Will Kobe Bryant go to Japan to Treat his Knee Arthritis?

Japan Accelerates Regenerative Medicine with Regulatory Reforms

Why the United States Must Follow Their Lead

Sign the online petition supporting Regenerative Medicine

Kobe Bryant, an elite professional athlete from the National Basketball Association’s Los Angeles Lakers, has gone to Germany multiple times to be treated with a portion of his own blood for his creaky, arthritic knees.  The reason why he went to Germany is simple.  He wanted to have the best chance to play at the highest level in the NBA and he had exhausted all his options in the United States.  He went there to be treated with a component of his own blood that targets the inflammation associated with knee osteoarthritis.  The treatment he received is not approved here in the United States. 

Will he go to Japan next time to get the most advanced therapy?  That may happen because in November 2014 Japan enacted legislation creating a new pathway that accelerates the approval process for regenerative medicine products.  We here in the United States need to figure out how to best accelerate our own regenerative medicine efforts or continue to watch our elite athletes and other patients seek treatment beyond our shores.  Let’s explore why Japan acted boldly in favor of regenerative medicine. 

A Nobel Prize was awarded to Japanese researcher and former orthopedic surgeon, Dr. Shinya Yamanaka in 2012 for his pioneering work on how to reprogram mature skin cells into pluripotent stem cells.  His potentially life saving work and the national pride associated with it helped Japan become a worldwide leader in stem cell research.  Importantly, Japan has also prospectively pursued and passed legislation that will dramatically stimulate regenerative medicine.  The country took a leap into a bright future last week with the implementation of regulatory reforms directed at accelerating the development of cell-based treatments. 

The new law established a separate pathway for regenerative medicine products apart from traditional drugs and medical devices. The regulations also created a system that fosters faster commercialization of novel biologic products and can lead to time limited approvals for up to seven years.   Post market data analysis will continue to confirm the safety and efficacy of the regenerative medicine products with the potential to revoke approvals. 

The action by the Japanese government creates the proper equilibrium between the need for accelerated approvals for cell based therapies that have established efficacy while ensuring product safety.  The typical phase one, phase two and phase three trials for new drugs are not a proper pathway for cell-based therapies that have highly complex mechanisms of action that may or may not be identified even with elite preclinical models.  Importantly, many cell-based products come directly from a patient’s own body and therefore have a dramatically higher safety profile. 

Americans are screaming for new treatments for a variety of difficult problems such as arthritis, heart disease and diabetes.  Regenerative medicine and especially cell-based treatments have a chance to help treat and potentially cure these problems.  We need to follow the Japanese lead and create similar pathways in the United States.  Last year during a visit to Japan and its PMDA (the equivalent of the FDA), I was staggered by how engaged they were about regenerative medicine and receptive they were to understanding how to bring safe and effective biologic products to their populace.

The United States can learn a great deal from Japan’s enlightened approach to regenerative medicine.  Safety of course should be paramount.  The idea of a conditional, time-limited approval with reimbursement strikes a perfect chord as we seek better treatments for our patients at more affordable prices.  Competition will arise to obtain approvals based on phase two trials that confirm safety and show a solid degree of efficacy.  Importantly, more competition will lead to better options and faster innovation similar to the computer industry over the last several decades. 

We need to also emulate our Silicon Valley technology colleagues and call for a Medical Moore’s Law.  Identify a specific clinical problem, create a novel solution and within five years double the efficacy and decrease the price by fifty percent.  Data analysis via powerful graphical algorithms should assist with new discoveries and also help with better management of many diseases.  

We must seek dramatically higher horizons instead of being satisfied with iterative improvements.  The Japanese government should be congratulated for passing regulatory reform and implementing transformative solutions.  Sooner, not later, we need to find ways to execute our own regulatory reforms here in the United States to help our patients and to remain competitive on the world stage in regenerative medicine.

Perhaps, then Kobe will be treated in California instead of Germany or Japan.

Allan Mishra, MD

TotalTendon


Sign the online petition supporting Regenerative Medicine

Please post any comments or suggestions about how to safely accelerate regenerative medicine.

References

(http://www.nobelprize.org/nobel_prizes/medicine/laureates/2012/yamanaka-facts.html)

Accessed 11/30/14

http://www.pmda.go.jp/english/events/2014taiwan_sympo/14_Keynote1.pdf

Accessed 11/30/14

Platelet Rich Plasma (PRP) Helps Patients

Platelet Rich Plasma (PRP) has been used now for more than a decade to treat a variety of orthopedic conditions.  Hundreds of thousands of patients have been treated with a stellar safety record.  The efficacy of PRP has evolved over the years but there are now multiple randomized controlled trials supporting the use of PRP.  This data has been presented at major medical conferences all over the world and published in peer reviewed elite journals such as the American Journal of Sports Medicine.

Below are the highlights from a few of the published papers:


Large Randomized Controlled Trial using PRP for Chronic Tennis Elbow Patients
American Journal of Sports Medicine 2014 

82.1% had successful treatment using PRP  compared to 60.3% in the active control group at six months.  (P = 0.008)  (See Figure)

There was also significantly less elbow tenderness in the PRP treated patients compared to the active control group at six months. (P = 0.009)

PRP Beats Cortisone for Chronic Tennis Elbow at 2 year Follow up
American Journal of Sports Medicine 2011 (100 patient trial)
Patients treated with PRP had dramatically better success rates at 2 years compared to cortisone.
(P < 0.001)

These two trials used the same protocol and same PRP device (Biomet GPS PRP).  There were no significant complications in either study.   Successfully treated patients were able to avoid more invasive and expensive surgical interventions.  This is clear evidence supporting the use of PRP for chronic tennis elbow.

PRP More Effective than Placebo in the Treatment of Knee Osteoarthritis
American Journal of Sports Medicine 2013 (156 knees)
50% improvement in pain scores was noted using PRP compared to worsening of pain in the placebo group at 6 months.  (P < 0.001)

There are now over 7400 references to PRP on PubMed with more than 500 publications last year alone.  This is an indication of the worldwide interest in this topic.   There are literally hundreds of published papers supporting the use of PRP and other blood components to treat disease.  More research and development will always be needed but using a patient's own blood to treat their injuries and disorders simply makes intuitive and scientific sense.  

Patients and providers with experience with platelet rich plasma or other biologic treatments are encouraged to post comments below.

AM
TotalTendon

Tennis Elbow Stretches

Tennis elbow is a very common problem.  Most often it can be treated with rest, activity modification and some simple exercises.

Check out the TotalTendon Tennis Elbow Stretching Protocol.



In future posts, I will demonstrate a strengthening protocol and discuss other treatment options.

AM
TotalTendon

Biologic Orthopedics, Forbes, Sports Illustrated and ESPN

This week the Rothman Institute in Philadelphia has organized a meeting dedicated to exploring biologic orthopedics and sports medicine in a unique format.  The group has invited researchers and clinicians from around the world to participate with elite media representatives from Forbes, Sports Illustrated, and ESPN among others.  Dr. Noriyki Tsumaki from the the 2012 Nobel Prize winning CIRA Center in Kyoto Japan will also be lecturing.  Discussion about the FDA regulation and economics of biologic orthopedics will also occur.

Stem Cell and Biologics in Sports Medicine Summit

The meeting represents a special opportunity to bring together a unique group of individuals that are interested in how to best treat tendonitis, arthritis and other orthopedic conditions with stem cells, platelet rich plasma and other biologic therapies.  The moderators of the scientific panels will be editors from world renowned publications.  I expect to have spirited discussions about the state of the art in 2014 in addition to perhaps identifying novel pathways that lead to transformative treatments for professional, collegiate and weekend warrior athletes.

I will report my finding in this space and will tweet out real time information via:  @BloodCure

AM
TotalTendon

Why patients are seeking out platelet rich plasma and other biologic treatments.

Platelet rich plasma (PRP) and adult stem cell treatments derived from bone marrow are rapidly evolving into the mainstream of medicine.  As you can see from the chart above, the number of hits for "platelet rich plasma" is rising dramatically.  There are also over 7400 PRP references on PubMed.org.  Let's explore why.

Patients are seeking out less invasive treatments.  When presented with the option of surgery or an office procedure, patients typically will choose the office procedure.  Surgery often carries significant more risk and certainly more cost.

Patients want to return to sports, work or life as quickly as possible.
Botox and Lasik eye surgery provide patients with almost immediate improvement for wrinkles and vision.  Patients now expect other specialities to deliver similar almost instantaneous success.   Elite athletes are especially interested in returning to the highest level of function as quickly as possible.  They have been one of the primary drivers of PRP and other biologic treatments.

Patients are dissatisfied with the surgical treatments we have been offering them.
This is particularly true when it comes to knee arthritis.  Presently, there is very little definitive evidence supporting the use of many common treatments and there is a Grand Canyon size hole in our ability to effectively manage tens of millions of patients.  Biologic therapies will likely fill this void within the next five years.

Patients intuitively understand the regenerative abilities of your own blood and bone marrow.  Evidence is mounting across a several specialties supporting the use of blood and bone marrow to treat a variety of conditions.  A new study will begin this fall evaluating the utility of giving Alzheimer's patients blood transfusions from healthy volunteers under 30.  (Stanford Blood-Alzheimer's study)

Patients are willing to be treated without perfect supporting data.

Patients do not often understand the need for large clinical trials and are impatient with the time and effort it takes to generate meaningful clinical data.  The use of their own blood (PRP) or bone marrow simply make sense to them and they are willing and often eager to try a new treatment instead of undergo surgery.

We are presently scrambling to figure out how to develop, execute and pay for the clinical trials needed to best understand how to utilize biologic orthopedic therapies.  The good news is:  hundreds of clinicians, researchers and medical device professionals are working diligently on dozens of new treatment options.

Please post any comments about why you may think patients and clinicians are using PRP, stem cells or other biologic treatments.

AM   (@BloodCure on Twitter)
TotalTendon

Biologic Orthopedic Society crosses over 2500 Member Mark

The Biologic Orthopedic Society (BOS) is a group of professionals dedicated to the research and development of biologic treatments for musculoskeletal injuries and disorders.  This group has now grown to over 2500 members worldwide.  Much of the group's focus has been on the use of platelet rich plasma, stem cells and bone marrow concentrate (BMC) for tendonitis, arthritis and degenerative spinal disc disease.

The growth of the Biologic Orthopedic Society (BOS) is a testimony to the rapidly rising interest in biologic solutions to difficult musculoskeletal problems.  Significant progress has been made in terms of better published data supporting the use of biologic therapies in the last 2-3 years.  Clearly, more information and research is still needed.  As the group continues to grown, more and more connections are being made.  Ideas and projects are advancing.  All of this should give hope to those patients in search of better treatments.  Many hard working professionals are striving to deliver better biologic options.  

I'll predict within another 5-10 years, we will be staggered by how much will be accomplished.

Thanks to my many colleagues and friends within the BOS for a fantastic journey so far.

If you are a professional working in the area, please consider joining the group.  

Biologic Orthopedic Society

AM

Total Tendon

Hamstring Injuries Treated with Platelet Rich Plasma Return to Play Faster than Rehab Alone

Hamstring muscle injuries are very common in a variety of sports including track, soccer, football and basketball.  A recently published study in the American Journal of Sports Medicine (AJSM) found athletes that were treated with platelet rich plasma (PRP) injections returned faster to their sport when compared to rehabilitation alone.  In the study, the PRP patients returned at an average of 26.7 days compared to 42.5 days in the control group (P = .02).  (reference) This greater than two week difference in time to return to play after this common injury is clinically and competitively important.

Another recently published in the New England Journal of Medicine (NEJM) found no difference between PRP injections (2 injections spaced about a week apart) and a control group.  Interestingly, both groups in this study returned to play at 42 days, very similar to the control group in the AJSM study.  (reference)

Why are these results conflicting?

One important difference between the two studies is the type of PRP used to treat the patients.  In the study that did show a difference, white blood cell enriched PRP (leukocyte enriched PRP) was used.  In the study that did not show a difference, white blood cell  poor PRP (leukocyte poor PRP) was used.  This is a clear example of why PRP formulation matters.

The data published in elite, peer reviewed journals suggests leukocyte enriched PRP helps return athletes more than two weeks faster than rehabilitation alone after an acute hamstring injury.  No difference in return to play can be expected if leukocyte poor PRP is used in this patient population.

As PRP and other cell therapies continue to evolve, it will become increasingly clear that formulations much match indication.  Patients, researchers, and clinicians need to realize not all PRP is the same.

AM
TotalTendon

Can Stem Cells Cure Knee Arthritis?

Can Stem Cells Cure Knee Arthritis?

Unfortunately, the answer to that question is not known today.  It is clear, however, that many novel regenerative therapies are emerging to help the tens of millions of patients worldwide that are suffering from knee arthritis.

First, we must explore what type of stem cells could be helpful in the treatment of arthritis.  Stem cells of various types can be obtained from your blood (peripheral derived stem cells), bone marrow (mesenchymal stem cells), fat (adipose derived stem cells), and even from umbilical cord blood.  Studies today are exploring various ways to extract, purify and concentrate many types of stem cells.  The cells can then be injected as a suspension into your knee, used as part of surgical procedure or even injected after an operation.

Microfracture of Damaged Knee Cartilage

One recent study (Vangsness et al 2014) showed how an injection of mesenchymal stem cells could lead to more meniscus tissue after a knee arthroscopy.  24% of the treated group were found to have at least 15% increased meniscal volume.  This is a small amount in only a a quarter of the patients but it does represent a start.  Another study published last year (Saw et al 2013), injected peripheral derived stem cells after a microfracture procedure and noted improvement in the cartilage quality.  Other approaches (Pak et al 2014) use adipose derived stem cells from liposuction in combination with platelet-rich plasma to treat meniscus tears.  Finally, a review (Anderson et al 2013) of potential stem cell therapies for knee cartilage outlines many potential and emerging options.

Also, a variety of procedures also use non-stem cells to treat arthritis of the knee.  One of the oldest is called autologous chondrocyte implantation.  This is where a biopsy of your own cartilage is taken and then grown in a lab.  The expanded cells and then reimplanted into an arthritic lesion of the knee.  Another procedure simply penetrates the bone under the defective cartilage.  This leads to leakage of some of the bone marrow along with your own the stem cells within the marrow into the defect.  This is called microfracture.  Yet another procedure uses juvenile cartilage that is minced and then glued into a arthritic zone of the knee.

It is clear that there are many competing approaches to the use of cells and stem cells to treat knee arthritis.  None have "cured" the problem.   There is, however, an earnest worldwide research effort that will produce clinically meaningful options for clinicians and patients.

Millions worldwide are waiting for that day.

AM
TotalTendon

References
Anderson et al 2013
Saw et al 2013
Vangsness et al 2014
Pak et al 2014

Platelet Rich Plasma, Stem Cells and Biologic Orthopedics on Dr. Radio

On Monday May 12th, I will be on Sirius-XM Doctor Radio (Channel 81, 7 pm EST, 4 pm PST) discussing platelet-rich plasma, stem cells and other biologic orthopedic treatments.  It is an exciting time for this topic because research in these areas has progressed significantly just in the last few months.  Also, patients and payers are demanding less invasive and more effective treatments for difficult problems such as knee osteoarthritis and degenerative disc disease.  So, tune in at 7 pm EST, 4 pm PST on Monday May 12th to learn more about the frontiers of musculoskeletal medicine and surgery.  

AM

TotalTendon

Platelet Rich Plasma Helpful for Patellar Tendonitis in Athletes

A new study published in the American Journal of Sports Medicine that ultrasonic guided platelet rich plasma  (PRP) injections improved pain and function in athletes with chronic patellar tendinopathy.  (See abstract below)

Patellar tendinopathy typically affects running and jumping athletes such as tennis, volleyball and basketball players.  It manifests itself with pain in the front of the knee and typically is worse with repeated jumping activities.  Most often, it will resolve with appropriate non-invasive treatment such as rest, icing and physical therapy.  It can be difficult to treat.  When the symptoms persists, published data supports the use of PRP injections.

AM
TotalTendon

1. Christophe Charousset, MD*,†, 
2. Amine Zaoui, MD‡, 
3. Laurence Bellaiche, MD§ and 
4. Benjamin Bouyer, MD∥

+Author Affiliations

1. ^†Institut Osteo Articulaire Paris Courcelles, Paris, France
2. ^‡Laboratory of Bioengineering and Biomechanics for Bone Articulation, University of Paris, Paris, France
3. ^§Centre D’image Médicale Bachaumont, Paris, France
4. ^∥Biostatistics and Epidemiology Department, Hotel Dieu Hospital 1, Paris, France
5. Investigation performed at the Institut Ostéo Articulaire Paris Courcelles, Paris, France

1. ↵* Christophe Charousset, MD, Institut Osteo Articulaire Paris Courcelles–60 Rue de Courcelles, 75008 Paris, France (e-mail: dr.charousset@ioapc.fr).

Abstract

Background: Chronic patellar tendinopathy (PT) is one of the most common overuse knee disorders. Platelet-rich plasma (PRP) appears to be a reliable nonoperative therapy for chronic PT.

Purpose: To evaluate clinical and radiological outcomes of 3 consecutive ultrasound (US)–guided PRP injections for the treatment of chronic PT in athletes.

Study Design: Case series; Level of evidence, 4.

Methods: A total of 28 athletes (17 professional, 11 semiprofessional) with chronic PT refractory to nonoperative management were prospectively included for US-guided pure PRP injections into the site of the tendinopathy. The same treating physician at a single institution performed 3 consecutive injections 1 week apart, with the same PRP preparation used. All patients underwent clinical evaluation, including the Victorian Institute of Sport Assessment–Patella (VISA-P) score, visual analog scales (VAS) for pain, and Lysholm knee scale before surgery and after return to practice sports. Tendon healing was assessed with MRI at 1 and 3 months after the procedure.Results: The VISA-P, VAS, and Lysholm scores all significantly improved at the 2-year follow-up. The average preprocedure VISA-P, VAS, and Lysholm scores improved from 39 to 94 (P < .001), 7 to 0.8 (P < .0001), and 60 to 96 (P < .001), respectively, at the 2-year follow-up. Twenty-one of the 28 athletes returned to their presymptom sporting level at 3 months (range, 2-6 months) after the procedure. Follow-up MRI assessment showed improved structural integrity of the tendon at 3 months after the procedure and complete return to normal structural integrity of the tendon in 16 patients (57%). Seven patients did not recover their presymptom sporting level (among them, 6 were considered treatment failures): 3 patients returned to sport at a lesser level, 1 patient changed his sport activity (for other reasons), and 3 needed surgical intervention.

Conclusion: In this study, application of 3 consecutive US-guided PRP injections significantly improved symptoms and function in athletes with chronic PT and allowed fast recovery to their presymptom sporting level. The PRP treatment permitted a return to a normal architecture of the tendon as assessed by MRI.

http://ajs.sagepub.com/content/42/4/906.abstract

Best Overall Exercise: PowerKnee Bike Program (Knee OA Part 4)

The PowerKnee Bike Program uses an upright exercise bike to work out all of your leg muscles.  It is the best overall exercise for knee pain and arthritis because it can do so much for you without significant impact on the joint.   By simply riding the exercise bike for 30 minutes 3 times per week you can also improve your cardiovascular fitness and burn a bunch of calories.  See the video below for details.

Record the calories you can burn in 30 minutes and compare your results week by week for a month.  If you are consistent in applying the PowerKnee Bike Program you have an excellent chance of decreasing your pain and improving your knee function.

As always, check with your doc before beginning any exercise program.

AM
TotalTendon

Best Initial Knee Exercise: The QuadCrunch (TM) (Knee OA Part 2)

There are dozens of knee exercises you can do to strengthen the muscles around your joint.  One crucial muscle to strengthen is the quadriceps or "Quad".  Too often, however, this muscle simply does not cooperate.  We need a simple way to get started.  We need an exercise than can be done anywhere, anytime without any equipment.  Now, we have one, the QuadCrunch (TM).  

The QuadCrunch (TM) helps initiate and reinforce the contraction of the most important component of the Quad---the Vastus Medialis Obliquus or VMO for short.  

QuadCrunch (TM) Video

Simply, straighten out your leg and place your fingers over the inside portion of your thigh just above your knee.  This is where the VMO lives.   With your leg fully straight and your heel on the ground, push your leg toward the ground and try to contract the muscle.  If you are successful, you will see your kneecap move.  The reason to put your fingers on your muscle is to help your brain know it is contracting the muscle.  This helps reinforce the contraction.  

I recommending doing a set of 5 contractions, holding each contraction for 5 seconds, 5 times per day.  

This elementary exercise is often ignored but serves as the foundation for more advanced strengthening programs.  It can be helpful for people who want to strengthening their legs for any reason.  It may also be useful for patients with knee arthritis, patellofemoral pain, knee tendonitis and even meniscus tears.  (Always check with your doctor before beginning any exercise program)

Good luck and get started today.  Remember, this exercise can be done in shorts, pants and almost anywhere.  Simply place your fingers on your quad muscle and straightening your knee with your heel on the ground.  It is best if your are sitting on the edge of a chair.  

It is best to record how many sets per day you do.  That will help you be compliant with the exercise.  We will discuss exercise compliance more in a later post.  

Post any questions, comments or suggestions below.

AM

TotalTendon

The Best Initial Treatment for Knee Arthritis (Part 1)

What is the best initial treatment for knee arthritis?

The answer is diet and exercise.

It isn't easy but diet and exercise are highly effective at reducing pain and improving function.  In a recent study of about 400 patients the combination of diet and exercise decreased pain scores by 45%.  This is impressive because most injection therapies improve pain by 30-40% and often only last 6 months.  This study showed benefits up to 18 months.   Patients who also completed both a diet and exercise program were able to walk 136 feet more than patients who only dieted during a 6 minute walking test. (Messier et al JAMA 2013)  This is a simple and inexpensive way to treat a problem that affects 10 million Americans and millions more worldwide.

Too often patients and clinicians fail to select this strategy.  Patients often do not recognize how overweight they are and may even get angry if their physician points it out to them.  Physicians lack the time and tools to appropriate help patients begin an diet and exercise program.  With 69% of Americans either overweight or obese, it is very likely that weight reduction should be part of most knee arthritis treatment plans.

So, here are some suggestions to get started.
(Always check with your own physician before beginning any program.)

Give your knee a pain rating from 0-10 overall as a baseline measurement.

1.  Weight yourself and calculate your Body Mass Index.  (BMI Calculator)
     Be honest about the weight.  Record your weight daily.

2.  Set a goal to lose 5 pounds in two months and KEEP IT OFF.

3.  Lose weight by trying the One Less Diet (TM)
     One less dessert, one less sugary soda, one less beer, one less bagel, etc
     Use any other safe and effective means to lose weight.

Weekly, update your pain rating for your knee.  After two months, compare your baseline weight and pain to your new weight and pain.  You may find that if you simply lose weight your knee will begin to feel better.  The side effects of losing weight will also be good for your heart and your waistline.

In the next post, we will discuss a simple exercise plan.

AM
TotalTendon