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.

Keywords: Bone; Osteoporosis.

Fig. 1

Interaction among key genetic components of signaling pathways involved in bone formation (Rosen, 2017).

Fig. 2

Model of normal calcium balance: normal serum 1.25(OH)₂D levels promote intestinal absorption, when dietary calcium supply is low-normal to normal, and stimulate renal calcium reabsorption in the distal tubules. These pathways deliver sufficient calcium for adequate bone matrix mineralization. VDR signaling in osteoprogenitors increases RANKL expression and stimulates osteoclastogenesis, whereas VDR action in mature osteoblasts has anti-catabolic actions, by decreasing RANKL, and anabolic activity by increasing LRP5 expression (Mafi Golchin et al., 2016).