Saturday, October 12, 2013

With Knee Studies, It Pays to Read the Fine Print and Do Some Digging

Last summer, I wrote this post:

News Flash: Injections of Hyaluronic Acid May Do Your Knees More Harm Than Good.

That, at least, was the conclusion of a “meta-analysis” by Swiss researchers of 89 clinical trials that looked at the effectiveness of “viscosupplementation.” This procedure aims to bolster a knee pain sufferer’s synovial fluid, which when healthy is a viscous lubricant that acts like a cushion too. When unhealthy, it thins out and performs its essential functions poorly.

The Swiss researchers found that, in 18 large-scale trials, viscosupplementation made such a small difference as to be “clinically irrelevant.” What’s more, some studies suggest the procedure can lead to a higher risk of cardiovascular and gastrointestinal problems.

So that’s settled?

Not quite.

Along comes a new meta-analysis of 29 studies that finds “intra-articular hyaluronic acid injections provided significant improvement in pain and function compared to saline injections.” The authors of this analysis note that all products in these studies were FDA-approved, unlike in the earlier Swiss investigation.

So whose meta-analysis is correct?

Well, the most recent one has a couple of big red flags that should give anyone pause.

* Follow the money.

The end of the Business Wire release for the latest meta-analysis contains an interesting disclosure:
The meta-analysis was supported by the Hyaluronic Acid Viscosupplementation Coalition, a collaborative of hyaluronic acid injection marketers.
Hmm. That doesn’t smell good.

Let’s face it: Viscosupplementation has grown into a sizable medical business. When a meta-analysis claims that this procedure -- which a number of companies have probably spent millions of dollars developing and testing products for -- is useless, well, what do you expect them to do? Fight back.

Now it could be that the first meta-analysis got everything all wrong. Sure, that’s possible. But I’d rather that a set of neutral, disinterested researchers determine that than a couple of what appear to be Phd consultants.

And how was their meta-analysis “supported” (a lovely weasel word, with positive connotations and an utter lack of specificity)? Were they paid to do the meta-analysis? And what guidance were they given by the coalition, if any?

* Consider the source.

At least the results of the meta-analysis were published in the New England Journal of Medicine, right?

Uh, not quite.

In fact, I was left scratching my head after reading the title of the publication: Clinical Medical Insights: Arthritis and Musculoskeletal Disorders. I’ve perused lots of medical papers related to knee pain and treatments for the problem. So I’m familiar with many of the names of publications. But not this one.

Who’s behind Clinical Medical Insights (it appears a number of sister publications use this same moniker)? This is where things get interesting.

An outfit called “Libertas Academia” puts out the Clinical Insights series. It belongs to the ranks of so-called open access publishers. In theory, the concept of “open access” sounds great, especially if you (like me) have run headfirst into a paywall when trying to get a copy of the published results of a particular medical study. What’s more, the per-article rates for regular journals are invariably steep ($30 to $40 say). But with open access, the publisher makes the content free.

Great -- except where does the money come from to support such an operation? Answer: the authors seeking publication. Libertas Academia says here that it charges from $950 to $1,980 as an “article processing fee.” (Which raises a curious question: Who paid for the report on this latest meta-analysis that found positive benefits of viscosupplementation? Maybe the Hyaluronic Acid Viscosupplementation Coalition?)

If this business model is starting to make you squirm, you’re not the the only one. This writer, in reviewing nine open-access publishers (including Libertas Academia), labels them “predatory.” He explains, “Their mission is not to promote, preserve, and make available scholarship; instead, their mission is to exploit the author-pays, open-access model for their own profit.” The publishers provide “little or no peer-review,” he alleges.

Also they “spam” academics, inviting them to submit articles which sometimes aren’t even in their field, according to this frustrated researcher who said he got eight spam e-mails from Libertas Academia, despite requests to stop. Not surprisingly, open-access publications have acquired the nickname “vanity journals.”

If you’re still not convinced, check out this tale of a nonsense-filled, spoof academic paper submitted by a Science magazine editor to open-access journals. More than 100 accepted it despite errors so blatant, “Any reviewer with more than a high-school knowledge of chemistry and the ability to understand a basic data plot should have spotted the paper's short-comings immediately.”

Anyway the point here:

Just as not all knee studies are created equal, so all meta-analyses are not either. Caveat emptor (or whatever the “patient beware” version of that Latin saying is). Viscosupplementation may help your particular knees, true. But be wary of “research” supported by makers of the products. They may not be the best neutral source of information, to say the least.


  1. Good message Rich. Should be known this stuff has been done in animals with success for a while and europe before the us. Some studies add HA after surgery (microfracture) and it has significant increases. Look up the saw study. They also add stem cells on top of the HA. Interesting result is the difference between HA and nothing is greater than HA + stem cells and nothing. Of course, the researchers only mention the stem cells + HA is what made the great result and not the fact HA seemed to help a lot. Another OP.

    1. Actually I was mistaken. It wasn't a true isolate every variable study. They only compared MX + HA to MX + HA + SC's. Not MX alone.

    2. I have Condromalacia 4 degree (maybe because the lateral movement of patella and 3 years of triathlon). I have only worst crepitus, no pain yet. I did hyaluronic acid infiltrations 4 months ago, but the crepitus are the totally the same. I just read the book and it helped me to understand the situation better more than 10 doctors that I visited in last 18 months.
      Richard, I didn’t understand a situation in the book: you had problems with the patella cartilage, no with the cartilage of the articulation, right? Why you had pain when you where bag pack or heavy fan? Otherwise: is it bad for my knee cap cartilage to where my 3yo child on my shoulders (because I have to do this every day)
      Thank you a lot!
      Marius Alexandru DRAGU

    3. Good question, Marius. I thought a lot about that too. Why would I have symptoms that would seem to be related to problems in the cartilage between the femur and tibia, if my symptoms were mainly patellofemoral and an MRI showed irregularities in the tissue under the kneecap, but not elsewhere?

      Okay, here are my thoughts: (1) The problems I had with standing and with carrying heavy objects were later-stage symptoms. I think my condition basically started under the kneecap, then my joint just started falling apart, in a larger way. (2) A typical MRI doesn't see the quality of the cartilage, so it's possible that the MRI didn't pick up some early-stage problems in tissue in other parts of the joint. (3) I think my synovial fluid was fairly sick, in the sense it wasn't working well, and so this may have contributed to problems I had when standing/carrying items, because I wasn't getting enough support from this lubricant/cushion. And of course (4) is possible too -- something else was going on that I didn't quite understand.

      So: Is it bad for you to carry around a three-year-old on your shoulders? Well, it'd be a shame to miss out on that fun (I have a four-year-old myself who likes riding up there). I think you've got to figure out: Do symptoms flare up after you do this? Do you think it's creating any issues for your knees? If not, it could very well be fine to keep doing.

  2. Hello Richard!
    Thank you for your response! Actually, I don’t want to bother you with my private issue, please pay attention only if you find something interesting. I started doing enduring sport (Ironman&Maraton) after about 40 years of sedentary life (no background). This experience revealed me some talent and I reach podiums relatively quickly. The result was that I succeed to destroy my right knee in 3 years (I am overpronator, but the right leg has much overpronation than the left). I am from Romania, but I am living in Belgium. I visited a lot of doctors and kinesiotherapists from bought countries and I did some simple investigations. The advices were diversified, but you know this movie yet…I have awful crepitus inside the right knee (you said: as a purse of chips) and no pain (or very low and rare pain), but the magnetic resonance disclosed that I have only a very thin cartilage on the patella. Because I don’t have pain, I cannot conclude exactly what activity is doing wrong for my knee and what is helpful for it. This miscommunication with my knee is a little bit strange, but I am happy because I am aware that I have a problem and I decreased dramatically my running and cycling activities since 6 months (any good sign till now from my knee). As I told you, I did some Hyaluronic Acid infiltrations, but any result (for few days, the crepitus sound was like I putted full of oil in the chips purse, but totally nothing after that. Here:;search_string=crepitus;#4587919 , in the last post there are 2 pictures with my knees: first relaxed, and the second with my quads tensionless its are relieving that I have some important deviations.
    Thanks again and keep in touch!
    Marius Alexandru DRAGU

    1. Interesting history. I don't have much time right now but (1) I wouldn't dwell too much on crepitus -- only as an early warning sign. (2) You may not have pain because it sounds like you're well-conditioned and quite active (though your cartilage is thin yes). How to thicken cartilage? My hunch is a lot of easy to moderate cycling might do the trick. Just a hunch. :) Anyway, be grateful you don't have pain ... if you're pain-free, there are a lot of joint-friendly activities you should be able to do without problems.