© 2019 The Authors 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.