TOPICS > Health

FDA Urges Caution Over Long-Term Use of Bone-Density-Building Drugs

May 10, 2012 at 12:00 AM EDT
Millions of women grapple with whether to take bone-density-building drugs to treat or prevent osteoporosis, but the FDA this week warned that long-term use of bisphosphonates can lead to rare fractures and side effects. Margaret Warner and Maine Medical Center's Dr. Clifford Rosen discuss the risks outlined by the FDA.

JUDY WOODRUFF: Next, new cautions are raised over drugs to help your bones.

Margaret Warner has our story.

MARGARET WARNER: Millions of women as they age grapple with whether to take bone-density-building drugs to treat or prevent osteoporosis. This week, the Food and Drug Administration in an article in “The New England Journal of Medicine” urged caution about long-term use of so-called bisphosphonates, like Fosamax, Boniva, and Actonel. Long-term use has been linked to rare fractures and side-effects.

Osteoporosis afflicts some eight million women and two million men in the U.S., and another 34 million have reduced bone mass that raises their risk for the disease. The FDA analysis, drawing on two earlier industry-funded studies, found many of these women derive little or no benefit from the drugs after three to five years.

For more, we turn to Dr. Clifford Rosen, director of clinical research at Maine Medical Center’s Research Institute, and a professor at Tufts University Medical School. He co-wrote the article accompanying the FDA study.

And, Dr. Rosen, thanks for being with us. There’s been. . .

DR. CLIFFORD ROSEN, Maine Medical Center Research Institute: Thank you for having me, Margaret.

MARGARET WARNER: There’s been an ongoing debate about these drugs.

What new — what is new here in this analysis that the FDA has just provided?

DR. CLIFFORD ROSEN: Well, I think what they did is, they asked the question, are these drugs continually being beneficial if they’re administered over a long period of time?

We know that the drugs work over three to five years. And the question they were asking is, are they still effective if you continue to take them? There’s really been no statement or no data on what — how long individuals should take these drugs.

And with some side effects being reported with increasing frequency, still rare, but there are some side effects, the FDA decided to go back and look very carefully at all the trials that were conducted that looked at long-term treatment, that is, more than three to five years.

MARGARET WARNER: And who is taking these drugs and how widely is it — are they prescribed?


So, that’s been the problem. We — when these drugs came out — they’re great drugs. They reduce fracture risks. They protect individuals against osteoporosis. We initially thought that we should give them for a lifetime, and nobody was really clear, should there be a stop time? Should there be — should they come off and then go back on?

And as people started taking them for up to 15 years now, since the first drug was approved, there were these occurrences of side effects. And I think every one of us got concerned and asked, what is the optimal duration of treatment? And I think this is where the investigation began.

MARGARET WARNER: And when you say side effects, what are you talking about, the serious ones?

DR. CLIFFORD ROSEN: So, interestingly enough, there were very rare side effects where the jaw — there was problem with the jaw with infection.

But, then, over the last five years, there have been reports of fractures actually occurring in women who have been taking long-term therapy with these drugs, which we call the bisphosphonates. And it was this, I think, that alarmed both regulators and investigators and clinicians to go back and look at the long-term studies.

MARGARET WARNER: Explain, if you would, how these drugs work when they’re — when they’re working right in the early going.


So they’re very effective in the early going. And what they do is, they block the body’s ability to dissolve the bone. Every 10 years, we get a new skeleton. It’s surprising and we don’t notice it, but we get a new skeleton. And part of that process is the repair process.

First, the bone is digested, and then it’s repaired. If the digestion is too great, then there’s bone loss. And what these drugs do, where they’re very effective, it’s stopping this bone — what we call bone reabsorption, or dissolution of bone.

So they build bone density by keeping the bone that you already have and actually enhancing it. So the theory is great. And they actually work for the first three to five years.

MARGARET WARNER: So if they do increase the density of your bones, what is it about them that then would make after five years, you’re actually at — at least some people are at greater risk for a serious fracture?


So we don’t think that there’s a greater risk of fracture, but we don’t think there’s any additional benefit. So for reasons we really don’t understand, we know that the density will continue to increase, but when you look at rate of fractures, that begins to plateau.

So the protection, which was 50 percent to 70 percent reduction in fractures that we saw in the first three to five years, then gradually disappears, even though the bone density is going up. So that means there’s probably other factors going on.

So what the FDA found was that, if you continue the drugs beyond five years, there’s no additional benefit. Now, we don’t know the true risk of these rare side effects. And that’s one of the issues that has to be resolved.

But the fact that there’s no continued benefit made them come out with these findings and review all the data that was available.

MARGARET WARNER: So what’s the takeaway message for women who may have — who have been told they either have osteoporosis or they’re in that broader category — I think it’s called osteopenia — where they have some bone density loss?


MARGARET WARNER: What should they do?

DR. CLIFFORD ROSEN: So I think the bottom-line message is, if you have very low bone density and/or you have had a fracture of your spine and your bone density is very low, you are still at very high risk of fracture.

Those individuals — and we tried to point that out in our article — those individuals should be maintained on the current drugs we have. But if your bone density has gotten a lot better, or if you’re in that osteopenic range, we found — and the FDA did as well — that continuing therapy is not necessarily needed, because the drugs stay in the system for a fair amount of time, and there’s no additional protection.

MARGARET WARNER: Well, Dr. Clifford Rosen, thank you so much.