January 31, 2012

expert reaction to study linking PPIs with increased risk of hip fracture

A new BMJ paper strengthened the association between regular use of proton pump inhibitors (PPIs) – a treatment for heartburn, ulcers and reflux – and risk of hip fracture in post-menopausal women.

Donald Singer, Professor of Clinical Pharmacology & Therapeutics, University of Warwick, said:

“This was an older study among nurses in the US from data collected from 2000 up to 2008. The report by Chan and his team suggests a small but potentially important higher risk of hip fracture in current or ex-smokers on treatment with the anti-ulcer drugs proton pump inhibitors. The risk was small – one extra hip fracture per year for every 2000 women treated – and greater the longer the treatment with a PPI. The link is biologically plausible as both PPIs and smoking have actions on the body which could increase the risk of hip fracture. The authors were careful to state that the risk did not apply to non-smokers and for those at risk they were unable to attribute this to any specific type of PPI.

“This report is another example illustrating that drug choice and duration should be based on balancing clinical benefit against potential risk of adverse drug effects.

“However a weakness of the study is that it was nor a randomized controlled trial. The report was based on following a cohort of people some of whom happened to be on PPI treatment: that means that the findings may be subject to bias i.e. there may be reasons unrelated to the PPIs to explain the hip fracture risk, although the authors did their best to control for obvious sources of bias.

“Patients who are concerned should consult their GP or pharmacist for advice.”

Dan Greer, Royal Pharmaceutical Society spokesperson on gastroenterology medicines, said:

“This is a useful study, that has taken account of the other factors that can affect hip fractures such as smoking, calcium intake, and obesity, that has been missing from other studies looking at the link between PPIs and hip fracture. It suggests there may be a small increase in hip fracture risk associated with these medicines, so called “PPIs”, in a high-risk group (post-menopausal women). Women should be reassured though that the absolute risk is small – 1 extra hip fracture for 2,000 patients treated with PPI for 1 year.

“This study strengthens the current recommendations for PPI use, in that for the majority of patients with symptoms of indigestion PPIs should only be used for short courses (1-2 months), with repeat courses offered at the lowest dose that controls symptoms.”

Tobie de Villiers, President of the International Menopause Society, said:

“Although the relative risk of hip fracture is significantly raised in users of PPI, when compared to non-users, the absolute risk increase is small (about one extra event per 2000 person years). This is still important in view of the widespread use of PPIs and the significant burden of disease of hip fractures on affected individuals and the health care system. It is worrying that even the use of common anti-fracture drugs do not affect this association. The conclusion of this study will need to be considered in clinical practice as it is biologically plausible and supported by other studies.”

‘Use of proton pump inhibitors and risk of hip fracture in relation to dietary and lifestyle factors: a prospective cohort study’ by Hamed Khalili et al., published in the BMJ on Tuesday 31st January.