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In addition to a good efficacy to lower blood glucose without hypoglycemia, thiazolidinediones(TZDs) have been proved to have the effects to increase plasma adiponectin, and actually decrease the cardiovascular events in several randomized clinical trials, while some adverse effects have also been demonstrated such as increase of heart failure and born fracture, and fear of bladder cancer. Since TZDs could intervene the pathogenesis of adipocytes' hypertrophy and inflammation in adipose tissue, atherosclerotic lesions and liver by modulating PPARγ of adipocytes and macrophages, TZDs are still considered at the special position among other diabetic drugs, and require further evidence for their efficacy and safety.

Effects of vitamin K(2) (menatetrenone) and alendronate on bone mineral content and bone mechanical property in rats fed a low-magnesium diet. Recent clinical studies have shown that the occurrence of new fractures does not always depend on bone mineral density. Therefore bone quality has become an important issue in osteoporosis research. No animal model for evaluating bone quality has been established. In this study, we found that the treatment of rats with a low-magnesium (Mg) diet reduced their bone strength without decreasing bone mineral content (BMC), so the low Mg diet model is considered to be a good model for examining bone quality. Using this model, we investigated the effects of vitamin K(2) (V.K(2)) and alendronate (ALN). V.K(2) increased maximum load and elastic modulus without influencing BMC. ALN increased maximum load with increasing BMC. By using Fourier transform infrared microscopic analysis, the low-Mg diet treatment increased the mineral/matrix ratio of bones, and V.K(2) suppressed the increase in this ratio. These findings suggest that the mineral/matrix ratio may be a factor involved in bone quality, and that V.K(2) may improve bone quality.

Two experiments were carried out using 7-week-old male Wistar rats. Exp. 1: Rats in the intact group were fed with normal diet (0.5% Ca, 0.09% Mg). Ca/Mg deficient rats were fed low Ca (0.01%) diets containing 0.003, 0.015 or 0.09% Mg for 4 weeks. After 4 weeks, the bone mineral density (BMD) and maximum load in the femur were decreased in Ca/Mg deficient rats, but this was not dependent on dietary Mg concentration. The elasticity, stiffness, and Mg concentration in the femur of these rats were also decreased and Ca deposition in the kidney were increased, compared to those of normal rats, which were related to Mg concentration in the diet. From these results, Mg may play an important role in qualitative changes in bone (i.e., reduced stiffness). Exp. 2: We investigated the effects of V.K2 on the changes in BMD and bone strength in femur induced by low Ca/Mg (0.01%/0.003%) diet for 8 weeks. Compared to the intact group, Ca and Mg levels in serum and femur and cortical thickness, cortical area, and maximum load of the femoral midshaft were decreased in the Ca/Mg-deficient group. In these rats, PTH in the serum and renal Ca concentration were increased. In V.K2-treated rats, these changes in the serum Ca, Mg and PTH levels and the renal Ca concentration were improved. V.K2 also improved the decrease in maximum load in spite of no influence on the cortical thickness, cortical area and Mg concentration in the femur. These findings suggest that V.K2 may affect the qualitative change in bone.