Abstract
Summary: Macro- and microarchitectural, bone material property, dynamic histomorphometric, and bone turnover marker data were studied in normal bone mineral density (BMD) post-menopausal women with fragility fracture. Women with fracture had thinner iliac cortices and more homogeneous bone material properties in cortical bone than age/BMD-matched non-fracture women. Low cortical thickness and bone tissue heterogeneity in normal BMD women are associated with prevalent fragility fracture. Introduction: Bone mass (bone mineral density, (BMD)) of the spine and hip is today’s best single measurement for evaluating future fragility fracture risk. However, the majority of fragility fractures occur in women with BMD T-score above the WHO osteoporotic BMD threshold of − 2.5, indicating that non-BMD endpoints may play a role in their fragility fractures. We hypothesize that in non-osteoporotic women, bone micoarchitecture, bone material properties, dynamic histomorphometric endpoints, and bone turnover markers are related to fragility fracture. Methods: Two groups (N = 60 each) of post-menopausal women with total hip BMD T-score ranging from + 0.3 to –2.49 were recruited: fragility fracture and age/BMD-matched, non-fragility fracture women. Normal (T-score > − 0.99) and osteopenic (T-score ≤ − 1.0) BMD cohorts were designated within both the fracture and non-fracture groups. Transiliac biopsy specimens were obtained to evaluate dynamic histomorphometric and microarchitectural endpoints and bone material properties by static and dynamic nanoindentation testing. All variables for fracture and non-fracture women within each BMD cohort were compared by the Wilcoxon signed-rank test (P < 0.01). Results: Compared to non-fracture/normal BMD women, fracture/normal BMD women display lower iliac cortical thickness (− 12%, P = 0.0041) and lower heterogeneity of hardness (− 27%, P = 0.0068), elastic modulus (− 35%, P = 0.0009), and storage modulus (− 23%, P = 0.0054) in the cortical bone tissue, and lower heterogeneity of hardness (− 13%, P = 0.0088) in the trabecular bone tissue. Osteopenic women had no abnormalities related to fracture status. Conclusion: Post-menopausal women with normal BMD and fragility fracture have low cortical thickness and heterogeneity of several bone material properties in cortical and trabecular mineralized bone tissue. These differences may explain a portion of the excess bone fragility in women with normal BMD and fragility fracture.