Ask the Researcher
Jeffery Driban, PhD, ATC, CSCS
Novel Assessment Strategies for Osteoarthritis
Osteoarthritis is characterized by multi-tissue organ failure of synovial joint(s) and is the most common form of arthritis. If a patient has a history of a knee injury then they are four times more likely to develop knee osteoarthritis (another way to think of this: if you tear your ACL or meniscus there is roughly a 50% chance you will have symptomatic osteoarthritis within 20 years). Globally, over 77 million people have symptomatic osteoarthritis and by 2050 it estimated that over 195 million people will suffer osteoarthritis. To mitigate the global burden of OA, researchers are pursuing disease-modifying interventions to slow, halt, or reverse disease progression. Unfortunately, there is still no FDA approved disease modifying osteoarthritis intervention. There are numerous theories for why disease modifying interventions, which may work in animals, fail in humans (for example, the animal models don’t reflect human osteoarthritis, the measurements of osteoarthritis are not sensitivity enough, we treat patients to late in the disease process when we can no longer save the joint). Another reason why the treatments might not work is that osteoarthritis can be very variable among patients: some progressing faster than others, some with more severe pain, etc. Some researchers have proposed that osteoarthritis might not even be one disease but a collection of diseases with a common end-point.
My research interest is in exploring new quantitative assessment strategies for osteoarthritis using magnetic resonance imaging and biochemical markers. I have done research with animals and humans to explore how osteoarthritis develops and progresses as well as what might make one group of patients unique from another. I believe that by understanding the characteristics of each patient (or subset of patients) and their osteoarthritis we can target treatments more effectively to the correct patients and eventually find ways to prevent or at least slow the progression of osteoarthritis.
This week I will be glad to answer questions about osteoarthritis; including but not limited to risk factors for osteoarthritis, clinical evidence for interventions, disease progression, and emerging trends. I will try to answer your questions with objective responses and links to articles but some of these answers will represent my opinions on the available data and do not represent the opinions of SMR, the other collaborators to the blog, my research collaborators, or my medical institution.
I look forward to hearing from you and answering your questions.
In the November 2010 NATA News Dr. Ryan Tierney and I also wrote an article discussing the need for sports medicine clinicians to take an active role in promoting our patient’s long-term quality of life.
Written by: Jeffery Driban
Reviewed by: Stephen Thomas
I have recently had some open discussions with colleagues in regards to the use of Glucosamine with Knee OA.
My initial thoughts were that if it was going to be effective it would be with individuals on the more mild side of OA (looking at the amount of DJD and compliants/functional limitations and exam).
I have been told that some of the reasons it is not effective is bc the way it is taken.
1500 mg daily, but needs to be split up t/o day for max effectiveness. Not 1500 mg as one dose.
What are your thoughts on the use??
Would you define glucosamine as effective if it changed the person’s symptoms or altered the rate of joint degeneration? This is a major question these days.
For structure modification (slowing disease progression) a lot of people would agree with your first comment that disease modifying treatments may be optimal before the joint changes get to severe (I personally agree with this theory for various reasons). However, we don’t know when the “point of no return” occurs.
To answer the rest of your question, I will focus on structural modification. I’ll provide some details from some randomized, placebo-controlled trials (links at the bottom):
Pavelka K et al (2002): Glucosamine sulfate (1500 mg once a day) slowed the rate of joint space narrowing during a 3-year study
Reginster JY et al (2002): Glucosamine sulfate (1500 mg once a day) slowed the rate of joint space narrowing during a 3-year study
Sawitzke AD et al (2008; GAIT Study): Glucosamine sulfate (500 mg three times/day) had no significant difference to placebo during a 2-year study.
Rozendaal RM et al (2008): Glucosamine sulfate (1500 mg once a day) had no significant difference to placebo during a 2-year study (hip).
Towheed TE (2009) provides a Cochrane Review of glucosamine for osteoarthritis
I focused on structural changes because it’s a more objective outcome than symptoms. The GAIT study found that the combination of glucosamine and chondroitin sulfate was more effective at reducing pain compared to placebo among individuals with moderate-severe pain but not those with mild pain. The authors cautioned readers from taking this finding to far because this was a secondary analysis on groups with small sample sizes. I think we need more information like this secondary analysis to describe who is responding and who is not responding to glucosamine. For example, there’s some compelling research that disease modifying interventions are not as effective at slowing down joint space narrowing when the joint is malaligned. Some believe that biochemical treatments (for example, glucosamine) cannot overcome adverse biomechanics.
The other thing to keep in mind is that the treatment effect of glucosamine tends to be small in the general population and these studies require daily use for several years. It’s hard to tell at this point if there’s a big difference between 1500mg/day taken in one dose or spread out over three. I haven’t seen enough data to decide if it matters.
Side note: On clinicaltrials.gov there’s several clinical trials for glucosamine actively recruiting new participants and a few that are no longer recruiting but still active (so new data is on the way). Also, the FDA and Osteoarthritis Research Society International are expected to release new guidelines this year for defining osteoarthritis interventions as disease modifying (this could have a significant impact on clinical trials).
I hope this helps if you want me clarify anything just let me know.
Pavelka K https://www.ncbi.nlm.nih.gov/pubmed/12374520
Reginster JY https://www.ncbi.nlm.nih.gov/pubmed/11214126
Sawitzke AD https://www.ncbi.nlm.nih.gov/pubmed/18821708
Rozendaal RM https://www.ncbi.nlm.nih.gov/pubmed/18283204
Towheed TE https://www.ncbi.nlm.nih.gov/pubmed/15846645
GAIT Study https://nccam.nih.gov/research/results/gait/qa.htm
Heres another Jeff
For Knee OA
Has there been anything to support that increasing strength and improving balance/prop awareness will correlate with decreased pain or increased function?
Understanding the differing degrees of OA and the structural changes that can occur with the process.
I know from discussing this with some Ortho's, many will push PT (or a consistent HEP) to put off the inevitable TKA. More and more seem to be avoiding scopes. I assume bc of poor outcomes and in some cases progressing the degenerative process.
I would love your opinions based on you experiences too.
There is some positive literature for exercise and rehabilitation for osteoarthritis; particular knee and hand osteoarthritis (we need more data for hip OA but I suspect it will work out). Almost every treatment guidelines/recommendation for osteoarthritis states that patients should be advised to do exercise and/or be referred to rehabilitation. Beyond that the guidelines are vague. Furthermore, I think research articles have not caught up with our improved rehab philosophy that includes more balance, proprioception, neuromuscular control, etc.
There is a growing body of evidence that exercise and rehab can improves strength and proprioception as well as decreases knee symptoms.
I often get asked back, when I defend strengthening and neuromuscular training, why many epidemiology studies don’t find a relationship between strength or proprioception and symptoms. My response is typically:
1. Some of those studies (definitely not all) focus on one muscle group in an open chain test; we should be testing their strength in close chain activities (it also ignores other possible contributors; for example hip abductors).
2. I think it might not always be a matter of strength but also how they use that strength (the neuromuscular control/mechanics they use to do activities).
There is a huge need for physical therapists and athletic trainers to get more involved in osteoarthritis research on both the prevention side and the management side. The researcher community could really benefit from hearing some of the things that we take for granted each day (for example, concepts of kinetic chain or neuromuscular control).
I think the next generation of OA rehab studies are going to start showing the full potential of rehab. Tufts Medical Center is getting ready to do a comparative effectiveness study of Tai Chi and PT (https://clinicaltrials.gov/ct2/show/NCT01258985). I think studies like this one will end up helping promote rehab for knee OA.
Systematic Reviews with Positive Outcomes:
Rehab and Hand OA: https://arthritis-research.com/content/13/1/R28
Strength Training: https://www.ncbi.nlm.nih.gov/pubmed/18821647
Land-based Exercises and Knee OA:
Physical Therapy and Knee OA: https://search.pedro.org.au/pedro/browserecord.php?record_id=1502
There’s not enough data on the hip at this time.