Abstract
Although osteoporosis reduces overall bone mass causing bone fragility, our recent studies have shown that bone tissue composition is altered at the microscopic level, which is undetectable by conventional diagnostic techniques (DEXA) but may contribute to bone fracture. However, the time sequence of changes in bone microarchitecture, mechanical environment and mineral distribution are not yet fully understood. This study quantified the longitudinal effects of estrogen deficiency on the trabecular microarchitecture and mineral distribution in the tibia of Female Wistar rats (6 months) that underwent ovariectomy (OVX, n=10) or sham surgery (SHAM, n=10). Weekly micro-CT scans of the proximal tibia were conducted at 15µm resolution for the first month of estrogen deficiency. Morphometric analysis was conducted to characterise the trabecular bone microarchitecture. The bone mineral composition was characterised with analysis of bone mineral density distributions (BMDD). There was significantly reduced trabecular bone volume fraction at 2 weeks in OVX rats compared to controls (p<0.01). There was no difference in mineral distribution between the OVX and control animals. This study provides the first evidence in uncovering the temporal nature of changes in bone microarchitecture and mineral distribution, showing that structure changes before composition. In-vivo µCT analysis for later time points (week 8, 14 and 34) is ongoing to comprehensively examine these longitudinal compositional changes. Moreover, we are conducting ex-vivo mechanical analysis (nanoindentation), and together these will uncover the time-sequence and respective contribution of changes in bone mass and composition to the integrity of the bone tissue at these stages of estrogen deficiency.
