**3.1 Pathophysiology**

PPIs are strong inhibitors of stomach acid secretion, which is thought to be important for calcium absorption by enhancing the solubility of calcium salts that are insoluble leading to decreases intestinal calcium absorption and ultimately causing a decline in bone mineral density [15]. Regarding the impact of PPI use on calcium absorption, there is a paucity of clinical evidence and inconsistent findings. Furthermore, PPI use may induce hypomagnesemia, which could increase the fracture risk, although this is also controversial [17]. Increased fracture risk after 1–7 years of treatment. Risk factors include age > 50, "high dose" and longer duration. Zhou et al. [20] stated that PPI use for less than a year was also linked to an increased risk of hip fracture. This finding may undermine the idea that PPI use increases the risk of fracture through biochemical mechanisms (such as changes in calcium absorption or bone mineral density). Further research is required to elucidate any other pathways that may exist and have an impact on bone mineralization or bone quality directly [19, 20].
