Identification and Characterization of Novel regulator of osteoporosis from endogenous and exogenous sources

Abstract

Osteoporosis is a bone metabolic disorder with compromised bone strength due to low bone mineral density (BMD). It is characterized by low bone mass with impaired bone mineralization, decreased bone strength and worsening of micro-architecture of bone as a result of which bone fragility and frequency of non-traumatic fracture increases (Kanis et al., 2002; Hak et al., 2018; Lupsa et al., 2015; Kiberstis et al., 2000). Main cause of osteoporosis is imbalance in bone remodeling (bone formation and resorption) due to which more bone loss occurs than bone formation, resulting to an adverse effect on both trabecular and cortical bone that finally leads to the loss of connectivity and thinning in cortical bone thereby increasing porosity of bone (Eastell et al., 2016; Manolagas et al., 2000; Parfitt et al., 2002). In 19th century, German and French physicians coined the term ―osteoporosis‖ during investigating histology of the osteoporotic bone (Javaid et al., 2002). Due to silent nature with an asymptomatic condition, disease remains undiagnosed that may cause low-trauma fracture of the hip, pelvis, spine, proximal humerus and wrist (Cosman et al., 2014). According to the recent report by International Osteoporosis Foundation (IOF), on every 3 sec, about 200 million osteoporotic women in the world suffer from an osteoporotic fracture which accounts for 8.9 million fractures occurring in a year (Kanis et al., 2007; Johnell et al., 2006). Osteoporosis is more frequent in women and the main cause for it is post-menopausal estrogen deficiency (Stevenson et al., 1982). In men, the rate of osteoporosis is less frequent having increased chances with aging associated with the peak incidences of fractures occurs in every ten years as compared to women (Tabacco et al., 2019). Also, in India osteoporotic patients are on the rise with around 50 million patients is estimated to be either osteoporotic or having low bone mass (Ishimi et al., 2015). Due to the silent nature of the disease (osteoporosis) with few symptoms, it is regarded as a major health problem among men and women with an average age above 50 years (Kinsella et al., 2009). In the USA alone, 10 million people (age group of more than 50 years) suffer from hip fractures due to osteoporosis. Similarly, in European countries, more than 3.5 million fractures occur each year due to age related osteoporosis, which prevails in around 27.6 million people (Manolagas et al., 2000; Malhotra et al., 2008). Based on the available data and clinical experience, 50- 60 million Indian people are affected by osteoporosis (Sharma et al., 2000; Kinsella et al., 2009). It is estimated that the number of people in the world with an age group ≥65 years is expected to double between 2010 and 2040, which eventually leads to a considerable rise in global fractures over the next 30 years (Burge et al., 2007). It is also estimated that the economic cost of these fractures is high, with an annual cost exceeding $25 billion each year by 2025 in the USA [18] and €37 billion in Europe Kinsella et al., 2009; Sharma et al.,2000). Hence, it is very important to manage and cure osteoporosis to improve the quality of life and reduce the economic burden. There are many treatments available to cure osteoporosis, but there is scope for better therapeutic agents. There are two types of drugs available in the market, i.e antiresorptive and anabolic. An anti-resorptive drug decreases the rate of bone resorption while anabolic drug increases the rate of bone formation (Tu et al., 2018). The antiresorptive drugs include bisphosphonates (BPs), estrogen agonist/antagonist, estrogens, calcitonin and denosumab, while anabolic drug includes parathyroid hormone that is FDA (Food and Drug Administration) approved to treat postmenopausal osteoporosis