By E.J. Mundell
HealthDay Reporter

THURSDAY, Nov. 11 (HealthDayNews) -- The success of Prozac in easing
depression in children may come at the price of impaired bone growth,
suggests a study in mice.

Researchers say cellular mechanisms important to bone growth may shut down
in the presence of the drug, hindering healthy skeletal development. Growing
mice exposed to Prozac for even a few weeks averaged 9.4 percent less bone
formation in their thighbones compared to unexposed mice, the researchers
report.

"This is a mouse study, however, and I wouldn't take people off Prozac based
on just this study," stressed lead researcher Stuart Warden, an assistant
professor of physical therapy at Indiana University School of Medicine.
"Still, as a researcher, I would start to think about planning trials to
address this in a clinical population."

In a statement, representatives from Eli Lilly & Co., the makers of Prozac,
said "the findings warrant consideration, and should be placed in the
context of the established record of safety and efficacy of fluoxetine
[Prozac] in humans."

The study is published in the November issue of Endocrinology.

Prozac is just one of a family of antidepressants called selective serotonin
reuptake inhibitors (SSRIs), which also include Celexa, Paxil and Zoloft.
All of these drugs interact with nerve cells to increase production of the
neurotransmitter serotonin, which is low in people with depression.

However, researchers recently discovered that 5-HTT -- a serotonin
transporter molecule that is key to this process -- is also found in cells
responsible for building and maintaining bone.

"If you have serotonin around these cells and these cells have receptors,
serotonin actually influences the activity of those bone cells," Warden
explained.

Using the same logic, his team theorized that serotonin-targeted SSRI drugs
such as Prozac might also affect bone development.

To find out, they first examined bone growth in mice genetically engineered
to lack functioning 5-HTT serotonin transporters in bone cells. A shutdown
of this transporter "would be similar to being on lifelong Prozac, Zoloft or
any other SSRI," Warden explained.

Compared to normal mice, these animals had bones that were between 6 percent
to 13 percent narrower on average. Their bones were also weaker and less
dense.

The researchers then shifted their focus to short-term Prozac exposure,
giving young, growing mice daily injections of either low- or high-dose
Prozac, or placebo, for four weeks.

"When we gave Prozac to really young mice that were still rapidly growing,
it reduced the amount of bone they gained," Warden said. "It reduced their
bone growth -- not how long the bones were, but how wide, and how thick."

Compared to unexposed mice, young mice exposed to relatively high doses of
Prozac displayed a 6 percent and 9.4 percent reduction in bone formation in
their spines and thighbones, respectively, according to the researchers.

Warden stressed that the study focused on Prozac because it is the sole SSRI
currently granted U.S. Food and Drug Administration approval for use in
children. He believes other SSRIs would have similar effects on bone.

"There's no reason to believe Prozac is unique here," Warden said.

For their part, representatives at Lilly said the study is far from
conclusive. They point out, for example, that mice exposed to Prozac were
somewhat less active than unexposed mice, offering an alternate explanation
as to differences in bone mass.

They also defended Prozac's safety record. "Lilly has sponsored five
clinical trials of Prozac in children, and all have been published in
independent, peer-reviewed journals," the company said in a statement. "The
safety and efficacy of Prozac is well-studied, well-documented, and
well-established."

But Warden believes that larger clinical trials are warranted. He pointed to
studies in adults that linked long-term SSRI use with an increased risk for
hip fracture, as well as reduced bone mineral density in the neck and spine.

Prozac has already faced intense public scrutiny recently, following reports
suggesting that it and other SSRIs might raise suicide risks in children.

"The main point of our study is not to induce panic in people on these
drugs, but to highlight that further research is necessary," Warden said.
"We need to have independent studies looking at these drugs, so things
aren't brushed under the carpet."

More information

For the latest on the risks and benefits of antidepressant use by children,
go to the U.S. Food and Drug Administration.