Do proton pump inhibitors influence bone in postmenopausal women?


Although clinicians and patients may have concern about the safety of PPIs, a recent study suggests that this concern might not be warranted.



Neither dexlansoprazole nor esomeprazole meaningfully impact bone mineral density, parathyroid hormone levels, serum or urine levels of minerals, or intestinal calcium absorption, according to a randomized, double-blind multicenter study of 115 healthy postmenopausal women.

“I am not surprised by these trial results, given that other prospective cohort studies have found no differences in the trajectory of bone mineral density, when comparing adults who take proton pump inhibitors (PPIs) to that of adults who do not take this class of medications,” said lead author Karen Hansen, MD, MS, an associate professor of medicine at the University of Wisconsin in Madison.

Dr. Hansen said clinicians and patients are very concerned about the safety of PPI therapy, because epidemiologic studies link long-term use of the therapy to a higher risk of osteoporotic fracture. 

“The current study provided an opportunity to identify a mechanism by which this link might occur, or disprove a causal/mechanistic connection,” Dr. Hansen told Contemporary OB/GYN. “The study also builds on my prior work, which concluded that PPI therapy had no effect on intestinal calcium absorption.”

The current study, published in the journal Gastroenterology, was conducted between November 2010 and August 2014. Women were randomly assigned to one of three groups: dexlansoprazole (60 mg), esomeprazole (40 mg) or placebo daily for 26 weeks.

The two primary outcomes were percent changes in plasma levels of procollagen type 1 N-terminal propeptide (P1NP) and C-terminal telopeptide of type 1 collagen (CTX) between weeks 0 and 26.

From baseline to week 26, both the dexlansoprazole and the esomeprazole group had small increases in levels of the bone formation marker P1NP at week 26 (18.2% and 19.2%, respectively, compared to the placebo group). The two medication groups also experienced increases in levels of the bone breakdown marker CTX at week 26 (22.0% and 27.4%, respectively, versus the placebo group).

“However, despite these increases in P1NP and CTX levels, their values remained within normal ranges, and bone formation and resorption were coupled,” Dr. Hansen said. “PPI therapy did not alter mineral homeostasis, calcium absorption or bone mineral density. After 26 weeks of therapy, PPIs had no metabolic effects that would reduce bone mineral density and increase the risk of fracture.”

Dr. Hansen said for those individuals who must take PPIs long term, “they can be reassured by this study, which identified no specific mechanism by which this class of drugs would cause osteoporosis. Patients should continue to be screened for osteoporosis just as they normally would, if not taking a PPI.” 

Epidemiologic studies can only suggest, but not prove, a causative relationship between an exposure and an outcome, according to Dr. Hansen. “People who take PPIs have more medical conditions, and twice the number of medical visits per year, compared to non-users,” she said. 

Dr. Hansen said that at this point in time, it appears that PPI therapy might simply be a marker for poor health – and therefore a greater likelihood of osteoporosis – rather than directly causing osteoporosis. 


Dr. Hansen reports no relevant financial disclosures.

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