Purpose: Osteopenia and skeletal fragility are considered to be the complications associated with type 2 diabetes mellitus (T2DM). The relationship between glucose metabolism, skeletal quality, and vitamin D have not been completely understood. We aimed to demonstrate a comprehensive bone quality profile in a T2DM model subject and to investigate whether 1, 25-dihydroxy vitamin D3 could prevent osteopenia and skeletal fragility in the diabetes model rats. Methods: Daily calcitriol (a 1, 25-dihydroxy vitamin D3 formulation, 0.045 μg/kg/day) treatment was administered to 21-week-old male Goto-Kakizaki (GK) rats (a genetic non-obese and non-insulin-dependent spontaneous diabetes rat model) for 20 weeks and the results were compared with those in untreated GK rats, and wild-type animals. Results: Micro-computed tomography, histomorphometry, and bone mineral density analysis demonstrated that T2DM induced significant osteopenia, and impairment of bone microarchitecture and biomechanical properties in GK rats. T2DM also significantly decreased bone formation and increased bone resorption parameters in three regions of the skeleton (proximal tibia, mid-shaft of the tibia, and lumbar vertebrae), and increased carboxy-terminal type I collagen crosslinks, tartrate-resistant acid phosphatase, muscle ubiquitin C, and bone thioredoxin interacting protein (TXNIP) expression. Calcitriol treatment significantly alleviated bone loss, and improved bone microarchitecture and biomechanical properties and also decreased serum glucose and glycated serum protein levels. Biomarkers of bone formation were significantly increased, while muscle ubiquitin C and bone TXNIP expression were significantly decreased following calcitriol treatment. Conclusions: These results suggest that 1,25-dihydroxy vitamin D3 treatment effectively attenuates osteopenia, and improves bone and muscle quality in GK type 2 diabetes model rats.
Background/Aims: In this study we assessed histomorphometric changes induced by thyroxine (T4) in 3-month-old hyperthyroid male rats and examined whether the potential mechanism of these changes is related to bone changes. Methods: Rats were classified as either hyperthyroid following administration of 250 µg/kg/day freshly prepared T4 by gavage for 2 months or euthyroid following administration of vehicle alone (n = 8 per group). We measured bone mineral density (BMD), bone biomechanical properties, and bone histomorphometric changes. Levels of serum indicators were also measured, and three right femurs from the two groups were selected for proteomic investigation. Results: Compared with the control rats, hyperthyroid rats showed a reduction in the fifth lumbar vertebral BMD as well as in the entire femoral BMD (p = 0.033 and 0.026, respectively). Histomorphometric analysis of the proximal tibial metaphysis showed that the percentage of the trabecular area, trabecular number, and percentage of the cortical bone area in the hyperthyroid rats significantly decreased compared with those of the control rats. Conversely, bone formation rate (per unit of bone surface and bone volume), percentage of the osteoclast perimeter, trabecular separation, and endosteal mineral apposition rate in the hyperthyroid rats significantly increased compared with the control rats (all p < 0.05). Except for stiffness (p = 0.24), all bone biomechanical properties of the femur showed a significant decreasing trend in the hyperthyroid rats versus the control rats (all p < 0.05). Serum levels of osteocalcin, alkaline phosphatase, terminal telopeptides of type β collagen, and tartrate-resistant acid phosphatase were higher in the hyperthyroid rats than in the control rats (all p < 0.05). Using isobaric tags for relative and absolute quantification (iTRAQ), the expression levels of 1,310 proteins were found to be significantly different between the hyperthyroid and control rats (711 proteins were upregulated and 599 were downregulated in hyperthyroid rats). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses showed that most of the enzymes in the glycolysis–tricarboxylic acid (TCA) cycle–oxidative phosphorylation signalling pathway were upregulated in hyperthyroid rats, and seven differentially expressed proteins were selected to verify the iTRAQ results using western blotting. Conclusion: Energy metabolism via the glycolysis–TCA cycle–oxidative phosphorylation pathway is positively associated with T4-induced bone histomorphometric changes in rats.
, a 70-year-old man presented with persistent vertigo and vomiting for 1 week, and intractable hiccups of about 3 years' duration. The frequency of hiccups was about 15-20 per minute, and it was not affected by eating and drinking. His hiccupping was persistent during the day, and it had not responded to metoclopramide, domperidone, omeprazole, or even traditional Chinese medicine. However, it stopped spontaneously while he was asleep. The physical and general medical examinations were normal, as was B-mode ultrasound of the abdomen and radiograph of the chest. Computed tomography of the head showed a single hyperintense spaceoccupying lesion (approximately 6.2 Â 6.3 cm 2) in the right frontotemporal lobe but mostly located in the frontal lobe, which was referred to as meningioma. Further contrast-enhanced scanning of the lesion showed that its signal intensity was obviously enhanced. A hypointense edema zone was found around the space-occupying lesion. Moreover, the right ventricle and left ventricle anterior horn became narrow, and the midline deviated about 1.5 cm to the left side (Figure). The space-occupying lesion was resected, and histologic examination confirmed the diagnosis of fibroblastic meningioma, World Health Organization grade I. Furthermore, the intractable hiccupping disappeared right after the operation without any antihiccup treatment drugs. As of now, no recurrences of persistent hiccups have been reported.
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