Ken Jenks Comments on Bone Demineralization


The Problem with Bones

Human bones slowly lose calcium (and other minerals) in space. This isn't very strange -- human bones lose calcium all the time. But on Earth, most of the time, they build up calcium just as fast as they lose it. This part of _homeostasis_ is called _remodelling_.

We don't know for sure why bones lose minerals in space, but it seems significant that not all bones lose bone mineral density (BMD) at the same rate. For example, the bones in the upper body don't seem to lose minerals at all, while the weight-bearing bones in the legs and lower back lose can lose a large percentage of their bone mineral content over several months in space (up to 20% loss has been observed in some bones of some space travelers).

Bone mineral loss in space travelers happens slowly. On short duration Space Shuttle missions, not enough bone mineral is lost to significantly increase the observed risk of bone fractures, and bone mineral content returns to normal over a period of several months after space flight.

The Problem with Stones

While the bones are losing minerals, those minerals are transported by the blood to the kidneys, where normal renal action removes excess minerals for excretion in the urine. However, the prolonged elevated levels of calcium in the body, called _hypercalciuria_, can lead to kidney stone formation.

Theory

The prevailing theory in bone mineral loss is that the reduced forces experienced by the weight-bearing bones in space lead to reduced stresses in those bones, and then to reductions in bone mineral content. Wolff's Law hypothesises that reduced biomechanical stress leads to reduced tissue formation, but the mechanism for stress transduction and tissue formation in responses to those stresses is not known.

We know that some proteins regulate bone calcification, but we still don't know all of the endocrinology and blood chemistry which links bone decalcification to kidney stone formation.

We frequently use long-term bed rest studies and limb immobilization to study bone demineralization on Earth.

Countermeasures

Because hypercalciuria can cause kidney stones, we can't simply add calcium supplements to the astronauts' diets. Kidney stones are painful build-ups of calcium deposits in the renal system, and are not especially dangerous on Earth, but in space, because the usual methods of removing kidney stones (lithotripsy and surgery) are not available, kidney stones can be a dangerous disabling condition.

Drugs are available which have some effect on bone calcium loss, but (like calcium supplements) these have side effects, and they act on all of the bones in the body, not just the weight-bearing bones which lose calcium in space. The effect of systemic drugs is a buildup in unwanted bone calcium in some bones, while preventing mineral loss in others.

Exercise has been proposed as a countermeasure to bone demineralization, but the forces required to prevent demineralization in the weight-bearing bones seem to be on the order of one times the body weight of the individual. (This makes sense from a homeostatic viewpoint; most people neither gain nor lose bone mineral density during normal terrestrial activities.) However, it is difficult to design exercise equipment which can generate that level of force in a manner which is comfortable for the astronaut to use. Various methods have been proposed and tried, including bungees, springs, bicycles, treadmills, etc., but attaching the load-bearing portion of the exercise equipment to the body in a comfortable way has been a stumbling block. Straps tend to cut into the shoulders and hips, and the human shoulder is not designed to carry one body-weight loads for long durations or intensive exercise.

Research

Various researchers, both at NASA and elsewhere, are developing ground-based protocols for understanding the mechanism of bone loss and changes in calcium metabolism that occur during space flight; to investigate bone demineralization, changes in bone collagen, the pathogenesis and prevention of disuse osteoporosis, and the potential for the formation of renal stones consequent to prolonged hypercalciuria; to develop methods and instruments to non-invasively monitor bone size, density, mineral content and strength; and to develop countermeasures to prevent the loss of bone tissue and function during space flight, including exercise, pharmacological, electrical and/or mechanical interventions. These ground-based research protocols include human and animal studies. The human studies may involve prolonged bed rest as a microgravity analog, and the animals studies may involve limb immobilization and other techniques.

After development of these ground-based research protocols, we will proceed with flight experiments on Shuttle, Mir and International Space Station Alpha.


Editor's note: This comment was originally published in Space Science Digest V1 117, Dec 22, 1994 by Ken Jenks, NASA/JSC/SD561, Space Biomedical Research Institute, kjenks@gothamcity.jsc.nasa.gov (713) 483-4368