Study shows effectiveness of doxycycline in slowing
osteoarthritis progression

RxPG News
June 29, 2005, 13:02

By Arthritis & Rheumatism Journal

A tetracycline antibiotic, doxycycline, has been
successfully used to treat a wide-range of bacterial
infections. In addition to its effects as an antibiotic,
doxycycline has other actions as a drug and, in
laboratory studies with animals and with human tissue,
can inhibit the degradation of cartilage in a way that
could be useful for the treatment of osteoarthritis (OA).
OA is a common form of arthritis associated with pain and
disability related to the breakdown of cartilage, the
tissue in the joint that absorbs shock and promotes
smooth movement

On the strength of preclinical evidence, a team of
rheumatologists affiliated with six clinical research
centers across the United States conducted the first
long-term clinical trial to determine the benefits of
doxycycline in the treatment of OA--particularly, OA of
the knee. Their findings, featured in the July 2005 issue
of Arthritis & Rheumatism
(http://www.interscience.wiley.com/journal/arthritis  ),
suggest that doxycycline may slow the progression of
joint damage and point to the need for further research
into the drug's effect on the signs and symptoms of this
disease.

For the trial, the team recruited 431 overweight women
between the ages of 45 and 64 with moderately advanced OA
in one knee. The subjects were randomly assigned to
receive either 100 milligrams of doxycycline or a placebo
twice a day for 30 months. At baseline, the 2 treatment
groups were roughly equal with respect to all demographic
variables, body mass index, and types of drugs taken for
pain, as well as for the x-ray severity of OA in the
affected knee and the level of knee pain and functional
impairment. OA progression was assessed by measuring
joint space narrowing in the medial tibiofemoral
compartment through X-rays obtained at baseline, 16
months and 30 months. Severity of joint pain was assessed
every 6 months after a washout period of all nonsteroidal
anti-inflammatory drugs (NSAIDs) and analgesics.

71 percent of the subjects completed the treatment
protocol. Radiographs were obtained from 85 percent of
all subjects at 30 months. After 16 months of treatment,
the mean loss of joint space width in the diseased knee
in the doxycycline group was 40 percent less than in the
placebo group. After 30 months, it was 33 percent less.
Yet, despite significantly slowing disease progression,
doxycycline did not reduce the severity of joint pain.
However, mean pain scores at baseline were low in both
treatment groups, leaving only limited opportunity to
demonstrate improvement in joint pain. On the other hand,
the drug significantly reduced the frequency with which
subjects reported increases in knee pain 20 percent or
greater than the level of pain they had at their previous
semi-annual visit.

Notably, doxycycline seemed to have no effect on joint
space narrowing or pain in the relatively disease-free
knee. In both knees in both treatment groups, the rate of
joint space narrowing was more than twice as rapid in
subjects who reported frequent increases in pain than in
those with a stable pain score. "Joint pain may serve as
an indicator of synovitis that leads to cartilage
destruction," observes the study's leading author,
Kenneth D. Brandt, M.D.

Throughout the trial, fewer than 5 percent of all
subjects reported side effects. In general, doxycycline
seemed to be well tolerated. Subjects in the active
treatment group experienced the unexpected side benefits
of fewer urinary tract and upper respiratory tract
infections than their placebo counterparts.

In conclusion, in this study, doxcycyline showed benefits
in slowing the rate of joint space narrowing in knees
with established OA. Whether this drug has any value in
the early treatment and symptomatic management of OA,
however, will require further investigation.  

References

1. "Effects of Doxycyline on Progression of
Osteoarthritis: Results of a Randomized, Placebo-
Controlled, Double-Blind Trial," Kenneth D. Brandt,
Steven A. Mazzuca, Barry P. Katz, Kathleen A. Lane,
Kenneth A. Buckwalter, David E. Yocum, Frederick Wolfe,
Thomas J. Schnitzer, Larry W. Moreland, Susan Manzi, John
D. Bradley, Leena Sharma, Chester V. Oddis, Steven T.
Hugenberg, and Louis W. Heck, Arthritis & Rheumatism,
July 2005; 52:7; pp. 2015-2025.

Related Link
www.interscience.wiley.com/journal/arthritis

More at:
http://www.rxpgnews.com/research/orthopaedics/arthritis/article_1783.shtml

Study Shows Effectiveness of Doxycycline in Slowing
Disease Progression.

I-Newswire

A tetracycline antibiotic, doxycycline, has been
successfully used to treat a wide-range of bacterial
infections. In addition to its effects as an antibiotic,
doxycycline has other actions as a drug and, in
laboratory studies with animals and with human tissue,
can inhibit the degradation of cartilage in a way that
could be useful for the treatment of osteoarthritis (OA).
OA is a common form of arthritis associated with pain and
disability related to the breakdown of cartilage, the
tissue in the joint that absorbs shock and promotes
smooth movement.  

(I-Newswire) - On the strength of preclinical evidence, a
team of rheumatologists affiliated with six clinical
research centers across the United States conducted the
first long-term clinical trial to determine the benefits
of doxycycline in the treatment of OA-particularly, OA of
the knee. Their findings, featured in the July 2005 issue
of Arthritis & Rheumatism (
http://www.interscience.wiley.com/journal/arthritis ),
suggest that doxycycline may slow the progression of
joint damage and point to the need for further research
into the drug's effect on the signs and symptoms of this
disease.

For the trial, the team recruited 431 overweight women
between the ages of 45 and 64 with moderately advanced OA
in one knee. The subjects were randomly assigned to
receive either 100 milligrams of doxycycline or a placebo
twice a day for 30 months. At baseline, the 2 treatment
groups were roughly equal with respect to all demographic
variables, body mass index, and types of drugs taken for
pain, as well as for the x-ray severity of OA in the
affected knee and the level of knee pain and functional
impairment. OA progression was assessed by measuring
joint space narrowing in the medial tibiofemoral
compartment through X-rays obtained at baseline, 16
months and 30 months. Severity of joint pain was assessed
every 6 months after a washout period of all nonsteroidal
anti-inflammatory drugs ( NSAIDs ) and analgesics.

71 percent of the subjects completed the treatment
protocol. Radiographs were obtained from 85 percent of
all subjects at 30 months. After 16 months of treatment,
the mean loss of joint space width in the diseased knee
in the doxycycline group was 40 percent less than in the
placebo group. After 30 months, it was 33 percent less.
Yet, despite significantly slowing disease progression, d
oxycycline did not reduce the severity of joint pain.
However, mean pain scores at baseline were low in both
treatment groups, leaving only limited opportunity to
demonstrate improvement in joint pain. On the other hand,
the drug significantly reduced the frequency with which
subjects reported increases in knee pain 20 percent or
greater than the level of pain they had at their previous
semi-annual visit.

Notably, doxycycline seemed to have no effect on joint
space narrowing or pain in the relatively disease-free
knee. In both knees in both treatment groups, the rate of
joint space narrowing was more than twice as rapid in
subjects who reported frequent increases in pain than in
those with a stable pain score. "Joint pain may serve as
an indicator of synovitis that leads to cartilage
destruction," observes the study's leading author,
Kenneth D. Brandt, M.D.

Throughout the trial, fewer than 5 percent of all
subjects reported side effects. In general, doxycycline
seemed to be well tolerated. Subjects in the active
treatment group experienced the unexpected side benefits
of fewer urinary tract and upper respiratory tract
infections than their placebo counterparts.

In conclusion, in this study, doxcycyline showed benefits
in slowing the rate of joint space narrowing in knees
with established OA. Whether this drug has any value in
the early treatment and symptomatic management of OA,
however, will require further investigation.

Article - "Effects of Doxycyline on Progression of
Osteoarthritis: Results of a Randomized, Placebo-
Controlled, Double-Blind Trial," Kenneth D. Brandt,
Steven A. Mazzuca, Barry P. Katz, Kathleen A. Lane,
Kenneth A. Buckwalter, David E. Yocum, Frederick Wolfe,
Thomas J. Schnitzer, Larry W. Moreland, Susan Manzi, John
D. Bradley, Leena Sharma, Chester V. Oddis, Steven T.
Hugenberg, and Louis W. Heck, Arthritis & Rheumatism ,
July 2005; 52:7; pp. 2015-2025. Article is available via
Wiley InterScience at
interscience.wiley.com/journal/arthritis  .

http://www.rheumatology.org

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Published on 2005-07-17

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