Osteoporosis: A Silent Disease with Complex Genetic Contribution

Golchin, Maryam Mafi; Heidari, Laleh; Ghaderian, Sayyed Mohammad Hossein; Akhavan‐Niaki, Haleh

doi:10.1016/j.jgg.2015.12.001

Cited by 47 publications

(28 citation statements)

References 104 publications

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“…However, the most prominent study to date, a meta-analysis conducted by Estrada et al (2012), identified 56 loci associated with BMD, osteoporosis and/or fracture that accounted for ~ 6% of the variation in BMD. Overall, more than 66 genetic loci have been associated with (DXA derived) BMD via GWAS method, as well as many others through candidate gene association studies, and this number continues to increase, emphasising the extremely polygenic nature of BMD (Golchin et al 2016). A further 153 loci have been associated with BMD estimated by quantitative ultrasound of the heel (Kemp et al 2017).…”

Section: Genetic Association With Bmdmentioning

confidence: 99%

The interactions of physical activity, exercise and genetics and their associations with bone mineral density: implications for injury risk in elite athletes

et al. 2018

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Low bone mineral density (BMD) is established as a primary predictor of osteoporotic risk and can also have substantial implications for athlete health and injury risk in the elite sporting environment. BMD is a highly multi-factorial phenotype influenced by diet, hormonal characteristics and physical activity. The interrelationships between such factors, and a strong genetic component, suggested to be around 50–85% at various anatomical sites, determine skeletal health throughout life. Genome-wide association studies and case–control designs have revealed many loci associated with variation in BMD. However, a number of the candidate genes identified at these loci have no known associated biological function or have yet to be replicated in subsequent investigations. Furthermore, few investigations have considered gene–environment interactions—in particular, whether specific genes may be sensitive to mechanical loading from physical activity and the outcome of such an interaction for BMD and potential injury risk. Therefore, this review considers the importance of physical activity on BMD, genetic associations with BMD and how subsequent investigation requires consideration of the interaction between these determinants. Future research using well-defined independent cohorts such as elite athletes, who experience much greater mechanical stress than most, to study such phenotypes, can provide a greater understanding of these factors as well as the biological underpinnings of such a physiologically “extreme” population. Subsequently, modification of training, exercise or rehabilitation programmes based on genetic characteristics could have substantial implications in both the sporting and public health domains once the fundamental research has been conducted successfully.

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Section: Genetic Association With Bmdmentioning

confidence: 99%

The interactions of physical activity, exercise and genetics and their associations with bone mineral density: implications for injury risk in elite athletes

et al. 2018

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“…However, despite the fact that the pathogenetic mechanisms of this disease were intensively investigated, factors that contribute to the development of osteoporosis are rather complicated and yet need to be further defined. Recently, accumulating evidence suggested that, besides individual lifestyle and environmental factors, certain genetic factors may be relevant to the development of osteoporosis . Furthermore, twin and family studies also demonstrated that genetic influences accounted for 70% of individual variances in bone mineral density (BMD), the major determinant of fracture risk .…”

Section: Introductionmentioning

confidence: 99%

The associations of TNF‐α gene polymorphisms with bone mineral density and risk of osteoporosis: A meta‐analysis

Wang

et al. 2019

Int J of Rheum Dis

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Objective Fracture is a common consequence of osteoporosis and is associated with high morbidity and mortality. Recently, increasing evidence has suggested that polymorphisms in tumor necrosis factor‐α (TNF‐α) gene were associated with osteoporosis risk and bone mineral density (BMD), but results remain conflicting. We herein performed a meta‐analysis based on evidence currently available from the literature to make a more precise estimation of these relationships. Methods The PubMed, EMBASE, Cochrane Library, CNKI (China National Knowledge Infrastructure) and Wan Fang databases were searched for eligible studies. Articles meeting the inclusion criteria were comprehensively reviewed and all available data were accumulated. The pooled odds ratios (ORs) or mean differences (MDs) and corresponding 95% confidence intervals (CIs) were applied to assess the strength of the relationships. Results A total of 15 studies involving 5273 subjects were included in our meta‐analysis. The GG genotype of TNF‐α G308A was associated with an increased risk of osteoporosis under a mutant model (GG vs GA+AA: OR = 0.63, 95% CI: 0.51‐0.77, P < 0.0001, I2 = 31%). Additionally, we also observed a significant association between G308A polymorphism and BMD of lumbar spine (AA vs GG: P = 0.01, I2 = 53%). However, TNF‐α T1031C, C857T and C863A polymorphisms had no obvious impacts on osteoporosis risk. Conclusions The present meta‐analysis demonstrated that TNF‐α G308A polymorphism may act as a potential candidate biomarker for screening, diagnosis, and treatment of osteoporosis, which will help improve individualized therapy of osteoporosis patients in clinics.

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“…15,16 It is widely accepted that dysregulation of osteogenesis-related genes is responsible for the poor healing performance of bone injury in T2DM, osteoporosis, or other systemic diseases patients. [17][18][19] In this regard, certain osteogenesis-related miRNAs would be expected to be involved, while very little work has been done in this field, especially in the context of bone regeneration and oral implantation. It has been reported that miR204 acts as a negative regulator during BMSC osteogenic differentiation by directly repressing runt-related transcription factor 2 (Runx2), 20 a key transcription factor in osteogenesis.…”

Section: Introductionmentioning

confidence: 99%

Delivery of antagomiR204-conjugated gold nanoparticles from PLGA sheets and its implication in promoting osseointegration of titanium implant in type 2 diabetes mellitus

Liu¹,

Tan²,

Zhou³

et al. 2017

IJN

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Impaired osseointegration of the implant remains the big hurdle for dental implant therapy in diabetic patients. In this study, the authors first identified that miR204 was strikingly highly expressed in the bone mesenchymal stem cells (BMSCs) of diabetic rats. Forced expression of miR204 repressed the osteogenic potential of BMSCs, while inhibition of miR204 significantly increased the osteogenic capacity. Moreover, the miR204 inhibitor was conjugated with gold nanoparticles (AuNP-antagomiR204) and dispersed them in the poly(lactic-co-glycolic acid) (PLGA) solution. The AuNP-antagomiR204 containing PLGA solution was applied for coating the surface of titanium implant. Electron microscope revealed that an ultrathin sheet was formed on the surface of the implant, and the AuNPs were evenly dispersed in the coated PLGA sheet. Cellular experiments revealed that these encapsulated AuNP-antagomiR204 were able to be released from the PLGA sheet and uptaken by adherent BMSCs. In vivo animal study further confirmed that the AuNP-antagomiR204 released from PLGA sheet promoted osseointegration, as revealed by microcomputerized tomography (microCT) reconstruction and histological assay. Taken together, this study established that miR204 misexpression accounted for the deficient osseointegation in diabetes mellitus, while PLGA sheets aided the release of AuNP-antagomiR204, which would be a promising strategy for titanium implant surface functionalization toward better osseointegration.

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Osteoporosis: A Silent Disease with Complex Genetic Contribution

Cited by 47 publications

References 104 publications

The interactions of physical activity, exercise and genetics and their associations with bone mineral density: implications for injury risk in elite athletes

The interactions of physical activity, exercise and genetics and their associations with bone mineral density: implications for injury risk in elite athletes

The associations of TNF‐α gene polymorphisms with bone mineral density and risk of osteoporosis: A meta‐analysis

Delivery of antagomiR204-conjugated gold nanoparticles from PLGA sheets and its implication in promoting osseointegration of titanium implant in type 2 diabetes mellitus

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