Saturday, March 10, 2018

Why I’m So Optimistic About Cartilage Healing, Take 2

I got a comment from a reader below this post. If you remember, I was looking at a two-year study that showed a surprising number of improvements in cartilage defects (well, I found the number surprising anyway). This reader was less enthusiastic:
If I am interpreting the study correctly, most of the defects of the patella actually progressed. For younger people, perhaps for the majority of this site readers, this is bad news. Perhaps, I am wrong, but it seems to me that most of us here suffer from chondromalacia, of one degree or another, and as it is about patella cartilage damage, there isn't much joy in that study. There's another one from 2008, where the level of degradation of patella lesions was high compared to all the investigated knee compartments and the percentage of cases where improvement of a lesion was observed was abysmal.
First, let me address a couple of quick things: (1) Yes, I’ve seen a study too where defects in the patella cartilage didn’t improve as often as defects in cartilage elsewhere in the knee – but still, there were some instances where they did improve. (2) To clarify, the study I reference in the post isn’t looking at just defects in the cartilage behind the patella, but rather, throughout the knee.

Okay, a quick recap:

The table below is from a study, “Factors Affecting Progression of Knee Cartilage Defects in Normal Subjects Over Two Years.” The 86 people who participated had MRIs done of their knees at the start of the study, then two years later.

The condition of each subject’s cartilage was graded for five different knee compartments (at baseline, and after two years). The scoring again goes like this:
Grade 0 = normal
Grade 1 = focal blistering
Grade 2 = irregular surface and loss of thickness of less than 50%
Grade 3 = deep ulceration with loss of thickness of more than 50%
Grade 4 = full-thickness wear of cartilage with bone exposed












Okay, so did most of the defects in the study progress? Well, yeah. Of course. But it doesn’t matter because you have to adjust for the “floor” and “ceiling” effect.

In this case, “floor” means a defect can’t get worse. “Ceiling” means it can’t get better.

Example: If a defect is graded “0” at baseline, two years later, it can only be “0” or worse. It can’t get any better than 0. There is no -1! Conversely, a defect graded “4” at baseline can only stay the same or (if indeed cartilage can heal) can get better.

Now, look at the number of defects that have a “ceiling” effect (grade of 0) or a “near ceiling” effect” (i.e., defects initially graded 1).

There are 117 that start out with a “ceiling” effect (just add the numbers in the first row) and 196 with a “near ceiling” effect (that's the second row). So for this group of 509 defects, there’s a high chance they’re going to get worse. Sure enough, we find a whopping 389 got worse. Awful, right?

Not at all.

Look at the bottom of the table. Here, our attention turns to the “floor” effect (defects with an initial grade of 4) and “near floor” effect (initial grade of 3). There are 5 defects with a “floor” effect and 14 with a “near floor” effect.

How many defects improved? Only 10 – which seems like a small number compared with 389, but consider that we started with only 19 (yes, I know, “small sample size” alert).

Of course, when you look at the number of changes overall, many more defects got worse because most faced the ceiling effect. But look at raw percentages, and the story becomes more interesting:

Defects that started in the “ceiling” or “near ceiling” effect categories
Got worse: 76%
Stayed the same or got better: 24%

Defects that started in the “floor” or “near floor” effect categories
Got worse: 26%
Stayed the same or got better: 74%

Wow! Almost a perfect inversion!

Now, why does this matter (once again) if you really care about cartilage healing (which, again, you shouldn’t obsess about in the first place, because pristine cartilage isn’t a sine qua non for eliminating knee pain).

Because if cartilage really can’t heal, all those defects graded 3 or 4 should be staying the same or getting worse; three-quarters of them shouldn’t improve!

One last fun thing in closing: is there a line in the table (you’ve probably already spotted it) where we can escape the “floor” and “ceiling” effects as defined here? Sure: at baseline, 88 defects landed smack dab in the middle of the table, receiving a score of 2. That means a loss of thickness of less than 50 percent.

Now notice what happened to them two years later. Yes, eight were found to be worse. But more than three times as many, or 27, improved to a grade of 1.

So that’s why I see the glass as half full (even though, for the umpteenth time, don’t obsess over cartilage healing!).

14 comments:

  1. Hey Richard.. have you heard of the bio-chip trials? it's an EU funded trial in stage 2 right now, and they are using cultured cartilage cells from the nose to generate knee cartilage, implanting it, and having good results so far.

    Might be interesting content for your blog.

    Here you go:
    http://biochip-h2020.eu/category/news/

    ReplyDelete
    Replies
    1. I've heard of harvesting cartilage from the nose to grow and transplant to the knee in general. We'll see what the studies show after enough people have had the operation done and an independent researcher examines the results, thanks.

      Delete
    2. neptronix@gmail.comMarch 17, 2018 at 12:13 PM

      Okay, just thought i'd tip you off. :)

      While i've got you here.. i was wondering if you had any kind of misalignment in your feet.. a leg length discrepancy.. or some biomechanical fault like that, which has lead to your initial patellafemoral issues?

      Also, how much cartilage did you have on your x rays? was it lookin' scarily depleted, or what? i forget if you mentioned that in your book or not.

      -David

      Delete
    3. My cartilage looked irregular, but not scarily depleted at all. I've got flattish feet, but I doubt that contributed to the knee pain. Also, most people have at least a small leg-length discrepancy, and I probably have one too. That, too, I think means little in the knee pain context.

      Delete
  2. This was a post from a guy called Terry42 on the Kneegeeks website which really gave me hope that cartilage can heal - the full thread is here: http://www.kneeguru.co.uk/KNEEtalk/index.php?topic=35811.0

    "It has been four years since I posted about my knee pain.

    Early on, I decided against surgery, and quickly gave up on physical therapy. I am almost 50 years old now. Over the last four years, I've tried to remain somewhat active. But the more aggressive the activity that I attempted, the more I would feel sharp pain around my knee-cap the next few days. I pretty much quit doing things that would aggravate my knee, which was about anything but walking or easy biking. But gradually over the years, I noticed my knee-cap pain was decreasing. Every few months, I would try some physical activity that I used to enjoy (hockey, basketball, running), and the result was always the same -- limping around for the next few days, and feeling depressed. But about one year ago, I tried playing hockey and noticed that my knee was sore, but not the extreme soreness that I'd felt in the past. I've continued to play hockey over the last year, and for the last few months, I am having neither knee pain during the activity, nor any knee pain the next day. I can run, jump, and play basketball again.

    Do I really have a full-thickness fissure in my cartilage, or was I mis-diagnosed? Probably I have some damage in my knee.
    Is my knee healed? I don't know.
    If I keep playing sports, am I headed for more trouble? Maybe.
    If I would have had surgery, and I ended up feeling as good as I do now, would I think that the surgery healed my knee? Definitely.

    Years ago, when I used to read this forum frequently, I always wanted to know if people recovered from their injuries -- how were they doing years later. But not to many people give long term updates. It was quite depressing. I decided that if my knee ever got better, I would give an update.

    It is not all doom and gloom. You can recover from a knee injury."

    ReplyDelete
    Replies
    1. Thanks for posting. That's a really good, thoughtful summary of his recovery. Interesting, and very hopeful.

      Delete
    2. Thank you, I remember reading that post years ago and it gave me hope. My journey is similar to his, except I'm having another MRI preformed this week to quantify the physical changes, stay tuned...

      Delete
    3. Erik - are you now recovered? I would be very interested in hearing about your MRI results, and your journey to recovery.

      Delete
    4. Hi sir, thanks for asking, please see my comments here: https://savingmyknees.blogspot.com/2017/02/with-glucosamine-studies-it-pays-to.html

      Delete
  3. Thanks, Triagain.

    I also have another interesting link for Richard.

    Merck is working on a drug that helps regenerate cartilage. It's looking like versus placebo, the full dose of the drug is producing a 1.5% cartilage growth over the period of a year ( assuming that a normal meniscus is 2mm ), which is astounding, considering that the placebo group lost 1% per year.

    This drug has passed the phase 2 clinical trials.

    https://www.prnewswire.com/news-releases/merck-kgaa-darmstadt-germany-presents-late-breaking-clinical-data-from-phase-ii-trial-of-sprifermin-for-osteoarthritis-disease-modification-300549720.html

    ReplyDelete
  4. Hi Richard, through your studies have you looked at much on microfracture on the patella? My surgeon did this to my patella when he was in there to do my plica. Now the pain is far worse - 11 months post surgery. Is there any hope of this getting better?

    ReplyDelete
    Replies
    1. I looked into microfractures mainly to compare them with ACI (they do as well as the much more expensive ACI). So anyway, I don't have a great knowledge of the rate at which complications resolve. Maybe someone else here does?

      Delete
  5. Hi Richard: I just finished reading your Saving My Knees book and found it educational and enlightening. My right knee is my main problem having been diagnosed by three Orthopedic surgeons with bone on bone, end stage osteoarthritis. I know you repeatedly say that your knees were not this bad and your book doesn't apply to such cases, however, it seems to me that some of the cartilage healing ideas could apply to even my problem. And yes, I know that Doug Kelsey's book also is very clear that his program does not apply to my situation. Nonetheless, maybe I'm just grasping for straws.

    ReplyDelete
  6. True, you may have a big uphill battle, but I don't think that's grasping at straws exactly. You might look for a very gentle, high-repetition activity (cycling? cycling backwards with no resistance?) that doesn't cause any pain, and just keep plugging away at it. Also, you'd have to be very careful about everyday activities that stress your knees.

    Also there's this to cheer you up:
    http://savingmyknees.blogspot.com/2018/03/why-im-so-optimistic-about-cartilage.html

    Anyway, please check back in later and let us know how things go!

    ReplyDelete