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An insight into the paradigms of osteoporosis: From genetics to biomechanics.

ABSTRACT: Considered as one of the major epidemics of the 21st century, osteoporosis affects approximately 200 million people globally, with significant worldwide impact on rates of morbidity and mortality and massive socioeconomic burdens. Mainly characterized by decreased bone mineral density (BMD) and increased risk of bone fragility/deterioration, this devastating silent epidemic typically has no symptoms until a fracture occurs. The multifactorial disease, osteoporosis is instigated by complex interactions between genetic, metabolic and environmental factors, with severe impact on the biomechanics of the musculoskeletal system. This article provides a review of the epidemiology, genetic and biomechanical aspects of primary osteoporosis. The review begins with a summary of the epidemiology and global prevalence of osteoporosis. Sections 1 and 2 discuss the genetic associations and molecular signaling pathways involved in normal and pathological osteogenesis while Section 3 explores the biomechanics of osteoporosis and its quantitative damaging effects on critical bone mechanical properties, and associated bone remodeling. Overall, this review summarizes the recent findings about osteoporosis and emphasizes the importance of an integrative holistic approach in investigating osteoporosis towards providing better informed, more effective preventive and treatment modalities. Importantly, this work also explores the limited available literature on the various aspects of osteoporosis in the United Arab Emirates (UAE), Gulf Cooperation Council (GCC), and Middle East despite its alarming prevalence in the region, and highlights the need for further research and studies taking into consideration the importance of the vitamin D receptor (VDR) gene influencing the development of osteoporosis.

SUBMITTER: Al Anouti F

PROVIDER: S-EPMC6661363 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Imaging genetics studies involving participants with major depressive disorder (MDD) have expanded. Nevertheless, findings have been inconsistent. Thus, we conducted a systematic review and meta-analysis of imaging genetics studies that enrolled MDD participants across major databases through June 30th, 2017. Sixty-five studies met eligibility criteria (N?=?4034 MDD participants and 3293 controls), and there was substantial between-study variability in the methodological quality of included studies. However, few replicated findings emerged from this literature with only 22 studies providing data for meta-analyses (882 participants with MDD and 616 controls). Total hippocampal volumes did not significantly vary in MDD participants or controls carrying either the BDNF Val66Met 'Met' (386 participants with MDD and 376 controls) or the 5-HTTLPR short 'S' (310 participants with MDD and 230 controls) risk alleles compared to non-carriers. Heterogeneity across studies was explored through meta-regression and subgroup analyses. Gender distribution, the use of medications, segmentation methods used to measure the hippocampus, and age emerged as potential sources of heterogeneity across studies that assessed the association of 5-HTTLPR short 'S' alleles and hippocampal volumes. Our data also suggest that the methodological quality of included studies, publication year, and the inclusion of brain volume as a covariate contributed to the heterogeneity of studies that assessed the association of the BDNF Val66Met 'Met' risk allele and hippocampal volumes. In exploratory voxel-wise meta-analyses, MDD participants carrying the 5-HTTLPR short 'S' allele had white matter microstructural abnormalities predominantly in the corpus callosum, while carriers of the BDNF Val66Met 'Met' allele had larger gray matter volumes and hyperactivation of the right middle frontal gyrus compared to non-carriers. In conclusion, few replicated findings emerged from imaging genetics studies that included participants with MDD. Nevertheless, we explored and identified specific sources of heterogeneity across studies, which could provide insights to enhance the reproducibility of this emerging field.

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An insight into the paradigms of osteoporosis: From genetics to biomechanics.

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