance our mechanistic understanding of decreased bone strength in osteoporosis. Women with (n=68) and without (n=101) a history of postmenopausal fragility fracture had aBMD measured by DXA, trabecular plate and rod microarchitecture measured by HR-pQCT image-based individual trabeculae segmentation (ITS) analysis, and whole bone and trabecular bone stiffness by micro finite element analysis (μFEA) of HR-pQCT images at the radius and tibia. DXA T-scores were similar in women with and without fractures at the spine, hip and 1/3 radius, but lower in fracture subjects at the ultradistal radius. Trabecular microarchitecture of fracture subjects was characterized by preferential reductions in trabecular plate bone volume, number, and connectivity over rod trabecular parameters, loss of axially aligned trabeculae, and a more rod-like trabecular network. In addition, decreased thickness and size of trabecular plates were observed at the tibia. The differences between groups were greater at the radius than the tibia for plate number, rod bone volume fraction and number and plate-rod and rod-rod junction densities. Most differences between groups remained after adjustment for T-score by DXA. At a fixed bone volume fraction, trabecular plate volume, number and connectivity were directly associated with bone stiffness. In contrast, rod volume, number and connectivity were inversely associated with bone stiffness. In summary, HR-pQCT-based ITS and μFEA measurements discriminate fracture status in postmenopausal women independent of DXA measurements. Moreover, these results suggest that preferential loss of plate-like trabeculae contribute to lower trabecular bone and whole bone stiffness in women with fractures. We conclude that HR-pQCT-based ITS and μFEA measurements increase our understanding of the microstructural pathogenesis of fragility fracture in postmenopausal women.

Premenopausal Women with a Distal Radial Fracture Have Deteriorated Trabecular Bone Density and Morphology Compared with Controls without a Fracture

“…The relationship between bone microarchitecture and fractures in postmenopausal women and older men has been studied previously 14,19,21 . The results have indicated that postmenopausal women with a history of fragility fractures have lower total and trabecular bone density, trabecular thickness, and trabecular number after adjusting for hip bone mineral density.…”

“…Studies utilizing this technology have demonstrated worse trabecular and cortical bone microarchitecture in postmenopausal women and older men with a history of fragility fractures [13][14][15][16][17][18][19][20][21] . In some instances, differences in bone microarchitecture remained after fracture, even after adjusting for lower bone mineral density 14,17,22 .…”

Trabecular Plate Loss and Deteriorating Elastic Modulus of Femoral Trabecular Bone in Intertrochanteric Hip Fractures

“…As suggested by previous studies, there is a significant change from plate-like to rod-like trabeculae in aging and osteoporosis (12,16). However, quantification of the amount of trabecular plates or rods was limited.…”

“…Furthermore, femoral neck trabecular bone biopsies from fracture patients showed lower modulus and ultimate stress as measured by mechanical testing experiments (10). A more recent study examined the microstructural differences in femoral neck trabecular bone between hip fracture patients and controls, and confirmed significant decrease in bone volume fraction and a transition from plate-like to rod-like trabeculae in hip fracture patients (12). However, microstructural and biomechanical changes associated with intertrochanteric fractures have not been studied, and cannot be derived from the previous femoral neck studies due to heterogeneous trabecular bone distribution in the proximal femur (13)(14).…”

“…Also, ITS analysis has revealed the key differences between Caucasian American and Chinese American skeleton, demonstrating that higher plate/rod ratio accounted for reduced fracture risk in Chinese Americans in spite of similar aBMD (20). In addition, ITS and micro finite element (µFE) analyses were able to distinguish postmenopausal women with and without fragility fractures independent of aBMD (12).…”