“Sometimes the most difficult thing is to be able to see the most obvious thing!” 

Mehmet Murat Ildan


It was more than 70 years ago when the Arthritis Foundation was formed. It’s purpose was in helping to curb what was then deemed “the oldest crippling disease known to man.” 

By 2040 the number of adults with arthritis is expected to hit 78.4 million, most of whom will have the most common form of arthritis known as osteoarthritis or OA. (1)

Today there are 54 million adults in the U.S. with doctor-diagnosed arthritis (2). Newly adjusted estimates believe the true number to be near 92 million adults having joint symptoms consistent with arthritis (3)

There are over 100 forms of arthritis, and osteoarthritis (OA) is the most common form of the joint disease. OA presents as a wearing or breaking down of the joint cartilage, weakening of the surrounding soft tissues, as well as a deformity in the shape, spacing, and function of the joint. Its causes have been identified as aging, obesity, and prior joint injury.

Pain, limitation of movement, and neurological symptoms (numbness, tingling, weakness) are very real and common OA-related effects. OA impacts multiple body areas – with the knees, hips, neck and lower back most commonly affected.

As of this current writing, there has been no science showing that the joint degeneration from OA is in any way reversible. Moreover, due to the degenerative process of OA, continual joint use, weightbearing, co-morbidities, and cartilage being an avascular tissue type (without blood supply), OA progresses in a “feed forward” or positive feedback loop.

Science is now recognizing that when the chondrocytes or cartilage cells break down in OA, they not only trigger a low-grade inflammation, but that the inflammation itself causes cells NOT to reproduce structural proteins and other molecules. These items are necessary for the cartilage cells, and cumulatively the cartilage tissue to have the perfect blend of load-absorbing stiffness coupled with elasticity.

Let’s look at some of the numbers associated just with OA:

  • Annual all-cause costs (both direct and indirect) attributed to OA and allied disorders averaged $486.4 billion nationally between 2008 and 2014. And from 2013-2015, about 30% of adults aged 18-64 reported a work limitation or not working at all, due to arthritis (4)
  • Despite a whopping 62% reduction in length of hospital stay, from 8.9 days in 1992 to 3.4 days in 2013, the United States Bone & Joint Initiative (USBJI) reports that total hospitalization charges just for knee replacements have increased by five times – $8.4 billion in 1998 to $41.7 billion in 2013 (4).

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And what of surgeries related to OA? Here are some current statistics (in US):

I’m not going to debate the need surgeries and joint replacements. I will certainly concede that knee and hip replacements are far better quality and carry greater success than years before.

But how many less of these surgeries would have to be done IF the patient had known everything about their damaged joints far sooner – say, years before in the process? Far before the pain, cartilage degeneration, and joint damage set in?

What about the opportunities for medical device companies and imaging companies to invest further into, and perhaps be a part of solutions that better communicate the severity of OA to patients sooner. Perhaps that means getting on a targeted therapy, and having orthopedic and neurologists becoming

How much less would patients or self-insured employers have to spend on costly joint surgeries – especially given the skyrocketing inflation in healthcare service prices and coverage costs?

The medical profession has largely been taught to treat patients on OA in a more reactive vs. proactive manner. This is largely because of key limitations:

1) OA has been traditionally thought-of and managed as a disease whose treatment and management steams from the patient requiring pain and symptoms. Yet science and imaging clearly show that there is often a period of years and even decades between the early stages of cartilage damage and biochemical changes associated with OA – and its first pain or symptom.

  • The latest thinking around OA points to the fact that the mechanical damage to the joint and the tissues are the disease – and the pain is the symptom. Additional thinking is that the nerves within the joint itself, allow the body to monitor and adjust weightbearing to take ‘micro-pressures’ off the OA joints throughout a typical day.

2) When the pain and stiffness come with later stages of OA, often medicine provides pain medication to reduce the symptoms. But in cases of mild to moderate pain, are long-term prescription drugs truly a help or a harm?

  • What is the impact of joint damage that potentially accelerates when OA patients are on these pain-masking medications? Do individuals that feel good from the medication continue to do the wrong activities or keep on the weight that would speed up the process – as they don’t feel significant pain as a signal for change?

3) The primary way OA is diagnosed today is often through X-ray, CT, or MRI. However, by the time it is seen the joint change and/or damage is irreversible.

Additionally, many images of the OA-ridden joints are taken each day and though seen by radiologists and other medical professionals. However, they fail to properly communicate the existence and/or relevance of OA to their patients. They may also mention it dismissingly, as a normal age variant.

To surmise, osteoarthritis is a monster healthcare challenge that is extremely common, carries high costs, impacts employment and productivity, is often poorly communicated with patients, lacks in patient management, and shows no signs of slowing down. In fact, every major and trusted resource for disease estimates shows a hypergrowth of people expected to get, suffer from, be negatively impacted by, and require surgery for OA-related issues.

Apart from people staying thin, avoiding ever injuring a joint, and never aging – what can be done?

EARLY DETECTION – A Moonshot for Osteoarthritis

The other day I looked at the onboard computer for my car. When I got to tire pressure, the image showed me all four tires, and the current pressure of each – presented against the normative values.

Imagine if any individual could know in present time, the ‘health’ of their structural joint integrity. As aging, cumulative traumas, weight, flexibility, and strength fluctuate, so should the health of our individual joints. Certainly, it would be unreasonable to think that in a lifetime, all joints age exactly the same.

In many ways OA presents its biggest challenge from a perspective of time. That is, the ability for an individual to know the early stages of when their joints begin to go through the degenerative OA process – and perhaps to what current degree and speed of progression.

joint, arthritis, knee, cartilage

The latest research in early OA detection has been heavily focused on biomarkers and MRI-based cartilage imaging techniques.

As a primer, a typical joint is made up of two different bones that share a common space. Covering each of the bone end surfaces is articular cartilage.

As the bones and their cartilage coverings face one another, there is encapsulated synovial fluid that lubricates in between the cartilage surfaces. All this lubricated, shared-surface space is enveloped in a synovial membrane, which itself is enveloped in a joint capsule.

The articular cartilage itself, on a molecular level consists of about 70-75% fluid, 25% extracellular matrix, and only about 2% chondrocytes. The extracellular matrix (EM) gives the cartilage its strength and structure – and is made up of collagen, glycoproteins, proteoglycans, and hyaluronan. Chondrocytes regulate and secrete EM and its components to maintain and sustain the cartilage.


Biomarkers are objectively measured characteristics and indicators of a biologic process – or a response indicator to a therapeutic intervention. During the degenerative process of OA in a joint, there are many biomarkers that arise from the breakdown of cartilage – especially in the early stages, well before even the mildest of viewable bone changes.

Such biomarkers are found in blood, serum, synovial fluid, urine, and cartilage tissue. The different types of biomarkers include those from the degradation and synthesis of cartilage and synovium tissues, as well as the extracellular matrix, inflammatory chemicals, etc.

Biomarkers, especially of the biochemical type, are critical in OA research, drug development, clinical trials, and eventually in therapeutic monitoring. It may also lend well to personalized treatment – depending on the severity of the OA. The ultimate goal being to identify and then properly target a therapy that stops and perhaps even reverses the degenerative process – leading to healthier joint tissues, creating cartilage, and reducing the inflammation process.


In the earliest stages of OA, before joint damage can be normally seen, the cartilage undergoes small levels of reduction of its collagen and proteoglycans in its extracellular matrix. This reduces the elasticity of the cartilage, and thereby allows the water component to become more mobile.

These changes show up quantitative MRI ‘mappings’, where a new technique is applied to better target tissue composition and biochemical changes within. Adding what is known as T2 mapping to a normal MR protocol improved sensitivity from 73% to almost 97%. (9)

A new technique known as 3D TBM is showing early promise, by combining a machine learning technique to patterns relating to image-to-image shift of water in cartilage for knee OA (KOA) patients. The creators are seeking to better map and phenotype those people who would and would not progress from early biochemical changes to early osteoarthritis.

Another imaging technique is called gagCEST sodium imaging. This is also done within an MRI and picks up loss of glycosaminoglycans on the surface of the articular cartilage. See the image below. 

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In 2018 researchers from Stanford University’s Department of Radiology presented a new technique for combining imaging with early metabolic and cellular markers for early knee OA.

I won’t get into specifics, but the process is a combination of positron emission tomography (PET) and quantitative MRI techniques. This and future technology on early OA detection will continue to thrive – especially in light of the new era in patient-centric healthcare and precision medicine.

I would LOVE…absolutely relish the opportunity to lead a moonshot on osteoarthritis. One whose investment would fund public awareness, better education, plus top-notch research on therapeutics, testing, biomarkers, and early detection.

Do you hear me investors? Drug companies? Healthcare organizations that want to tackle a monster chronic disease?

One of the biggest gaps in OA is the vast misunderstanding about and poor communication on the disease. Many individuals, current patients, and a sizeable percentage of healthcare professionals have framed osteoarthritis as a normative aging process, an x-ray variant carrying little credence – except in cases of significant pain or neurological symptoms.

OA is a chronic disease. Yet unlike heart disease or cancer, it doesn’t cause death. It carries major costs to our healthcare system in dollars, and impacts productivity in being a top cause for disability. But until it is de-linked from symptoms and objective testing can be affordability and effectively implemented – it will remain addressed in its later, irreversible stages.

A moonshot is needed, as education and proper framing of OA is equally as important as developing a drug, therapeutic, or test for early detection. People have a right to know, and healthcare professionals an obligation to properly communicate that OA is not just an ‘old person’s disease’. Rather, that our joint injuries earlier in life cause unequal and accelerated aging, dysfunction, and damage that will impact our healthcare journeys.

Heed the call – life science companies, venture capital firms, state and federal organizations, medical schools, provider organizations, and payers. It’s time to step up and make a well-needed investment into all aspects of osteoarthritis – for the good of our health consumers, patients, policies, costs, and cumulative improvement in quality of life.


Am I saying that we should develop and use biomarker assays and MRI mappings like preventative blood pressure or lab test screenings?

Absolutely. Because what we are doing now, at least in the management of osteoarthritis (OA) is so unintelligent and costly. I simply ask these questions:

  • Would people who knew of pre-symptomatic or asymptomatic OA have better reasons to change their lifestyle and their exercise habits?
  • How would this fit into today’s efforts toward chronic disease, population health, personalized medicine, and empowering greater patient awareness?
  • What type of therapeutics and drugs could be better developed, knowing the biochemical biomarkers needed to catalyze or block?
  • Why should people not know if they have real damage in their joints?

For the last question, if you’re saying because an MRI is too expensive, then I would agree – noting that healthcare already has a critical and largely unsustainable pricing problem. Using price as a barrier of progress in driving greater awareness and paradigm change is sorely shortchanging the very consumers who pay for and support the health system.

Perhaps MRI pricing could change based on reactive vs. proactive use. The last I checked, everything about OA, including medication, surgeries, and costs are all skyrocketing. If costs and healthcare spending are truly targets for improvement, then why not look at the high numbers of joint surgeries due to longstanding, undermanaged, and poorly communicated instances of OA.

At some point the healthcare industry is going to have to recognize that time and detection play a pivotal role in osteoarthritis, just like in other chronic diseases. Though OA may not cause death, its degenerative process contributes to pain, suffering, economic and job-related costs, as well as millions of surgeries in the US each year.

We are now at the point where we must, for the good of patient care and better outcomes, seek to look at smarter paradigms through earlier detection, greater awareness, and earlier patient empowerment toward this joint disease. Plus, to drive well-targeted and more successful therapeutic solutions that are designed to add into or block facets of the OA degenerative process – for better results.



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DR. STEVE AMBROSE is a healthcare veteran of 25 years who carries subject matter expertise in joint health, disc, and musculoskeletal care. He champions healthcare consumerism, patient-centered care, and transformational solutions; and is seeking his next leadership role. 

He is reached by email at: [email protected]



  1. Hootman, J. M., Helmick, C. G., Barbour, K. E., Theis, K. A. and Boring, M. A. (2016), Updated Projected Prevalence of Self-Reported Doctor-Diagnosed Arthritis and Arthritis-Attributable Activity Limitation Among US Adults, 2015–2040. Arthritis & Rheumatology, 68: 1582–1587. doi:10.1002/art.39692
  2. https://arthritis.org/getmedia/e1256607-fa87-4593-aa8a-8db4f291072a/2019-ABTN-final-March-2019.pdf
  3. https://onlinelibrary.wiley.com/doi/full/10.1002/art.40355
  4. United States Bone and Joint Initiative: The Burden of Musculoskeletal Diseases in the United States (BMUS), Fourth Edition, Forthcoming Rosemont, IL. Available at https://www.boneandjointburden.org/fourth-edition/iiib10/osteoarthritis
  5. Ibid
  6. Foreman Stephen M., Croft Arthur C. Whiplash Injuries: The Cervical Acceleration/Deceleration Syndrome. 2nd ed. Philadelphia, Lippincott Williams and Wilkins, 1995 p-340
  7. https://journals.lww.com/clinorthop/Citation/1975/06000/Soft_Tissue_Injuries_of_the_Neck.6.aspx
  8. Is it time to get your knee replaced? – St. Anthony Regional Hospital. (2021). https://www.stanthonyhospital.org/news/blogs-from-stanthony/is-it-time-to-get-your-knee-replaced/
  9. Alsayyad, M. A. I., Ali Shehata, K. A., & Khattab, R. T. (2021). Role of adding T2 mapping sequence to the routine MR imaging protocol in the assessment of articular knee cartilage in osteoarthritis. Egyptian Journal of Radiology and Nuclear Medicine52(1). https://doi.org/10.1186/s43055-021-00453-w