Short-term PPI therapy may not be harmful to bone

Last Updated: 2018-12-13

By Lorraine L. Janeczko

NEW YORK (Reuters Health) - Short-term proton-pump inhibitor (PPI) therapy has no clinically meaningful effect on bone turnover, a new study suggests.

PPIs have been linked with osteoporotic fractures, but whether they directly cause osteoporosis remains unclear, researchers note in Gastroenterology, online November 13.

"We found no evidence that six months of PPI therapy altered calcium absorption, serum or urine mineral levels, parathyroid hormone, vitamin D status or bone-mineral density. Bone turnover increased, but remained coupled, with increases in both bone formation and bone resorption," Dr. Karen E. Hansen of the University of Wisconsin School of Medicine and Public Health in Madison said by email.

"PPI therapy did not alter bone or mineral metabolism in a manner expected to cause osteoporosis. Thus, we found no mechanism by which PPI therapy would directly cause osteoporosis," she told Reuters Health.

Dr. Hansen and her colleagues conducted a prospective double-blind study of 115 healthy, postmenopausal women between 45 and 75 years of age, with normal calcium intake and vitamin D status, over almost four years at 12 centers in the United States. Women were randomized to receive dexlansoprazole (60 mg), esomeprazole (40 mg), or placebo daily for 26 weeks.

The research team monitored plasma levels of procollagen type 1 N-terminal propeptide (P1NP) and C-terminal telopeptide of type 1 collagen (CTX) at baseline and at 13 and 26 weeks. They measured percent changes in P1NP and CTX as well as changes in serum and urine levels of mineral, bone-mineral density, and parathyroid hormone (PTH) in all patients, and true fractional calcium absorption (TFCA) in 30 patients.

Between baseline and week 26, the researchers found no significant within-group differences in bone turnover markers; but they did detect a small increase in CTX levels in the dexlansoprazole group (0.12 ng/mL).

Women in the esomeprazole and dexlansoprazole groups had significantly increased levels of P1NP (18.2% and 19.2%, respectively) and CTX (22.0% and 27.4%, respectively) at week 26 compared with those on placebo, and these values remained at normal levels.

There were no statistically significant differences between groups in serum or urine levels of minerals, bone-mineral density, or PTH at week 26; and PPI therapy did not lower TFCA.

Dr. Joshua D. Miller, the medical director of diabetes care for Stony Brook Medicine and an assistant professor of endocrinology and metabolism at Stony Brook University in New York State, said, "The study demonstrates a somewhat novel understanding of the relationship between proton-pump inhibitors and bone homeostasis. For years, we have thought that long-term PPI use was harmful to bones. Thus, I generally recommend that patients using the medications for more than six months discuss alternative therapies with their prescribing doctor."

"While the present study mentions an insignificant increase in markers of bone turnover in patients taking PPIs, I would like more information regarding bone architecture in the same study group," Dr. Miller, who was not involved in the study, told Reuters Health by email. "Moreover, the study duration is rather short. I would be curious to see what happens to bone turnover beyond 26 weeks."

"The potential negative effect of PPIs on bone-mineral density and fractures is an important topic, especially due to the extensive use of these medications," Dr. Asim Khokhar, a gastroenterologist and assistant professor of medicine at Stony Brook University, told Reuters Health by email. "This study is interesting because it looks at the effect of PPIs on markers of bone turnover, which has not been studied extensively."

Dr. Khokhar, who also was not involved in the study, agreed with Dr. Miller about the limitations of the short-term follow-up.

"Most of the prior literature suggesting decrease in bone-mineral density or increase in fractures has suggested a negative correlation in long-term (beyond one year) PPI use," noted Dr. Khokhar. "It would be useful to study these markers in future longer-term studies."

Takeda Pharmaceuticals International, Inc., a manufacturer of dexlansoprazole, funded the study. Takeda was responsible for the study design, data collection and interpretation, and manuscript writing.

Drs. Hansen and several coauthors reported financial ties to the company.

SOURCE: https://bit.ly/2QrkS6g

Gastroenterology 2018.