Stopping alendronate after five years and proton pump inhibitors' relation to hip fracture
JAMA 2006; 296. Effects of Continuing or Stopping Alendronate After 5 Years of Treatment. Black DM, and others. URL. This study involved 1,099 women who had taken alendronate (Fosamax) for at least five years and who then discontinued therapy for another five years. They were tested to see the effect upon hip and other bone mineral density (BMD), biochemical markers of bone resorption and hip fracture when women who stopped therapy were compared to those who continued alendronate for the full ten years. There was about a 2.5% reduction in total hip BMD and a 3.7% reduction in spine BMD for women who stopped alendronate therapy after five years. There was also an increase in markers of bone turnover in those stopping alendronate. Those stopping therapy after five years had no increased risk of nonvertebral fractures, but there was a significantly lower risk of clinically recognized vertebral fractures (5.3% for placebo and 2.4% for alendronate; RR, 0.45; 95% CI, 0.24-0.85) but no significant reduction in morphometric vertebral fractures (11.3% for placebo and 9.8% for alendronate; RR, 0.86; 95% CI, 0.60-1.22). The authors conclude: “Women who discontinued alendronate after 5 years showed a moderate decline in BMD and a gradual rise in biochemical markers but no higher fracture risk other than for clinical vertebral fractures compared with those who continued alendronate. These results suggest that for many women, discontinuation of alendronate for up to 5 years does not appear to significantly increase fracture risk. However, women at very high risk of clinical vertebral fractures may benefit by continuing beyond 5 years.” Editor's comments: Alendronate has a very long half life which probably explains why there is so little effect from stopping therapy for five years. There have been recent studies suggesting that microcracks might develop that would reduce the strength of bone treated long term with alendronate. The findings of this study show no such decrease in bone strength with the long-term therapy and should be reassuring to those of us who have been taking alendronate for ten or more years. The authors also note that no one in this study developed osteonecrosis of the jaws, supporting the finding that the risk of this serious condition is highest in those on intravenous bisphosphonate therapy that is often used for cancer therapy. For a review of osteonecrosis of the jaws related to bisphosphonate therapy see the recent Update on this site.
JAMA 2006; 296:2947-2953 Long-term Proton Pump Inhibitor Therapy and Risk of Hip Fracture. Yang Y, and others. URL This United Kingdom study involved 13,556 hip fracture cases and 135,386 controls. Comparison was made between 50 year old, or older, users of proton pump inhibitors (PPIs) and those not using them. PPIs are often prescribed to reduced stomach acid production which could interfere with calcium absorption or may reduce bone resorption through inhibition of osteoclastic vacuolar proton pumps. The authors found a 44 percent increase in hip fracture for those taking PPIs for more than one year. Additionally, the longer participants took PPIs, the greater the risk of hip fracture. There was also a much higher fracture rate in those taking high-dose PPIs for more than one year. Editor's comments: These results appear alarming, but probably require several additional studies to find out exactly what the risk is and who is at risk. For example, if you are taking an osteoporosis medication are you still at increased risk? What is the effect of increased vitamin D and/or calcium consumption? I suggest if you have osteoporosis and are taking a PPI that you contact your care provider and discuss options. If you don't have a serious problem and can control your acid reflux with non-PPIs, that might be a good option. I happen to be one of these people taking PPIs daily and my gastric condition is one that definitely requires the PPIs. I am, therefore, going to discuss having my bone density testing done more frequently than is normally suggested. Biochemical markers of bone breakdown might be helpful, too, since they would indicate a change in bone metabolism that is probably caused by the PPIs. I plan on posting additional information on this topic as more becomes available. There is also an interesting online review of this article on medpage Today that you might want to read.