Original Article

Osteoporosis International

, Volume 20, Issue 12, pp 1989-1998

First online:

Fracture risk in patients receiving acid-suppressant medication alone and in combination with bisphosphonates

  • F. de VriesAffiliated withUtrecht Institute for Pharmaceutical Sciences, Universiteit UtrechtGeneral Practice Research Database, MHRA Email author 
  • , A. L. CooperAffiliated withBridge Medical Centre
  • , S. M. CockleAffiliated withServier Laboratories Ltd.
  • , T.-P. van StaaAffiliated withUtrecht Institute for Pharmaceutical Sciences, Universiteit UtrechtGeneral Practice Research Database, MHRA
  • , C. CooperAffiliated withMRC Epidemiology Resource Centre, University of SouthamptonNorman Collisson Chair of Musculoskeletal Sciences, University of Oxford

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Previous studies have found an association between acid suppressants and fracture risk. We assessed fracture risk in patients taking concomitant acid suppressant and bisphosphonates. Positive associations were observed for any hip and vertebral fracture. The effect size was modest; however, the significance lies in the widespread prescribing of acid suppressants.


Previous studies have found that acid-suppressive medication (ASM) is associated with an increased risk of fracture. Bisphosphonates can cause upper gastrointestinal problems, and patients may be prescribed ASM to minimise these effects.


A retrospective cohort study using the GPRD was conducted in patients aged 40 years and older starting proton pump inhibitors (PPI, N = 234,144), H2 receptor antagonists (H2RA, N = 166,798) or bisphosphonates (N = 67,309). Fracture risk in current versus past use of ASM and concomitant use of bisphosphonate plus ASM versus bisphosphonate alone was compared using time-dependent Cox regression.


In the 6 months before initiating bisphosphonate therapy, 20.1% of patients received a PPI and 7.5% an H2RA. Current PPI use was associated with an increased risk of any (adjusted relative rate (ARR) 1.15, 95% CI 1.10–1.20), hip (ARR 1.22, 95% CI 1.10–1.37), and vertebral fracture (ARR 1.40, 95% CI 1.11–1.78); and concomitant bisphosphonates and PPIs with an increased risk of any (ARR 1.08, 95% CI 1.01–1.16) and hip fracture (ARR 1.24, 95% CI 1.08–1.42).


ASM is associated with an increased risk of fracture when taken alone or in combination with bisphosphonates. Given the frequency of coprescription of ASM and bisphosphonates, this issue requires further investigation.


Bisphosphonate Cohort study Fracture risk H2 receptor antagonists Osteoporosis Proton pump inhibitors