“…Alternatively in OP, chronic pathological levels of pro-inflammatory cytokines and mediators promote bone resorption via osteoclast differentiation and activation, enhancement of RANKL expression, and the inhibition osteoblast survival (Clowes et al, 2005 ). Indeed, systemic inflammation is implicated in the dysregulation of multiple processes related to bone homeostasis: OP pathology propagates through a complex interplay of endocrine (estrogen; Almeida et al, 2017 ; Levin et al, 2018 ; Wu et al, 2018 ; Farr et al, 2019 , parathyroid hormone; Camirand et al, 2016 ; Noordin and Glowacki, 2016 ; Williams et al, 2018 ; Lou et al, 2019 , androgen; Shin et al, 2018 ; Joseph et al, 2019 ) immune (T-lymphocytes, cytokines), small molecule (Vitamin D; Ebeling and Eisman, 2018 ; Shill et al, 2019 ), and canonical signal pathway (Wnt/β-catenin; Johnson and Recker, 2017 ; Amjadi-Moheb and Akhavan-Niaki, 2019 ) regulators (see Figure 3 ).…”