Proton Pump Inhibitors, But Not H2-receptor Antagonists, Are Associated With Incident Fractures Among Kidney Transplant Recipients.

Lyu B ，Jorgenson MR ，Hansen KE ，Djamali A ，Astor BC ... -  《-》

Associations between Proton Pump Inhibitor and Histamine-2 Receptor Antagonist and Bone Mineral Density among Kidney Transplant Recipients.

In the general population, use of proton pump inhibitor (PPI) has been linked to higher risk of osteoporotic fractures. PPI is commonly prescribed in kidney transplant recipients (KTRs). However, the effect of PPI on osteoporosis in KTRs is largely unstudied. A total of 1,774 adult KTRs in the Wisconsin Allograft Recipient Database with at least one eligible bone mineral density (BMD) measurement at least 3 months after transplantation were included in the analyses. Associations between use of PPI and histamine-2 receptor antagonist (H2RA) at 3 months after transplantation and subsequent slope of T-score were assessed. A total of 1,478 (83.3%) participants were using a PPI at 3 months after transplantation. Compared to the use of H2RA, use of PPI was not significantly associated with annualized slope of hip T-score (β = -0.0039, 95% CI -0.00497 to 0.0021) or annualized slope of spine T-score (β = -0.017, 95% CI -0.049 to 0.083) after adjustment for potential confounders. Similarly, no significant association between use of PPI and slope of T-score was observed when defining PPI/H2RA exposure as use within 6 months of the initial BMD measurement, or only including participants with at least 2 BMD measurements, or stratified by different age and sex. Use of PPI was not associated with an increased rate of BMD loss in KTRs. Our results support previous findings that PPI use does not have a significant effect on bone mineral loss.

Lyu B ，Hansen KE ，Jorgenson MR ，Astor BC ... -  《-》

Comparison of fracture risk between proton pump inhibitors and histamine-2 receptor antagonists in ANCA-associated vasculitis patients: a nested case-control study.

Whether acid suppressants [proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RAs)] are associated with bone fractures in patients with ANCA-associated vasculitis (AAV) treated with glucocorticoids remains unclear. This study compared PPIs with H2RAs in terms of the risk of bone fractures in patients with AAV who received in-hospital induction therapy with glucocorticoids. We retrospectively identified 149 patients with fractures among 22 821 patients newly diagnosed with AAV in 1730 hospitals using a nationwide inpatient database from July 2010 to March 2018. We conducted 1:4 case-control matching. Age, sex, duration of AAV treatment and fiscal year were matched between the cases and controls. A conditional logistic regression analysis was conducted to assess the association between acid suppressants and fractures. Of all enrolled patients with fractures, the median age was 77 years, and 99 (66%) were female. The median duration from AAV treatment to fracture was 52 days. The proportion of patients using PPIs was 91.3% (136 of 149) and 80.2% (478 of 596) in the case and control groups, respectively. Compared with H2RA use, PPI use was significantly associated with fractures after adjustment for age, sex, BMI, smoking habit, Charlson comorbidity index, renal failure, bisphosphonate and same fiscal year according to a multivariate analysis (adjusted odds ratio, 3.76; 95% CI: 1.37, 10.3). PPI users had a higher risk of fractures than H2RA users among mostly advanced-age patients with AAV with remission induction therapy.

Miyano S ，Michihata N ，Sada KE ，Uda K ，Matsui H ，Fushimi K ，Nangaku M ，Yasunaga H ... -  《-》

Meta-analysis: risk of fractures with acid-suppressing medication.

Recent studies have suggested an increased risk of fractures with proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RAs). We planned to perform a meta-analysis of fractures in patients taking PPIs and H2RAs. We searched MEDLINE and EMBASE in September 2010 for observational studies reporting on the risk of fractures with acid-suppressing medication (PPIs and H2RA). We also checked the references lists of included studies and regulatory authority websites for additional data. We performed random effects meta-analysis of odds ratios (OR) according to fracture type and conducted subgroup analyses by duration of exposure. Heterogeneity was assessed using the I(2) statistic. Our review included 12 studies covering 1,521,062 patients. Pooled analysis of PPI use showed significant risk for spine fractures (4 studies, OR 1.50, 95% CI 1.32-1.72, p<0.001, I(2)=0%) but this was not significant for H2RA (3 studies, OR 1.05, 95% CI 0.92-1.19, p=0.50, I(2)=0%). Similarly for hip fractures, there was a significant risk of fractures with PPIs (10 studies, OR 1.23, 95% CI 1.11-1.36, p<0.001, I(2)=72%), but not for H2RAs (9 studies, OR 1.12, 95% CI 0.99-1.27, p=0.06, I(2)=75%), respectively). Analysis of fractures overall (based on all 12 studies covering a mixture of fracture types) yielded an OR of 1.20 (95% CI 1.11-1.30, p<0.001, I(2)=78%) for PPIs, and OR of 1.08 (95% CI 1.00-1.18, p=0.06, I(2)=82%) for H2RA. However, aside from the risk of spine fractures, all the other analyses were limited by substantial heterogeneity. One study that reported on a direct comparison between acid-suppressing medications found an increased risk with PPIs vs. H2RA for hip fractures, OR 1.34 (95% CI 1.14-1.38). There is some evidence for a modest association between PPI use and risk of fractures, which was not seen with H2RA exposure. The association is most consistent for spine fractures, while there is substantial heterogeneity in the magnitude of risk for other fractures. Clinicians who are concerned about patients with high fracture risk may wish to consider the option of H2RAs instead of PPIs.

Kwok CS ，Yeong JK ，Loke YK 《-》

Fracture risk of young adults receiving proton-pump inhibitors and H2-receptor antagonists.

Proton-pump inhibitors (PPI) and histamine (type 2) receptor antagonists (H2RA) have the potential to interfere with calcium metabolism. Several authors have evaluated the effect of these medications on fracture incidence in older adults. A recent large epidemiologic study demonstrated a higher risk of fractures in young adults receiving PPI. To evaluate the effect of PPI and H2RA use on fracture incidence in a large retrospective cohort of military recruits representative of general population of young adults. A retrospective cohort of 254 265 male and 234 670 female non-combat military conscripts ages 18-25. Subjects were divided into three groups by PPI use (no PPI use, 1-100 tablets and more than 100 tablets) and two groups by H2RA use (no H2RA use, any H2RA use). Multivariate logistic regression was used to adjust fracture risk for age, BMI, education level, socio-economic level, ethnic origin, occupation and duration of follow-up in months. At least one fracture during the study period. Use of PPI and H2RA was not associated with an increased risk of fractures. In men, the predictors of an increased fracture risk were higher BMI (OR = 1.007, P < 0.001), origin from a developing country (OR = 1.15, P < 0.001) and service as a driver (OR = 1.11, P < 0.001). Higher education, higher socioeconomic status and service as an officer or as an administrative worker had a protective effect on fracture incidence. In women, fractures were associated with higher BMI (OR = 1.035, P < 0.001). Origin from a developed country, as well as service as an officer or an administrative worker was associated with lower fracture risk. There was no association between the use of PPI or H2-antagonists and fracture incidence in this retrospective cohort of healthy young military recruits.

Fedida B ，Schermann H ，Ankory R ，Rotman D ，Shichman I ，Yoffe V ，Shlaifer A ，Luger E ... -  《-》