Long-Term use of PPI therapy did not adversely affect measures of bone strength

PPIs as a class have had an excellent track record of safety and efficacy since their introduction in the mid and late 1980s. However, the class has come under intense scrutiny (including in the lay press) in the last 10 years due to multiple retrospective cohort studies showing an association of PPI use with various, sometimes serious, adverse events. In particular, PPIs have been associated with an increased risk of osteoporotic fractures (hip, wrist, and spine). What has NOT been shown, however, strong evidence showing causality and a clear mechanism for this effect are lacking to “prove” this association.  (Arch Intern Med 2010; 170:765)

In a recent Canadian study, no differences in bone density or bone strength were seen in PPI users compared with nonusers. The authors assessed bone strength and structure in 52 patients with >5 years of PPI use compared with 52 matched nonusers (mean overall age, 65). Metabolic markers of bone turnover and osteoblast activity were also measured metabolic markers and markers of osteoclast function (calcium, magnesium, PTH, osteocalcin, vit D, and C-telopeptide).

In short, there was no difference between the users and non-users in any measure of bone strength, structure, bone mineral density, or metabolic markers, indicating no greater fracture risk for users of long-term PPI. In essence, this well-done study from Canada solidifies the absence of any direct causal link between PPI use and bone disease. What confounders produce the association seen in previous studies remains unknown. Both patients and providers can feel comfortable based on current evidence that, when indicated, long-term use of PPIs does NOT cause bone fractures.