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La Tunisie MedicaleA potential role of hyperhomocysteinemia in bone metabolism has been considered from the observation of high prevalence of osteoporosis in subjects with homocystinuria...
INTRODUCTION
A potential role of hyperhomocysteinemia in bone metabolism has been considered from the observation of high prevalence of osteoporosis in subjects with homocystinuria about 50 years ago.
AIM
To examine the association of homocysteine level and its determinants Methylenetetrahydrofolate Reductase [MTHFR] C677T Polymorphism, folates and vitamin B12 levels with bone mineral density [BMD] and the prevalence of vertebral fractures [VF] on postmenopausal women.
METHODS
Through a cross-sectional study, one hundred and twenty-two healthy postmenopausal women gave their informed consent to participate in this study. Women were recruited through advertisements and mouth to ear between January 2017 and May 2017. One serum tube and one EDTA tube were collected from fasting patients. Bone mineral density was determined by a Lunar Prodigy® Vision DXA system®. Vertebral fracture [VF] assessment image was inspected visually by 2 clinicians.
RESULTS
We found that a high level of homocysteine and low vitamin B12 and folate levels are not associated with bone mineral density and are not risk factors for VF in healthy postmenopausal women. Whereas, the presence of VF was associated with the number of years since menopause and with the osteocalcin levels.
CONCLUSION
The MTHFR C677T polymorphism, the high levels of HCY, or low levels of folate and vitamin B12 would not be risk factors for osteoporosis and VF in healthy postmenopausal women.
Topics: Humans; Female; Bone Density; Cross-Sectional Studies; Homocysteine; Folic Acid; Vitamin B 12; Spinal Fractures; Osteoporosis
PubMed: 36571739
DOI: No ID Found -
Journal of Nanobiotechnology Oct 2022Osteoporosis (OP) is characterized by a loss in bone mass and mineral density. The stimulation of the canonical Wnt/β-catenin pathway has been reported to promote bone...
Osteoporosis (OP) is characterized by a loss in bone mass and mineral density. The stimulation of the canonical Wnt/β-catenin pathway has been reported to promote bone formation, this pathway is controlled by several regulators as secreted frizzled-related protein-1 (Sfrp-1), antagonist of the pathway. Thus, Sfrp-1 silencing therapies could be suitable for enhancing bone growth. However, the systemic stimulation of Wnt/β-catenin has been correlated with side effects. This work hypothesizes the administration of lipid-polymer NPs (LPNPs) functionalized with a MSC specific aptamer (Apt) and carrying a SFRP1 silencing GapmeR, could favor bone formation in OP with minimal undesired effects. Suitable SFRP1 GapmeR-loaded Apt-LPNPs (Apt-LPNPs-SFRP1) were administered in osteoporotic mice and their biodistribution, toxicity and bone induction capacity were evaluated. The aptamer functionalization of the NPs modified their biodistribution profile showing a four-fold increase in the bone accumulation and a ten-fold decrease in the hepatic accumulation compared to naked LPNPs. Moreover, the histological evaluation revealed evident changes in bone structure observing a more compact trabecular bone and a cortical bone thickness increase in the Apt-LPNPs-SFRP1 treated mice with no toxic effects. Therefore, these LPNPs showed suitable properties and biodistribution profiles leading to an enhancement on the bone density of osteoporotic mice.
Topics: Mice; Animals; beta Catenin; Bone Density; Tissue Distribution; Nanoparticles; Polymers
PubMed: 36309688
DOI: 10.1186/s12951-022-01674-5 -
Cell Death and Differentiation Sep 2014
Topics: Animals; Bone Density; Cell Differentiation; Homeodomain Proteins; Homeostasis; Male; Osteoblasts; Transcription Factors
PubMed: 25109593
DOI: 10.1038/cdd.2014.94 -
Nature Reviews. Drug Discovery Feb 2011Osteoporosis, a syndrome characterized by thin bones and fractures, has become more prevalent in both women and men. Established therapies for treating this disorder... (Review)
Review
Osteoporosis, a syndrome characterized by thin bones and fractures, has become more prevalent in both women and men. Established therapies for treating this disorder consist primarily of drugs that prevent bone loss, such as the bisphosphonates and selective oestrogen receptor modulators. Although these drugs have been shown to reduce fractures in randomized trials, there is an urgent need for treatments that could lower fracture risk further without additional adverse effects. The introduction of parathyroid hormone (teriparatide), which significantly increases bone mineral density, albeit for a relatively short duration, raised expectations that drugs that stimulate bone formation might cure osteoporosis. After outlining current approaches for treating osteoporosis, this Review focuses on emerging therapeutic opportunities for osteoporosis that are based on recent insights into skeletal physiology. Such novel strategies offer promise not only for reducing age-related bone loss and the associated risk of fractures but also for restoring bone mineral density to healthy levels.
Topics: Animals; Bone Density; Bone Density Conservation Agents; Bone Diseases, Metabolic; Bone Regeneration; Fractures, Bone; Humans; Osteoporosis; Signal Transduction
PubMed: 21283108
DOI: 10.1038/nrd3299 -
Current Osteoporosis Reports Jun 2011It is well established that excessive consumption of high-fat diets results in obesity. However, the consequences of obesity on skeletal development, maturation, and... (Review)
Review
It is well established that excessive consumption of high-fat diets results in obesity. However, the consequences of obesity on skeletal development, maturation, and remodeling have been the subject of controversy. New studies suggest that the response of the growing skeleton to mechanical loading is impaired and trabecular bone mass is decreased in obesity and after high-fat feeding. At least in part, this occurs as a direct result of inhibited Wnt signaling and activation of peroxisome proliferator-activated receptor-γ (PPAR-γ) pathways in mesenchymal stem cells by fatty acids. Similar effects on Wnt and PPAR-γ signaling occur after chronic alcohol consumption as the result of oxidative stress and result in inhibited bone formation accompanied by increased bone marrow adiposity. Alcohol-induced oxidative stress as the result of increased NADPH-oxidase activity in bone cells also results in enhanced RANKL-RANK signaling to increase osteoclastogenesis. In contrast, consumption of fruits and legumes such as blueberries and soy increase bone formation. New data suggest that Wnt and bone morphogenetic protein signaling pathways are the molecular targets for bone anabolic factors derived from the diet.
Topics: Alcohol Drinking; Bone Density; Humans; Nutritional Status; Nutritive Value; Obesity; Osteogenesis; Osteoporosis; Oxidative Stress; PPAR gamma
PubMed: 21360285
DOI: 10.1007/s11914-011-0049-0 -
Osteoporosis International : a Journal... Oct 2017Sedentary behaviour (SB) is a potential risk factor for suboptimal bone deposition in youth. (Review)
Review
BACKGROUND
Sedentary behaviour (SB) is a potential risk factor for suboptimal bone deposition in youth.
RESULTS
Total SB was negatively associated with lower extremity bone outcomes, while no association was observed with total body bone outcomes. Insufficient evidence was found for an association between total SB and lumbar spine bone outcomes.
CONCLUSION
This review highlights the heterogeneity of the available evidence and emphasizes the need for well-designed studies.
Topics: Adolescent; Bone Density; Exercise; Femur Neck; Health Behavior; Humans; Sedentary Behavior; Young Adult
PubMed: 28879434
DOI: 10.1007/s00198-017-4195-9 -
The Journal of Nutrition Jun 2008Racial differences in bone become apparent during puberty. Studies of areal bone mineral density (aBMD) generally show the greatest aBMD in African Americans followed by... (Review)
Review
Racial differences in bone become apparent during puberty. Studies of areal bone mineral density (aBMD) generally show the greatest aBMD in African Americans followed by American white, Hispanic, and Native Americans, with the least aBMD in Asian Americans. Racial differences in fracture risk, however, do not exactly follow racial variation in aBMD. These group differences in bone mass are largely explained by differences in bone size, although calcium intake and physical activity are also significant predictors of aBMD and bone mineral content. Racial differences in calcium metabolism, as influenced by calcium and sodium intake, explain much of the black vs. white differences in skeletal calcium accretion during puberty. The relative importance of calcium and sodium in calcium metabolism has not yet been elucidated among Asians. Predictors of aBMD have been reported for African American and American white adults and predictors of aBMD in Chinese American women have recently been studied. Much remains to be studied regarding interactions between race and diet.
Topics: Body Weight; Bone Density; Diet; Female; Fractures, Bone; Humans; Life Style; Male; Osteoporosis; Racial Groups; Risk Factors; United States
PubMed: 18492866
DOI: 10.1093/jn/138.6.1256S -
Bone Nov 2015Skeletal muscle and bone rely on a number of growth factors to undergo development, modulate growth, and maintain physiological strength. A major player in these actions... (Review)
Review
Skeletal muscle and bone rely on a number of growth factors to undergo development, modulate growth, and maintain physiological strength. A major player in these actions is insulin-like growth factor I (IGF-I). However, because this growth factor can directly enhance muscle mass and bone density, it alters the state of the musculoskeletal system indirectly through mechanical crosstalk between these two organ systems. Thus, there are clearly synergistic actions of IGF-I that extend beyond the direct activity through its receptor. This review will cover the production and signaling of IGF-I as it pertains to muscle and bone, the chemical and mechanical influences that arise from IGF-I activity, and the potential for therapeutic strategies based on IGF-I. This article is part of a Special Issue entitled "Muscle Bone Interactions".
Topics: Animals; Bone Density; Humans; Insulin-Like Growth Factor I; Muscle, Skeletal; Regeneration; Signal Transduction
PubMed: 26453498
DOI: 10.1016/j.bone.2015.04.036 -
Endocrinology Jan 2021Through a genome-wide analysis of bone mineral density (BMD) and muscle mass, identification of a signaling pattern on 17p11.2 recognized the presence of sterol...
Through a genome-wide analysis of bone mineral density (BMD) and muscle mass, identification of a signaling pattern on 17p11.2 recognized the presence of sterol regulatory element-binding factor 1 (SREBF1), a gene responsible for the regulation of lipid homeostasis. In conjunction with lipid-based metabolic functions, SREBF1 also codes for the protein, SREBP-1, a transcription factor known for its role in adipocyte differentiation. We conducted a quantitative correlational study. We established a zebrafish (ZF) SREBF1 knockout (KO) model and used a targeted customized lipidomics approach to analyze the extent of SREBF1 capabilities. For lipidomics profiling, we isolated the dorsal muscles of wild type (WT) and KO fishes, and we performed liquid chromatography-tandem mass spectrometry screening assays of these samples. In our analysis, we profiled 48 lipid mediators (LMs) derived from various essential polyunsaturated fatty acids to determine potential targets regulated by SREBF1, and we found that the levels of 11,12 epoxyeicosatrienoic acid (11,12-EET) were negatively associated with the number of SREBF1 alleles (P = 0.006 for a linear model). We also compared gene expression between KO and WT ZF by genome-wide RNA-sequencing. Significantly enriched pathways included fatty acid elongation, linoleic acid metabolism, arachidonic acid metabolism, adipocytokine signaling, and DNA replication. We discovered trends indicating that BMD in adult fish was significantly lower in the KO than in the WT population (P < 0.03). These studies reinforce the importance of lipidomics investigation by detailing how the KO of SREBF1 affects both BMD and lipid-signaling mediators, thus confirming the importance of SREBF1 for musculoskeletal homeostasis.
Topics: Animals; Bone Density; Gene Deletion; Gene Expression Regulation; Lipid Metabolism; Muscle, Skeletal; Sterol Regulatory Element Binding Protein 1; Zebrafish
PubMed: 33068391
DOI: 10.1210/endocr/bqaa189 -
Frontiers in Endocrinology 2022This Mendelian randomization (MR) study aimed to explore the causal relationship between polyunsaturated fatty acids (PUFAs) and bone mineral density (BMD).
BACKGROUND
This Mendelian randomization (MR) study aimed to explore the causal relationship between polyunsaturated fatty acids (PUFAs) and bone mineral density (BMD).
METHODS
We conducted a two-sample MR analysis to figure out if there is any causal effect of PUFAs on BMD through the summary data from the genome-wide association study (GWAS). Relationships were evaluated through inverse variance weighted (IVW), MR-Egger, weighted median, and maximum likelihood methods. The MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO) test was performed to detect the horizontal pleiotropy.
RESULTS
Our findings revealed that omega-6 fatty acids were negatively related to the TB-BMD (beta-estimate: -0.0515; 95% confidence interval [CI]: -0.0911 to -0.0119; standard error [SE]: 0.0201; p-value: 0.0106). The reverse direction MR analysis showed that TB-BMD was linked to the omega-6 FAs (beta-estimate: -0.0699; 95% CI: -0.1304 to -0.0095; SE: 0.0308; p-value: 0.0265). No statistically significant correlations between PUFAs and BMD were observed after adjusting the interactions between metabolites.
CONCLUSION
This two-sample MR analyses produced strong and new genomic evidence that there was a causal relationship between omega-6 FAs and BMD. Further investigations are still required to elucidate the potential mechanism.
Topics: Bone Density; Fatty Acids, Unsaturated; Genome-Wide Association Study; Mendelian Randomization Analysis; Polymorphism, Single Nucleotide
PubMed: 35872990
DOI: 10.3389/fendo.2022.858851