The evolution of arthritic knees

Evolutionary study links subtle modifications in the morphology of the bipedal knee to osteoarthritis later in life

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The human knee is a triumph of design. The joint, which evolved fairly rapidly from our common ancestor with the chimpanzee to accommodate our bipedalism, likely contributed to our success as a species. However, as modern medicine extends the human lifespan, our species have learned pain in the form of osteoarthritis that can accompany the locomotion of this biomechanical masterpiece.

In a new study of the genetic features that help make this sophisticated joint possible, an international team of researchers found that the regulatory switches involved in the development of the knee also play a role in osteoarthritis, a partially heritable disease that afflicts at least 250 million people worldwide. The findings are published in the journal Cell.

Terence D. Capellini, Richard B. Wolf Associate Professor in the Department of Human Evolutionary Biology and the paper’s corresponding author, explained it in terms of the burden our knees literally endure:

“From an evolutionary standpoint, the primate knee went from something that accommodated the forces of walking on four legs to placing all the weight on two legs,” he said. “Going from a quadruped to a biped changes the force distribution. All our weight is being transmitted through our hips and our knees down to our ankles. The cells in the joint and the shape of the joint had to change to accommodate those new forces.”

With such a specific task – and limited by its origins in the older primate knee – the optimized bipedal knee developed what is known as a constrained morphology, that is, it did not allow much variation. “As you can imagine, when you’re designing a part for an airplane, you don’t want to stray too much,” Capellini said.

To understand how this complex mechanism came to be, researchers looked for evidence of accelerated natural selection: the series of mutations that aided us in walking upright.

“We wanted to know whether or not we could see signs of ancient evolution – ancient selection – in the regions of the genome that specifically sculpt the knee,” said Capellini. To do this, they searched for traces of specific regulatory switches, pieces of DNA “responsible for turning on and off the genetic material that make the knee a human knee.”

What they found reflects what Capellini suggests is indicative of “positive selection” – evidence that this new knee gave the fledgling bipeds an evolutionary advantage. The highest functioning knees would have been selected, reducing variation in knee shape over time by decreasing the genetic variation in the switches that control the joint’s formation. What variation persisted likely didn’t substantially matter at that time.

“Later, as human populations expand and drift, you start getting these genetic variants that slightly modify how the knee is shaped or how the knee is maintained,” explained Daniel Richard, a Ph.D. candidate in human evolutionary biology and lead author on the paper. “Those slight deviations, acting on this constrained knee, lead to risk for developing osteoarthritis.”

Those traits did not affect the success of the bipedal knee because natural selection promotes traits that allow individuals to reach sexual maturity and successfully breed. In essence, because this new knee gave young adults an edge on passing on their genetic material, it continued despite these variants. Our eventual old age had little role in its selection.

“We think that these slight modifications don’t so much impact early life,” said Richard. “But when you keep on walking up until you’re 50 or 60, over that longer time span a super small change in your knee compounds over decades. Eventually it contributes to osteoarthritis disease in the elderly.”

As a proof of principle, Capellini and colleagues performed two additional experiments. By studying the knee switches in patients with osteoarthritis compared to the general population, they found that osteoarthritis patients have on average more genetic variants in switches than those who don’t have the disease. They also focused on a gene called GDF5 (Growth Differentiation Factor Five) that contributes to osteoarthritis risk in Europeans and Asians. Using CRISPR editing in mice and human cells, they pinpointed a genetic variant, present in billions of people, that effects the function of a key knee switch, thus changing knee shape and increasing osteoarthritis risk.

The stiffness and soreness humans feel today, therefore, may simply have piggybacked on an evolutionary advantage: the osteoarthritis came along with the knee. However, this painful feature may pay off in the study of human evolution, the researchers stress.

“The idea of tying new features with almost new diseases is a good mental framework to think of while studying these diseases of aging,” said Richard. “You can’t really have your cake and eat it too.”


Osteoarthritis – what are the signs and symptoms of Osteoarthritis?




Osteoarthritis

Osteoarthritis

The main symptoms of osteoarthritis are pain and stiffness in your joints, which can make it difficult to move the affected joints and do certain activities.




The symptoms may come and go in episodes, which can be related to things such as your activity levels and even the weather. In more severe cases, the symptoms can be continuous.

You should see your GP if you have persistent symptoms of osteoarthritis so they can confirm the diagnosis and prescribe any necessary treatment.

Other symptoms you or your doctor may notice include:

joint tenderness

increased pain and stiffness when you have not moved your joints for a while

joints appearing slightly larger or more ‘knobbly’ than usual

a grating or crackling sound or sensation in your joints

limited range of movement in your joints

weakness and muscle wasting (loss of muscle bulk)

Osteoarthritis can affect any joint in the body, but the most common areas affected are the knees, hips and small joints in the hands. Often, you’ll only experience symptoms in one joint or a few joints at any one time.

Osteoarthritis of the knee

If you have osteoarthritis in your knees, both your knees will usually be affected over time, unless it occurred as the result of an injury or another condition affecting only one knee.

Your knees may be most painful when you walk, particularly when walking up or down hills or stairs.

Sometimes, your knees may “give way” beneath you or make it difficult to straighten your legs. You may also hear a soft, grating sound when you move the affected joint.

Osteoarthritis of the hip

Osteoarthritis in your hips often causes difficulty moving your hip joints. For example, you may find it difficult to put your shoes and socks on or to get in and out of a car.

You’ll also usually have pain in the groin or outside the hip. This is often worse when you move the hip joints, although it can also affect you when you’re resting or sleeping.

Osteoarthritis of the hand





Osteoarthritis often affects three main areas of your hand:

the base of your thumb

the joints closest to your fingertips

the middle joints of your fingers

Your fingers may become stiff, painful and swollen and you may develop bumps on your finger joints. Over time, the pain may decrease and eventually disappear altogether, although the bumps and swelling can remain.

Your fingers may bend sideways slightly at your affected joints or you may develop painful cysts (fluid-filled lumps) on the backs of your fingers.

In some cases, you may also develop a bump at the base of your thumb where it joins your wrist. This can be painful and you may find it difficult to perform some manual tasks, such as writing, opening jars or turning keys.

Green-lipped Mussel Extract = Could this be a treatment for arthritis?




Given our ageing population, osteoarthritis is the most common arthritic disorder affecting the greatest number of people in the UK with more than eight million people estimated to be affected.

Green Lippled Mussels - a treatment for arthritis?

Green Lippled Mussels – a treatment for arthritis?




A couple of weeks ago I received a press release which, I have to say, bowled me a googly, but which did deserve a bit more investigation. Simply put the press release (which I have pretty much reproduced verbatim below) suggested that green-lipped mussel extract (GLME) can be used as a treatment for arthritis.

They very kindly gave me the opportunity to interview John Croft, a New Zealand marine scientist and one of the world’s leading experts on the life cycle of the green lipped mussel who have written extensively on GLME as a treatment for arthritis.

You can read my interview below as well.

Now I have no idea how well GLME works so if you have used it to treat arthritis then it would be great if you shared your story in the comments section below.

Arthritic disorders are one of the most significant causes of debilitating mobility and pain problems. Thanks very much.

So first up the PR story.




The number of people who have arthritis is thought to have risen four fold over 50 years and by 2030, it is estimated that 67 million adults will have doctor diagnosed arthritis with 37% of those estimated to report arthritis related activity limitations.

20% of adults in the UK consult their GP each year with a musculoskeletal problem accounting for one in six consultations, 8.8 million physiotherapy consultations and over 3.5 million calls per year to emergency services. The demands on the NHS are already considerable with experts predicting an unsustainable weight in years to come.

There are now more people over 60 years of age than there are children under five. Ensuring a quality of life for an ageing population is key. Prevention or cure for joint degeneration is not possible however, in many cases the progression can be slowed down. Knowing what treatments are best to take to maintain a lifestyle is well debated especially with some pain relieving products causing stomach discomfort and other side effects for a number of people that take them.

One such alternative which has been extensively researched is green-lipped mussel extract (GLME) which is the basis for a new book by renowned marine scientist, John Croft. John’s review, ‘Arthritis and Aging, Solutions from the Sea’ explores more than 40 years of international research into the use of marine based compounds in human and animal health. The findings within John’s review have particular relevance for sufferers of chronic rheumatoid arthritis, osteoarthritis and age-related degenerative disease.

John’s published review has indicated that the specific nature of GLME – known as Seatone in the UK – may help inhibit age related joint degeneration and may help reduce inflammation, pain and joint immobility caused by arthritic disorders.

Osteoarthritis isn’t just an age-related condition however and can also affect people with physically demanding lifestyles.

Joining Croft for the interview was Dr Chris Steele from ITV’s This Morning.

PATIENT TALK: Dr Chris first, what exactly is arthritis and what are the symptoms?

Steele – Arthritis is basically in an inflammation of a joint, and most of us will know somebody with arthritis – normally osteoarthritis – which is the most common form of arthritis. Osteoarthritis is a condition of wear and tear and inflammation in the joint that comes on over time and is more common in people over 55.

PATIENT TALK – What is the difference between as osteoarthritis and rheumatoid arthritis, and other forms such as gout?

Steele – Well there are many different types of arthritis, and it does get complicated.

Rheumatoid arthritis is a different type of disease process altogether. It’s not the wear and tear of osteoarthritis but a condition known as an autoimmune disease where the body attacks its own tissue – and we are not sure why. It tends to affect the joints of the fingers , wrist and the toes. Interestingly it tends to affect both sides. It is symmetrical and women are more affected than men. It also comes on in a younger age group, so 20 – 50 years of age.

PATIENT TALK – Is fibromyalgia a form of arthritis?

Steele – Myalgia means pain in the muscles, and fibro refers to fibres: tissues, tendons, ligaments etc. So with fibromyalgia you have got the inflammation or tenderness of muscles, tendons and ligaments which can cause acute tender spots, specific spots all over the body. It can cause fatigue, sleep disturbance and is one of those conditions for which there is no test: they can’t test you and say, ‘yes, the test is positive – you’ve got fibromyalgia’. But a lot of people suffer the symptoms of fibromyalgia.

PATIENT TALK – And what are the typical treatments for arthritis at the moment?

Steele – Well, basically if you have “twinges in your hinges”, pain in your knees and joints, and are over 55 years old, you will just try and help yourself – take some painkillers or stronger anti- inflammatory tablets you can get over the counter.

If you are not getting much response then you should probably be going to see your G.P who can give you something stronger or maybe a different type of medication, maybe get some physiotherapy booked for you and then see how it goes. But alongside all of this, a lot of people will look for alternative or complementary therapy even before they get to the G.P by just trying to help themselves.

PATIENT TALK – John, tell us about your research into arthritis and the possible benefits of this substance called ‘Green Lipped Mussel Extract?’

Croft – This dates back to 1972 in New Zealand. It was there that we learned that the green lipped mussel had anti- inflammatory properties and so we began the research with the University of Auckland and the department of medicine there.

They were able to make a powder from the extract which actually did work and helped both human and animal subjects. It has been in clinical trials in several countries. My contribution has also been on the laboratory side, finding out precisely how it works , what it does to help alleviate the symptoms of arthritic disorder, and now also with age-related joint degeneration.

PATIENT TALK – Can you tell us a little bit more about how you think it works?

Croft – What we now know is that has range of anti-inflammatory properties, the main one is due to carbohydrate component in the muscles which inhibits the immune cells, the white cells, in the blood stream from escaping, being over-excited, out of balance and attacking our own tissues, attacking good cells instead of just antigens.

The green mussel extract also contains omega 3 fatty acids naturally, which inhibit the components that actually cause the degeneration of cartilage in the joint.

PATIENT TALK – How long do you have to take it for before it starts to work?

Croft – For most people it takes 4 – 6 weeks for it to start working, slowly and progressively. The maximum time would be 12 weeks. If it hasn’t worked for someone in 12 weeks-time, well then it’s probably not suitable for that person.

PATIENT TALK – And have you taken this yourself?

Croft – I have taken it for the last 16 years because of my age, I’ve never had arthritis but I’ve now got age-related joint degeneration simply by growing old and I’m fully fit, I’m fully mobile and pain free, I’m grateful to say.

PATIENT TALK – What are the cost implications? Is this potentially an expensive treatment, or is it something that could be made available on the NHS?

Croft: I have no idea what it costs in the UK. I know what it costs in New Zealand, and it doesn’t seem expensive to me. I do know that you cannot get it on prescription. It is not a prescription item, but doctors can actually ask people or suggest that people try it.

PATIENT TALK – Would it also help with fibromyalgia and rheumatoid arthritis?

Croft: For rheumatoid arthritis, the anti-inflammatory compound in it can help there with chronic rheumatoid, not acute. With fibromyalgia, I can’t really comment as we have never looked at that disorder.

PATIENT TALK – Thank you both very much.

A drug free treatment for osteoarthritis – read our guest post from Mark Taylor Bryant.


Osteoarthritis

Osteoarthritis

Mark Taylor Bryant is 43 and from Manchester. He works as a long distance lorry driver. In this guest post he tells us about a drug free treatment for osteoarthritis he has been using. We though we would share as part of our on going series of blogs on pain management.

He writes “I was first diagnosed with osteoarthritis in my knees, shoulder and wrist joints over ten years ago. However, over recent years I’ve been suffering from severe pain, particularly in my knees. This is something that is exacerbated by my work as a long haul delivery driver, which sees me sitting in the driving position for up to 18 hours a day as I cover between 200,000 to 300,000 miles per year.

I was told by doctors that I was too young for a knee replacement . However, neither of these provided me with any relief. I also had two arthroscopy procedures performed on my knees to try and clear the damaged cartilage. However, these procedures both had minimal impact in terms of pain relief. It felt as though I was just going to have to accept the excruciating pain for the rest of my life and in particular during the winter months when the pain would be heightened.


However, during a routine delivery I mentioned my troubles to an office worker at the delivery address who told me about a company, FLEXISEQ, that manufactures a drug-free treatment for osteoarthritis. I tried out a sample soon after and almost immediately the pain started to subside. After two weeks I felt completely different and I now apply the gel twice a day to the affected joints to ensure that the pain does not return.

I’m currently not suffering from any pain in my joints. It’s not so much that FLEXISEQ helps the pain go away, it actually stops the pain from occurring – it’s incredibly effective and has had a measurable impact on the day to day quality of my life.

We were told In a clinical trial on 1395 adults with osteoarthritis of the knee, use of FLEXISEQ resulted in clinically relevant reductions in joint pain and stiffness and improvement in physical function that were equivalent to the effects of an anti-inflammatory . There have been no serious side effects reported relating to the use of Flexiseq. In clinical trials FLEXISEQ caused minor skin irritations, mainly erythema, dry skin and rash – usually mild to moderate intensity, transient and fading away by itself. A treatment interruption was not necessary. There are no known interruptions with other medicines.

Osteoporosis. An interview with an older patient about her new treatment options, exercise and use of dietary supplements!


Welcome to the latest in our ongoing series of PatientTalk.Org interviews.  Today we are

Osteoporosis

Osteoporosis

interviewing Elizabeth a 75 year old woman living in London, England who has been lucky enough to get a wide range of treatments which allow her to live a full life with Osteoporosis.  It is also worth mentioning that she suffers from Osteoarthritis.

We hope this interview will give you an idea about some of the options which are becoming more and more available to osteoporosis sufferers.

PatientTalk.Org:- How long have you had osteoporosis and what are your main symptoms?

Elizabeth:  In fact I can’t give a clear answer.  Twenty years ago when I was going through the menopause I was told that I was on the cusp of being diagnosed with osteoporosis.  Ten years later I tripped and broke my wrist.  A second scan revealed that my bone density appeared to be still in the range of normal for my peer group.  However at this stage I was given calcium and vitamin D tablets on a daily basis (which I still take).  Another ten years passed and I tripped once again running up some stairs and fractured the other wrist.  At this time  I was told that there was no point in another scan as two low-impact fractures at my age equalled osteoporosis.  I had been told that walking would help to maintain and strengthen my lower body bone density.  So I try and walk for at least one hour every day.

PatientTalk.Org:  So apart from the calcium and vitamin supplements what other treatments have you been offered?

Elizabeth:  Because I was aware that I’d lost a lot of upper body strength,  for example undoing jars became a real chore,  due to the broken wrists and open heart surgery which took place 25 years ago, I wanted some form of exercise which would improve my situation.  I was told by a friend that she was following a course of Nordic walking and this seemed to be the answer.

I contacted the local health service who were very helpful and invited me to a set of tests and check-ups to ascertain my suitability for a Nordic walking course.

They were happy for me to start the course but beforehand they wanted me to do a course of bone density exercises.  These took place at a course of  eight weekly sessions.  They consisted of a warm up, a series of about 10 different exercises each of 2 minutes, followed by a cooling down session.  They were supervised by exercise specialists who were extremely supportive.

During this course I learned of another 8 week course in Gold Zumba.  That is a type of Zumba more suitable for older people.  I’ve now been on the course for around 4 weeks.  And enjoy it.

PatientTalk.Org:  So what actually is Zumba?

Elizabeth:  I think it can be described as some form of dance which can be used as a fitness programme as well.  We are taught by a qualified instructor who specialises in Zumba as a therapy.  For me the combination of exercise with music means that I’m pushed just a little bit harder than other types of exercise.  This is good for co-ordination of the body and, in fact, my brain.  Zumba is great for balance as well.

PatientTalk.Org:  So have you noticed any improvements?


Elizabeth: This is difficult to say.  In fact it is not my main objective.  I am really looking to maintain my current body strength and flexibility.  I notice that as each session goes on that I’m more flexible and my balance is much better.

And I’m now in a position to start Nordic walking.

PatientTalk.Org: Are you using any other treatments?

Elizabeth:  I have now started a 3 year course of biannual subcutaneous injections for my osteoporosis.  There are other treatments but it was felt that my digestive system was not suitable for them.

PatientTalk.Org: What sort of medical education / advice were you give?

I was invited to a series of talks at either the hospital or local health centres by osteoporosis experts in

a)  General information about osteoporosis

b) Exercise and osteoporosis

c)   Diet and osteoporosis

PatientTalk.Org:What did you learn about diet and osteoporosis?

Elizabeth:  Apart from information about foods and drink which are particularly good for sufferers of osteoporosis which include dairy, lentils, fish and some vegetables,  we were advised that there were certain circumstances in which it was more efficacious to take the supplements.   These were not explained to me by my normal Doctor.    Indeed the supplements documentation contains only limited advice.  The lectures I attended however provided me with far clearer advice.  What concerns me is that many other people with osteoporosis are not getting the full benefits of the supplements they are taking.

PatientTalk.Org:Thanks very much for this.  Very useful for us and our readers.

So over to you.  What do you think of Elizabeth’s story?   It would be great if you could share your thoughts in the comments box below.  You might want to think in terms of the following questions:-

1) How long have you been diagnosed with  Osteoporosis?

2) What sort of treatments have you had and how effective have they been?

3) What sort of support did you receive in terms of education about the condition?

4) Do you feel you have been well advised regarding the use of supplements?

5) What sorts of exercise do you take for your osteoporosis?

Many thanks in advance!