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 《-》

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 ... -  《-》

Use of acid-suppressive drugs and risk of fracture: a meta-analysis of observational studies.

Eom CS ，Park SM ，Myung SK ，Yun JM ，Ahn JS ... -  《-》

Associations of Proton-Pump Inhibitors and H2 Receptor Antagonists with Chronic Kidney Disease: A Meta-Analysis.

Wijarnpreecha K ，Thongprayoon C ，Chesdachai S ，Panjawatanana P ，Ungprasert P ，Cheungpasitporn W ... -  《-》

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 ... -  《-》