Fracture Risk and Bone Mineral Density Reduction Associated with Proton Pump Inhibitors

Yuen Ting Lau, Pharm.D.; Nasiya N. Ahmed, M.D.

Disclosures

Pharmacotherapy. 2012;32(1):67-79. 

In This Article

Literature Search

We searched the MEDLINE and EMBASE databases to identify all relevant studies published in the English language between 1980 and February 2011. The following medical subject heading (MeSH) terms were used to identify studies on PPIs, all combined with the Boolean "OR" operator: proton pumps, proton pump inhibitors, antiulcer agents, and omeprazole. The following MeSH terms were used to identify studies on fracture risk and BMD reduction, all combined with the Boolean "OR" operator: bone fractures, hip fractures, osteoporosis, and bone density. We then combined these two searches by using the Boolean "AND" operator. Studies that compared fracture risk or BMD reduction between PPI users and nonusers or between current and past PPI users were selected. The references of all selected studies were manually searched for any additional studies. We also identified one article that was published online ahead of print from electronic alerts of medical journals.

The literature search identified 17 potentially relevant articles for full-text assessment. Three of these articles were excluded, including one study that limited the study population to patients undergoing hemodialysis (Figure 1).[4] The remaining 14 articles compared the risk of BMD reduction or fracture between PPI users and nonusers or between current and past PPI users and consisted of eight case–control studies and six cohort studies.[5–18] Nine studies evaluated cumulative or continuous exposure of PPI for more than 1 year, providing data on prolonged PPI use. Among the 14 studies, fracture risk was evaluated in the hip in 11 studies, vertebrae in five, and wrist in three; the effect of PPI use on BMD was evaluated in three studies. Eight studies[5,7,8,9,10,15,16,17] found an increased fracture risk at the hip, five studies[8,11,13,14,17] found an increased fracture risk at the spine, and one study[11] found an increased fracture risk at the wrist; however, none of the three studies on BMD found a consistent change in BMD associated with PPIs. A dose-response relationship measured by cumulative duration or doses was demonstrated in 4 of 10 studies. Four of five studies also showed that increasing daily dose increased the risk of fracture. Table 1[5–17] and Table 2[11,12,18] summarize the results of the studies that evaluated the risks of fracture and BMD reduction associated with PPIs.

Figure 1.

Flow diagram of the study selection process.

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