Disease Modifying Drugs versus Surgical Avoidance

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An entire generation of Osteoarthritis researchers has cut their teeth on the concept of the mythical DMOD. What’s that? Why is it important and how does it intersect with Orthobiologics? Is there a more realistic concept to measure the efficacy of Orthobiologics? Welcome to Surgical Avoidance. Let’s dig in.

What Is a DMOD?

DMOD stands for Disease-Modifying Osteoarthritis Drug. The idea is that an oral drug or injectable will reduce cartilage loss and modify the natural course of Osteoarthritis. This has been the holy grail of Osteoarthritis research. Basically, an unattainable or almost impossible goal.

There are no DMODs right now. However, there’s a whole drug development industry chasing this concept. In fact, I’ve blogged on that industry a few times.

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Is platelet-rich plasma a DMOD? The answer is that there are some studies that show that this could be the case. Let’s review some of that data.

First. there are two ways to determine a DMOD. The first is that the drug reduces the loss of cartilage over time. Those studies are much harder to do as you need to follow two groups for years, one that got the DMOD and one that got a placebo.

The second type of study looks at gains in cartilage thickness caused by the drug. These are easier studies to pull off in that you just measure the thickness on MRI before and after the drug. Hence, we tend to see many more of these published studies than the first type.

PRP DMOD Research

In animal studies, PRP reduces the loss of cartilage (3). However, some studies have shown while PRP improved pain and function, there was no change in cartilage thickness (4,6). However, could these studies have suffered from the same problem as the recent knee arthritis JAMA study (too low a dose of platelets)? Likely. A differently designed study did demonstrate that PRP could reduce cartilage loss, but that was dependant on making sure platelet concentrations were high (2). Other research has also demonstrated that PRP increased cartilage thickness (1,5).

So the literature here is mixed but likely linked to the way these researchers made PRP. If you read this blog you know that delivering properly concentrated PRP is something I have been discussing for many years. In fact, we just saw what happens when you deliver fake PRP (i.e. PRP that’s not concentrated enough).

DMOD vs Surgery Avoidance

In the Knee Osteoarthritis world, the single biggest thing of value to a patient, employer, or insurer is being able to push the need for a knee replacement down the road or avoid it altogether. I call this concept “Surgical Avoidance”. In fact, the entire field of Interventional Orthobiologics is based on Surgical Avoidance. Meaning, how do we replace invasive surgeries with less invasive precise injections of Orthobiologics like PRP. Hence, this should be our main research metric in this field.

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The Challenges of Measuring Surgical Avoidance

If this is clearly the sweet spot for Orthobiologics, why then aren’t we seeing more studies measure this concrete metric? Let’s go into this a bit because it’s an important topic.

Helping patients avoid surgery could be a 1-2 year measurement or could take MUCH longer. For example, if we’re talking about whether a patient can avoid an ACL surgery, then we could maybe know this in 1-2 years. Meaning, if an ACL surgery candidate had a precise injection of Bone Marrow Concentrate into the ACL using fluoroscopic guidance and in the first two years they were fully functional, happy, and never got the surgery, we could be reasonably sure they successfully avoided the procedure. However, even in that case, if we want to be 99% sure, we would likely need to stretch our follow-up to longer periods, say 3-5 years.

However, if we want to see if someone successfully avoided a knee replacement, then 1-2 years isn’t probably long enough to follow these patients. In fact, longer-term follow-ups out to 5, 10, or even 15 years would be more reasonable. That’s because we’re no longer treating an event-driven injury like an ACL tear, but a long-term degenerative disease. This is what the recent studies published by Hernigou reported; a 15-year follow-up after knee BMC procedures (7,8).

Here you’re starting to see why surgical avoidance isn’t used that much in clinical studies. Few researchers have the ability to follow patients for this length of time. That of course is different for Regenexx, where we’ve been tracking patients since 2005 in a registry. Meaning we can begin to use that data, the data reported by others, and data from our Randomized Controlled Trials and other published studies to get to Surgical Avoidance rates.


There are other common scientific measurements used by researchers to determine the value of a procedure. One is called QALY. Let’s dig in on this concept.

QALY stands for quality-adjusted life-year which is equal to 1 year of life in perfect health. QALYs are calculated by estimating the years of life remaining for a patient after a particular procedure and weighting each year with a quality-of-life score (on a 0 to 1 scale). While this isn’t Surgical Avoidance, it’s a more global way to look at much money you’re spending versus how much quality of life the patient is gaining.

At Regenexx, we’re involved in a study with the University of Utrecht’s THINC group that measures the QALY metrics around our Bone Marrow Concentrate Knee Arthritis procedure. That’s a direct comparison to knee replacement looking at the cost and quality of life of both procedures. This will be the first of many publications on the cost-effectiveness of Orthobiologics delivered in a closed network focused on high levels of quality assurance. To my knowledge, these research papers will the first of their kind in the field of Orthobiologics.

Introducing Surgical Avoidance as an Academic Concept

If DMOD is a holy grail concept that’s more aspirational than real, can we move toward something else? Meaning, while measuring cartilage loss is important, how much does it matter when all the patient wants to do is to be able to hike without knee pain or swelling? Most patients simply don’t care what’s on their MRI if they can do what they want to do. In addition, for Knee Arthritis, the single biggest patient ask is avoiding a knee replacement. That’s also the single biggest financial milestone for an insurer. In that world, avoiding a knee replacement means saving tens of thousands of dollars.

So how do we go from DMOD to Surgical Avoidance? We start publishing on the concept of Surgical Avoidance. This might look something like this:

Surgical Avoidance=[[Number of Treated Patients who Didn’t Convert to Surgery]/[Number of Treated Patients who Did Convert to Surgery]]/Time vs the same math for the untreated patients.

Meaning a 3.5/year for a treated patient population would mean that 3.5 times as many treated patients avoided surgery during that time. That could be compared to an untreated population that had a 0.5, meaning twice as many patients in that group converted to surgery during the same time period.

Obviously, this math could also be set up in other ways as well.

Let’s Begin These Studies

I plan on introducing this concept of Surgical Avoidance in several academic papers. I encourage my colleagues to follow suit, as this is what will move the needle with insurers. Meaning if we want these procedures to be covered, showing that they can avoid surgery is the way to do that while we can let the drug research community chase the mythical DMOD.

The upshot? In the world of Interventional Orthobiologics, what physicians and patients care about is avoiding surgery. Hence, let’s start studying this as an academic concept.



(1) Çalış, Havva Talay et al. “Efficacy of Intra-Articular Autologous Platelet Rich Plasma Application in Knee Osteoarthritis.” Archives of Rheumatology 30 (2015): 198-205.

(2) Bansal, H., Leon, J., Pont, J.L. et al. Platelet-rich plasma (PRP) in osteoarthritis (OA) knee: Correct dose critical for long term clinical efficacy. Sci Rep 11, 3971 (2021). https://doi.org/10.1038/s41598-021-83025-2

(3) Asjid R, Faisal T, Qamar K, Khan SA, Khalil A, Zia MS. Platelet-rich Plasma-induced Inhibition of Chondrocyte Apoptosis Directly Affects Cartilage Thickness in Osteoarthritis. Cureus. 2019;11(11):e6050. Published 2019 Nov 1. doi:10.7759/cureus.6050

(4) Şen Eİ, Yıldırım MA, Yeşilyurt T, Kesiktaş FN, Dıraçoğlu D. Effects of platelet-rich plasma on the clinical outcomes and cartilage thickness in patients with knee osteoarthritis. J Back Musculoskelet Rehabil. 2020;33(4):597-605. doi: 10.3233/BMR-181209. PMID: 31594201.

(5) Baki M. Abdel Noha ,Nawito O. Zeinab ,Abdelsalam M. S. Nehal ,Sabry Dina , Elashmawy Hossam,Seleem A. Nagy ,Taha Ali Abdel-azeem Azza , El Ghobashy Mohamed, “Does Intra-Articular Injection of Platelet-Rich Plasma Have an Effect on Cartilage Thickness in Patients with Primary Knee Osteoarthritis?”, Current Rheumatology Reviews 2021; 17(3) . https://doi.org/10.2174/1573397117666210114151701

(6) Şen Eİ, Yıldırım MA, Yeşilyurt T, Kesiktaş FN, Dıraçoğlu D. Effects of platelet-rich plasma on the clinical outcomes and cartilage thickness in patients with knee osteoarthritis. J Back Musculoskelet Rehabil. 2020;33(4):597-605. doi: 10.3233/BMR-181209. PMID: 31594201.

(7) Hernigou P, Bouthors C, Bastard C, Flouzat Lachaniette CH, Rouard H, Dubory A. Subchondral bone or intra-articular injection of bone marrow concentrate mesenchymal stem cells in bilateral knee osteoarthritis: what better postpone knee arthroplasty at fifteen years? A randomized study. Int Orthop. 2020 Jul 2. doi: 10.1007/s00264-020-04687-7. Epub ahead of print. PMID: 32617651.

(8) Hernigou P, Delambre J, Quiennec S, Poignard A. Human bone marrow mesenchymal stem cell injection in subchondral lesions of knee osteoarthritis: a prospective randomized study versus contralateral arthroplasty at a mean fifteen year follow-up. Int Orthop. 2020 Apr 23. doi: 10.1007/s00264-020-04571-4. Epub ahead of print. PMID: 32322943.

Chris Centeno, MD is a specialist in regenerative medicine and the new field of Interventional Orthopedics. Centeno pioneered orthopedic stem cell procedures in 2005 and is responsible for a large amount of the published research on stem cell use for orthopedic applications. View Profile

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