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Gastrointestinal diseases, such as inflammatory bowel disease (5), rheumatoid arthritis (6) and myeloma bone disease (7), also induce osteoporosis. INK 128 research buy In addition, the incidence of osteoporosis following gastrectomy has become a clinical issue. Although numerous studies have examined bone metabolic disorders following gastrectomy since it was first reported by Sarasin (8), the pathophysiology and the treatment of these disorders have not been fully elucidated. Based on experimental results using rat models, general nutritional deficiencies (9), calcium malabsorption (10), vitamin D deficiency (11), loss of gastric acid (12) and secondary hyperparathyroidism (13) have been suggested as possible causes of bone metabolic disorder following gastrectomy. However, fully understanding the morbidity and developing clinical therapies for skeletal disorders is critical for improving patient quality of life. Recent epidemiological studies have shown that long-term therapy with proton pump inhibitors (PPIs) significantly increases the risk of osteoporosis and pathological hip fracture in patients with gastroesophageal reflux disease (14). It is thought that PPIs reduce the production and secretion of hydrochloric acid in stomach, increase the pH in the stomach and inhibit absorption of insoluble calcium in the small intestine, thus leading to malabsorption of calcium phosphate Quinapyramine and bone metabolism disorder (15,16). PPIs also reportedly inhibit bone resorption by osteoclasts (17,18). However, the irreversible PPI mediated Capmatinib manufacturer by the PPIs requires a specific pH environment. PPIs are all prodrugs that require two sequential protonation steps for activation (19). In the first step, a pyridine radical is activated, and in the second step, a benzimidazole radical is activated. The first step is required for accumulation of the PPI in the intracellular secretory canaliculus, and the second step is necessary for binding of the PPI with the proton pump. The pKa in the second step does not significantly differ (