Use of proton pump inhibitors and risk of hip fracture in relation to dietary and lifestyle factors: a prospective cohort study

Abstract

Objective To examine the association between chronic use of proton pump inhibitors (PPIs) and risk of hip fracture.Design Prospective cohort study.Setting Nurses' Health Study, which originally recruited from the 11 most populous states in the US.Participants 79 899 postmenopausal women enrolled in the Nurses' Health Study who provided data on the use of PPIs and other risk factors biennially since 2000 and were followed up to 1 June 2008. Main outcome measure Incident hip fractureResults During 565 786 person years of follow-up, we documented 893 incident hip fractures. The absolute risk of hip fracture among regular users of PPIs was 2.02 events per 1000 person years, compared with 1.51 events per 1000 person years among non-users. Compared with non-users, the risk of hip fracture among women who regularly used PPIs for at least two years was 35% higher (age adjusted hazard ratio 1.35 (95% confidence interval 1.13 to 1.62)), with longer use associated with increasing risk (P trend <0.01). Adjustment for risk factors, including body mass index, physical activity, and intake of calcium did not materially alter this association (hazard ratio 1.36 (1.13 to 1.63)). These associations were also not changed after accounting for reasons for PPI use. The relation between PPI use and fracture differed by smoking history (P interaction =0.03). Among current and former smokers, PPI use was associated with greater than 50% increase in risk of fracture, with a multivariate hazard ratio for fracture of 1.51 (1.20 to 1.91). In contrast, among women who never smoked there was no association (multivariate hazard ratio 1.06 (0.77 to 1.46)). In a meta-analysis of these results with 10 prior studies, the pooled odds ratio of hip fracture associated with PPI use was 1.30 (1.25 to 1.36). ConclusionChronic use of PPIs is associated with increased risk of hip fracture, particularly among women with a history of smoking. IntroductionProton pump inhibitors (PPIs) are among the most commonly used drugs worldwide. 1 In the US, PPI use increased dramatically since 2003 after the Food and Drug Administration approved the drugs for "over the counter" use. Primarily used for the treatment of heartburn symptoms, gastroesophageal reflux, or peptic ulcer, PPIs antagonise hydrogen-potassium adenosine triphosphatase pumps located on gastric parietal cells, 2 thereby reducing acid production to a greater extent than histamine receptor-2 (H 2 ) blockers. 3 Although short term use of PPIs is generally well tolerated, concern has grown over potential association between long term use and bone fractures, especially of the hip, which are known to be associated with substantial morbidity and mortality. [4][5][6] PPIs may inhibit calcium absorption, 7 directly interfere with osteoclast function, 8 or induce hypergastrinaemia, resulting in reductions in bone mineral density related to hyperparathyroidism. 9 Several studies have investigated the association between PPI use and risk of hip fracture.3 10-17 Many of these studies have had important lim...

Prescription of Proton Pump Inhibitors in Elderly Subjects in Real Life: A Retrospective Study in a Gastroenterology Department

“…• The infections, particularly, the bacterial pneumopathies [24] and the intestinal infections, especially to Clostridium difficilae [25] • Osteoporotic fractures [26,27] • On the other hand, medicines decreasing the acid gastric secretion such as the long-term PPI would be theoretically capable of leading the genesis of gastric tumors, and even colorectal; in fact, the hypergastrinemia is led by these treatments [28,29].…”

Proton pump inhibitors overuse: only inappropriate prescriptions or further iatrogenic damage?

“…Moreover, some confounding variables, that may bias results, are present. [89][90][91][92] Of note, PPIs use is associated with greater than 50% increase in fracture risk among current and former smokers; in contrast, there is no association among women who never smoked. 89 The results of other studies are different.…”

Practical considerations in the management of proton-pump inhibitors

“…Bone fractures have also been linked in several observational studies (27). A crossover study analyzed bone mineral density of the hip and lumbar vertebrae, and it showed no association between PPI use and osteoporosis (28).…”