Promise of Tetracycline Antibiotic for Osteoarthritis
14 Jul 2005
Study Shows Effectiveness of Doxycycline in Slowing Disease
Progression. 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, 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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Antimicrob Agents Chemother. 2000 Mar;44(3):763-6. Related Articles,
Links
Iron-chelating activity of tetracyclines and its impact on the
susceptibility of Actinobacillus actinomycetemcomitans to these
antibiotics.
Grenier D, Huot MP, Mayrand D.
Groupe de Recherche en Ecologie Buccale, Faculte de Medecine Dentaire,
Quebec, Canada.
Daniel.Grenier@greb.ulaval.ca
Three tetracyclines (tetracycline, doxycycline, and minocycline) were
found to possess iron-chelating activity in a colorimetric siderophore
assay. Determination of MICs indicated that the activity of doxycycline
against the periodontopathogen Actinobacillus actinomycetemcomitans was
only slightly influenced by the presence of an excess of iron that
likely saturates the antibiotic. On the other hand, the MICs of
doxycycline and minocycline were significantly lower for A.
actinomycetemcomitans cultivated under iron-poor conditions than under
iron-rich conditions.
PMID: 10681353 [PubMed - indexed for MEDLINE]
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