Science AMA Series: We are Eddie Schwarz and Mike Zuscik, arthritis researchers at the University of Rochester Medical Center. We are here, during National Arthritis Awareness Month, to answer your questions about how arthritis research advances patient care. AMA!

Abstract

Hi, Reddit! I’m Eddie Schwarz, Ph.D., Burton professor of Orthopaedics and director of the Center for Musculoskeletal Research at the University of Rochester Medical Center in Rochester, New York. As director of the CMSR, I oversee research on many different types of arthritis – rheumatoid, psoriatic, osteo-, and juvenile (Yes, you can get arthritis as a child!). My own research focuses on how the lymphatic system acts during rheumatoid arthritis flare. We found that arthritis flares when the lymphatic vessels that drain a joint breakdown due to chronic inflammation and effective treatments can reverse this. We recently started a clinical trial using a new imaging technique to assess lymphatic vessel contractions in the hands and arms of rheumatoid arthritis patients and healthy controls to identify biomarkers that can help us diagnose arthritic flare and develop new drugs.

Hi, Reddit! I’m Mike Zuscik, Ph.D., associate professor of Orthopaedics at the University of Rochester Medical Center in Rochester. I’m interested in understanding why osteoarthritis is more aggressive in people who are obese and/or have type 2 diabetes. Spoiler alert: it is NOT simply because those people weigh more and that puts greater mechanical stress on their joints. My team has uncovered some interesting reasons that obesity/type 2 diabetes makes osteoarthritis worse, and some of those reasons relate to the microbes that live in our colon! Agents that affect these microbes could be new drugs to treat this disease.

We'll be back at 1 pm to answer your questions, ask us anything!

Thanks for doing this AMA! I have two questions:

First, I've recently read that supplements with glucosamine and chondroitin in them can be really helpful for arthritis, and other studies that say that these are not really helpful. What have you found (if anything) related to supplements for arthritis?

Second, my mother has really bad osteoarthritis, in her upper 50's. She's been taking low doses of vicodin for years to help with the pain, but would like to get away from opiates if she can. Are there any arthritis pain management methods that are safe and effective?

Dancing_RN

Hi Dancing_RN: Great question. Glucosamine and chondroitin sulfate supplements, as well as various cartilage matrix components that are consumed orally are to some extend controversial - with some data suggesting that they support joint health and protect against arthritis progression. Scientific evidence that these agents improve cartilage includes data from animal models of arthritis, and patient-reported outcomes in humans also suggest positive effects. However, how they might be working is not determined. Recent advances suggest they might work to suppress inflammation by having effects on the microbes that live in the gut, suppressing immune system surveillance of the intestines and relaxing systemic inflammation overall. Many people benefit from using these agents, and it is certainly worth considering their use.

Regarding your second question, use of vicodin, opiates or NSAIDS long term to manage osteoarthritis pain has all sorts of bad consequences. Local injection of corticosteroids can be effective at mitigating pain for periods of months, as can local injection of hyaluronic acid (products like Synvisk) can also provide extended periods of relief. Pain management is a big focus in arthritis research now - hopefully we can develop new strategies to reduce pain without lots of undesirable side effects. -Mike


I have Rheumatoid arthritis. What is the hope for future treatments beyond current options like methotrexate or humira etc? Also, what suggestions would you give someone already diagnosed?

Edit to add: thank you for your contribution. I wouldn't be in a good way without my current medication. The impact for me is huge so I appreciate each test you make.

barnescommatroy

It is now known that Rheumatoid arthritis is a syndrome of diseases in which each patient has a unique condition. Thus, we will be moving towards more "personalized" medicine, similar to that of the cancer field. One area that we are actively investigating is lymphatic dysfunction in arthritic flare, in which we have observed that the loss of lymphatic drainage from inflamed joints makes arthritis worse. We are currently investigating drugs that could help this in the lab, and have started a clinical trial with a new imaging system that can see lymphatic vessels in the hand and arm. Thanks for your questions, Eddie Schwarz


Greetings, and thank you for the research you are doing.

In your research, have you studied the effects that gelatin may have in treating various forms of Arthritis?

They say ground chicken cartlige works the best, if you can find it. I take the next best thing, beef cartlige. (unflavored gelatin)

30 years ago, I lived in chronic pain, (from sports, military, construction work, aging, ect) At 30 years old, my knees were shot, my wrists elbows, shoulders ached constantly. The Doctors told me that I had arthritis, and bone spurs (from a lack of cartlige between joints) They wanted to replace one knee, and put me on pain management.

Long story short, having nothing to lose (after it was suggested to try gelatin) I started taking unflavored gelatin orally. (1 tablespoon daily, mixed with OJ and water) Well in three months I started to notice a difference, and in 6 months I was literally pain free, and off of analgesics completely. 30 yrs later I have a quality of life that even the Doctor's, with a knee replacement couldn't guarantee.

I swear by the stuff and have been taking it ever since. It is my (sacred cow)

Thank you for your time.

  • Tablespoon.
JoseMustardSeed

Hi JoseMustardSeed: I can say this: a seminal paper published in the journal "Science" in 1993 suggests that daily consumption of chicken cartilage (rooster comb, I believe) reduced joint inflammation in rheumatoid arthritis. Recent work has suggested the impact may be via effects on the gut microbes - keep your eye on the literature in the coming years as numerous investigators are now starting to focus on this as a mechanism of how such agents are protective.

The future is looking bright when it comes to understanding how chicken cartilage or other cartilage components may be acting to reduce inflammation and pain in arthritis. -Mike


How significant is our diet in helping to prevent osteoarthritis? Does it play a role at all?

digital_excess

Hi digital_excess: Indeed there is mounting evidence that diet has an impact on osteoarthritis. Not only are there components of the diet (fatty acids, for example) that can have direct effects on joints, but the food you eat can impact the microbes that live in the gut and alter inflammatory responses in many tissues including joints. -Mike


How much research is being done with regards to CBD (cannabidiol)? That stuff is a wonderful anti-inflammatory without any significant side effects, and seems perfect for the job.

HouselsLife

Hi HouseIsLife: Another great question - and it relates somewhat to the question asked by Dancing_RN above. There is no evidence that cannaboids have cartilage protective effects in joints or can prevent arthritis development or progression as a "disease modifier". However, the impact of cannaboids on sensitization and pain receptor signaling is well documented, and could be a consideration when considering it's potential for reducing pain in people suffering from arthritis.

Of course, if you live in Colorado, your access to cannabis to reduce pain in arthritis and all sorts of other diseases would be unfettered - but the legal implications in other areas of the country represent a barrier to access.

One last note - there are a few publications that have emerged in the osteoarthritis field suggesting the use of cannaboids can mitigate pain and sensory nerve signaling in animal models - more research is warranted, but these are interesting findings that support the concept ...

-Mike


Thanks for the good work! Two questions:

  1. Why is my osteo worse on my non-dominant side. From the xrays and bone scans of my cervical vertebrae to my toes, it's way worse on left side.

  2. What is the role, if any, of primary hypoparathyroidism in osteoarthritis?

Anne314

Thanks for your interesting questions. While the answers are unknown, I'll give you my thoughts. 1) We have experimental evidence that so called "morning stiffness" is due to the accumulation of lymph in the joint, as this lymph is usually pumped out of the joint by movement. By this reasoning, we would expect that more active joints (dominant side) have more efficient pumping of lymph, which would protect the joint over time. 2) Hypoparathyroidism is effectively the loss of parathyroid hormone (PTH), whose primary function is to regulate calcium and bone. Interestingly, the body also produce a similar protein call parathyroid hormone related peptide (PTHrP), which regulates cartilage. A few years ago we published a study demonstrating that PTH can preserve cartilage after injury. Thus, loss of PTH from primary hypoparathyroidism could promote osteoarthritis if this model is true. Best regards, Eddie Schwarz


  1. Is Arthritis it's own disease, or a symptom of something else? Ex: hundreds of years ago, when someone was sick, they would say that they 'had the fever'. Now a days, we would ask, "okay they had a fever, but what caused the fever?". Is it a similar case with arthritis?

  2. If the above points to it being a symptom of different and multiple causes, does more research go in to stopping the symptoms or the individual causes?

  3. What kind of disconnect have you found (if any) between the researchers on the cutting edge, and the doctors who administer their findings? Is there a better way to bridge the disconnect?

Thanks!

melophobia-phobia

Excellent questions. 1) It is now known that Rheumatoid arthritis is a syndrome of diseases in which each patient has a unique condition. Thus, we will be moving towards more "personalized" medicine, similar to that of the cancer field. 2) Yes. There needs to be a lot more research to develop personalized medicines for arthritis. One area that we are actively investigating is lymphatic dysfunction in arthritic flare, in which we have observed that the loss of lymphatic drainage from inflamed joints makes arthritis worse. We are currently investigating drugs that could help this in the lab, and have started a clinical trial with a new imaging system that can see lymphatic vessels in the hand and arm. 3) The major disconnect I have found between what we know from cutting edge research and clinical practice is the bias that Rheumatoid arthritis "is an autoimmune disease." While this thinking is based on the presence of autoantibodies (known as ACPA and rheumatoid factor) that are present in some patients, the major signs and symptoms patients have are not caused by autoimmunity. The only way to bridge this disconnect is through research that uncovers the underling mechanisms responsible for a patient's clinical symptoms. Thanks for your questions, Eddie Schwarz


Not sure if you'd consider this related or not... Does excessive sugar exacerbate joint inflammation, or is that something that might be more person to person (i.e. allergy)?

Lone_Wolf

Hi Lone_Wolf: The idea that the high fat and/or high sugar western diet can either initiate or exacerbate arthritis has been a focus in our field for a number of years - over the past decade, really. In terms of high sugar specifically, its ability impact insulin production and signaling may have huge effects on cartilage cells and cells in the synovium (the membrane that encloses many joints). The impact of sugar can indeed be pro-inflammatory in general, and ramping up inflammation in joints is a primary driver of joint degeneration in disease.

Like anything else - too much of it in the diet can be bad - do you best to avoid consuming a high sugar diet - stay in the recommended ranges to be sure these effects that are pro-inflammatory are reduced. -Mike


How does diet impact arthritis and osteoporosis, is there a correlation between the consumption of either animal products, red meats and saturated fats and the rates or severity of osteoporosis?

How does dietary calcium intake relate to arthritis?

Megaloceros_

Interesting questions. To my knowledge the only direct correlation between consumption of animal products and arthritis pertain to gout, which is caused by urate crystal that form from a meat breakdown product (purine) and can accumulate in joints. Osteoporosis can be caused by the body's inability to absorb calcium from a normal diet, which leads to bone loss. Thus, supplementing a normal diet with calcium is a practical way to help overcome the absorption problem. However, I am not aware of any dietary calcium intake issues that relate directly to arthritis. Hope this helps, Eddie Schwarz


How does diet impact arthritis and osteoporosis, is there a correlation between the consumption of either animal products, red meats and saturated fats and the rates or severity of osteoporosis?

How does dietary calcium intake relate to arthritis?

Megaloceros_

Hi Megaloceros: Diet has critical impact on arthritis and osteoporosis - not only from the perspective of proper nutrition and consumption of molecules we need for our body to support normal healthy tissue functions, but also because of the effect of diet on the microbes that live in our digestive system and the downstream implications that has on inflammation and gut barrier function. -Mike


Hey there, I live with my two elderly grandparents and I was wondering how I can help them with their arthritis day to day.

theghostecho

It's wonderful to hear that you care for your grandparents. Making sure they take their medicine as prescribed and getting some daily exercise would be very helpful. Best regards, Eddie Schwarz


What's the best way to prevent arthritis?

Fatmanbruh

Hi Fatmanbruh: There are certainly some established ways to prevent osteoarthritis for sure: Avoid having joint injuries as a good start - that is one of the biggest risk factors for developing osteoarthritis. Eating a healthy diet to control body mass and prevent type 2 diabetes is very important also - high BMI and diabetes are also risk factors. Also - exercise is terrific, not only for overall health, but to keep the cells in your cartilage healthy.
-Mike


Is it possible to stimulate the lymphatic drainage through application of heat or massage?

Sticky_D

Massage is an effective way to stimulate lymphatic drainage, and may be an explanation for how massage works. Thanks for your question. Eddie Schwarz


What is the relationship between exercise and osteoarthritis? Can I really use up my knees by running or is it protective? Also, is there a difference between repetitive exercise like running or lifting, and non-repetitive exercise like yoga and dancing (with regard to progression of arthritis)?

rbkc12345

Hi rbkc12345: There is substantial evidence that exercise can be very important for supporting joint health. It turns out that joint loading or cartilage loading can directly activate the cells to make new cartilage matrix, and can support the clearance of metabolic waste products from the dense cartilage matrix. However, overloading can be injurious - overloading joints with excessive weight or trauma can cause the cartilage cells to become less effective at maintaining the matrix. There may be differences between the effects of repetitive (cyclic) loading and yoga (I think of dancing as repetitive) - but in general these effects are thought to be positive as long as the ammount of loading is not injurious. -Mike


What is the relationship between exercise and osteoarthritis? Can I really use up my knees by running or is it protective? Also, is there a difference between repetitive exercise like running or lifting, and non-repetitive exercise like yoga and dancing (with regard to progression of arthritis)?

rbkc12345

Thanks for your excellent questions. There appears to be a double edged sword when it comes to exercise and osteoarthritis, as exercise is critical to our general health, and post-traumatic osteoarthritis is commonly caused by sports injuries. Although there is no definitive answer, I often suggest low impact sports including elliptical machines for folks that love to run, but have arthritis. Best regards, Eddie Schwarz


My mother has rheumatoid arthritis and has to switch medications when she gets immune to the one she's on. Is it possible to make a medication where she wouldn't eventually get immune? And is there research that can make rheumatoid arthritis curable? If so how close are you to finding the cure.

kulafa17

Sorry to hear of your mother's situation, which is very common. Indeed there is no cure for Rheumatoid arthritis, which is largely because it is a syndrome of diseases in which each patient has a unique condition. Since the clinical trials that are needed for drugs to be FDA approved are designed to see partial effects is a large group of patients, rather than cures in a select few, this is what we have. However, I believe we are moving towards more "personalized" medicine, similar to that of the cancer field. One area that we are actively investigating is lymphatic dysfunction in arthritic flare, in which we have observed that the loss of lymphatic drainage from inflamed joints makes arthritis worse. We are currently investigating drugs that could help this in the lab, and have started a clinical trial with a new imaging system that can see lymphatic vessels in the hand and arm. Thanks for your questions, Eddie Schwarz


Dr. Schwarz, my mom and sister were recently diagnosed with a type of spondylosis, and have told me to get tested for the HLA-B27 antigen. From what I gather 90 some percent of patients with Spondylosis have that antigen, but only 25 or so percent of people with HLA-B27 have Spondylosis. Is there a better way to discern if I have it, and any promising treatments on the horizon? Thank you!

hkgolding

Thanks for your questions. The information you have is correct. The vast majority of patients with spondyloarthropathy have the HLA-B27 gene, while only a fraction of people that have the HLA-B27 gene develop spondyloarthropathies. If you are suffering from pain or other symptoms, your doctor should be able to make a diagnosis or refer you to a rheumatologist. Best regards, Eddie Schwarz


Hi, thank you so much for your time!

What is the current understanding/research on using stem cells to treat arthritis? In cases of degenerative arthritis have stem cells been shown to help regenerate cartilage or reduce inflammation?

Miketysonspinal

Hi MikeTysonspinal: Great question! Stem cells and their use in arthritis is an area of active research, and has been for the past decade. It turns out that stems cells, when injected into arthritic joints, can be very anti-inflammatory, and people have been studying their potential use to generate new cartilage cells that could make cartilage matrix to repair degenerating or injured cartilage. Many tissue engineering methods are under development to use stem cells in scaffolds that could be implanted directly at sites where cartilage degeneration or loss is happening. Much of this work is in the development phase, mainly in animal models of disease, but there is a bright future - some day soon we may be able to literally replace diseased cartilage with a tissue construct that contains stem cells. -Mike


It seems to me that it should be fairly easy to take an imperfect joint and make it perfect. Why is that hard? A joint is not more complex than a car or smart phone. If we spent more on research, would we get there fairly soon?

SpinnerShark

Hi SpinnerShark: Provocative question. True, cars and smart phones are complex and we've done a pretty good job as a species sorting out how to make them work. BUT, in joints and many other organ systems of the body, we rely on the function of living cells to make and maintain matrix, to meditate inflammation, to signal via nerves, to activate muscles to do work, etc. Commandeering all of the cells in a joint to work together to achieve the same end in a coordinated way is ENORMOUSLY complex - orders of magnitude more complex that simple circuit building with resistors, capacitors and semiconductors. Everyday we learn a bit more - but progress is slow - obviously $$ is a big help, but the real way to accelerate progress is to recruit clever, creative and committed people to bring there ideas to the table. Getting young new minds into the mix is what we need to do to ensure the next new and big ideas keep coming! -Mike


Dr. Schwarz your research sounds very fascinating. Are there ways in which lymphatic vessels that have been damaged could be repaired such as with microfibers, synthetic drainage points designed to relieve fluid and pressure, or perhaps even stimulation of lymphatic vessel synthesis after pressure has been reduced? Also a question for Dr. Zuscik, what is the connection between them?! Is it greater presence of microbes resulting in higher immune system activity causing undo stress on lymph nodes near joints or do the microbes secrete some factors that have downstream effects resulting in worse osteoarthritis? Keep up the good work and thanks for the AMA!

nachomny

Excellent questions. Most recently we published a study demonstrating that anti-TNF therapy allows for damaged lymphatic vessels to be repaired. While there does appear to be a similar lymphatic vessel dysfunction in osteoarthritis, the relationship between microbes and arthritic flare is entirely unknown at this time. Thanks, Dr. Schwarz


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