Risker vid långtidsbehandling med protonpumpshämmare : Fokus på demens, järnbrist och osteoporos

Sammanfattning

Proton pump inhibitors (PPIs) are one of the most widely used groups of drugs in theworld. PPIs inhibit H+/K+ -ATPases, which is the final step in the secretion ofhydrochloric acid into the stomach. They do this by binding irreversibly to H +/K+-ATPases in the parietal cells. This yields an inhibition regardless of any hormonalstimuli. PPIs are considered safe and have few side effects during short-term use.However, with longer-term use, PPIs have been shown to cause side effects, includingdementia, osteoporosis-related fractures, intestinal infections, kidney damage, and irondeficiency. The primary form of dementia thought to be associated with PPI is Alzheimer’s disease,which is believed to be associated with the accumulation of amyloid beta plaques andneurofibrillary tangles. In addition to potential neurological effects, long-term PPI usemay also impair nutrient absorption, leading to deficiencies such as iron deficiency,which occurs when the daily intake of iron is insufficient to compensate for losses, oftendue to chronic blood loss. Furthermore, prolonged PPI use has been linked to anincreased risk of osteoporosis, a condition characterized by decreased bone density,commonly occurring in postmenopausal women when bone resorption exceeds boneformation. The aim of this study was to investigate the association of long-term PPI treatment withdementia, iron deficiency and osteoporosis, including osteoporosis-related fractures.This was done through a PubMed literature search, and the study included 5 articles. Study 1 examined the risk of dementia with PPI use over seven years in a post-hocanalysis of an RCT. No association was found between PPIs and dementia. Study 2analyzed the risk of iron deficiency, osteoporosis, and fractures using medical recorddata from the TriNetX database, with a 20-year follow-up period. There, an increasedrisk of iron deficiency, osteoporosis and fractures was seen with PPI use. Study 3 wasan RCT that investigated the risk of osteoporosis and fractures during 26 weeks of PPIuse. There, increased bone turnover was observed but no decrease in bone density.Study 4 investigated the risk of iron deficiency after 12 months of PPI use. There was adecrease in iron and ferritin levels but no increased risk of iron deficiency. Study 5investigated the risk of dementia, osteoporosis and fractures after three years of PPI use.No association was seen between PPIs and dementia, osteoporosis, or fractures. There have been several studies that have shown that PPI use is associated withdementia. The results of these have been difficult to replicate. There have also beenmany studies that did not show any association between PPIs and dementia. There haveeven been studies that have shown that PPIs can help prevent dementia. The samepattern is observed for iron deficiency, with some studies showing an association withPPI use, while others report no association. Regarding osteoporosis and fractures, a fewstudies show no association; however, the majority suggest an increased risk. In summary, the results suggest a potential association between long-term PPI use andan increased risk of dementia, iron deficiency, and osteoporosis, including osteoporosis-related fractures. At the same time, it remains unclear how large these risks are andwhat mechanisms underlie them. PPI use should therefore only occur when there is aclear need for treatment, and treatment should be regularly reviewed and discontinuedwhen the need no longer exists.