Revisiting Inflammation and the Ghost in the Machine

Amy Stevens left a good comment last week that got me thinking about the simple fact that there are so many things about chronic knee pain that we don’t understand:

I thought I was onto something by leaving work 6 months ago to rest, and I did manage to identify a lot of triggers I never suspected in that time (such as lifting the mattress a bit to make the bed each morning!) but unfortunately I have not improved simply by avoiding certain activities. My comprehensive knee diary isn't revealing any clear patterns at this point either. Interestingly, Coeliac Disease is looking increasingly likely in my case, as is the potential for my synovitis of the knees to be autoimmune in nature due to reacts to certain foods. Perhaps a change of diet will help.

Amy, by the way, often drops in to comment here, and if you haven’t clicked through on the URL embedded in her name, you should. I remember the first time I did and thinking, “Wow, what’s this all about?” She writes a blog about her adventures in Africa with her husband, Austin Stevens, who seems to be part snake wrangler and part naturalist.

Anyway, heading down this autoimmune path to try to understand one’s knee pain feels very familiar. Maybe Amy will find that certain foods trigger problems; that’s possible. Or there could be a harder-to-pinpoint systemic issue; these can be frustrating to chase.

I originally wrote about the ghost in the machine here. I followed up here about a study that showed that, contrary to what you may have been told, osteoarthritis is not the noninflammatory version of arthritis (rheumatoid arthritis supposedly being the inflammatory and out-of-control variety). Inflammation was found in osteoarthritis joints well before changes appeared in X-rays.

Why is inflammation so important? Well, in its chronic form, it can be a very destructive force from what I can tell. I know that in my attempts to heal, I was always fighting to bring that burning flame to its lowest point. I wanted as little inflammation as possible and was able to modify my behavior to achieve that. Luckily, I wasn’t working at the time and had the freedom to experiment and adjust and could reach a safe zone that I then enlarged little by little over time.

Some people can’t achieve that through modifying behavior. So what happens when inflammation sets up long-term? This is a fascinating question with no clear answer. I do wonder if inflammation in the knee may be something akin to a dog of hell on a leash that, if it isn’t brought to heel, might escape and plague your whole body. I had too many odd joint problems along with my knee pain for this to be coincidental, in my mind. When I mentioned my theory to a family doctor, he kind of pooh-poohed the idea, but now I think he was dead wrong.

Why? Not just because of my own experience, but because of your experiences. Too many of you have shared stories that resemble mine. There is something to this malevolent inflammation genie. I’m convinced of it.

Does Your Doctor Really Understand Your Level of "Physical Activity"?

I came across a study recently that came to a not-very-surprising conclusion: that a high level of leisure-time physical activity is good for your knee cartilage.

That’s nice to hear (again), but it’s hardly stop-the-presses news. Nor is it necessarily true without qualifiers. There is an appropriate amount of physical activity that’s good for knee cartilage, but you to make sure you get that amount right for you, especially if you have a difficult case of knee pain. Too much and you’ll further damage your knees.

What I found more interesting was this idea of “physical activity,” taken in its broadest sense. The study focused more on activities such as walking and Nordic walking, but “activity” can be almost anything: it’s crossing the room, kneeling to scrub the floor, walking to the mailbox, carrying your little niece on your shoulders. It’s all of that and much more.

This study got me thinking about something doctors and physical therapists usually don’t do: they don’t take anything resembling a comprehensive inventory of how you use your knees each day. Example: You have really bad knees and your doctor asks what sports you do. You say you don’t run or play basketball, but get in a few miles of slow walking each day.

Sounds great, right? So maybe your doctor writes down, “Sporting activity appropriate.” But what if you’re also lugging your two-year-old around all the time? That could be doing as much damage to your knees as playing basketball a few times a week.

In my book, I went into a lengthy criticism of a knee study that seemed to me to be a bit of a mess. One flaw concerned giving too much weight to how much time your knees spend in a certain kind of physical activity, like running or walking. That’s part of the picture, but it seems to me everything you do from the moment you wake up until you hit the sack at night is part of the picture. And if you’re not being asked about how you use your knees outside of sport, your health-care provider (or therapist) isn’t looking at the whole picture, but only at what might be a small piece.

One point I like to make about conquering knee pain is personal involvement in finding a solution. The experts are good, but they are limited: they only have a short time to spend with you, and there’s no way they can crawl inside your body and feel how your knees feel, and live with those joints for a few days to see how they’re being used, and how they’re irritated, and to what degree.

So I think it falls to everyone with knee pain to do this analysis themselves. Ask yourself, “How do I use my knees each day?” What knee-unfriendly things do I do? How much squatting, lifting, kneeling, carrying, walking? You may find activities in there you’re doing that you shouldn’t be – at least not until your knees are stronger.

Open Comment Forum Again, Your Turn to Speak!

I thought today that once more I'd turn over the mike to all of you. The open comment posts have turned into some of the best read recently!

Again, you're all welcome to discuss whatever you want. If, however, anyone is searching for a topic, here's one that's a bit different: What are some of the best resources you've found online that have helped you with your knee pain (this website excluded of course; I'm not scrounging for compliments :))

Otherwise, hope you're all well, and looking as forward to the end of winter as I am (okay, none of this applies to our friends south of the equator; forgive me for being Northern Hemisphere-centric). I want to ride my bike again but it's hard when the temperature is 16 degrees at six o'clock, like today. Cheers!

Your Bad Knees Are Someone's Market Opportunity

This article recently caught my attention, with its lead:

The global knee cartilage repair market had a valuation of US$1.6 billion in 2014. The market’s valuation is expected to rise to US$2.7 billion by 2023, indicating a [compound annual growth rate] of 5.8% between 2015 and 2023.

That $1.6 billion actually sounds low to me, but still: It’s a considerable chunk of change. The estimate is from a market intelligence company that blames our increasingly sedentary lifestyle for our knee woes. Still, this isn’t an exhort-couch-potatoes-to-get-moving article.

It’s identifying a market opportunity. Yup, that’s right, your bad knees are a market opportunity. So let that sink in a little, what it means to be a market opportunity. That means there’s gold in them thar joints.

Maybe not golden outcomes unfortunately, but gold for the guy who’s wielding the scalpel and for the company that made the artificial knee joint, or that developed a process to grow cartilage cells in a lab dish, or that makes arthritis medication.

So just keep that in mind when you ask your orthopedic doctor: What should I do about these bad knees?

Most doctors are very conscientious, very ethical people, but be aware there’s a little conflict of interest tugging at even the best among them. They have become vested in surgical procedures. What would you think if you had spent many hours perfecting cartilage-trimming operations, investing in equipment for the same, receiving sizable paychecks for surgery – then someone said, “Hey, you know, clinical studies show doing that’s usually a waste of time.”

I bet on some level you’re going to resist that conclusion.

Also, all these companies that have developed drugs and procedures, they have something at stake – maybe stock prices, impatient investors, shiny new facilities. The drug makers employ pretty young representatives (my brother was married to one) who smile their way into the office of your crusty old physician, who takes some samples and maybe later writes a few ‘scrips – and that attractive young woman, she’ll know exactly how many Doctor X wrote, believe me, and she’ll be back later, trying to induce him to write a few more.

So, as a patient, you just need to remember there’s gold in your bad joints -- $2.7 billion by 2023, it appears – and that when there’s money to be made if you do thing X (surgery/medication) but no money if you do thing Y (try to heal on your own or through physical therapy), you have to be aware of that and weigh your options wisely.

With Glucosamine Studies, It Pays to Read the Fine Print

As many of you reading this know, I’m a skeptic when it comes to glucosamine supplements for treating knee pain. Of course my usual disclaimer applies: If it works for you, go ahead and keep taking it. I don’t think the supplements are actually harmful (unless you’re diabetic). For most people, the only damage will occur in the region of their wallet.

Occasionally a clinical study on glucosamine will catch my eye. Here’s one with an impressive headline: “Glucosamine-containing supplement improves locomotor functions in subjects with knee pain – a pilot study of gait analysis.”

First, let’s get right to the researchers’ exciting conclusion:

Our data based on gait analysis using a motion capture system suggest that supplements [containing glucosamine] can increase walking speed through increased stride length and increased force of kicking from the ground during steps, and these improvements may be associated mainly with alleviated knee pain and direct effects on muscle.

Well, this certainly sounds good. But one odd thing you’ll note if you look closely at this study. There didn’t seem to be a control group. In fact, the researchers make a damning admission near the end of their article:

There are some limitations to the present study. First, it was conducted as an open label study.

Hmm. An “open label study.” What the heck is that? Well, the gold standard would be a double-blind study. In such a clinical trial, the patients don't know whether they are receiving real glucosamine or a placebo. What’s more, the “double blind” means that the researchers don't know whether they are evaluating subjects who have taken glucosamine or a placebo.

So in other words, in a figurative sense, it’s like the subjects and the researchers are both wearing blindfolds until the very end. This ensures no placebo effect for patients and also that researchers won’t be swayed when they evaluate the results, because they happen to personally believe, or not believe, in the efficacy of glucosamine.

So what would be the opposite of a double-blind study? A study where both researchers and patients know who's taking the medicine that’s supposed to improve their joint health – thus fairly effectively polluting the integrity of the results? Well, that would be – you guessed it – an open label study.

Well, if the researchers weren’t at all conflicted, this still might work. Maybe. Maybe? Ah well so much for that. Four of the authors, it turns out, work for Suntory Wellness, which made the glucosamine supplement used in the trial.

Now you’re probably wondering: Who would publish such a conflicted study?

The article appeared in a publication of Dove Press, an “open-access” publisher that has taken some heat before for its business practices and has been tarred as a “predatory” open-access scholarly publisher. Such publishers “are predatory because 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.”

I think the very fact this study includes FOUR authors who work for the company that makes the supplement being tested, and was “open label,” should be enough to send any smart knee-pain sufferer running in the other direction. Remember to read the fine print!

Don’t Be Afraid to Question Your Doctor

Warning: this post will be only tangentially about knees.

First, I was going to write about crashing my bike last week. I went down hard at 25 miles an hour after the guy in front of me braked hard and our wheels brushed, and I ended up bouncing and sliding on the pavement. My goodness, the litany of injuries: road rash on my face, swelling over one cheekbone, sprained wrist and finger, scrape on one forearm, bruising on my hip, and then knees banged up with cuts on both and a little swelling on the right one.

I was fully clothed, this being winter, yet still the crash was violent enough that I had bloody rashes under my garments. But the upshot: a week later, I’m in pretty decent shape, and the two knees feel pretty good (the scabs aren’t pretty, but they’ll go away soon). I’m a healer! :)

So that was going to be the post, then my daughter caught the flu, and my wife called me yesterday from the pharmacy to say she had bought Tamiflu for both Joelle (7) and Elliot (three and a half). Elliot didn’t have the flu, so he would be given the Tamiflu in a prophylactic way – to hopefully lessen his chances of contracting the virus.

It cost a heckuva lot -- $78, and that’s reduced from $600 with no insurance. But something else was sticking in my mind as I got off the phone with her. Tamiflu ... Tamiflu ... hmm, what do I know about Tamiflu?

I started poking around on the internet, and immediately started getting a bad feeling about this drug. It sounded a bit controversial. It also sounded like it was of uncertain efficacy. And one side effect I found rather chilling: “neuro-psychiatric events.” So kids can have nightmares, insomnia, delusions. Those aren’t typical side effects of say aspirin or Ibuprofen.

Now for those of you who don’t know me well, let me be clear. I’m not some nutter when it comes to medicine. I’m not anti-vaccine. I’m pro flu shot. I try to keep an open mind, and always consider the scientific evidence and the statistical likelihood of outcomes.

And I have loads of respect for well-run scientific studies. I’ve cited the Cochrane Collaboration before, as they tend to do “meta-analysis,” sifting through a wide range of studies for the best ones, and then combining all the findings to reach a conclusion. Here’s what they reportedly had to say in the BMJ in 2014 on Tamiflu (underscoring is mine):

Compared with a placebo, taking Tamiflu led to a quicker alleviation of influenza-like symptoms of just half a day (from 7 days to 6.3 days) in adults, but the effect in children was more uncertain. There was no evidence of a reduction in hospitalizations or serious influenza complications; confirmed pneumonia, bronchitis, sinusitis or ear infection in either adults or children. Tamiflu also increased the risk of nausea and vomiting in adults by around 4 percent and in children by 5 percent. There was a reported increased risk of psychiatric events of around 1 percent when Tamiflu was used to prevent influenza.

That “psychiatric events” warning bothers me. Now, taken literally, an increase of pyschiatric events of 1 percent may not be much at all. As in, say that among 10,000 people with the flu, there are normally 100 “psychiatric events.” On its face, this statement implies that there would be 101 among Tamiflu takers, an increase of one in a population of 10,000. Not much to worry about there, right? Hardly even statistically significant.

Yes, seemingly, but – the nightmares and delusions appear to have a long anecdotal tail when it comes to Tamiflu. Japan banned its use for teens after a couple of suicides and other incidents, including some kid running into traffic. Now, a hundred anecdotes don’t make a statistic, and it could be just some bad batches of Tamiflu, or the kid was going to dart into traffic anyway – but it is a little disconcerting that these cases pop up with some frequency on the internet.

What’s Tamiflu doing in the brain anyway, you fledgling biologists might wonder. Isn’t there this thing called a brain-blood barrier that effectively blocks most chemicals from crossing into the seat of our reasoning mind? Apparently, Tamiflu normally can’t cross the channel. But when the tissue is inflamed, as with a flu, the barrier may become more permeable.

May be. Perhaps. Some incidents. Anecdotes. This isn’t hard science. Hell, I’d the first to admit that I haven’t done a helluva lot of research. But I did call the doctor who prescribed it. Once upon a time, before my knee pain saga, I never would’ve done such a thing. But I’m a bit bolder now. Doctors don’t always get things right. So I asked her reasoning for prescribing this drug.

She explained that she presented it as an option; she didn’t recommend it. She was very nice the whole time we spoke. My tone was perhaps a touch less friendly. But something she said surprised me: A mother had called her office that very day saying her daughter was taking Tamiflu and having delusions. The doctor, thank goodness, told her to take the child off the drug. (Full disclosure: she did say it was the first case of delusions directly reported to her in 14 years of practicing.)

In the end, I told my wife that it was partly her decision too whether to give it to the kids. Me, I wouldn’t. I’m ready to put the whole $78 of the stuff right out on the doorstep, if someone else wants to roll the dice with it. This anti-viral medicine seems to be powerful stuff. I don’t like giving my kids stuff that powerful unless they absolutely need it.

My daughter had a temperature of 104.7 yesterday. Today it’s about 101 and going down. I think she’s going to be fine.

On Skepticism About Cartilage Healing

Recently I’ve seen some comments popping up questioning the idea that cartilage can heal. So I wanted to devote a post to that. Some of what I’m about to say will sound a bit different from what’s in Saving My Knees, because my thinking has changed somewhat. However, my belief that damaged cartilage can improve remains as strong as ever.

First, what’s changed: I don’t see knee pain through such a cartilage-centric lens anymore. Knee pain sufferers often do fine with some cartilage defects, and curing these shouldn’t become an obsession. I did note in the book that some people with cartilage defects have no knee pain; others that appear to have fine cartilage have lots of knee pain. Cartilage flaws and knee pain certainly don’t correlate perfectly.

Do I still think my problem was my knee cartilage? I think that was at least some of it, yes. My knees made awful crunching noises; they are much quieter now. But how much of that could be from improvements in the synovial fluid and how much from better cartilage? On that, I honestly don’t know. What’s changed in my analysis: I think some of my problem lay in the bone endings and could have been detected with a bone scan.

Again, these are just theories. What I do know is I had knee pain that the best doctor I saw said would never get better, and I smiled outwardly and inside I said, “Screw you, I think you’re wrong.” And I devoted more than a year of my life to proving he was. Recovering from chronic knee pain was the hardest thing I’ve ever done, and the achievement I’m most proud of (getting into Harvard was only about doing well on some tests and writing a good essay by comparison; I am extremely proud of my children, but they are their own accomplishment).

Occasionally – and I must say very occasionally, because this blog has some really terrific followers – I catch a whiff of a newcomer probing, trying to figure out what kind of fraud I might be. “Hmm, cartilage can heal? Curious that this fellow says so, when my doctor says it can’t, and my physical therapist says it can’t. But I bet you can sell a lot of books that way. So let’s see if he can produce some evidence that his cartilage regrew.”

(Please check out this post where I address head on the question “Why don’t you get a second MRI to show all the cartilage healing that you claim occurred?”)

My more expansive reply to a skeptic is: Don’t get distracted by thinking your end goal is to walk out the other end of the tunnel with pristine cartilage. That’s a waste of time. You need for the cartilage to get stronger, more resilient, more capable of handling day-to-day loads. Whether it’s once again as smooth as a baby’s bottom ... that’s not the main issue.

Today, I feel confident that mine is much stronger than it was than when I had constant knee pain.

But let’s backtrack for a moment and tackle the tough question directly. Can cartilage improve? Can it be restored in spots where it’s vanished? On this, don’t waste your time looking at my knees. Just consider the studies I cited in the book. There were two that I recall; they’re in the bibliography for anyone to track down.

Let’s consider one briefly. It’s called “A Natural History of Knee Cartilage Defects and Factors Affecting Change.” You can find it here (at least until it disappears behind a paywall, which I hope it never does, but one never knows).

What amazed me about this study, and I hope this came across in the book, is that researchers found that cartilage defect scores got better at about the same rate they got worse. Also, this was the same for knee pain sufferers as for pain-free subjects. At the time, the implications seemed mind-blowing. Changes in cartilage are a two-way street. You don’t just get worse.

So you may wonder: Well, those that got better, what were they doing differently? Answer: we don’t know. Notice this study is called a “natural history.” That means the point wasn’t to test whether walking or Pilates is better for rehabilitating bad knees; it was simply to observe the knees of more than three hundred subjects over a longish (two-year) period and see how they changed naturally.

Do you get why that’s so great? Think about it for a moment. People who weren’t trying to do anything in particular to “save their knees” saw an improvement in cartilage defects over this period. Imagine what they might have accomplished had they actually been trying to save their knees! I can’t tell you how much this study buoyed my hopes. I drank it down like a thirsty man with a glass of cold water and, once I fully grasped the implications, thought to myself, “Damn, I really can do this.”

And then there's also this other study (“Factors Affecting Progression of Knee Cartilage Defects in Normal Subjects over 2 Years”). It showed five cases where researchers saw bare bone on an MRI and two years later, in four of those cases, some cartilage had appeared (Rheumatology 2006, 45:79-84, page 81). That table I reference is in the upper left; an image showing improvement is below. Check it out.

Could it be that all these MRI readings were wrong, that the researchers are fraudulent, that the whole thing is some lousy hoax? Of course, but it’s also possible that my mild-mannered mother is secretly a Russian agent. Lots of things are possible. But what makes more sense: that we’d be created with bodies containing some tissue that just wears out, and that’s it, or that it have some capacity to heal, at least slowly? (After all, most of the rest of our body can heal; even neural networks can rewire after damage.)

I operated on the optimistic premise – not because I’m some dumb Pollyanna. I actually skew more toward the dark-humored pessimistic end of the spectrum. I operated on the optimistic premise because, at the end of the day, it seemed most rational. And it was.