PFPC Daily - November 11, 2004

Prozac May Stunt Growing Bones

Forbes - November 11, 2004

By E.J. Mundell


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."

SOURCE: http://www.forbes.com/