Hyperparathyroidism Associated with Long‐Term Proton Pump Inhibitors Independent of Concurrent Bisphosphonate Therapy in Elderly Adults

Hinson, Andrew M.; Wilkerson, Bekka M.; Rothman‐Fitts, Ivy; Riggs, Ann T.; Stack, Brendan C.; Bodenner, Donald

doi:10.1111/jgs.13661

Cited by 33 publications

(21 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Low circulating calcium triggers secretion of parathyroid hormone (PTH) from the parathyroid gland to enhance bone resorption. PPI users had significantly higher PTH levels compared with that of non-users 33,34 . However, T2DM is also associated with impaired calcium metabolism, which may increase bone fragility 35 .…”

Section: Discussionmentioning

confidence: 84%

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

Chou

Jiang

et al. 2020

Sci Rep

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 84%

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

Chou

Jiang

et al. 2020

Sci Rep

View full text Add to dashboard Cite

show abstract

“…There may be other viable mechanisms behind the PPI-induced fracture risk other than impaired bone structure. Despite research findings that PPI use is associated with hyperparathyroidism and hypocalcemia, it is still unclear whether PPI use induces hypocalcemia and secondary hyperparathyroidism or whether gastrointestinal disorders caused by hyperparathyroidism or hypocalcemia increase PPI use [25].…”

Section: Plos Onementioning

confidence: 99%

Association between proton pump inhibitor use and risk of fracture: A population-based case-control study

et al. 2020

View full text Add to dashboard Cite

The purpose of this study was to reconfirm the association between the risk of fracture and proton pump inhibitor use and to establish evidence for defining a high-risk group of patients among proton pump inhibitor users. Methods A nested case-control study was performed using data from the National Health Insurance Sharing Service database from the period January 2007 to December 2017. The study population included elderly women aged �65 years with claims for peptic ulcer or gastro-esophageal reflux disease. The cases were all incidental osteoporotic fractures, and up to two controls were matched to each case by age, osteoporosis, and Charlson comorbidity index. Conditional logistic regression was used to calculate the adjusted odds ratio and 95% confidence interval (CI). Results A total of 21,754 cases were identified, and 43,508 controls were matched to the cases. The adjusted odds ratio of osteoporotic fractures related to the use of proton pump inhibitors was 1.15 (95% CI: 1.11-1.20). There was a statistically significant interaction between proton pump inhibitor and bisphosphonate use (p<0.01). The risk of fracture in patients using proton pump inhibitors was 1.15 (95%

show abstract

“…Studies have explored the potential effects of PPIs on calcium absorption 40 , bone mineral density (BMD) 41–44 , bone metabolism 45, 46 , increased histamine release 47 , or their association with fall risk 16, 23 . In addition, it has been hypothesized that PPI use may be associated with hyperparathyroidism 48 , which has been recently reported in a cohort of elderly subjects 49 . We further investigated the association between PPIs and hyperparathyroidism in AERS-DM, and did find a signal (PRR 3.1837, χ 2 40.001).…”

Section: Discussionmentioning

confidence: 94%

Proton Pump Inhibitors and the Risk for Fracture at Specific Sites: Data Mining of the FDA Adverse Event Reporting System

Wang

Cao

et al. 2017

Sci Rep

View full text Add to dashboard Cite

Proton pump inhibitors (PPIs) are widely used to treat gastric acid-related disorders. Concerns have been raised about potential fracture risk, especially at the hip, spine and wrist. However, fracture risk at other bone sites has not been as well studied. We investigated the association between PPIs and specific fracture sites using an aggregated knowledge-enhanced database, the Food and Drug Administration Adverse Event Reporting System Data Mining Set (AERS-DM). Proportional reporting ratio (PRR) was used to detect statistically significant associations (signals) between PPIs and fractures. We analyzed both high level terms (HLT) and preferred terms (PT) for fracture sites, defined by MedDRA (Medical Dictionary for Regulatory Activities). Of PPI users reporting fractures, the mean age was 65.3 years and the female to male ratio was 3.4:1. Results revealed signals at multiple HLT and PT fracture sites, consistent for both sexes. These included fracture sites with predominant trabecular bone, not previously reported as being associated with PPIs, such as ‘rib fractures’, where signals were detected for overall PPIs as well as for each of 5 generic ingredients (insufficient data for dexlansoprazole). Based on data mining from AERS-DM, PPI use appears to be associated with an increased risk for fractures at multiple sites.

show abstract

Hyperparathyroidism Associated with Long‐Term Proton Pump Inhibitors Independent of Concurrent Bisphosphonate Therapy in Elderly Adults

Abstract: Based on the present study, chronic PPI exposure in elderly adults is associated with mild hyperparathyroidism regardless of concurrent oral BP administration.

Cited by 33 publications

References 26 publications

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

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

Association between proton pump inhibitor use and risk of fracture: A population-based case-control study

Proton Pump Inhibitors and the Risk for Fracture at Specific Sites: Data Mining of the FDA Adverse Event Reporting System

Contact Info

Product

Resources

About