It seems that once you get to “a certain age” (around 50, give or take a few), you may start to experience pain and stiffness when getting out of bed in the morning. After you move about for a while, discomfort subsides, but never completely disappears.

You sit at your computer for a couple of hours, and, bingo, your lower back reminds you that something is amiss. Your other joints don’t escape the ravages of age either. For some, the knee joint becomes stiff and painful when walking or running. In others, the shoulder joints become painful.

What is this happening? And, more importantly, what can be done about it?


Anatomy of the normal joint

This picture shows a normal knee joint, but the basic anatomical features are the same in all joints. The space between the bones is separated by cartilage, a sponge-like rubbery tissue made up of interweaving fibers of collagen type II proteins richly decorated with sugar molecules called glycosamingoglycans (GAG). These molecules are important to understanding how cartilage works.

Collagen type II is extra-strong, more than skin collagen (collagen type I). The sugar molecules attached to the core protein of GAG attract water, keeping the cartilage well-hydrated.

Anatomy of the normal knee (Picture credit: Wikipedia)
Anatomy of the normal knee (Picture credit: Wikipedia)

The joint is bounded by a thin membrane, synovial membrane, that constantly secretes fluid, the synovial fluid, which fills the spaces between the fibers and also forms a thin layer of fluid on the upper and lower surfaces of the cartilage. The rubbery tissue provides a cushion and the synovial fluid provides lubrication, to prevent damage to the cartilage by the moving surfaces of the bone.


What happens when we age?

When we age, the synovial membrane loses its structural integrity and the amount of fluid it secretes is reduced. This, in turn, reduces the lubrication between bone and cartilage. The result is the progressive destruction of the cartilage until, in extreme cases, you end up with bone-on-bone friction.

This is the basis for osteoarthritis, the “wear and tear” disease of aging joints. Sometimes, inflammatory cells attack the synovial membrane and cause its destruction. The effect on the cartilage is predictable; it gets destroyed, just like in osteoarthritis. This is the basis for rheumatoid arthritis.

Normal & arthritic joints
(Photo credit: BodyWiki)


Current conventional treatments

Mild-moderate arthritic pain can be treated with simple exercise. One of the best exercises for low back pain is walking. I walk the dog first thing in the morning, so both of us benefit (or as cliché-prone folks like to say, it’s a win-win). I also do stretching exercises for the back, and this is enough for me to avoid taking any medications.

NSAID drugs
NSAID drugs

If this is not enough, the second line of defense is NSAIDs (pronounced EN-saids), or non-steroidal anti-inflammatory drugs. These include aspirin, ibuprofen (such as Motrin, Advil), and naproxen (Naprosyn, Aleve).

Recently, the FDA strengthened its long time warning about the risks of heart attacks and strokes from use of these drugs. Although they are still considered safe enough to be sold over-the-counter, if you have any concerns about taking them, you should consult with your physician.

You can also try acetaminophen (Tylenol) for arthritic pain. It is pretty good for pain relief, but it lacks a crucial property. It is not anti-inflammatory. The NSAIDs do both.

For people with inflammatory arthritis, such as rheumatoid arthritis, there is a range of new drugs that can be used. Some are expensive, can compromise the immune response, and increase susceptibility to infection. They all should be used while under the care of a specialist, such as a rheumatologist.


What about glucosamine/chondroitin sulfate supplements?

The most credible study of these drugs, the GAIT study, was funded by NIH, not by industry, and included 1,583 patients. Here are the main results:

  • Overall, there were no significant differences between the treatments tested and placebo.
  • For a subset of participants with moderate-to-severe pain, glucosamine combined with chondroitin sulfate provided statistically significant pain relief compared with placebo—about 79% had a 20% or greater reduction in pain versus about 54% for placebo. According to the researchers, because of the small size of this subgroup, these findings should be considered preliminary and need to be confirmed in further studies.
  • For participants in the mild pain subset, glucosamine and chondroitin sulfate together or alone did not provide statistically significant pain relief.

Surprising? Not at all. Just consider this. These compounds break down in the acidic environment of the stomach. They also get digested in the small intestine. Whatever escapes these hurdles gets digested in the blood. How much actually reaches the joints? Well, several studies failed to find any.


Microfracture surgery anyone?

Not to slight the rheumatologists and orthopedic surgeons, there is a surgical procedure called microfracture, which consists of making tiny incisions in the cartilage, with the hope that the repair mechanism will stimulate formation of new cartilage tissue.

Good idea, except that it doesn’t work as advertised (scroll to the bottom of this post for references). The wound is repaired by fibroblasts, which secrete collagen type I, as they do in any scar tissue. This type is weaker than the cartilage-specific type II, which is secreted by chondrocytes, cells specially dedicated to cartilage formation. So, good try, but…


And, now for something completely different

What’s been written so far is not very encouraging. At most, we can slow down the destructive process with NSAIDs, but we cannot bring back our healthy cartilage. But there is a glimmer of hope, I am happy to say.

A 2012 paper in PNAS by a group of bioengineers at Johns Hopkins headed by Jennifer H. Elisseef describes what looks like regeneration of new cartilage could be within reach.

In the laboratory, researchers created a nanofiber-based network using a process called electrospinning, which entails shooting a polymer stream onto a charged platform, and added chondroitin sulfate to serve as a growth trigger.

After characterizing the fibers, they made a number of different scaffolds from either spun polymer or spun polymer plus chondroitin. They then used goat bone marrow-derived stem cells (a widely used model) and seeded them in various scaffolds to see how stem cells responded to the material.

electrospinning for joint pain
via Wikipedia

Elisseef and her team watched the cells grow and found that compared to cells growing without scaffold, these cells developed into more voluminous, cartilage-like tissue.

The investigators then tested their system in an animal model. They implanted the nanofiber scaffolds into damaged cartilage in the knees of rats and compared the results to damaged cartilage in knees left without the scaffold implants.

They found that the use of the nanofiber scaffolds improved tissue development and repair as measured by the production of collagen type II, a natural component of cartilage, and much more durable than collagen type I, which makes up scar tissue.

So when will this be available? Rats are not humans (you knew that, right?) and clinical trials can take several years. Although there is not a commercial product yet available, research in this area continues to evolve.


The future

When this or another artificial tissue matrix does reach the market, it is my fervent that one day folks on the other side of 50 will be able to get up in the morning and go out for a run—on the knees they were born with and no pain.

(Featured Photo Credit: Michael)

Dov Michaeli, MD, PhD
Dov Michaeli, MD, PhD loves to write about the brain and human behavior as well as translate complicated basic science concepts into entertainment for the rest of us. He was a professor at the University of California San Francisco before leaving to enter the world of biotech. He served as the Chief Medical Officer of biotech companies, including Aphton Corporation. He also founded and served as the CEO of Madah Medica, an early stage biotech company developing products to improve post-surgical pain control. He is now retired and enjoys working out, following the stock market, travelling the world, and, of course, writing for TDWI.



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