- age of 50 years or older
- at least 5 years since the last menstrual period
- lumbar spine or total hip BMD corresponding to a T-score of –2.5 or worse, or a T-score of –2.0 or worse with at least one prevalent vertebral fracture.
The primary efficacy endpoint was the mean percentage of change in BMD at the lumbar spine.
Findings: At 2 years, the mean change for both delayed-release arms was significantly greater than for the 5-mg immediate-release dose. The authors concluded that the 35-mg weekly delayed-release regimen—whether taken at least 30 minutes before or after breakfast—is as effective and safe as the 5-mg daily immediate-release regimen.
WHAT THIS EVIDENCE MEANS FOR PRACTICE
Oral, delayed-release risedronate (35 mg weekly) is similar in efficacy and tolerability to the immediate-release formulation (5 mg daily). By minimizing the impact of concomitantly ingested food on the bioavailability of risedronate, the delayed-release formulation can make it easier for patients to accept and comply with the regimen, thereby maximizing absorption and improving efficacy of the drug in clinical practice.
Do proton-pump inhibitors increase the risk of fracture?
Targownik LE, Leslie WD. The relationship among proton pump inhibitors, bone disease and fracture [published online ahead of print May 20, 2011]. Expert Opin Drug Saf. doi: 10.1517/14740338.2011.586628.
Yu EW, Bauer SR, Bain PA, Bauer DC. Proton pump inhibitors and risk of fractures: a meta-analysis of 11 international studies. Am J Med. 2011;124(6):519–526.
Ye X, Liu H, Wu C, et al. Proton pump inhibitors therapy and risk of hip fracture: a systematic review and meta-analysis. Eur J Gastroenterol Hepatol. 2011;23:794–800.
In May 2010, the FDA revised prescription and over-the-counter (OTC) labels for proton-pump inhibitors to include new safety information about a possible increased risk of fractures of the hip, wrist, and spine with use of these medications.
Proton pump inhibitors are so named because they prevent hydrogen ion (proton) secretion into the gastric lumen, thereby reducing acid in the stomach. Esomeprazole magnesium (Nexium), dexlansoprazole (Dexilant), omeprazole (Prilosec), omeprazole with sodium bicarbonate (Zegerid), lansoprazole (Prevacid), pantoprazole (Protonix), rabeprazole (Aciphex), and naproxen with esomeprazole magnesium (Vimovo) are available by prescription to treat conditions such as gastroesophageal reflux disease (GERD), ulcers of the stomach and small intestine, and inflammation of the esophagus. Delayed-release omeprazole magnesium (Prilosec OTC, Zegerid OTC) and delayed-release lansoprazole (Prevacid 24HR) are sold OTC for treatment of frequent heartburn.
The new safety information was based on an FDA review of several epidemiologic studies reporting an increased risk of fractures of the hip, wrist, and spine with PPI use. Some studies found that those at greatest risk of fracture received high doses of PPIs or used them for 1 year or longer. Most of the studies involved individuals 50 years and older; the increased risk of fracture was observed primarily in this age group.
Although the greatest risk of fracture involved people who had been taking a prescription PPI for at least 1 year or who had been taking a high dose of a prescription PPI, the FDA took the precaution of altering the “Drug facts” label on OTC agents as well. (Over-the-counter PPIs are indicated for 14 days of continuous use.) However, in March 2011, the FDA reversed its decision and retracted the wording on the label of OTC formulations. Following a thorough review of safety data, the agency concluded that the risk of fracture with short-term, low-dose use of PPIs is unlikely. Nevertheless, the FDA acknowledged that consumers sometimes use a PPI longer than the directions advise. Therefore, the agency recommends that health-care professionals be aware of the risk of fracture if the patient uses an OTC PPI at a higher dose or longer time than the label advises.
Two meta-analyses find a modestly increased risk of fracture
Yu and colleagues analyzed 11 observational case-control or cohort studies that involved mostly older adults. They found a modestly increased risk of hip fracture among individuals taking a PPI, compared with nonusers (relative risk [RR], 1.30; 95% CI, 1.19–1.43). They also found an increase in spinal (RR, 1.56; 95% CI, 1.31–1.85) and any-site fractures (RR, 1.16; 95% CI, 1.04–1.30) among PPI users. They acknowledged that residual confounding could not be excluded.
A separate meta-analysis by Ye and colleagues included seven studies. They found a statistically significant increase in the risk of hip fracture, compared with nonusers (odds ratio [OR], 1.24; 95% CI, 1.15–1.34). However, because of different effects of PPIs at different durations of therapy, Ye and colleagues concluded that evidence was insufficient to support a causal relationship between PPI use and hip fracture. Further investigation is warranted.