Commonly prescribed
antidepressants associated with lower bone
Ddensity in older men and women
Newswise — The class of antidepressant
medications known as selective serotonin
reuptake inhibitors may be associated with an
increased rate of bone loss in older men and
women, according to two articles in the June 25
issue of Archives of Internal Medicine, one of
the JAMA/Archives journals.
Selective serotonin reuptake inhibitors (SSRIs)
treat depression by inhibiting the protein that
transports serotonin, a neurotransmitter
involved in sleep and depression, according to
background information in the articles. This
protein has recently been discovered in bone as
well, raising the possibility that SSRIs may
affect bone density and the risk of fracture.
SSRIs account for about 62 percent of
antidepressant prescriptions in the United
States, and are often prescribed to the elderly.
Susan J. Diem, M.D., M.P.H., University of
Minnesota, Minneapolis, and colleagues
studied 2,722 older women (average age 78.5
years) beginning in 1997 through 1999. At
that time and again an average of 4.9 years
later, researchers measured women’s total
hip bone density and also that of two
subregions. At each visit, the participants
were asked to bring in all the medications
they had used within the past two weeks,
including SSRIs and tricyclic
antidepressants, which work through a
different mechanism.
A total of 198 (7.3 percent) of the women were
SSRI users, 118 (4.3 percent) took tricyclic
antidepressants and 2,406 (88.4 percent) took
neither (those who took both were not included
in the analysis). After the researchers adjusted
for other factors affecting bone density and
antidepressant use, including depression
severity and calcium supplement use, bone
mineral density at the hip decreased 0.82
percent in SSRI users. This compared with a
decrease of 0.47 percent among those who used
tricyclic antidepressants and also in those who
did not take any antidepressants. Higher rates
of bone loss were also observed at the two hip
subregions among SSRI users.
“One potential explanation for our findings is
that SSRI use may have a direct deleterious
effect on bone,” the authors write. “This theory
is supported by findings of in vitro and in vivo
laboratory investigations.” Some data suggest
that SSRIs may interfere with the function of
osteoclasts and osteoblasts, cells responsible
for the regular breaking down and rebuilding of
bone in the body.
“Our findings suggest that, in this cohort, use
of SSRIs is associated with increased rates of
hip bone loss,” the authors conclude. Although
some of this association may have occurred
because women who were prescribed SSRIs were
different from those who were not prescribed
SSRIs, “further investigation of SSRI use and
rates of change in bone mineral density in other
populations with longer follow-up is warranted
given the recent description of serotonin
transporters in bone.”
In a related paper, Elizabeth M. Haney, M.D., of
Oregon Health & Sciences University, Portland,
and colleagues conducted a similar study with
5,995 men age 65 and older (average age 73.7).
The men’s bone density at the hip, including
subregions, and at the base of the spine were
measured between 2000 and 2002. Participants
were asked to bring all medications to their
clinic visit, where they were also given a
physical examination and asked about other
health and lifestyle factors.
A total of 160 (2.7 percent) men reported using
SSRIs, 99 (1.7 percent) reported using tricyclic
antidepressants and 52 (0.9 percent) reported
using trazodone, a third type of antidepressant.
Total hip bone mineral density was 3.9 percent
lower among SSRI users than among men who didn’t
use any antidepressants. Similarly, spine bone
mineral density was 5.9 percent lower among SSRI
users than among non-users. There was no
significant difference in either hip or spine
density between men who took tricyclic
antidepressants or trazodone and those who did
not take antidepressants.
“These associations are biologically plausible
and clinically important,” the authors conclude.
“Because SSRI use is prevalent in the general
population, our findings have a potentially
important public health impact. If confirmed,
people using SSRIs might be targeted for
osteoporosis screening and preventive
intervention.”
(Arch Inter Med. 2007;167:1240-1245 and
1246-1251. Available pre-embargo to the media at
www.jamamedia.org.)
Editor’s Note: Please see the articles for
additional information, including other authors,
author contributions and affiliations, financial
disclosures, funding and support, etc.
Editorial: Physicians Must Balance Between
Treating Minds, Sparing Bones
Although these studies do not prove definitively
that SSRIs cause a reduction in bone mineral
density, they do raise concerns that physicians
must consider when they write prescriptions for
antidepressant medications, writes Kenneth Saag,
M.D., M.Sc., of the University of Alabama at
Birmingham in an accompanying editorial.
“The SSRI risk-benefit ratio should be compared
against traditional antidepressants as well as
alternative approaches such as newer drugs,
psychotherapy and even electroconvulsive
therapy,” Dr. Saag writes.
For many patients, the benefits of SSRIs are
likely to out weight the risks, Dr. Saag
continues. “Although it is not appealing to use
a second medicine to ‘chase’ the adverse effects
of a first one, if needed, there are many good
options that exist to prevent bone loss.”
As medicine advances, it is not surprising that
physicians are finding new ways to improve one
health problem while worsening another, he
concludes. “The astute clinician individually
tailors therapies, tries to balance benefits
against potential risks and provides appropriate
and informed consent for all drugs prescribed.
In the case of the depressed patient, good
clinical acumen and thoughtful adverse event
monitoring can help avoid having healthier minds
at the expense of sicker bones.”
