Abstract:Long-term treatment with antiepileptic drugs (AEDs) is accompanied by reduced bone mass that is associated with an increased risk of bone fractures. Although phenytoin has been reported to adversely influence bone metabolism, little is known pertaining to more recent AEDs. The aim of this study was to evaluate the effects of gabapentin or levetiracetam on bone strength, bone mass, and bone turnover in rats. Male Sprague-Dawley rats were orally administered phenytoin (20 mg/kg), gabapentin (30 or 150 mg/kg), or… Show more
“…Interestingly, butyric acid is a type of short-chain fatty acid that can increase calcium deposition in osteoblasts by affecting the Runx and osteoprotegerin signaling pathways and stimulate bone formation by increasing the production of bone sialoprotein and osteopontin (Katono et al, 2008;Tyagi et al, 2018), can also stimulate the expression of osteoblast gene, promote the differentiation of osteoblasts and inhibit the differentiation of osteoclasts (Lee et al, 2006;Lucas et al, 2018). Butyric acid may also indirectly affect BMD by affecting the function of endocrine factors related to bone metabolism (Kanda et al, 2017;Tang et al, 2017). Therefore, Faecalibacterium can regulate bone metabolism by producing butyric acid, promote bone formation, and inhibit bone resorption.…”
Object: Primary osteoporosis (PO) is the most common bone disease, which is characterized by decreased bone mass, damage of bone tissue microstructure, increased bone fragility, and is prone to fracture. Gut microbiome may be involved in bone metabolism of PO through gut-brain axis regulation of immune system and endocrine system, however, the specific mechanism is still unclear. The purpose of this study was to characterize the gut microbiome of patients with PO and its possible role in the occurrence and development of the disease. Methods: Fecal samples were collected from 48 PO patients and 48 healthy controls (HC). The composition of gut microbiome community was analyzed by 16s rDNA amplification sequencing, and the difference of gut microbiome composition between PO patients and HC individuals was compared. PICRUSt was also used to predict the biological function of gut microbiome in patients with PO, and to explore its possible role in the occurrence and development of this disease. The classification model is constructed by random forest algorithm so as to screen the key biomarkers. Result: The diversity of gut microorganisms in PO patients was significantly higher than that in HC group (p < 0.05) and there was significant difference in microbial composition in PO group. The abundance of Dialister (0.036 vs. 0.004, p < 0.001) and Faecalibacterium (0.331 vs. 0.132, p < 0.001) were significantly enriched which were the key flora related to PO. Although no significant correlation between bone mineral density and the richness of microbial communities are found, PICRUST results show that there are a wide range of potential pathways between gut microbiome and PO patients, including genetic information processing, metabolism, environmental information processing, cellular processes, human diseases, and organic systems. Notably, the discriminant model based on dominant microflora can effectively distinguish PO from HC (AUC = 93.56). Conclusions: The findings show that PO is related to the change of gut microbiome, especially the enriched Dialister and Faecalibacterium genera, which give new clues to understand the disease and provide markers for the diagnosis and new strategies for intervention treatment of the disease.
“…Interestingly, butyric acid is a type of short-chain fatty acid that can increase calcium deposition in osteoblasts by affecting the Runx and osteoprotegerin signaling pathways and stimulate bone formation by increasing the production of bone sialoprotein and osteopontin (Katono et al, 2008;Tyagi et al, 2018), can also stimulate the expression of osteoblast gene, promote the differentiation of osteoblasts and inhibit the differentiation of osteoclasts (Lee et al, 2006;Lucas et al, 2018). Butyric acid may also indirectly affect BMD by affecting the function of endocrine factors related to bone metabolism (Kanda et al, 2017;Tang et al, 2017). Therefore, Faecalibacterium can regulate bone metabolism by producing butyric acid, promote bone formation, and inhibit bone resorption.…”
Object: Primary osteoporosis (PO) is the most common bone disease, which is characterized by decreased bone mass, damage of bone tissue microstructure, increased bone fragility, and is prone to fracture. Gut microbiome may be involved in bone metabolism of PO through gut-brain axis regulation of immune system and endocrine system, however, the specific mechanism is still unclear. The purpose of this study was to characterize the gut microbiome of patients with PO and its possible role in the occurrence and development of the disease. Methods: Fecal samples were collected from 48 PO patients and 48 healthy controls (HC). The composition of gut microbiome community was analyzed by 16s rDNA amplification sequencing, and the difference of gut microbiome composition between PO patients and HC individuals was compared. PICRUSt was also used to predict the biological function of gut microbiome in patients with PO, and to explore its possible role in the occurrence and development of this disease. The classification model is constructed by random forest algorithm so as to screen the key biomarkers. Result: The diversity of gut microorganisms in PO patients was significantly higher than that in HC group (p < 0.05) and there was significant difference in microbial composition in PO group. The abundance of Dialister (0.036 vs. 0.004, p < 0.001) and Faecalibacterium (0.331 vs. 0.132, p < 0.001) were significantly enriched which were the key flora related to PO. Although no significant correlation between bone mineral density and the richness of microbial communities are found, PICRUST results show that there are a wide range of potential pathways between gut microbiome and PO patients, including genetic information processing, metabolism, environmental information processing, cellular processes, human diseases, and organic systems. Notably, the discriminant model based on dominant microflora can effectively distinguish PO from HC (AUC = 93.56). Conclusions: The findings show that PO is related to the change of gut microbiome, especially the enriched Dialister and Faecalibacterium genera, which give new clues to understand the disease and provide markers for the diagnosis and new strategies for intervention treatment of the disease.
“…BMC (milligrams), bone volume (cubic centimeters), and BMD (milligrams per cubic centimeter) were calculated using LaTheta software (version 1.00). The minimum moment of inertia of cross-sectional areas (milligram-centimeter), which represents flexural rigidity, and the polar moment of inertia of cross-sectional areas (milligram-centimeters), which represents torsional rigidity, were calculated automatically by LaTheta software [22,23].…”
Section: Bone Densitometry and Body Composition Analysesmentioning
Materials and methods
MaterialsBovine LF was supplied by NRL Pharma, Inc. (Kanagawa, Japan). Dexamethasone sodium phosphate (DEX) was purchased from Wako Pure Chemical Industries, Ltd. (Osaka, Japan). All other chemicals were obtained commercially at the purest grade available.
Animals and experimental proceduresForty-eight 7-week-old male ICR mice (Japan SLC Inc.
“…Recently, several other drugs were also clearly shown to cause bone fragility. We have previously reported the effects of antidiabetic (11) and antiepileptic (12,13) agents on bone metabolism; these led to enhanced bone fragility. The present study investigates the effects of calcineurin inhibitors, which are immunosuppressants that have greatly contributed to the advancement of transplant therapy in recent years, on bone metabolism.…”
Immunosuppressive therapy is considered as one of the factors inducing to the onset of osteoporosis after organ transplantation. Chronic immunosuppressive therapy after transplantation is required for organ transplant patients, and it is important to prevent the occurrence of osteoporotic fractures to maintain the quality of life in patients. In this study, we examined the effects of cyclosporine and tacrolimus on bone metabolism in rats. Five-week-old male Wistar rats were treated orally with 15 mg/kg cyclosporine or 1.5 mg/kg tacrolimus daily for 4 weeks. Each of cyclosporine and tacrolimus significantly reduced the bone strength of the femoral mid-diaphysis and bone mineral density of the tibia and femur. Bone histomorphometry showed that the administration of both drugs resulted in a decrease in bone volume, number and thickness of trabeculae, and an increase in trabecular separation. Bone formation parameters such as osteoid volume, osteoblast surface, mineralizing surface, mineral apposition rate, and bone formation rate significantly increased in the cyclosporine-treated group. Bone resorption parameters such as eroded surface, osteoclast surface, and osteoclast number significantly increased in both the cyclosporine- and the tacrolimus- treated groups. These results showed that cyclosporine increases both bone formation and bone resorption, leading to a high-turnover bone loss, and that tacrolimus increases bone resorption without affecting bone formation, leading to bone loss.
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