February 14, 2011 – According to online results of an observational study reported in the Archives of Internal Medicine, “Concurrent use of proton pump inhibitors (PPIs) is associated with a dose-dependent loss of protection against hip fracture with alendronate in elderly patients.”

PPIs are widely used in elderly patients and are frequently co-administered in users of oral bisphosphonates. Biologically, PPIs could affect the absorption of calcium, vitamin B12 and bisphosphonates and could affect the osteoclast proton pump, thus interacting with bisphosphonate antifracture efficacy. Moreover, PPIs themselves have been linked to osteoporotic fractures.

This population-based, national register–based, open cohort study observed 38,088 new users of alendronate sodium for a period of mean duration 3.5 years.

• The risk for hip fracture was evaluated in relationship to alendronate prescription refill, based on recent pharmacy records.
• For hip fractures, there was a significant interaction (P < .05) with alendronate for PPI use.
• In patients who were not PPI users and had complete refill compliance to alendronate, there was a significant treatment response, with a 39% risk reduction in hip fractures (hazard ratio [HR], 0.61; 95% confidence interval [CI], 0.52 – 0.71; P < .001).
• However, risk reduction was not significant in concurrent PPI users who had complete refill compliance to alendronate (19%; HR, 0.81; 95% CI, 0.64 – 1.01; P = .06).
• PPI dose and patient age affected the degree of attenuation of the risk reduction.
• Unlike the effect of PPIs, concurrent use of histamine H2 receptor blockers had no significant effect on the treatment effect of alendronate.

Concurrent PPI use was associated with a dose-dependent loss of protection against hip fracture with alendronate in elderly patients, the study authors write. This is an observational study, so a formal proof of causality cannot be made, but the dose-response relationship and the lack of impact of prior PPI use provides reasonable grounds for discouraging the use of PPIs to control upper gastrointestinal tract complaints in patients treated with oral bisphosphonates.

Ref :   http://www.medscape.com/viewarticle/737427?src=mpnews&spon=34