UCSF

Studies have shown that hypertension is associated with abnormalities of calcium metabolism, and it may lead to increase the risk of fractures and osteoporosis. However, several recent clinical findings in the past decade revealed an inverse correlation between bone mineral density (BMD) and hypertension in large cohorts of old male subjects. In this report, we further investigated whether this positive correlation between bone loss and hypertension could be also observed in animal models of hypertension. The use of animal models (Spontaneously Hypertensive Rats, SHR) can lead us to a better understanding of the correlation without other confounding factors. We used high-resolution micro-computed tomography to investigate the BMD and bone structure differences in the tibial and vertebral regions of two-year-old male SHRs in comparison to those in normotensive rats (Wistar-Kyoto, WKY). Moreover, we also applied the finite element analysis (FEA) and the bone biomarker test to further examine whether there are significant differences between these two groups. Surprisingly, almost all bone quality indices of the tibial region showed significant statistical differences (p<0.01) between the SHR and the WKY. In the tibial metaphysis part, the SHR group showed significant increase in the bone fraction (BV/TV, 29.5%), bone number (Tb.N, 31.4%), connectivity density of bones (Conn.D, 138%), and decrease in the bone separation (Tb.Sp, -27.9%), cortical thickness (Ct.Th, -18.2%), cortical bone density (Ct.TMD, -1.9%), and structure model index (SMI, -21.6). In addition, the 2-dimensional histomorphometric scan on the tibial diaphysis region also showed that the bone quality is better in SHR than WKY rats. On the contrary, SHRs significantly lost concentrations of two bone formation markers (Vitamin D25H and P1NP), and had elevated S-CTX concentrations (a bone resorption marker) compared to WKYs. In this reports we revealed that even the loss of bone mass continued happening in old-male SHRs, through the changes of bone microarchitectures, the bone quality was getting better at the same time.