Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2015 Apr 15;8(4):4899-910.
eCollection 2015.

Bone fracture and the interaction between bisphosphonates and proton pump inhibitors: a meta-analysis

Si-Dong Yang  1 , Qian Chen  1 , Hai-Kun Wei  1 , Feng Zhang  2 , Da-Long Yang  1 , Yong Shen  1 , Wen-Yuan Ding  3
Affiliations

Bone fracture and the interaction between bisphosphonates and proton pump inhibitors: a meta-analysis

Si-Dong Yang et al. Int J Clin Exp Med. .

Abstract

Objective: Recent studies suggested an increased risk of fractures with interaction between bisphosphonates (BPs) and proton pump inhibitors (PPIs). We performed a meta-analysis of fractures between patients taking BPs/PPIs and those taking BPs only.

Methods: We conducted a PubMed database and Ovid database search, as well as Cochrane Library search (up to July 2014) for studies assessing the association between fractures and BPs or/and PPIs. We performed random effects meta-analysis of odds ratios (OR) according to fracture type and conducted subgroup analyses by race and BP subtypes. Heterogeneity was assessed using Q statistics and I(2) statistic.

Results: After study selection, 4 unique studies (5 comparisons) including 57259 patients were available for this meta-analysis. Pooled analysis of overall fracture risk of BP+PPI group versus BP group showed a significant increase in risk of fractures (OR = 1.52, P = 0.025), with substantial heterogeneity. However, heterogeneity was drastically reduced in subgroup of Asian (I(2) = 24% and P = 0.251), and fracture risk showed a significant increase (OR = 1.75, P = 0.026). In contrast, heterogeneity was little eliminated in subgroup of European, and fracture risk was no statistical difference (OR = 1.42, P = 0.068). Three studies including 4 comparisons reported on spine fracture were included in the pooled analysis demonstrating an increased spine fracture risk associated with BP/PPI interaction (OR = 1.60, 95% CI 1.13-2.26, P = 0.008, I(2) = 58.6%).

Conclusions: This meta-analysis suggests that there is an interaction associated with increased fracture risk (particularly for spine and Asian race) between BP and PPI use. Clinicians should carefully evaluate such risk factors for osteoporosis in patients taking BPs, before routinely prescribing PPIs, and make a careful judgment as to whether PPIs may be safe for patients at high risk of fractures.

Keywords: Fracture; bisphosphonate; meta-analysis; proton pump inhibitor.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Flow diagram of study selection.
Figure 2
Figure 2
Summary graph of risk bias. Review authors’ judgments about each risk of bias item for each included study. + is ‘‘yes’’, - is “no”, null is “unclear”.
Figure 3
Figure 3
Forest plot of comparison between BP+PPI group and BP group in all included studies. BP, bisphosphonates; PPI, proton pump inhibitors; OR, odds ratio; CI, confidence interval.
Figure 4
Figure 4
Sensitivity analysis of all included studies. OR and 95% CI by omitting each study from the included studies.
Figure 5
Figure 5
Forest plot of comparison between BP+PPI group and BP group after omitting the study of Abrahamsen 2. BP, bisphosphonates; PPI, proton pump inhibitors; OR, odds ratio; CI, confidence interval.
Figure 6
Figure 6
L’Abbé graph for heterogeneity analysis among all included studies.
Figure 7
Figure 7
Forest plot of comparison between BP+PPI group and BP group by race. BP, bisphosphonates; PPI, proton pump inhibitors; OR, odds ratio; CI, confidence interval.
Figure 8
Figure 8
Forest plot of comparison between BP+PPI group and BP group by spine fracture. BP, bisphosphonates; PPI, proton pump inhibitors; OR, odds ratio; CI, confidence interval.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Kanis JA, Burlet N, Cooper C, Delmas PD, Reginster JY, Borgstrom F, Rizzoli R. European guidance for the diagnosis and management of osteoporosis in postmenopausal women. Osteoporos Int. 2008;19:399–428. - PMC - PubMed
    1. Black DM, Delmas PD, Eastell R, Reid IR, Boonen S, Cauley JA, Cosman F, Lakatos P, Leung PC, Man Z, Mautalen C, Mesenbrink P, Hu H, Caminis J, Tong K, Rosario-Jansen T, Krasnow J, Hue TF, Sellmeyer D, Eriksen EF, Cummings SR. Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N Engl J Med. 2007;356:1809–22. - PubMed
    1. Black DM, Thompson DE, Bauer DC, Ensrud K, Musliner T, Hochberg MC, Nevitt MC, Suryawanshi S, Cummings SR. Fracture risk reduction with alendronate in women with osteoporosis: the Fracture Intervention Trial. FIT Research Group. J Clin Endocrinol Metab. 2000;85:4118–24. - PubMed
    1. Harris ST, Watts NB, Genant HK, McKeever CD, Hangartner T, Keller M, Chesnut CH 3rd, Brown J, Eriksen EF, Hoseyni MS, Axelrod DW, Miller PD. Effects of risedronate treatment on vertebral and nonvertebral fractures in women with postmenopausal osteoporosis: a randomized controlled trial. Vertebral Efficacy With Risedronate Therapy (VERT) Study Group. JAMA. 1999;282:1344–52. - PubMed
    1. Prieto-Alhambra D, Pagès-Castellà A, Wallace G, Javaid MK, Judge A, Nogués X, Arden NK, Cooper C, Diez-Perez A. Predictors of fracture while on treatment with oral bisphosphonates: a population-based cohort study. J Bone Miner Res. 2014;29:268–74. - PMC - PubMed

LinkOut - more resources