Preventing bone loss in space

Astronauts’ bones become thinner the longer they stay in space. On a long mission to the planet Mars, a broken bone would be a major problem.

Astronauts on the International Space Station tend to lose about two percent of their body’s bone mass for each month they spend in space.

That’s because bone is living tissue. It’s constantly broken down by some cells and rebuilt by others. Without gravity and regular exercise, that balance is upset and less bone is added. Eventually, a loss of bone density can lead to bone fractures and breaks. Jay Shapiro is a team leader for bone loss studies at NASA’s National Space Biomedical Research Institute.

Jay Shapiro: Our particular project involves using patients who have spinal cord injury as a model for the kind of bone loss that occurs in astronauts during space flight.

Patients with spinal cord injuries are like astronauts in that they aren’t using their lower limbs. They seem to suffer about the same rate of bone loss in their lower bodies as astronauts. Shapiro’s project involves administering zoledronate — a drug used to prevent bone loss — to those with spinal cord injuries. Half receive the drug. The other half receive a placebo. The patients take the drug for several months, while their bone densities are regularly measured.

If the drug helps those with spinal cord injuries, it might also help astronauts maintain strong bones on future multi-year missions to Mars.

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Bone is living tissue. It’s constantly broken down by some cells and rebuilt by others. Without gravity and regular exercise, that balance is upset and less bone is added. Fred Wezeman, orthopedic surgeon at Loyola University in Maywood, Illinois, added, “If you’ve ever had a fracture and had a cast, you’ll notice your affected arm is smaller. If you don’t use it, you lose it.”

Jay Shapiro is a medical researcher at the Uniform Services University in Bethesda, Maryland and a team leader for bone loss studies at NASA’s National Space Biomedical Research Institute.

Shapiro can’t announce preliminary results of his zoledronate work yet, because even he doesn’t know them. That’s because it’s a “double blind study” — in other words, the patients don’t know if they’re getting the real drug and the doctors don’t know which results match with which particular patient. The study is expected to end in February 2004.

Excerpts from interview with Dr. Shapiro:

ES: What specific research project are you most involved with?

Our particular project involves using patients who have spinal cord injury as a model for the kind of bone loss that occurs in astronauts during space flight. There are not great models for studying the kind of bone loss that occurs in space flight. In terms of the location of the bone loss, where the bone is lost from and the rate at which the bone is loss, there is not a good model on Earth. A lot of studies are done on animals. A lot of the studies are done on normal healthy patients who agree to confine themselves to bed for several weeks and during that time, they’ll lose bone.

And NASA is interested in bone loss over a much larger time period. And for that reason, we looked at patients with spinal cord injury who can not move the lower part of the body as a model of both the rate and location of bone loss that occurs in astronauts and it turns out that our assumption that this would be the case is correct. That the people who have spinal cord injuries lose bone from the lower parts of their bodies as do astronauts when they’re weightless. And they also lose it at about the same rate, which on the average is about 2 percent of their bone mass per month. Largely from the lower body. The astronauts will lose some from their spine, at a somewhat slower rate. But they still lose a significant amount from their spine. People with spinal cord injury may not lose a lot from their spine because they’re able to sit up in a wheel chair and that’s enough to load the spine to cut down on bone loss. In the spine in space flight, there is no loading. There is no mechanical loading, so some bone is lost from the spine as well.

ES: Can you walk me through your drug study work?

We see patients who have had a spinal cord injury within a matter of approximately 8 weeks of their injury. So we get as close to the original time of the injury as we can. And what we do is we measure the density of bone — how much bone there is at that point — and we measure how much muscle mass there is around the thigh. And we can do that with x-ray techniques that are pretty simple.

Another part of that is to get a CT scan — and I think people are familiar with CT scans — of the hip. And colleagues of ours at the Johns Hopkins Applied Physics Laboratory are using that information to reconstruct the hip in terms of what happens to it … in terms of the estimated fracture risk would be.. done by a process called 3-D finite element analysis, where the hip is essentially taken apart and the bone in the hip is taken apart by a computer and then … on the structure and strength of that bone.

Then patients are divided into two groups. Some of them are treated with an active principal — which in this study is called zoledronate, which is made by the Novartis company — and the other group receives a placebo, that is to say they do not receive the active agent. And the two groups are followed over a period of six months and even as long as a year.

At this point, I can’t tell you what the results have been thus far. And the reason is that this is a double masked protocol — that is to say neither the patient nor the doctors know whether the patient’s been given the active principal or the placebo and we’re not going to have that information for about six months when the study ends. So we can’t say now whether it’s effective. In February [2004] we’ll have some idea whether this has been effective or not.

ES: How many people are in the study?

In total, there will be about 24 people involved. Right now I think we have about 17 or 18.

They’re staggered in time because one can not accumulate this number of this kind of patient in any one setting. People come in unfortunately when they have their injury. So we recruit those patients when they’re available — which is not a problem at all. When people have spinal cord injuries, it takes a while for them to settle down — both in terms of some recovery from some things that happen when you’re in that setting. For example, someone’s in an automobile accident and the may have a spinal cord injury, but they also may have broken their leg or have punctured a lung and all these terrible things that have happened. And it takes time for them to get over that, so they can’t come into our study until about 8 weeks have gone by. And indeed they’re staggered.

ES: So what are the biggest challenges in this work?

Well, we found other things about how you lose bone in this setting. And that has turned out to be very interesting. There’s a layer of firm tissue on the outside of bone called the periosteum. It’s the outside covering of bone and it’s made of fibrous tissue. It turns out from the studies that we’ve done that when people are in a non-weight-bearing setting, they tend to lose bone from the inside surface of the bone, but they can’t make bone, they can’t increase bone on the outside through the periostial layer. Now the reason that’s important is that during normal aging, when people just get older, they also lose bone from the inside surface of their bone, but they compensate for this by laying down bone in the periostial layer of bone. And we find that both in spinal cord injury patients and where studies have been done in astronauts that the difference from normal is that these people are much less effective in laying down periostial bone.

Where studies have been done in animals rodents after space flight, it turns out that the same thing happens in rodents. So being non-weight-bearing appears to impair your ability to compensate for bone loss by adding out bone on the outside layer or periostial bone and that weakens the bone because you haven’t compensated for bone loss within the cortex of bone.

It certainly does. And our group is pursuing that. It also suggests that perhaps in people who are non-weight-bearing like someone in a nursing home or someone after certain types of surgery, if you want to make their bones strong, maybe there are other ways of going about it besides the conventional therapy that people tend to get in these settings. So it focuses now on the place that might be the target of preventing bone loss much more so than it has been the case in the past.

ES: Please tell me more about the drug you’re testing.

We’re using a drug called zoledronate, which is currently being used in patients that suffer from osteoporosis of aging. The reason it’s attractive is that it has a very prolonged duration of action. It can last up to a year after a single intravenous infusion. And that intravenous infusion takes about 15 minutes. So it’s a very potent drug with very, very, long lasting effects compared to the bisphosphonate drugs that are currently on the market. And it’s long lasting action is what would be of interest to NASA because it would be possible [cough], for example, to pretreat individuals and then retreat them at widely spaced intervals, as much as a year, in order to limit the rate of bone loss they would have when they’re in a non-weight-bearing setting.

This is relatively new. It’s currently under FDA review. But there have already been published investigations showing it to be pretty effective — and lasts as long as a year. Everything has its drawbacks.

ES: What do you love most about your job?

What do I enjoy about my job? Well, I think that physicians who are involved in clinical investigation are sort of hooked on a drug called new discovery. And the reason people pursue these things is because they’re interested in expanding knowledge.

Now I’m dealing with two populations, which are in a sense needy populations. One of them are patients with spinal cord injuries who are losing much more bone and have a greater chance of fracture than have been appreciated before. The second group of people are the astronauts where their loss of bone constitutes a tremendous hazard not only to their own health but to the success of their mission. So that what we’re learning from both of these populations is complimentary and now as I described a few minutes ago starts to open up some new questions and new areas of investigation which may over time make for better drug applications … and those kinds of modalities all aimed at maintaining their bone strength and decreasing the chance of a fracture…

What you have in your mind?