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Bones and brain have complex ties

January 29, 2007|Mary Beckman

A study reported last week that people who take anti-depressants known as selective serotonin reuptake inhibitors (SSRIs) put themselves at greater risk for fractures. Researchers are working to understand how depression and its therapies affect skeleton strength. One thing they know: Several hormones and neurotransmitters affect, to varying degrees, the building and breaking down of bone.


From the outside, bones look stiff, unyielding, unchanging. But the inner sanctum of bones hardly resembles their exterior. "Really, they are quite dynamic, always being built up and broken down," says Patrick Mantyh, director of the Neurosystems Center at the University of Minnesota, Twin Cities. Bone cells known as osteoblasts build bone up, while other cells called osteoclasts break it down. Normal wear and tear on bones results in tiny fractures, perhaps daily. The osteoclasts dissolve these fractures, then osteoblasts fill in with new, healthy bone.

While the busyness of the two kinds of cells usually balances out, age or disease reduces the activity of bone-builders and lets bone-breakers run amok. That's why bones thin as we get older.

Several compounds in our body can alter the action of these cells. The female hormone estrogen, for example, stimulates osteoblasts to lay down bone and inhibits osteoclasts from chewing it up. The net result: strong, healthy bones. Loss of estrogen at menopause allows the osteoclasts to finally thin bones.

The appetite regulator leptin controls the density of bones by inhibiting the bone-building cells. (It sends a signal to the skeleton via nerve cells.) Mice that are obese because they lack leptin have chunky, thick bones.

Then there's the neurotransmitter serotonin, which is linked to mood disorders. Experts think depression results from too little serotonin residing in the spaces between neurons. SSRIs fight depression by raising levels of serotonin at those sites -- by blocking the action of proteins called transporters that suck serotonin back into nerve endings.

Ricardo Battaglino, a staff scientist at the Forsyth Institute in Boston, has found the serotonin transporter protein also exists on the surface of osteoclasts. In a 2006 study, he found that rodents injected with SSRIs had thicker leg bones -- suggesting that SSRIs inhibit the bone-chewing osteoclasts. Other studies have found differently. In another 2006 study, researchers observed that SSRIs at lower concentrations than those used by Battaglino's group instead stimulate osteoclasts.

Bottom line: Scientists will have to learn more before they know whether SSRIs send osteoclasts into overdrive or to sleep.

There may be other ways that depression and its treatment influence bone. A 2006 study found that rodents that had a mouse form of depression (yes, scientists really do study mouse depression) had fewer bone-building osteoblasts and also thinner bones. "The crucial question is, what is the relationship between depression, treatment for depression, and the complications of depression on fracture risk?" says Dr. Michael Bliziotes, an associate professor at Oregon Health & Science University in Portland.

Until that's figured out, experts recommend keeping an eye on bone density if taking antidepressants for the long term. And, says Mantyh, don't forget load-bearing exercise and vitamin D. "You need skeletal health to lead a happy, productive life," he says.

- Mary Beckman

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