Proton pump inhibitor use and risk of hip fracture in patients with type 2 diabetes

Abstract

Type 2 diabetes mellitus (T2DM) is associated with a high rate of comorbidity, including osteoporosis and peptic ulcers. Proton pump inhibitors (PPIs) are a group of acid-suppressing drugs commonly used for treating peptic ulcers. However, observational studies have reported an association between PPI therapy and osteoporotic fractures. This study investigated the association between PPI use and hip fracture (HFx) among patients with T2DM. We conducted this population-based propensity-matched retrospective cohort study using the National Health Insurance Research Database in Taiwan. Patients newly diagnosed with T2DM between 2000 and 2008 were identified. After excluding those who previously used PPIs or suffered HFx, 398,885 patients were recruited (44,341 PPI users; 354,544 nonusers). HFx risk data from 2000 to 2013 were collected to calculate the cumulative rate of HFx in these two groups. Sensitivity analyses were conducted to evaluate the effects of PPI dose. After propensity score matching of 1:4, 44,431 and 177,364 patients were assigned to the PPI user and non-user groups, respectively. PPI user group showed an increased risk of HFx with an adjusted hazard ratio of 1.41 (95% CI 1.29-1.54) without dose-response relationship. Thus, there is an increased risk of HFx in patients with T2DM receiving long-term PPI treatment. Type 2 diabetes mellitus (T2DM) is a common metabolic disease worldwide. In Taiwan, diabetes is one of the 10 leading causes of death. The global prevalence of diabetes mellitus has more than doubled in the past 30 years 1. Common comorbidities of T2DM include osteoporosis 2-5 , peptic ulcer 6-8 , heart and blood vessel disease, diabetic neuropathy, diabetic retinopathy, liver cirrhosis, and delayed wound healing 9. The risk of osteoporosis and associated fragility fracture is increased 1.2-fold in patients with T2DM 5. Among associated fragility fractures, hip fracture (HFx) is one of the most serious, with a 1-year mortality rate ranging from 2.4% in Japan to 34.8% in Hungary 10. Previous studies have shown a higher incidence of perforated peptic ulcer disease and related mortality rates in patients with T2DM compared with those in patients without the disease 6-8. Proton pump inhibitors (PPIs) are a group of acid-suppressing drugs commonly used in the treatment of peptic ulcers. However, several studies have reported an association between treatment with PPIs and risk of fractures, especially HFx 11-15. Although most of these studies report a higher risk of fractures in patients with high-dose and long-term use of PPIs 11,12,16,17 , the association and mechanisms involved remain controversial. The literature lacks information about risk of HFx in patients with T2DM receiving PPI treatment. The present study was a population-based cohort study using data from the National Health Insurance Research Database (NHIRD) at the National Health Research Institutes (NHRI) in Taiwan to elucidate the association between use of PPIs and risk of HFx among patients with T2DM.

Establishing the Association Between Osteoporosis and Peptic Ulcer Disease: A Systematic Review

“…Several studies have demonstrated a significant positive association between osteoporosis and PUD [2,[12][13][14][15][16][17][18][19]. However, one study yielded a conflicting result regarding the association [26].…”

“…Despite excellent efficacy and trivial short-term side effects, rising concerns regarding long-term adverse effects of PPI use such as the risk of osteoporosis-related fracture, vitamin B12 deficiency, renal injury, Clostridium difficile infection, community-acquired pneumonia, and dementia is emerging [11]. Several studies have demonstrated a significant positive association between PUD, long-term PPI use, and increased incidence of osteoporotic fracture risk [2,[12][13][14][15][16][17][18][19]. Therefore, this systematic review aims to explore the association between osteoporosis and PUD and understand the different mechanisms by which osteoporosis emerges as a complication of PUD.…”

Common Pitfalls in the Management of Patients with Micronutrient Deficiency: Keep in Mind the Stomach

“…Several authors showed the presence of a positive association between the use of proton pump inhibitors (PPIs) and hip fractures in postmenopausal women [92], men [93], elderly subjects [94,95], and also in patients with type 2 diabetes [96]. Recently, it has been observed that PPI use was associated with bone fractures in a dose-dependent fashion and also in patients with liver cirrhosis [97].…”

Macrophage Colony Stimulating Factor as Predictive Marker of Osteoporosis in T2DM Patients

“…Diabetes mellitus type 2 (T2DM) is a widespread metabolic condition globally. [2]. It affects bone homeostasis leading up to 3-fold elevated hip fracture hazard comparing to those healthy individuals.…”