The osteoporosis drug alendronate
works so well that many patients can safely stop taking
it entirely — at least for a time — after
as few as five years of therapy.
Bisphosphonates have been quite
the success story right from the start, and none more
so than class champion alendronate. But ever since the
breakthrough drug was licensed — despite the lack
of long-term data — physicians have hoped rather
than known that patients would continue to do well after
several years of therapy. There was no reason to believe
that long-term use of alendronate wasn't safe, but there
was no real proof of it either, and it was commonly
assumed that patients who were prescribed the drug would
be taking it for life.
As it turns out, that's not quite
the case. The long-awaited results of the Fracture Intervention
Trial Long-term Extension (FLEX), recently reported
in the Journal of the American Medical Association,
indicate that long-term use of alendronate is not only
safe, but its effects are so powerful that some patients
can enjoy lasting benefits even if they haven't taken
a pill in years.
THE
GOOD SURVIVES
FLEX, carried out at 10 US centres, grew out of the
Fracture Intervention Trial, which helped establish
alendronate's efficacy in the first place. But it picked
up further down the treatment road than the original
study left off. While the average follow-up in FIT was
just under four years, subjects in FLEX had already
been taking alendronate for an average five years when
the study began.
The design was simple. The 1,099
subjects were randomized to continue taking alendronate
at 5mg (329 subjects) or 10mg daily dose (333 subjects),
or to switch to placebo (437 subjects). The principal
outcome measure was hip bone mineral density (BMD),
but fracture incidence was also tracked.
Discontinuing alendronate resulted
in statistically significant decreases in both hip and
spine BMD, measured at about 2.4% and 3.9% respectively.
But while these patients didn't maintain the robust
scores of those who continued treatment, their BMD was
still higher on average, even after five years off the
drug, than it had been before they began taking alendronate.
Serum markers of bone turnover
also increased significantly in the placebo group, but
again remained lower than they had been 10 years earlier
when the patients first began treatment.
(NOT)
ALL ABOARD
Even more encouraging was the fact that test results
were, to some extent at least, borne out by clinical
events — the proportion of nonvertebral fractures
was identical among patients who discontinued alendronate
and those who kept taking it (19% versus 18.9%).
In terms of vertebral fractures,
things were a little more complicated. There was no
significant additional risk of vertebral fractures identified
by measurement among the discontinuation group (11.3%
versus 9.8% in the continued treatment group). Nor was
there a significant difference in height loss. But there
was a statistically significant extra burden of clinically
recognised vertebral fractures among those who took
the drug holiday (5.3% versus 2.4%).
"These results suggest that for
many women, discontinuation of alendronate for up to
5 years does not appear to significantly increase fracture
risk. However, women at very high risk of clinical vertebral
fractures may benefit by continuing beyond 5 years,"
the authors conclude.
HOLIDAY
RULES
Dr Cathleen Colón-Emeric, a geriatrician at Duke
University whose research focuses on fracture and fall
prevention, agrees that women with a history of vertebral
fractures probably shouldn't take a break (for more
on preventing falls in the elderly, see "What to tell
your patients" on page 13). In general, she adds, those
whose BMD responded well to initiating alendronate therapy
are probably better placed to take a holiday from the
drug than those whose results were a bit disappointing.
"In those cases, I think, the wisest move would be to
talk to their physician about switching to some other
class of treatment," she says.
It's perhaps worth asking why women
would want to take any chances by quitting alendronate.
After all, the drug's patent expired in Canada in 2005,
slashing the price, and it's generally considered a
well-tolerated drug. "Cheap" and "well-tolerated", Dr
Colùn-Emeric argues, are both relative concepts.
"It still costs about $70USD a
month, and there are potential side-effects," she says.
There are possible gastrointestinal complications, such
as colon ulcers, as well as a small risk of oesophageal
rupture. "That's rare, but it's extremely serious when
it does happen. And there are a lot of people taking
this drug," Dr Colùn-Emeric cautions.
In Canada, alendronate can usually
be had somewhat cheaper. The 5mg and 10mg formulations
typically differ little in cost at the pharmacy, but
keeping a patient on either regimen in Canada is still
likely to cost about $500 a year — not a sum to
be sniffed at.
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