The effects of metformin and alendronate in attenuating bone loss and improving glucose metabolism in diabetes mellitus mice.

BACKGROUND: To explore the anti-osteoporosis and anti-diabetes effects and potential underlying mechanisms of treatment with metformin and alendronate in diabetes mellitus mice. METHODS: Eight-week-old C57 BL/KS db/db and db/+ female mice were evaluated according to the following treatment group for 12 weeks: control group, diabetes mellitus group, diabetes mellitus with metformin group, diabetes mellitus with Alendronate group, diabetes mellitus with metformin plus alendronate group. Glucose level, glucose tolerance test, bone mineral density, bone microarchitecture, bone histomorphometry, serum biomarkers, and qPCR analysis. RESULTS: Combined metformin and alendronate can improve progression in glucose metabolism and bone metabolism, including blood glucose levels, blood glucose levels after 4 and 16 hours fasting, glucose tolerance test results, insulin sensitivity and reduces bone loss than the diabetes group. The use of alendronate alone can increase significantly serum glucagon-like peptide-1 levels than the diabetes group. The use of metformin alone can improve bone microstructure such as Tb.Sp and Tb.N of spine in diabetic mice. CONCLUSION: The combined use of alendronate and metformin has an anti-diabetes and anti-osteoporotic effect compared with diabetic mice, but they appear to act no obvious synergistically between alendronate and metformin.

Discordance in diagnosis of osteoporosis by quantitative computed tomography and dual-energy X-ray absorptiometry in Chinese elderly men.

OBJECTIVE: The objective of this study was to investigate the diagnostic discordance of osteoporosis by quantitative computed tomography (QCT) and dual-energy X-ray absorptiometry (DXA) in Chinese elderly men. METHODS: A total of 313 males older than 60 years, who underwent both spinal QCT and lumbar spine and hip DXA in our department, were included. The diagnostic criteria established by the World Health Organisation in 1994 were used for DXA to diagnose osteoporosis, and the criteria recommended by the International Society of Clinical Densitometry were used for QCT. The osteoporosis detection rate by the two techniques was calculated, and the difference was compared. The minor discordance was considered present when the different diagnostic classes between the two techniques were adjacent. Major discordance was present when the diagnosis by one technique was osteoporosis and the other was normal. The computed tomography images were reviewed by radiologists to assess whether vertebral fracture, aorta calcification or degeneration was present. RESULTS: In the 313 participants (mean age, 79.6 ± 7.2 years), the osteoporosis detection rate was 10.9% for DXA (lumbar spine and hip) and 45.1% for QCT, a significant difference (p < 0.001). The major discordance, minor discordance and concordance of diagnosis between the two techniques were seen in 8.3%, 50.8% and 40.9%, respectively. QCT detected osteoporosis better than DXA. The causes of this discordance were degeneration of spine, abdominal aorta calcification and vertebral fractures. CONCLUSION: Our study demonstrated that discordance was common when using QCT and DXA to diagnose osteoporosis and that spinal degeneration, aorta calcification and fracture obscure the bone mineral density measurement of spine by DXA. QCT is a more sensitive method of choice to identify osteoporosis in elderly Chinese men. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: This study investigated the diagnostic discordance of osteoporosis by quantitative computed tomography (QCT) and dual-energy X-ray absorptiometry (DXA) in Chinese elderly men. The results demonstrated that QCT is a more sensitive method of choice to identify osteoporosis in elderly Chinese men. This work may help clinicians make an appropriate choice of technique for the accurate diagnosis of osteoporosis and identify the patients at high risk of osteoporosis who should be treated early to prevent fractures. This may influence the therapeutic plan and the overall prognosis of patients.

The hemodynamic effect of the support mode for the intra-aorta pump on the cardiovascular system.

Intra-aorta pump is a novel rotary ventricular assist device. Because of the special structure and connection with the native heart, the hemodynamic effect of support mode of this pump on the cardiovascular system is not clear. In this work, three support modes, including "constant speed" mode, "co-pulse" mode, and "counter-pulse" mode, have been designed for the intra-aorta pump to evaluate the hemodynamic effect of different support modes on the cardiovascular system. Simulation results demonstrate that that both "co-pulse" mode and "counter-pulse" mode can achieve better unloading performance than "constant speed" mode. The intra-aorta pump controlled by "co-pulse" mode is beneficial for improving coronary flow. Moreover, the external work, which is defined as the product of left ventricular pressure and cardiac output, under "co-pulse" mode is the minimum of the three support modes (0.783 w vs. 0.615 w vs. 0.702 w). The pulsatility ratio, defined as the ratio of the peak-to-peak value of arterial pressure (AP) to the mean arterial pressure value, under "co-pulse" mode is the maximum of the three modes (24% vs. 32.8% vs. 23.7%). The equivalent afterload value, which is the ratio of pulsatile pressure at the pump inflow and pulsatile pump flow, is larger than other support modes (0.596 mm Hg.s/mL vs. 0.9704 mm Hg.s/mL vs. 0.55 mm Hg.s/mL). In brief, the intra-aorta pump under "co-pulse" mode support is beneficial for improving myocardial perfusion and restoring pulsatility of AP, while "counter-pulse" mode is beneficial to the perfusion of vital organs.

Hemodynamic simulation study of a novel intra-aorta left ventricular assist device.

The intra-aorta pump proposed here is a novel left ventricular assist device (LVAD). The mathematic model and the in vitro experiment demonstrate that the pump can satisfy the demand of human blood perfusion. However, the implantation of LVAD will change the fluid distribution or even generate a far-reaching influence on the aorta. At present, the characteristics of endaortic hemodynamics under the support of intra-aorta pump are still unclear. In this article, a computational fluid dynamics study based on a finite-element method was performed for the aorta under the support of intra-aorta pump. To explore the hemodynamic influence of intra-aorta pump on aorta, fully coupled fluid-solid interaction simulation was used in this study. From the flow profiles, we observed that the maximum disturbed flow and nonuniform flow existed within the aortic arch and the branches of the aortic arch. Flow waveforms at the inlets of aortas were derived from the lumped parameter model that we proposed in our previous study. The results demonstrated that the intra-aorta pump increased the blood flow in the aorta to normal physiologic conditions, but decreased the pulsatility of the flow and pressure. The pulsatility index changed from 2,540 to 1,370. The pressure gradient (PG) for heart failure conditions was 18.88 mm Hg/m vs. 25.51 mm Hg/m for normal physiologic conditions; for intra-aorta pump assist conditions, normal PG value could not be regained. Furthermore, our experimental results showed that the wall shear stress (WSS) of aorta under heart failure and normal physiologic conditions were 1.5 and 6.3 dynes/cm, respectively. The intra-aorta pump increased the WSS value from 1.5 to 4.1 dynes/cm.