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The Use of Glucosamine and Chondroitin Sulfate for Knee Arthritis

A recent review from the January 2009 issue of the Journal of Arthroscopy reviewed the use of glucosamine and chondroitin sulfate for knee osteoarthritis.  Considering the vast amount of people suffering from knee arthritis and the increasing cost of medical care for these patients, the use of any type of supplement to reduce symptoms is welcome.

Research into the efficacy of glucosamine and chondroitin sulfate is certainly not new with studies dating back to 1969.  However, the literature has been filled with many poorly controlled studies, some of which were funded by glucosamine manufacturers!This particular paper reviewed the results of 23 studies that involved double-blind, placebo-controlled, randomized control trials as well as several meta-analyses.

The effectiveness of Glucosamine and Chondroitin Sulfate

The overall results of the review show that there are inconsistent results, but that the results do favor improvement of pain and joint function in patients with arthritis.  The authors also note that one of the most consistent trends between studies involved the length of use of the supplement.  The best results from glucosamine appear to occur after several months of use.  Studies are referenced that show positive results in 3-6 months and even up to 9 months.

In general, if you looked hard enough, you could probably find more articles that say that the use of glucosamine is effective than you could find saying it is not effective.  I realize and agree that there is not overwhelming evidence in support of glucosamine or outlined the exact mechanism of symptom improvement.  However, when we start to run out of options for our patients, I would say there is enough evidence to support it’s use, as long as the supplement is safe.

The Safety of Glucosamine and Chondroitin Sulfate

A potentially more important finding of the current review was that the use of glucosamine and chondroitin sulfate appears to be safe, at least as safe as placebo supplementation.  To me, this is the most important finding for me clinically.  If we are going to recommend the use of a supplement with inconsistent findings, as long as the supplement is safe I have no problem recommending a patient try glucosamine.

Recommended Use of Glucosamine and Chondroitin Sulfate

I have spent a lot of time over the last several years trying to find a consensus statement on the use of glucosamine and chondroitin sulfate.  Unfortunately, this does not appear to exist.  I have taken information from many sources, including the excellent recommendations of noted orthopedist Dr. Frank Noyes of Cincinnati Sports Medicine and information from the Osteoarthritis Research Society International to provide the following information.  I recommend that you read Dr. Noyes’ recommendations, it is a great resource.  Also, realize that you should consult with your own personal physician before taking any supplements and that glucosamine may not be indicated for you personally.  The below information are just basic guidelines for healthcare providers when considering the use of glucosamine:

  • Cosamin DSGlucosamine should be taken with chondroitin sulfate to maximize it’s effectiveness
  • Supplements that include magnesium and vitamin C may help the absorption rate of glucosamine and chondroitin sulfate.
  • To date, the specific brand that has received the highest recommendations appears to be Cosamin DS.
  • Dosage should vary based on body weight:
    • If less than 120 lbs: G 1000mg + CS 800mg
    • Between 120-200 lbs: G 1500mg + CS 1200mg
    • If greater than 200 lbs: G 2000mg + CS 1600mg
  • Supplements should be taken for at least 3 months for noticeable results.  If no response within 6 months, may discontinue.

I have found decent results from the use of glucosamine in my patients, have you?

C VANGSNESSJR, W SPIKER, J ERICKSON (2009). A Review of Evidence-Based Medicine for Glucosamine and Chondroitin Sulfate Use in Knee Osteoarthritis Arthroscopy: The Journal of Arthroscopic & Related Surgery, 25 (1), 86-94 DOI: 10.1016/j.arthro.2008.07.020

Image by scottfeldstein

Autologous Chondrocyte Implantation or Microfracture?

The current issue of AJSM has two great articles regarding articular cartilage repair  procedures that go very well together.  I think this is an amazing aspect of orthopedics as we are making ground on developing ways to restore normal cartilage.  The Cartilage Defectimplications of this are staggering.  If you share an interest in articular cartilage repair, I recommend you read the special issue of JOSPT on articular cartilage and meniscal repair procedures that I guest edited, specifically my guest editorial and my article on postoperative rehabilitation following articular cartilage repair procedures.

 

Autologous Chondrocyte Implantation Compared to Microfracture

The first study is a comparison of outcomes between microfracture and second-generation autologous chondrocyte implantation (ACI).  80 patients with grade III-IV cartilage defects of the femoral condyle or trochlea were enrolled in the study and split evenly between groups.  The second-generation ACI procedure used Hyalograft C. 

microfracture pickingBoth groups showed significantly greater results at the 5 year post-op mark, however, the ACI group showed greater improvements in the International Knee Documentation Committee objective and subjective scores.  Even more interestingly, the return to sports rate between groups was similar at the 2-year mark and remained stable for the ACI group, but decreased for the microfracture group.

 

Results of Autologous Chondrocyte Implantation in Patients with Failed Prior Treatment

The second study prospectively assess the results of 126 patients undergoing ACI after a failure of a previous articular cartilage repair procedure.  This is a very large and prestigious study by the STAR group (Study of the Treatment of Articular Repair), which consists of all the best cartilage repair surgeons in the country.  The past procedures included predominantly debridement (48%) and microfracture (27%), as well as subchondral drilling, abrasion arthroscopy, and osteochondral autograft.

Results of the study were good with 76% of subjects showing successful results for a long duration.  All measurements showed a statistically significant and clinically meaningful improvements after ACI.  However, these results are lower than many of the previously reported outcomes following ACI when used as the first surgical procedure.  Here are photos of before (top) and after (bottom) of ACI for a femoral condyle defect (left) and patella defect (right):

ACI implant on condyle and patella

 

Clinical Implications

Putting the results of these two studies together leads to a very interesting and meaningful result.  While ACI and microfracture may yield similar post-op results at the 2-year follow-up, the ACI procedure continues to show durable results while the microfracture group slowly deteriorates over time.  This is significant when looking at these two studies together.  Although ACI appears to be a valuable surgical procedure for failed articular cartilage repair procedures, results of ACI used as the primary procedure are better than when used secondary after another procedure (such as microfracture) fails.  Based on these results, it may be better to have the ACI in the first place rather than try a microfracture.

These results make sense, as the ACI procedure has been shown to result in Type II collagen tissue similar to native articular cartilage while the microfracture is predominantly Type I collagen.  Think of the ACI procedure as restoring cartilage while the microfracture just creates a “scab” of a fibrin clot that simply covers the defect.  Because this tissue is inferior to Type II collagen, it does not hold up as well to weightbearing and functional loading.  Unfortunately the negative of the ACI procedure is a long rehab course and longer time to return to full activities, but based on these studies the slight delay may be worth it to prevent future complications.

Have you seen these results in your clinic?  Would you agree or disagree?  There are a lot of pros and cons with both procedures.  Hopefully as we continue to improve our knowledge and techniques all repair procedures will show better results.

E. Kon, A. Gobbi, G. Filardo, M. Delcogliano, S. Zaffagnini, M. Marcacci (2008). Arthroscopic Second-Generation Autologous Chondrocyte Implantation Compared With Microfracture for Chondral Lesions of the Knee: Prospective Nonrandomized Study at 5 Years The American Journal of Sports Medicine, 37 (1), 33-41 DOI: 10.1177/0363546508323256

K. Zaslav, B. Cole, R. Brewster, T. DeBerardino, J. Farr, P. Fowler, C. Nissen (2008). A Prospective Study of Autologous Chondrocyte Implantation in Patients With Failed Prior Treatment for Articular Cartilage Defect of the Knee: Results of the Study of the Treatment of Articular Repair (STAR) Clinical Trial The American Journal of Sports Medicine, 37 (1), 42-55 DOI: 10.1177/0363546508322897

 

The Use of Postoperative Bracing Following ACL Reconstruction

How often do you use an immobilizer after ACL reconstruction?  The January 2009  issue of American Journal of Sports Medicine is out and there a few interesting articles I wanted to feature.  The first of which discusses the use of knee bracing and immobilization postoperatively following ACL reconstruction using a hamstring tendon graft

The Use of Postoperative Bracing Following ACL Reconstruction

DSC01582In this study, 82 patients were randomized into two groups: 1) a group of patients that wore an unhinged knee immobilizer and 2) a control group that did not use a brace.  At 2 week postoperatively, the authors report that there were no differences between groups for pain, medications consumed, complications, and range of motion.

The authors conclude that an unhinged postoperative knee brace is not recommended following ACL reconstruction for the purpose of pain control.  That is the exact phrasing that was used.  The last part of the sentence is significant, “for the purpose of pain control.”  The paper is centered around pain control more than any other variable, it is even in the title of the paper.

 

Methodological Issues

There are a couple of methodological flaws that I found that are likely significant in the presentation of the results

  • Compliance for brace use was extremely low and only documented by subjective reports.  Only 86% of subjects in the immobilizer reported wearing their brace from day 7-13 and by day 14 only 26% of subjects reported wearing their brace as instructed.  Since this is only self-reported, you can assume that these numbers are best-case scenario as I wouldn’t be surprised if a few subjects were not completely honest.  Regardless, taking these numbers into consideration, you can argue that the brace group consisted of only 11 patients and the non-brace group had 73 subjects.  Not sure that this low of compliance can lead to a good comparison.
  • All of the patients were on pain medication consisting of either Percocet or Tylenol with codeine and naproxen.  As previously mentioned, pain scales were of primary importance to the authors in the discussion section of the paper.  However, it appears that pain was controlled with pharmaceuticals and likely has no correlation to brace use.

 

Clinical Implications

I am not sure that based on the results of this study, my choice to use a brace or not following ACL reconstruction will be influenced.  Clinically, I have always used a postoperative knee brace following ACL reconstruction, though have always used a drop-lock hinged knee brace.  This allows the patient to have the knee free to move throughout the day, however can lock the brace into full knee extension during ambulation.DSC00996

While I feel that this is helpful for stability and protection of the knee postoperatively, these are not the reasons why I use a brace.  For me, it is for a much more simplistic reason:

The quadriceps are susceptible to reflexive inhibition due to the pain and effusion associated with surgery. 

Ambulating without full volitional control of the quadriceps encourages improper gait and makes the limb susceptible to “giving-way episodes” and potential harm.

The brace is utilized for the first 7-21 days depending on the patient and their ability to restore volitional control of the quad.  Many factors will affect the duration of the brace use, including patient selection, age, and previous activity level.  For example, an athlete that has an acute ACL reconstruction will likely restore their volitional control sooner than an older, sedentary patient.  The key is to assess and individualize.

Another interesting fact that I took from this paper really has nothing to do with the topic of the study, but nevertheless was interesting to me.  Look at the progression of reported pain on a VAS over the course of two weeks:

1 hour postoperatively20.0-20.8
Day 0 PM29.3-30.8
Day 1 AM28.7-34.1
Day 1 PM41.9-45.5
Day 2 AM35.1-40.8
Day 2 PM32.6-35.2
Day 727.5-29.3
Day 1412.9-14.1

Pain appears to peak at 36 hours after surgery and remain high day 1 and day 2 postoperatively before gradually decreasing to a fairly tolerable level by week 14.  This is important information for clinicians and patients.  When I see a patient immediately postoperatively, I commonly tell them that the first few days are the worst and that it is not uncommon to feel worse days 2 or day 3.  This helps assure them that they have not reinjured themselves when pain worsens.

This is also helpful regarding pain’s role in the inhibition of the quadriceps.  Based on these numbers, it wouldn’t surprise me if a patient was having difficulty with volitional control of the quadriceps 1 week after surgery despite appropriate rehabilitation.  If you were using a brace for this reason, as I suggest above, it looks like day 7 may be too early to discharge the brace and that 2 weeks may be more appropriate for many patients.

Food for thought either way I guess.  How common do you use brace immediately after ACL reconstruction?  What is the duration?  What is your reasoning?  Would love to hear what other centers are doing.

L. A. Hiemstra, S. M. Heard, T. M. Sasyniuk, G. L. Buchko, J. G. Reed, B. J. Monteleone (2008). Knee Immobilization for Pain Control After a Hamstring Tendon Anterior Cruciate Ligament Reconstruction: A Randomized Clinical Trial The American Journal of Sports Medicine, 37 (1), 56-64 DOI: 10.1177/0363546508322896

What is the Source of Patellofemoral Pain? It Might Not be Chondromalacia…

Patellofemoral pain is one of the most commonly diagnosed knee pathologies.  Despite the prevalence of the diagnosis, the exact mechanism and source of pain continue to be unclear.  This lack of clarity is likely the reason why we continue to use such vague, non-descriptive terminology such as “patellofemoral pain.”  As rehabilitation specialists, it is often our job to disregard a diagnosis like this and instead rely on our clinical examination to find functional deficits, such as loss of strength or joint mobility, to lead our treatment plans.

The source of patellofemoral pain has long been debated.  One of the most common theories involves the deterioration of the articular cartilage on the undersurface of the patella, or chondromalacia. 

If you haven’t read or at least heard about it, there is an amazing article that was published in the American Journal of Sports Medicine 10 years by Scott Dye, MD (Dye, Vaupel, Dye: AJSM ’08).  In the study, the researches sought to establish the source of patellofemoral pain by physically palpating various structure within the knee during arthroscopy.  What is truly amazing about the study is that Dr. Dye himself actually had his knee scoped without anesthesia so that he could consciously quantify the level of discomfort he felt!  Dr. Dye can never be accused of not sacrificing himself for the sake of the advancement of sports medicine!

Cartilage defects did not cause discomfort

The first finding that was surprising was that palpation of the undersurface of his patella cause no discomfort, even with the prescene of grade III-IV articular cartilage defects.  This immediately questions the cartilage being a source of patellofemoral pain. 

Moderate to severe pain was caused by the retinaculum and fat pad

Conversely, the two areas of the knee that caused moderate to severe discomfort were the retinacular tissue and infrapatellar fat pad.  Even more interesting was that even though these areas produced discomfort, it was difficult for the subject to localize the source of pain.
This may also at least partially explain why patellofemoral pain is so vague in our patients.  This information coincides with that of Fulkerson (Clinical Orthopedics ’85) and Sanchis-Alfonso (AJSM ’98).  Fulkerson reported that patellofemoral pain may be caused by enlargement and small injuries of the nerve fibers in the retinaulum.  Sanchis-Alfonso report that patients with patellofemoral pain tend to have a higher amount nerve fibers and histological changes of the neural tissue.Interesting findings that seem to make sense.  

The cartilage tissue is avascular and fairly aneural where the fat pad and retinaculum is highly highly vascularized and full of neural tissue.  Patients with patella instability and chronic elongation of the medial retinaculum and tightening of the lateral retinaculum may have symptoms due to the chronic changes of the tissue and the corresponding stress on the neural fibers.

Clinical Implications

So what does this mean and how does this change the way we treat patients?  For one, I am not overly cautious with exercises and their effect on patellofemoral compression, unless this reproduces the patient’s symptoms.  Strengthening of the quadriceps is always going to be a large part of the treatment plan for these patients.  In order to do this most effectively you knee to perform open kinetic chain knee extension and work into deeper ranges of motion with closed kinetic chain exercises.  My rule of thumb is that if the exercise does not cause pain or excessive crepitation, I don’t mind doing it as tolerated.  But I must stress as tolerated.

It is also likley that we should treat the iritation of the retinacular tissue even if the pain is difficult to localize.  This can include your choice of treatment techniques and anti-inflammatory modaliities.

I write this post in an attempt to motivate thought next time you evaluate a patient with patellofemoral pain.  There is still a lot of uncertainty on this topic but with time I am sure we will continue to learn more.  Have you had success directly treating the retinacular tissue?  If so please share your experience.