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Doxycycline for osteoarthritis of the knee or hip

  • Review
  • Intervention

Authors

  • Eveline Nüesch,

    Corresponding author
    1. University of Bern, Division of Clinical Epidemiology and Biostatistics, Institute of Social and Preventive Medicine, Bern, Switzerland
    • Eveline Nüesch, Division of Clinical Epidemiology and Biostatistics, Institute of Social and Preventive Medicine, University of Bern, Finkenhubelweg 11, Bern, 3012, Switzerland. enueesch@ispm.unibe.ch.

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  • Anne WS Rutjes,

    1. University of Bern, Division of Clinical Epidemiology and Biostatistics, Institute of Social and Preventive Medicine, Bern, Switzerland
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  • Sven Trelle,

    1. University of Bern, Institute of Social and Preventive Medicine, Bern, Switzerland
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  • Stephan Reichenbach,

    1. University Hospital, Department for Rheumatology, Clinical Immunology, and Allergology, Bern, Switzerland
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  • Peter Jüni

    1. University of Bern, Division of Clinical Epidemiology and Biostatistics, Institute of Social and Preventive Medicine, Bern, Switzerland
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Abstract

Background

Osteoarthritis is a chronic joint disease that involves degeneration of articular cartilage. Pre-clinical data suggest that doxycycline might act as a disease-modifying agent for the treatment of osteoarthritis, with the potential to slow cartilage degeneration.

Objectives

To examine the effects of doxycycline compared with placebo or no intervention on pain and function in patients with osteoarthritis of the hip or knee.

Search methods

We searched CENTRAL ( The Cochrane Library 2008, issue 3), MEDLINE, EMBASE and CINAHL up to 28 July 2008, checked conference proceedings, reference lists, and contacted authors.

Selection criteria

We included studies if they were randomised or quasi-randomised controlled trials that compared doxycycline at any dosage and any formulation with placebo or no intervention in patients with osteoarthritis of the knee or hip.

Data collection and analysis

We extracted data in duplicate. We contacted investigators to obtain missing outcome information. We calculated differences in means at follow-up between experimental and control groups for continuous outcomes and risk ratios for binary outcomes.

Main results

We found one randomised controlled trial that compared doxycycline with placebo in 431 obese women. After 30 months of treatment, clinical outcomes were similar between the two treatment groups, with a mean difference of -0.20 cm (95% confidence interval (CI) -0.77 to 0.37 cm) on a visual analogue scale from 0 to 10 cm for pain and -1.10 units (95% CI -3.86 to 1.66) for function on the WOMAC disability subscale, which ranges from 17 to 85. These differences correspond to clinically irrelevant effect sizes of -0.08 and -0.09 standard deviation units for pain and function, respectively. The difference in changes in minimum joint space narrowing was in favour of doxycycline (-0.15 mm, 95% CI -0.28 to -0.02 mm), which corresponds to a small effect size of -0.23 standard deviation units. More patients withdrew from the doxycycline group compared with placebo due to adverse events (risk ratio 1.69, 95% CI 1.03 to 2.75).

Authors' conclusions

The symptomatic benefit of doxycycline is minimal to non-existent. The small benefit in terms of joint space narrowing is of questionable clinical relevance and outweighed by safety problems. Doxycycline should not be recommended for the treatment of osteoarthritis of the knee or hip.

Plain language summary

Doxycycline for osteoarthritis

This summary of a Cochrane review presents what we know from research about the effect of doxycycline on osteoarthritis.

 

The review shows that in people with osteoarthritis:

- Doxycycline probably will not improve pain or physical function.

- Doxycycline probably causes side effects. We often do not have precise information about side effects and complications. This is particularly true for rare but serious side effects.

 

What is osteoarthritis and what is doxycycline?

Osteoarthritis (OA) is a disease of the joints, such as your knee or hip. When the joint loses cartilage, the bone grows to try and repair the damage. Instead of making things better, however, the bone grows abnormally and makes things worse. For example, the bone can become misshapen and make the joint painful and unstable.  This can affect your physical function or ability to use your knee.

Doxycycline is a type of antibiotic that seems to stop the process of damage to the joints.  It is taken in pill form.

 

Best estimate of what happens to people with osteoarthritis who take doxycycline:

Pain

- People with doxycycline and people with placebo are equally likely to respond to treatment (difference of 0%).

- People who took doxycycline rated their pain to be 2 on a scale of 0 (no pain) to 10 (extreme pain) after 30 months.
- People who took a fake medication (placebo) also rated their pain to be about 2 on a scale of 0 (no pain) to 10 (extreme pain) after 30 months.

 

Physical function

- People with doxycycline and people with placebo are equally likely to respond to treatment (difference of 0%).

- People who took doxycycline rated their physical function to be about 36 on a scale of 17 (no disability) to 85 (extreme disability) after 30 months.
- People who took a fake medication rated their physical function to be about 37 on a scale of 17 (no disability) to 85 (extreme disability) after 30 months.

 

Side effects

- 7 more people who took doxycycline withdrew or dropped out from the trial because of side effects (absolute difference of 7%).

- 17 people out of 100 who took doxycycline withdrew or dropped out from the trial because of side effects (17%).

- 10 people out of 100 who used a fake medication withdrew or dropped out from the trial because of side effects (10%).

 

Serious harms

- There was no difference in the number of people who experienced serious harms (difference of 0%). This could be the result of chance.

- 14 people out of 100 who took doxycycline experienced serious harms (14%)

- 14 people out of 100 who used a fake medication experienced serious harms (14%).