Doxycycline for osteoarthritis

This summary of a Cochrane review presents what we know from research about the effect of doxycycline on osteoarthritis. After searching for all relevant studies, they found two studies with 663 people.

The review shows that in people with osteoarthritis:

- doxycycline will not result in clinically important improvement of joint pain or physical function, while the small benefit in terms of joint space narrowing is of questionable clinical relevance;

- 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 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. However, instead of making things better 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.

It has been claimed that doxycycline, a type of antibiotic, might 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

- The effect of doxycycline in pain symptoms is not clinically important.

- People who took doxycycline rated improvement in their pain to be about 1.9 on a scale of 0 (no pain) to 10 (extreme pain) after 18 months.

- People who took a placebo rated improvement in their pain to be about 1.8 on a scale of 0 (no pain) to 10 (extreme pain) after 18 months.

Another way of saying this is:

- 33 people out of 100 who use doxycycline respond to treatment (33%).

- 31 people out of 100 who use placebo respond to treatment (31%).

- two more people respond to treatment with doxycycline than with placebo (difference of 2%).

 Physical function

- The effect of doxycycline in physical function is not clinically important.

- People who took doxycycline rated improvement in their physical function to be about 1.4 on a scale of 0 (no disability) to 10 (extreme disability) after 18 months.

- People who took a placebo rated improvement in their physical function to be about 1.2 on a scale of 0 (no disability) to 10 (extreme disability) after 18 months.

Another way of saying this is:

- 29 people out of 100 who use doxycycline respond to treatment (29%).

- 26 people out of 100 who use placebo respond to treatment (26%).

- three more people respond to treatment with doxycycline than with placebo (difference of 3%).

Side effects

- 20 people out of 100 who took doxycycline experienced side effects of any type (20%).

- 15 people out of 100 who took a placebo experienced side effects of any type (15%).

- five more people who took doxycycline experienced side effects of any type (absolute difference of 5%).

Authors' conclusions: 

In this update, the strength of evidence for effectiveness outcomes was improved from low to moderate and we confirmed that the symptomatic benefit of doxycycline is minimal to non-existent, while the small benefit in terms of joint space narrowing is of questionable clinical relevance and outweighed by safety problems. The CIs of the summary estimates now exclude any clinically relevant difference in improvement of symptoms and the small benefit in terms of joint space narrowing does not outweigh the harms.

Read the full 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. This is an update of a Cochrane review first published in 2009.

Objectives: 

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

Search strategy: 

We searched CENTRAL (The Cochrane Library 2008, issue 3), MEDLINE, EMBASE and CINAHL up to 28 July 2008, with an update performed at 16 March 2012. In addition, we 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 people 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 (RR) for binary outcomes.

Main results: 

We identified one additional trial (232 participants) and included two trials (663 participants) in this update. The methodological quality and the quality of reporting were considered moderate. At end of treatment, clinical outcomes were similar between the two treatment groups, with an effect size of -0.05 (95% confidence interval (CI) -0.22 to 0.13), corresponding to a difference in pain scores between doxycycline and control of -0.1 cm (95% CI -0.6 to 0.3 cm) on a 10-cm visual analogue scale, or 32% versus 29% improvement from baseline (difference 3%; 95% CI -5% to 10%). The effect size for function was -0.07 (95% CI -0.25 to 0.10), corresponding to a difference between doxycycline and control of -0.2 (95% CI -0.5 to 0.2) on the Western Ontario and McMaster Universities Arthritis Index (WOMAC) disability subscale with a range of 0 to 10, or 24% versus 21% improvement (difference 3%; 95% CI -3% to 10%). The difference in changes in minimum joint space narrowing assessed in one trial 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 (95% CI -0.44 to -0.02). More participants withdrew from the doxycycline group compared with placebo due to adverse events (RR 2.28; 95% CI 1.06 to 4.90). There was no evidence that participants in the doxycycline group experienced more serious adverse events than those in the placebo group, but the estimate was imprecise (RR 1.07; 95% CI 0.68 to 1.68).

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