Later, we have discussed the core mechanisms and pathways involved in the pathophysiology of osteoporosis, including the RANKL-OPG axis, Wnt/β-catenin signalling, Parathyroid hormone (PTH)/PTH1R (cAMP/PKA vs. sustained Ca<sup>2+</sup>/PKC) signalling, TGF-β/BMP-SMAD signalling, etc. Furthermore, we summarise the major risk factors, including ageing, sex hormones, nutritional deficiencies, lifestyle factors, and comorbidities and delineate their mechanistic links to bone loss. Here, PTH1R is linked to osteoporosis.