Insight into osteopenia from bed rest/space flight

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Rheumawire

Mar 19, 2004

Insight into osteopenia from bed rest/space flight

San Francisco, CA- New research has shed some light on the physiological

basis for the bone-density loss experienced by people subjected to

prolonged periods of bed rest and astronauts who fly lengthy missions

under the weightless conditions of space [1].

The work, conducted in rats and published in the March 2004 issue of the

Journal of Bone and Mineral Research, is an important step toward

developing therapies to prevent such bone loss, says senior author Dr

Bikle (University of California, San Francisco).

Osteopenia is quite a problem for astronauts. Data collected during the

Skylab and Salyut space missions (lasting 28 to 184 days) show that

astronauts not only lost bone density in space, they also failed to

recover prelaunch bone-density levels, even 5 years after their

missions. " The big problem that NASA is facing in their plans to send a

manned flight to Mars is how to get people there and back again without

having their skeletons turn to matchsticks, " Bikle comments in a press

release. " Yet discovering a way to stop bone loss from skeletal

unloading will [have an] impact [on] more than just a few astronauts.

Anyone who is immobilized in any way for a long period of time can

benefit. "

Skeletal unloading occurs when weight-bearing bones, such as those in

the spine and the legs, are relieved of their burden. To mimic this

effect in rats, Bikle and colleagues devised a cage with a free-moving

line that takes the weight of the animal's hindquarters while

maintaining normal weight and movement in the front legs. They then

cultured cells from loaded and unloaded bones, performing biochemical

analyses to investigate the pathways involved.

They found that when the bones are relieved of bearing weight, bone

precursor cells fail to respond to insulinlike growth factor 1 (IGF-1).

Although IGF-1 still binds to its receptor on the cell wall, it fails to

activate it. The researchers then showed that this inhibition of the

ability of IGF-1 to activate its receptor could be duplicated by

inhibiting integrin function, a finding that fit neatly into their

observation that integrin levels were reduced by skeletal unloading.

They concluded that inhibition of the activation of IGF-1 signaling

pathways is mediated, at least in part, through down-regulation of

integrin signaling.

No one has demonstrated this signaling feedback loop in bone before,

" but it makes sense, " Bikle comments. " Integrins are mechanosensors.

When the bone is moving and bearing weight, the integrins initiate a

signaling process within the cell. This signal, in turn, affects IGF-1's

ability to activate its receptor-signaling system inside the cell. "

" The next step, " says Bikle, " is to determine what's impeding production

of integrin during skeletal unloading and what mechanism links the

integrin signaling pathway to the IGF-1-receptor activation. Once we

understand these processes, we'll have some targets that we can address

to help us devise interventions to prevent bone loss from skeletal

unloading. "

Zosia Chustecka

Source

1. Sakata T, Wang Y, Halloran B et al. Skeletal unloading induces

resistance to insulin-like growth factor (IGF-1) by inhibiting

activation of the IGF-1 signalling pathways. J Bone Miner Res 2004;

19:436-446.

I'll tell you where to go!

Mayo Clinic in Rochester

http://www.mayoclinic.org/rochester

s Hopkins Medicine

http://www.hopkinsmedicine.org