Space Life Sciences Research Highlights

A Little Shake Up for Healthy Bones

Using a vibrating platform and a NASA-developed technique to simulate the effects ofmicrogravity on the musculoskeletal system in the rat, Clinton Rubin and Stefan Judex

have shown that the bone loss caused by unloading can be counteracted by ten minutes oflow magnitude, high frequency mechanical stimulation per day. This approach showsstrong potential for inhibiting space flight-related bone loss and treating osteoporosis.

Bone loss is a serious problem both in space andon the ground. In microgravity, astronauts canlose bone mass at rates of up to 1.6 percent per

month, even with the drug and exercise countermea-sures tried to date. While it is not known whetherdeterioration of weight-bearing bone continues indefi-nitely at these high rates, this risk to crew health andwell-being has led the Space Studies Board at theNational Research Council to identify microgravity-induced bone loss as the primary physiological ob-stacle to long-duration space travel.

Back on Earth, bone loss has a number of causes.Osteoporosis is generally associated with aging ormenopause but it can also arise under other conditionssuch as prolonged bed rest, lack of using the muscu-loskeletal system such as occurs in a sedentary lifestyle, steroid use, or malnutrition. The number ofsufferers is in the tens of millions in the United Statesalone, which costs our health services over 20 billiondollars each year. So, it is not surprising that ClintonRubin’s recent findings have drawn a good deal ofattention. His NASA-funded research has shown thatplacing rats on a vibrating platform for 10 minutes perday can mitigate the bone loss resulting from unload-ing of the musculoskeletal system.

Is Frequency More Important Than Force?

Bone is dynamic tissue. It is continually broken downand rebuilt in a cycle of two separate processesknown as resorption and formation. Normally,these processes are closely linked, but condi-tions such as aging, bed rest, and space flightcan throw the cycle out of balance. Resorptiongets the upper hand and bone loss results.

The standard view has been that large magni-tude forces like those we experience whilerunning or lifting weights are the best way tomaintain healthy bones or counteract conditionsthat result in bone loss. It is becoming clear,however, that under space flight conditions, thekinds of load-bearing exercise employed to dateare not as effective a countermeasure as hadbeen anticipated.

Rubin and Judex, based at the State University of NewYork at Stony Brook, have taken a different approach.They believe that as important as the high magnitude,low frequency forces of exercise are the low magnitude,high frequency forces that our bones experience con-tinually under more “omnipresent” conditions such asstanding. Our muscles generate these forces when wesit, stand, and walk in order to coordinate movementand to maintain balance and posture. In a study fundedthrough the NASA Biomedical Research and Counter-measures program, the Stony Brook researchers usedrats to determine whether these stimuli could counteractreduced bone formation levels resulting from disuse.Their results show that they can.

Proving the Point in Rats

The study used five groups of rats. The control groupwas allowed to move freely about and provided abaseline for normal bone formation rates. A secondgroup was also allowed normal activity but experiencedten minutes per day of low magnitude, high frequencyforces. The mechanical stimulation was delivered byplacing the rats in a standard cage with a vibratingfloor. The magnitude of this stimulus was such that ahuman would hardly notice it.

The remaining experimental groups all underwentvariations on an unloading regimen. This was accom-plished using a hindlimb tail suspension technique

Increased bone formation can be seen in this comparison of anormal, untreated rat femur (left) and one that received tenminutes of mechanical stimulation per day (right).

October 2003For additional information, contact: Office of Biological and Physical Research, National Aeronautics and Space Administration http://spaceresearch.nasa.gov

developed by Emily Morey-Holton at the NASAAmes Research Center to mimic microgravity effectson the musculoskeletal system. With this technique,rodents can move about their cages, but only theirforelimbs can touch the ground, thus reducing weightbearing on the hindlimbs. The unloaded groupreceived continuous hindlimb suspension for theduration of the four-week study as a measure of totalunloading. The unloaded plus weight-bearing groupreceived continuous hindlimb suspension interruptedby ten minutes of normal weight-bearing per day. Theunloaded plus mechanical stimulation group receivedcontinuous hindlimb suspension interrupted by tenminutes of low magnitude, high frequency stimula-tion per day (during stimulation, the animals werealso free to roam their cage).

These investigators found that unloading plus tenminutes of daily weight-bearing resulted in boneformation rates only marginally better than totalunloading. On the other hand, unloading plus me-chanical stimulation resulted in bone formation ratesroughly equivalent to normal activity. Couplingnormal activity with mechanical stimulation resulted inrates nearly double those of the baseline control group.

These results clearly indicate that low magnitude,high frequency forces foster bone formation and havethe potential to counteract the bone loss associatedwith microgravity, unloading, and osteoporosis.Additional animal studies with sheep, mice, andturkeys, as well as pilot studies with humans, supportthis conclusion.

Advantages Over Existing Countermeasures

Osteoporosis is an insidious disease that—on Earth—takes several decades to become symptomatic, whilein space the bone loss is so severe that a flight to Marsmay be hampered due to skeletal distress. If thesefindings do translate to humans, this form of therapymight have several advantages over existing counter-measures, namely load-bearing exercise and pharma-ceuticals. As already mentioned, exercise countermea-sures employed to date have shown only limitedeffectiveness in space. In addition, it occupies valu-able crew time and astronauts find the equipmentcumbersome. For many on Earth, regular exerciseappropriate for bone formation can be difficult orimpossible due to medical conditions.

Drug-based countermeasures tend to focus on reduc-ing bone loss by inhibiting resorption rather thanstimulating bone formation. While this helps toconserve overall bone mass, bone quality can becompromised since it is the cycle of resorption andformation that maintains the health and strength ofbones. Drugs also do nothing to specifically target the

weight-bearing bones that are most affected by disuse.“Another potential advantage of standing on this device,”says Rubin, is that, like exercise, “it is self-targeted to theareas that need it most—weight-bearing bones.” In addi-tion, the device has no apparent side effects or drug inter-action issues.

The vibration countermeasure would be easy to implementin space or on Earth. The device which generates thestimulus looks, as Rubin says, like a pizza box. A personsimply stands on this inexpensive vibrating box forseveralminuteseach dayto inhibitbone loss.In micro-gravity,somethingwould beneeded tohold theastronautagainstthedevice,but spaceand energy requirements would be extremely low, and theastronaut could perform other duties while receivingtreatment. The challenge will be to effectively administerthe vibration therapy to the entire musculoskeletal systemin the absence of gravity.

Rubin has a full research slate ahead. He has just begunworking with NASA on plans to test this intervention onastronauts in the International Space Station. With upcom-ing studies funded by NASA and the National SpaceBiomedical Research Institute, these researchers along withtheir colleague Michael Hadjiargyrou hope to explain whysome individuals are more susceptible to bone loss thanothers by using mice to explore the genetic mechanisms atwork and to map the active genes. In addition, theseinvestigators are working with the National Institutes ofHealth to investigate patient compliance, and subsequentlyset up a Phase 3 clinical trial with post-menopausal womento demonstrate the therapeutic value of low magnitude,high frequency forces for the treatment of osteoporosis.

References1. Judex S; Donahue LR; Rubin C. Genetic predisposition to low

bone mass is paralleled by an enhanced sensitivity to signalsanabolic to the skeleton. FASEB Journal 16(10):1280-2, 2002.

2. Rubin C; Xu G; Judex S. The anabolic activity of bone tissue,suppressed by disuse, is normalized by brief exposure toextremely low-magnitude mechanical stimuli. FASEB Journal15(12):2225-9, 2001.

3. Sommerfeldt DW; Rubin CT. Biology of bone and how itorchestrates the form and function of the skeleton. EuropeanSpine Journal 10 Suppl 2:S86-95, 2001.

The current exercisecountermeasuresbeing performed inspace could besupplemented byadministeringvibration therapyto the body to helpcounteract boneloss. KennethBowersox exerciseson ISS (NASA photoISS006-E-11016).