Verschiedene Studien legen eine erhöhte Rate an Knochenfrakturen bei Patientinnen und Patienten mit langfristiger PPI-Einnahme nahe. PPI greifen tief in den Stoffwechsel und den Knochenstoffwechsel ein. Das Auftreten dieser Knochenbrüche soll unabhängig von einer Osteoporose sein. Frakturen bei Patientinnen und Patienten, die PPI einnehmen wurden an verschiedenen Knochen beschrieben: Hüfte, Handgelenke, Wirbelkörper.


Publikationen die erhöhte Frakturrate unter PPI-Einnahme zeigen

Liu J, Li X, Fan L, Yang J, Wang J, Sun J, Wang Z. Proton pump inhibitors therapy and risk of bone diseases: An update meta-analysis. Life Sci. 2019 Feb 1;218:213-223.

Results of this meta-analysis suggest that PPI may moderately increase the risk of any-site, hip, spine fracture. Due to the widespread use of PPI and the impact of fractures on human health, clinicians should carefully evaluate the patient condition before prescribing PPI therapy.

Liu et al., 2019, Life Sci 218: 213-223

Hussain S, Siddiqui AN, Habib A, Hussain MS, Najmi AK. Proton pump inhibitors’ use and risk of hip fracture: a systematic review and meta-analysis. Rheumatol Int. 2018 Nov;38(11):1999-2014. doi: 10.1007/s00296-018-4142-x. Epub 2018 Aug 29.

This meta-analysis suggests that PPI user have a 26% increased risk of hip fracture as compared to non-PPI user. Physicians should take caution in prescribing PPI to patients who are at increased risk of hip fracture.

Hussain et al., 2018, Rheumatol Int 38: 1999-2014

Yang HC, Wu CC, Li YJ. Proton pump inhibitors and risk of hip fracture: a meta-analysis of observational studies. Osteoporos Int. 2019 Jan;30(1):103-114. doi: 10.1007/s00198-018-4788-y. Epub 2018

Fraser LA, Leslie WD, Targownik LE, Papaioannou A, Adachi JD; CaMos Research Group. The effect of proton pump inhibitors on fracture risk: report from the Canadian Multicenter Osteoporosis Study. Osteoporos Int. 2013 Apr;24(4):1161-8. doi: 10.1007/s00198-012-2112-9. Epub 2012 Aug 14.

In this large prospective population-based cohort study, we found an association between PPI use and increased risk of fragility fracture. Although the increased risk found was modest, this finding is important, given the high prevalence of PPI use and the excess morbidity and mortality associated with osteoporosis-related fractures.

Fraser et al., 2013, Osteoporos Int. 24: 1161-1168

Yang YX, Lewis JD, Epstein S, Metz DC. Long-term proton pump inhibitor therapy and risk of hip fracture. JAMA. 2006 Dec 27;296(24):2947-53.

Long-term PPI therapy, particularly at high doses, is associated with an increased risk of hip fracture.

Yang et al., 2006 JAMA. 296: 2947-2953

Cea Soriano L, Ruigómez A, Johansson S, García Rodríguez LA. Study of the association between hip fracture and acid-suppressive drug use in a UK primary care setting. Pharmacotherapy. 2014 Jun;34(6):570-81. doi: 10.1002/phar.1410. Epub 2014 Mar 13.

Patients treated with PPIs showed a modest increased risk of hip fracture after adjustment for potential cofounders. Any remaining association between PPI use and hip fracture risk may be attributable to residual confounding.

Cea Soriano et al., 2014, Pharmacotherapy 34:570-581

Wilson C. Bone: proton-pump inhibitors and fractures. Nat Rev Endocrinol. 2012 Nov;8(11):625.

Gray SL, LaCroix AZ, Larson J, Robbins J, Cauley JA, Manson JE, Chen Z. Proton pump inhibitor use, hip fracture, and change in bone mineral density in postmenopausal women: results from the Women’s Health Initiative. Arch Intern Med. 2010 May 10;170(9):765-71. doi: 10.1001/archinternmed.2010.94.

Use of PPIs was not associated with hip fractures but was modestly associated with clinical spine, forearm or wrist, and total fractures.

Gray et al., 2010, Arch Intern Med170:765-71

Zirk-Sadowski J, Masoli JA, Strain WD, Delgado J, Henley W, Hamilton W, Melzer D, Ble A. Proton-Pump Inhibitors and Fragility Fractures in Vulnerable Older Patients. Am J Gastroenterol. 2017 Mar;112(3):520-523. doi: 10.1038/ajg.2016.584.

Publikationen, die das erhöhte Frakturrisko unter PPI Einnahme in Frage stellen

Targownik LE, Leslie WD. The relationship among proton pump inhibitors, bone disease and fracture. Expert Opin Drug Saf. 2011 Nov;10(6):901-12. doi: 10.1517/14740338.2011.586628. Epub 2011 May 20

“Long-term PPI use is not associated with any changes in bone mineral density or bone strength that would predispose to an increased risk of fracture. These findings provide further evidence that the association between PPI use and fracture is not causal.”

Targownik et al. 2017, Am J Gastroenterol. 112: 95-101.

Targownik LE, Goertzen AL, Luo Y, Leslie WD. Long-Term Proton Pump Inhibitor Use Is Not Associated With Changes in Bone Strength and Structure. Am J Gastroenterol. 2017 Jan;112(1):95-101. doi: 10.1038/ajg.2016.481. Epub 2016 Nov 15.

“Overall, though multiple observational studies have demonstrated an association between PPIs and fragility fractures, the lack of a proven mechanism through which PPIs increase the risk of fracture suggests that this association may not be causal. At this time, the authors do not recommend discontinuing PPIs in patients with a history of fracture or those at increased risk of fracture. However, clinicians should still endeavor to avoid using PPIs in situations where benefits are minimal or clinical indications are lacking.”

Targownik & Leslie, 2011, Expert Opin Drug Saf. 10: 901-912.