There are four things an astronaut will always do during their time in space. Eat, sleep, calling home to family, and exercise. That last one is very important for maintaining their health. The reason is because the effects of zero gravity on the body over time are not good ones, and no one knows this more than astronauts who have returned from a long duration in space. What many astronauts experience upon return is fatigue, atrophied muscles, and loss of bone density. The problem lies in the way our bodies adapt to the type of work we do. When we work out, we gain muscle and bone density, however the exact opposite will also happen if you don't. To prevent this, they do as much as four hours of exercise per 16 hour period.
The amount of stress your bones take, in addition to calcium and magnesium, is essentially what determines your bone density. In a zero gravity environment, there is no stress to the bones, so even with a calcium rich diet your bones will start to break down. Researchers have shown that on average the human body will lose approximately 1-1.6% of their bone mineral density per month. This takes place primarily in the spine, neck, and pelvis. This is called skeletal unloading, and it happens because your body loses its ability to rebuild bone cells. The effects of this are similar to osteoporosis, and can lead to stress fractures and breaks. One piece of equipment to prevent this is a treadmill with straps that pull you down, like the effects of gravity.
If you think about it this way, zero gravity means zero weight, which rules out any exercise that requires lifting, like weights. Since nothing has any weight, you don't need to use any of your muscles. When you don't use something it atrophies, because your body sees no reason to keep it. It is just an extra expense of energy that you're not using. The only way to combat this is with tension style workouts. Like those thigh blasters and tension bands. Of course, this is NASA, so the equipment is more sophisticated than simple thigh blasters.
It is true that fatigue is a result of the muscle atrophy and bone density, but it is also a result of gravity. After months in space, astronauts are no longer used to the constant weight of life here on earth, and even simple tasks become tiring.
Even though they have plenty of exercise equipment, scientists are still looking for additional means to prevent this from happening, such as a vibrating plate to stand on, which stresses the bones. Even with regular exercise they will still experience the atrophy and bone loss.