What’s the Biochemical Basis for the Success of Continuous Passive Motion?

When it comes to dealing with knee pain, I believe strongly in the beneficial effects of motion. I often prefer the word “motion” to “exercise,” as the latter conjures up images of fitness buffs doing strenuous activities that may not be good for bad knees. Move, move, move (in the proper amounts, in the proper ways).

For those recovering from surgery (or maybe even for those who just have really bad knees), I think continuous passive motion can be a great idea. In Saving My Knees, I mention the experiments on rabbits that Robert Salter performed more than three decades ago. Salter discovered that the cartilage fell apart in rabbit knees that were immobilized, while the tissue improved in knees that were constantly flexed using a CPM device.

So continuous passive motion works. But why?

Well, one advantage of having a blog that’s read by lots of smart, well-informed people is that I’m constantly being alerted to interesting studies. Like this one from 2005: "Anti-Inflammatory Effects of Continuous Passive Motion on Meniscal Fibrocartilage." It’s another rabbit study, and one of the researchers is Salter.

Arthritis was induced in all the rabbits’ knees. It appears that the knees of half the animals received CPM for 24 or 48 hours, while the joints of the others were immobilized.

While rabbits certainly aren’t people, one “advantage” of experimenting on them (or disadvantage, if you’re one of the rabbits) is that their cartilage can be “harvested” for close-up, thorough inspection at the study's end because they’re generally euthanized.

What the researchers discovered were changes that may shed light on the biochemical reasons that CPM works (caveat: again, I’m reduced to summarizing an abstract because the full study lies behind a paywall).

Even after a timeframe as short as a day or two, the study noted significant differences between the knees that moved all the time and those that didn’t move at all.

The immobilized knees:

* Showed “marked GAG degradation.” GAGs, of course, are glycosaminoglycans, which contribute to the strength and resiliency of cartilage (Saving My Knees explains in more depth why glycosaminoglycans are important).

* Had higher levels of three different molecules that contribute to inflammation.

Knees that underwent continuous passive motion exhibited the converse of both these trends: there was a “rapid and sustained decrease” in glycosaminoglycan breakdown, and fewer molecules involved in inflammation were found. What’s more, CPM led to synthesis of an anti-inflammatory molecule.

The researchers conclude:

These studies explain the molecular basis of the beneficial effects of CPM observed on articular cartilage and suggest that CPM suppresses the inflammatory process of arthritis more efficiently than immobilization.

Now here’s my hunch:

Those molecular-level benefits of continuous passive motion will be found, in future studies, to apply to motion more broadly, and to knees more broadly (not just the ones that are post-surgery or arthritic). And that would be pretty good news for people battling chronic knee pain who are looking for a way out of the trap they’re in.

To Beat Knee Pain, You Don’t Have To Be Crazy, But It Helps

Time to tell a story on myself.

A friend of mine works out at the same gym I do. She often hops on one of the many cardio machines arranged in long rows near the front desk -- giving her a vantage point that lets her observe the club’s members as they first enter the workout area. Not long ago, she said to me something like:

“Every time you come in, you get some paper towels, then weigh yourself. Every single time. It’s funny.”

Yep.

It’s very much true. I’m a creature of habit.

Partly, I think, this sort of behavior arises from a desire to know what to expect in life. This pays off in mundane ways. For example, I don’t enjoy hunting high and low for lost keys. So I put them in a special place in the apartment. All the time.

So instead of muttering about my lost keys and roaming rooms in a fit of pique for 10 minutes, I can scoop up the keys and spend those 10 minutes doing something I enjoy.

Of course, not to paint this characteristic as all virtuous: there is a decidedly anal tendency at work here. Sure, it makes sense to get your paper towels right before your workout, before you leave sweaty palm prints on the handlebars of the stationary bike. But, even if you believe it’s a good idea to maintain a stable weight, do you have to weigh yourself three times a week?

Nah. Not really.

I’m just curious about how my weight fluctuates and, well, it’s a habit. You know.

What does all this have to do with winning the knee pain battle?

A lot, actually.

I developed a number of “healthy knee” habits while I was hurt and trying to recover. Like, for example, wearing a pedometer. This became such an ingrained habit that if I left my apartment building to go on a journey of more than a few hundred steps, and I wasn’t wearing my little blue step counter, I would stop in mid-stride on realizing my error.

And turn around and go get it.

Another habit, of course, was my daily walking. I was consistent about doing it, and making sure I did exactly the self-prescribed amount (in other words, I wasn’t walking 4,000 steps one day, 6,500 the next -- I stuck to one distance, until my knees were strong enough to graduate to the next level). I also walked the same old routes (which sounds boring, but helped me because, if I had an onset of knee discomfort, I knew it wasn’t because I had strayed from my routine and say walked up hills instead of over flat terrain.)

Dull.

Predictable.

But effective.

I think it’s effective because your knees know what to expect (no surprise 10-mile hikes). At the same time, you come to know what to expect from your knees (what makes them happy, what makes them grumble). And step by step, they start to grow stronger.

Not everyone is as “crazy” as I am, I’m sure, when it comes to their daily routines. Still, if you’re trying to beat a stubborn foe like knee pain, being a little crazy may not hurt.

Does a Structuralist Viewpoint Sometimes Make Sense?

Here’s a different study from the kind I normally cite:

Researchers in Sweden followed 75 junior elite basketball players, ages 14 to 20, over the course of a year. At the outset, they measured each player’s range when flexing his or her foot toward the shin.

The less flexible subjects had as much as a 30 percent risk of developing “patellar tendinopathy” (also known as “jumper’s knee”), compared with a 2 percent risk among the players who were more flexible. A dramatic difference, surely.

So what accounts for this? Could the study itself be flawed? Is it significant that the subjects don’t represent the broad population, but rather a taller-than-average subgroup of still-growing teenagers who were subjecting their knees to harsh physical demands?

Maybe. But what if -- at least for this population, and this condition -- the structuralist analysis makes the most sense. And, moreover, what if they should stretch (something I generally don’t believe is worthwhile)?

Now here’s the crazy thing about me: At any time, I’m willing to concede that all of what I believe may not be true (or, more likely, some of it may not be true). The epigraph to my book, remember:

The greatest obstacle to discovery is not ignorance -- it is the illusion of knowledge.

So it behooves curious, truth-seeking creatures to embrace flexibility of thinking, instead of stubborn certainty. Anyone who reads this blog a lot probably thinks of me as “that guy who hates structuralism.” Which isn’t quite true.

I dislike structuralism as the grand omni-explanation for nagging knee pain. It basically had nothing to do with my knee pain or how I fixed it. And, after doing a lot of research on the matter, I’m pretty sure it has nothing to do with a lot of other cases of chronic knee pain.

Still, show me a man with one leg six inches shorter than the other, who decides to take up running regularly, and I’ll show you a man who’s on his way to developing knee (and other) problems. At the extremes, structure certainly does matter.

Then you have the rest of us.

There is an enormous amount of variability among human beings. Obviously, we easily perceive the difference between the physique of person A vs. person B. But the concept of variability also applies to within the same individual as well, with regard to symmetry.

A famous example relates to eyes: We all typically have one eye bigger than the other. But this touch of asymmetry is surely true to some degree of our arms, legs and other bilateral structures as well. And some of us have another kind of variability: stronger quads than normal vis-a-vis calf muscles, or weaker gluteus vs. hip muscles -- or whatever.

Extreme deviations from the norm will naturally cause problems (e.g., the leg that is six inches longer than the other). Minor differences (such as a leg only 1 cm longer than the other) have been shown usually not to matter. Could, however, a certain amount of deviation from the norm, for certain anatomical structures, predispose a person to injuries/problems, at least somewhat?

Hmm. It sure seems likely. It passes the common sense “smell” test, if you will.

Given that, imagine two people, Jack and Tom. Jack can train by running 50 miles a week, no problem. But say that Tom -- because of a small difference in leg lengths, a slightly abnormal curvature of his spine, thicker bones, and a few other factors -- can run only 35. But he gets inspired by his friend Jack and starts training like him, running 50 miles weekly, and winds up with painful knees.

Now comes the interesting part. I’ve created a scenario where structure does matter (some). But what’s the most sensible way to treat poor Tom?

(1) Painstakingly go through and try to identify all the structural influences that may have predisposed him to the injury, correct them when possible (obviously you can’t change the thickness of his bones), then cross your fingers that you identified all the important factors and hope he gets better?

(2) Get Tom to work within an “envelope of function” so he doesn’t overstress his joints, and try to slowly expand that envelope over time, so he is comfortably running whatever number of miles a week his particular body can handle?

To me, #2 seems generally like a much smarter, more practical approach -- even if you believe that biomechanical (or structural) factors contributed in some way to his injury.

On Being a Sample Size of One

I recently finished reading a statistics “textbook” for fun (“textbook” is in quotes because it was one of those “make learning enjoyable” books, thus diminishing the nerd factor of the achievement). I had always wanted to take a stat course before. Expectation, variance, binomial and Poisson distributions ... I thought it was all pretty cool stuff.

One thing you learn when studying statistics: How to quantify the probability that an observed outcome for a trial/study/experiment is significant. In other words, is it likely that some causal agent A led to some outcome B, or were the study’s results probably due to chance?

One thing that helps in making this determination: sample size. The larger, the better.

Which brings us to my personal knee experiment. What does it mean to be a sample size of one?

Well, from a professional statistician’s viewpoint: not much. A sample size of one is a joke. Where are your control subjects? How could you possibly calculate, say, margin of error?

So what does it mean to say that, in a tightly controlled experiment, I improved the state of my knees by doing x and y, when I was the only subject in the experiment?

Again, statistically: not much.

But there’s another way to look at this.

And that’s by considering the likelihood that a given experiment can actually prove cause and effect.

See, it doesn’t matter if you have 100,000 subjects in a study, if that study is poorly designed and/or poorly executed, making it impossible to isolate cause and effect with a high degree of confidence. The study’s researchers may think that they have reached a conclusion that A leads to B (or doesn’t lead to B), but this is a dangerous sort of illusion if the study is fundamentally flawed. Long-term knee studies of the type, “Activity X is good/bad for knees” are especially prone to this problem. In Saving My Knees, I take a close look at one.

I won’t retrace that ground here. But consider an example to help illustrate what I mean: Suppose you run a one-year study in Smallville to see if daily swimming helps really bad knees. You believe that to be true, but at the end of the trial, you’re puzzled to find the swimming group actually does worse than the control group -- in a statistically significant way too. You publish the results.

“Swimming adversely affects knee joint health,” you proclaim.

But -- what if you discover the Smallville swimming pool is on the sixth floor of a building that has no elevator? And for the subjects in the study, who have really bad knees, climbing all those steps is too much for their joints?

This is the kind of problem you face in a study when important variables aren’t tightly controlled. Granted, my example is a bit extreme and far-fetched, but what’s undeniable is that, in studies that attempt to show “Activity X helps/hurts bad knees,” for about 98 percent of the time (during waking hours), the knees of the subjects will NOT be engaged in Activity X. And what they’re doing during that 98 percent of the time -- whether it’s ill advisedly climbing six flights of stairs or kneeling to scrub a floor or running to catch a public bus -- can be vastly significant and skew the results in a big way.

There are other flaws of long-term knee studies that attempt to show causal relationships, which are independent of sample size. In Chapter 8 of Saving My Knees, I mention some more.

My experiment, on the other hand, was closely observed and very well-controlled when compared to a typical study into what helps/hurts knees. Now you can argue that doesn’t matter -- that I have the constitution of a space alien, or that my patellofemoral pain syndrome was wholly unlike anyone else’s, so what I did to cure my bad knees won’t help others.

Of course, I would disagree. Further, I’d argue that sometimes you can learn a lot more from a one-person experiment that’s very well-conducted than a multi-thousand subject trial that isn’t.

So maybe it’s not so bad after all being a sample size of one.