PPI and Osteoporosis

PPIs are a class of drugs that decrease gastric acid secretion through inhibition of H+, K+-ATPase. H+, K+-ATPase is called the proton pump. It helps in the secretion of acid from the stomach glands. Currently, five PPIs are used widely as antisecretory agents-omeprazole (Prilosec), esomeprazole (Nexium), lansoprazole (Prevacid), pantoprazole (Protonix), and rabeprazole (Aciphex). These agents are prodrugs that must be activated by acid to effect inhibition of H+, K+-ATPase.

The PPIs are a remarkably safe and well-tolerated group of agents. The most commonly reported side effects are headache and diarrhea. In a recent study, it has been found that proton pump inhibitors (PPI) are associated with increased risk of hip fractures. The case control study was first published in JAMA in December 2006. The increased risk of hip fractures is attributed to osteoporosis caused by proton pump inhibitors. The absorption of calcium requires an acidic environment. PPIs suppress the secretion of acid in the stomach and make environment less acidic in the stomach.

The less acidic gastric environment created by PPIs may impair the absorption of calcium, particularly calcium supplements. A decrease in the absorption of calcium leads to low body calcium. Low body calcium levels make the bones weak by causing osteoporosis. Fractures are the most serious consequences of osteoporosis and hip fractures are the most common fractures in osteoporosis. It associated with a mortality rate at 1 year of 20%.

This study was conducted by Yu-Xiao Yang and his colleagues from the University Of Pennsylvania School Of Medicine in Philadelphia. Using the UK General Practice Research Database (1987 - 2003), the investigators studied a cohort of users of PPI therapy and nonusers of acid suppression drugs who were older than 50 years. Cases included all patients with an incident hip fracture (n = 13,556), and 135,386 controls were selected using incidence density sampling and matched for sex, index date, year of birth, and both calendar period and duration of up-to-standard follow-up before the index date.

According to the study, people over age 50 who take the drugs for more than one year have a 44% increased risk of breaking a hip. PPIs increased risk for fracture occurred to a greater degree in men than women. Overall, patients taking PPI or H2A for one year or longer had an increased risk of hip fracture. Use of high-dose PPIs further increased the risk for hip fracture when compared to regular dosing. The risk for fracture associated with regular dose PPI was similar to that associated with histamine-2-receptor antagonist therapy.