Friday March 23 2012
It's too early to say if Protelos will be useful for osteoarthritis
A £1-a-day drug can slow arthritis, The Independent has reported. According to the paper, it’s thought to be the first drug to slow the progress of the disease. The Daily Mail reported a similar story, but said that British scientists have developed an “80p-a-day pill”.
The news is based on research presented this week at a European conference of joint and bone health. Researchers presented details of a large trial of the drug strontium ranelate, marketed as Protelos. The trial examined whether the drug could be used to treat knee osteoarthritis. Over three years, daily doses of the drug were found to reduce degeneration of joint cartilage, assessed by the extent of joint space narrowing on X-ray. There was also some evidence that it may affect pain and function. Strontium ranelate is currently only licensed for the treatment of postmenopausal osteoporosis.
The findings of this trial sound promising and, as the charity Arthritis Research UK has been quoted as saying in press: “This the first time that a drug has been shown to slow progression of osteoarthritis, as existing treatments for osteoarthritis just focus on symptoms.” However, conference presentations often give only a brief, cursory presentation of results, and don’t reveal key details of the methods and findings of trials that are available when research is formally published.
Overall, these partial findings have no immediate implications for the current treatment of people with osteoarthritis, although data from the full study may clarify things when published later this year.
Where did the story come from?
This week saw the European Congress on Osteoporosis and Osteoarthritis, and news reports were based on a conference abstract published in the journal Osteoporosis International. The abstract presented brief findings of an arthritis study performed by researchers from the University of Liège, Belgium, and other international institutions. It examined the effects of a drug called strontium ranelate (brand name Protelos) on knee osteoarthritis. Full publication of the results is reported to be forthcoming in the journal Current Medical Research & Opinion.
Funding of the study was not mentioned in the abstract, but was reported to be by the Institut de Recherches Internationales Servier (France) on the Current Controlled Trials trial registry website. Servier is the pharmaceutical company that manufactures strontium ranelate.
The news headlines all highlighted that this is a cheap drug which could slow the progress of osteoarthritis. This may prematurely raise the hopes of many people with the condition. Generally, the news did not make it clear that these findings are only preliminary, are based on a conference abstract, or that the drug is not currently licensed for use in osteoarthritis.
What kind of research was this?
This conference abstract reported a randomised, placebo-controlled trial which investigated the effects of strontium ranelate (Protelos) on cartilage degeneration in osteoarthritis. Strontium ranelate is a drug that regulates bone turnover and is currently only licensed for the treatment of postmenopausal osteoporosis. A randomised controlled trial is the best way of investigating the effects of a treatment. However, as this was a conference abstract, only limited information on the study’s methods and findings is currently available.
Osteoarthritis is a common, degenerative joint condition associated with increasing age. It is more common in people who are overweight or have a family history of the condition. In osteoarthritis, the cartilage that lines the joints becomes rough and thin, and the bones of the joints gradually become worn down and damaged. The bones tend to change shape and form bony spurs called osteophytes. Osteoarthritis most commonly affects big joints like the knees and hips, but other joints can be affected, such as the big toe and finger joints. The most common symptoms are stiffness, pain and crunching when the joint is moved. No treatments have yet been developed that can reverse the process, so most treatments aim to control symptoms. Treatments used to control the symptoms include non-steroidal anti-inflammatory drugs such as ibuprofen or other painkillers. Sometimes steroids injection may be used or, when it is the only option, joint replacement surgery can be carried out.
What did the research involve?
This trial involved 1,683 people with osteoarthritis of the knee who had X-ray evidence showing joint space narrowing and bone spurs – typical signs of the condition. They were randomly assigned to take either a placebo or Protelos daily for three years (either at a low dose of 1g a day, or standard dose of 2g a day). The main outcome assessed was joint space narrowing on X-ray, measured at 12 months, two years and three years. Greater narrowing of the joint space indicates increasing osteoarthritic changes in the joint. Symptoms were also assessed using validated scores for pain, stiffness and function (WOMAC score).
What were the basic results?
Of the people enrolled, 1,371 patients (82%) were followed for an average of 2.5 years. The average age of people in the trial was 63 years, average BMI score was 30 (classed as overweight) and 69% were female.
The main findings were that people taking strontium ranelate showed less progression of their osteoarthritis based on an assessment of joint space.
The study found that:
- People who took 1g/day strontium ranelate had 0.231mm decrease in joint space.
- People who took 2g/day strontium ranelate had 0.271mm decrease in joint space
- People who took placebo had 0.371mm decrease in joint space.
- Differences between placebo and strontium ranelate were statistically significant for both the lower dose (0.14mm) and higher dose (0.10mm).
The conference abstract does not report at what point during the follow-up these results were obtained.
The 2g/day dose of strontium ranelate was reported to significantly improve overall symptoms, as measured by the total WOMAC score. There was also a significant improvement on the pain sub-score of this assessment and a “trend” for improved physical function sub-score with the 2g/day dose of strontium ranelate. These comparisons were presumably carried out against the placebo, though this is not explicitly stated. The effects of the 1g/day dose on symptoms were not mentioned in the abstract.
Strontium ranelate was reported to be well tolerated by the patients.
How did the researchers interpret the results?
The researchers concluded that both 1g/day and 2g/day doses of strontium ranelate had a
beneficial effect on joint structure in patients with knee osteoarthritis. They said that this structure-modifying effect was accompanied by symptom improvement with the 2g/day dose.
The findings of this study sound promising, although until the full research paper is published the merits of the study and its findings cannot be fully gauged. Results presented at conferences are often preliminary and may change once a final analysis is performed. Also, the abstract will not have been through the full peer-review process, where experts in the field look at potential limitations and problems with the study.
However, the results appear to be of interest to the press, medical professional and the public, with many high-profile news stories reporting on the study and many internet users commenting on the potential of Protelos. Professor Alan Silman of the charity Arthritis Research UK reportedly told The Independent that the research was as an “exciting development”. He added: “Although [the drug] doesn't reverse osteoarthritis, it slows down its progression in terms of X-rays, and appears to have a beneficial effect on pain, although the extent of this is still unclear. This is the first time that a drug has been shown to slow progression of osteoarthritis, as existing treatments for osteoarthritis just focus on symptoms.”
The conference abstract itself reveals some interesting details, with both doses of Protelos leading to less narrowing of the joints but the lower dose of 1g producing better results than the 2g dose. However, whether improvement seen in X-rays has an effect on everyday life is less clear at this stage. On face value, the difference in joint space narrowing suggests that the lower 1g dose may be superior to the 2g dose, but only the higher dose appeared to have a significant effect on the overall WOMAC score (a scale measuring pain, stiffness and function). Effects of the lower dose on pain and function were not explicitly stated, but the researchers’ conclusions suggest that they may not have been statistically significant.
Full publication of this trial is awaited. Strontium ranelate is currently only licensed for the treatment of postmenopausal osteoporosis. Further studies of the treatment in osteoarthritis may be needed to confirm its effects and assess the safety of the drug for this use before it is considered for licence extension. As with all drugs, strontium ranelate is not without risk. It can cause adverse effects, including nausea and diarrhoea, and it has been associated with causing blood clots in the veins and, is some people, severe allergic reactions.
These brief, partial findings have no immediate implications for the treatment of osteoarthritis.