Should Unloader Knee Braces Be Prescribed For Osteoarthritis Knee Pain BEFORE Total Knee Replacement?

Feature Image of an Unloader Knee Brace sourced from:

https://www.ossur.com/oa-solutions/research

An earlier blog post discussed autologous cartilage transplantation for defective knee cartilage:

Transplantation of One’s Own Knee Cartilage – Is this ‘The Bee’s Knees’ for Painful Knees?

Dear Pain Matters readers,

Introduction

Here’s a sobering thought:

The biggest cause of disability in the U.S. is osteoarthritis (OA), with the medial compartment (i.e. inside part) of the knee being most commonly affected (Vincent et al, 2012).

Most medical experts state that due to its avascular and aneural nature, articular cartilage cannot regenerate in vivo, especially during persistent inflammation following trauma or injury to cartilage (Huey et al, 2012).  

Other researchers believe that knee cartilage is able to regenerate in vivo, but only in a chondrocyte-friendly environment.  This would require nil ‘bone-on-bone’, nil localised inflammation, reduced or nil knee pain, healthy synovial fluid in the articular cavity and highly vascularised underlying subchondral bone (Lyu et al, 2011; Tiku & Sabaawy, 2015).

In the absence of effective treatment, deterioration of the knee joint may continue until finally, most if not all of the cartilage tissue is worn out and arthritic.  At this stage, total knee replacement (arthroplasty) may be the only option left.

As such, a proactive approach to knee health is important.  This is because a painful knee joint will either get better or worse.  Nothing stays the same.

The good news is that treatments do exist whereby ‘bone-on-bone’ knee pain may be reduced and even eliminated altogether in some instances.  These include non-weight-bearing exercises such as swimming, aquatic exercises and cycling.  Wearing a fitted unloader knee brace may also be helpful.   

Unloader Knee Braces

Regardless whether cartilage is able to regenerate in vivo or not, fitted unloader (or offloader) knee braces may offer benefits including relief from knee pain, increased knee stability and enhanced mobility.

By shifting the load-bearing weight toward the lateral (outside) part of the knee, the brace may help increase the gap between the femur bone and the medial (inside) part of the tibia.  (The lateral side is usually the ‘good’ side of the knee in patients with medial knee OA.)  This gap reduces ‘bone-on-bone’ and hence leads to reduced inflammation in an OA-affected knee joint. 

An unloader brace-induced gap can promote a chondrocyte- and mesenchymal stem cell**-friendly environment that might lead to cartilage regeneration. 

On the other hand, the absence of normal cartilage or the absence of a compensatory unloader knee brace may lead to ‘bone-on-bone’ between the connecting bones in the knee joint.  Without a gap between the bones, further knee joint deterioration occurs until finally, ‘bone-on-bone’ knee pain results.  Walking may become unbearable unless the patient opts for an unloader knee brace (if beneficial) or has total knee replacement.

Thus, OA knee patients may benefit from a prescription for a fitted unloader brace for walking, hiking and other light load-bearing activities.  Wearing an unloader brace may relieve knee pain, swelling and other symptoms as well as prevent further deterioration in the defective knee cartilage.

For some OA patients, wearing an unloader knee brace may be all that is required ‘to keep going’ and hence, defer costly total knee replacement indefinitely (Mistry et al, 2018).

A Friend’s Unloader Knee Brace Story

Several years ago, I kept running into a nice lady named ‘Jane’ (70) in a nearby park.  Appearing fit and trim while walking her dog, Jane always wore her unloader knee brace.

One day while chatting, I asked her why she wore a knee brace.  Jane replied that sadly, one of her knees was now ‘bone-on-bone’.  Consequently, Jane found walking very painful without her knee brace.  She added that luckily, she finally found pain relief while walking her dog as long as she wore her unloader brace. 

It all started when Jane’s orthopaedic surgeon stated that she needed total knee replacement due to ‘bone-on-bone’ knee pain.  When the surgeon proposed a date for this surgery, she realised that the date for surgery conflicted with a long-planned golfing holiday with her husband.  Since there were no other times available for surgery, her surgeon prescribed an unloader knee brace until her return.

From Jane’s perspective, this was the best treatment ever for her knee pain.  Jane was finally able to walk her dog for kilometres at a time without pain.  She was able to manage without a knee brace in her own house.

The story does not end here.  It only gets even better!

A year later, I saw Jane outside of her house while walking past.  She was not wearing her knee brace.  After a chat, I asked her how her knee was doing.

Jane’s answer took me by complete surprise.  Jane told me that she had cancelled her knee surgery indefinitely.  This was because she no longer needed her knee brace while walking her dog.

Lost for words, I asked, ‘Why not?’

Jane replied that recently, her small dog had run out of the house to chase another dog down the road.  Worried that her dog might get hit by a car and in a hurry to catch up to her dog, Jane forgot to put on her knee brace.  Instead, she ran as quickly as she could to chase down her beloved dog.  When Jane finally did catch up, she was relieved to find her dog safe and well.

On their way back home, Jane noticed something weird.  She was not wearing her unloader knee brace.  Even stranger, Jane had nil knee pain despite running after her dog without her knee brace! 

‘How is this even possible?’, she asked herself.

In Jane’s opinion, her knee cartilage may have regrown due to her wearing an unloader brace daily while walking her dog.  Jane would never have realised that her cartilage had regenerated if her dog hadn’t suddenly run out of their house that day.   This is because normally, Jane would never walk her dog without her knee brace.

Jane joked that her brace must have given her knee a much-needed ‘knee holiday’.

Thanks to Jane’s brace, her knee no longer endured ‘bone-on-bone’ pain while walking her dog.  This led to reduced irritation and inflammation as well as possible cartilage regeneration.

I thought it was fantastic that in lieu of total knee replacement, Jane was prescribed an unloader knee brace.  This knee brace enabled Jane to take long walks with her dog every day without knee pain.  Furthermore, Jane no longer needed her knee brace one year later.

Jane’s knee cartilage may have regrown thanks to the ‘knee holiday’ that her brace offered.  Despite no longer wearing her brace while walking her dog, Jane no longer had any ‘bone-on-bone’ knee pain.

Just as a dog can be a man’s (or a woman’s) best friend, an unloader knee brace may be an OA knee’s best friend.

An unloader knee brace was the only thing that Jane needed for ‘bone-on-bone’ knee pain.  And thanks to her misadventure with her dog, she found out that she no longer needed a knee brace one year later!

After listening to this incredible story, I was happy that Jane was able to defer total knee replacement surgery indefinitely.

Some questions:

What would have happened if Jane had done nothing at all?  In other words, what if Jane was not prescribed an unloader knee brace and had not considered total knee replacement surgery?

I suspect that if Jane had done nothing at all, her knee may have deteriorated even further.

A ‘bad’ knee sometimes degenerates to the point where walking becomes impossible without a cane, walker or wheelchair – until joint replacement.

As such, doing nothing is not usually a good option.  One needs to be proactive in the care of one’s own health including the health of one’s knees.

If one has painful knees, one should first seek out less invasive knee treatments.  This may include an unloader knee brace, physiotherapy, non-load-bearing exercises (e.g. swimming and other aquatic exercises, cycling), a healthier diet, losing weight and/or autologous cartilage transplantation (see link at top).

If conservative treatment(s) are pursued in a timely manner, it may be possible to save a knee joint, hence defer total knee replacement indefinitely.

Finally, what exactly went on inside Jane’s knee while she wore her unloader knee brace??

To try to answer this question, I explored the science behind Jane’s knee recovery.  This is what I found:

The Science Behind Jane’s Knee Recovery  

1-s2.0-S1877065715000561-gr1.jpg

Image of unloader (valgus) knee brace for medial knee OA sourced from:

https://www.sciencedirect.com/science/article/pii/S1877065715000561

Overview

A properly fitted unloader knee brace may help keep a patient on his/her feet while slowing or stopping further ‘bone-on-bone’ deterioration of the knee joint.  This may lead to reduced knee pain and increased mobility.

A fitted unloader brace is designed to alleviate the mechanical strain on the defective load-bearing cartilage.  As such, cartilage regeneration in vivo may occur in some OA patients after wearing an unloader brace for many months.

Whether cartilage regenerates or not is not the biggest issue.  It may even be impossible in most OA knee patients.

A greater concern is whether reduced (or nil) ‘bone-on-bone’ pain and increased mobility results while wearing an unloader knee brace during weight-bearing activity.  If yes, ongoing use of this brace is warranted as long as desired.

Some OA patients may prefer a non-invasive unloader brace over total knee replacement surgery, osteotomy, pain medication including knee injections or doing nothing at all.

Others may not qualify for total knee replacement surgery due to being younger than 50 or older than 80.  As such, patients aged less than 50 with a severely arthritic and painful knee may benefit from an unloader brace.

Patients with unicompartment knee OA* may benefit from unloader braces that may decrease (or eliminate) pain, enhance knee function and perhaps even slow OA progression.

Knee Joint Distraction Therapy

Knee joint distraction therapy involves applying an external force to the knee joint via an unloader knee brace (preferably, not via an invasive external fixation frame).  Such a brace can be adjusted to exert external forces to either the inside or the outside of the knee, depending on which side is affected by OA.

Pain relief and reduced swelling often occur following distraction therapy of the arthritic, load-bearing part of the knee.  This therapy may either shift load-bearing weight from the medial (i.e. inside; valgus) compartment to the lateral (i.e. outside; varus) compartment of the knee, or vice versa (depending on which side is affected by arthritis).

In other words, knee joint distraction therapy via an unloader brace shifts the weight away from the arthritic knee compartment including degenerated cartilage and toward the ‘good’ side of the knee joint.   

Furthermore, an unloader brace may improve the overall alignment of the knee joint.  

Finally, an unloader brace may alleviate the ‘bone-on-bone’ pain in the knee by slightly increasing the gap between the femur bone and tibia bone on the arthritic side of the knee joint.

For example, a knee unloader brace with valgus adjustments may be prescribed for medial unicompartment knee OA.  This may be desirable before considering other more invasive surgical options such as osteotomy or arthroplasty (Ramsey & Russell, 2009).

Summary

In summary, an unloader brace-induced chondrocyte-friendly knee joint may result.  This may lead to reduced or nil pain and swelling, increased mobility and perhaps even cartilage regeneration (Callaghan et al, 2015; Kirane et al; Lafeber et al, 2006; Lee et al, 2017; Mastbergen, 2013; Ornetti et al, 2015; Ramsey & Russell, 2009; Thoumie et al, 2018; Tiku & Sabaawy, 2015; van der Woude et al, 2016a; van der Woude et al, 2016b; van der Woude et al, 2017; Verkerke et al, 2014).

One last question:

Is cartilage regeneration more likely to occur if both:

  • An unloader knee brace is worn; and
  • Autologous cartilage transplantation is done (where appropriate)?

(The latter is discussed here:

Transplantation of One’s Own Knee Cartilage – Is this ‘The Bee’s Knees’ for Painful Knees?)

Unloader Knee Brace Patient Stories

Dermott Brereton 

39945.jpeg

Dermott Brereton 

Source:  https://www.unloader.com.au/knee-pain/dermott-brereton

Former Australian Football League Player, Dermott Brereton (54), endured painful OA in his left knee for more than 30 years after tearing his cartilage during a game in 1984, aged only 19.

Following unsuccessful knee surgery, his injured cartilage had to be removed a year later.  Sadly, Dermott was left with ‘bone-on-bone’ knee pain.  Quoting Dermott,

‘It’s been painful to walk on ever since and can be excruciating when the pain’s most acute.’

Dermott continued,

‘… People ask me what’s it like, ‘bone-on-bone’ [pain] … I describe it as biting on a bit of tin foil.  That’s what it is in between the 2 [bones] of your knee … 

Rather than having invasive total knee replacement surgery, Dermott decided to wear the Unloader One Lite knee brace … and he hasn’t looked back since!

Weighing only 296g and featuring Össur’s 3-Point Leverage System, the Unloader One Lite knee brace is the lightest unloader knee brace currently available.

Dermott has worn this unloader knee brace for several months with significant success.  In his words,

‘… The Unloader [knee brace] … pulls those 2 sensitive points apart …

… I’ve got enough confidence now to take on the [96km Kokoda] track again.  So these days, any sporting activity I take on, I’m wearing the Unloader knee brace …’
‘… I wear the brace when I go on longer walks and play golf and have found that it really reduces the strain and pain in my knee …’

More details are available in the 1-minute YouTube video as well as in the following links:

https://www.unloader.com.au/knee-pain/user-stories

https://www.unloader.com.au/knee-pain/dermott-brereton

Other Unloader Knee Brace Stories

Quoting a 61-year old retired male professional,

‘I have one of these [unloader knee] braces and I wish I had this 3 years ago. I now ride my Trike all over New Zealand.’

For additional positive unloader knee brace stories, see YouTube videos and testimonials by OA patients including by:

  • ‘Tony’, a father of 2 girls;
  • A 45-year old male who enjoys kite surfing;
  • 9 other men including fathers;
  • A female hiker (age unknown);
  • An Asian woman who practices yoga.
  • A female (61); and
  • A knee pain patient (gender unknown).

For ‘Stories From Unloader Brace Users’, click here:

https://www.unloader.com.au/knee-pain/user-stories

Summary

Osteoarthritis knee patients should wear fitted unloader knee braces before contemplating total knee replacement surgery.

One never knows … there may be some life left in many knees, thanks to fitted unloader knee braces.

Key

* Unicompartment knee OA involves degeneration of the knee joint including defective articular cartilage.  The medial part of the knee joint is more commonly affected than the lateral part.

** Mesenchymal stem cells are the progenitor of chondrocytes.  They originate and reside in peri-articular bone marrow and subchondral bone.  Mesenchymal stem cells are also present in cartilage, synovium, synovial fluid, infrapatellar/sub-synovial fat pad and adipose tissue (Mastbergen, 2013; McGonagle et al, 2017).

References

MEDIA

(1A) Global Orthopaedics leader Össur announces AFL Legend Dermott Brereton as ambassador for revolutionary osteoarthritis knee braces – Unloader One Lite. Össur.

https://www.unloader.com.au/knee-pain/user-storieshttps://www.unloader.com.au/knee-pain/dermott-brereton

(1B) Stories From Unloader Brace Users. Össur.

https://www.unloader.com.au/knee-pain/dermott-brereton

(2A) Bedard, Richard. Knee Cartilage Repair: How One Patient Proved His Doctors Wrong. Huffpost (16 Aug 2011).

https://www.huffpost.com/entry/knee-cartilage-repair_n_876946

(2B) Bedard, Richard. Saving My Knees: How I Proved My Doctors Wrong and Beat Chronic Knee Pain. Pages 1-208.

PEER-REVIEWED PAPERS

IS CARTILAGE REGENERATION POSSIBLE IN VIVO?

(1A) Lyu et al. Knee Health Promotion Option for Osteoarthritic Knee: Cartilage Regeneration is Possible, Osteoarthritis – Diagnosis, Treatment and Surgery, Prof. Qian Chen (Ed.) (2012).

ISBN: 978-953-51-0168-0, InTech,

http://www.intechopen.com/books/osteoarthritis-diagnosis-treatment-and-surgery/knee-health-promotion- option-for-osteoarthritic-knee-cartilage-regeneration-is-possible

(1B) Lyu et al. Arthroscopic cartilage regeneration facilitating procedure for osteoarthritic knee. MC Musculoskeletal Disorders (21 Nov 2012); 13: 226.

https://doi.org/10.1186/1471-2474-13-226

https://bmcmusculoskeletdisord.biomedcentral.com/articles/10.1186/1471-2474-13-226

(1C) Other papers and thoughts by Lyu et al on whether cartilage regeneration could occur by itself, and in vivo: 

https://www.researchgate.net/post/Is_it_possible_that_cartilage_regeneration_could_happen_by_itself

(1D) Ding et al. Natural History of Knee Cartilage Defects and Factors Affecting Change. Arch Intern Med (27 March 2006); 166(6): 651-658.

doi 10.1001/archinte.166.6.651

https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/410037

JOINT DISTRACTION THERAPY FOR OSTEOARTHRITIS USING UNLOADER KNEE BRACE (NOT INVASIVE EXTERNAL FIXATION FRAME)

(2A) Tiku & Sabaawy. Cartilage regeneration for treatment of osteoarthritis: a paradigm for nonsurgical intervention. Ther Adv Musculoskelet Dis (2015); 7(3): 76-87.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4426098/pdf/10.1177_1759720X15576866.pdf

(2B) Callaghan et al. (2015) A randomised trial of a brace for patellofemoral osteoarthritis targeting knee pain and bone marrow lesions. Ann Rheum Dis (16 January 2015); 74(6): 1164–1170.

doi 10.1136/annrheumdis-2014-206376

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4771926/

(2C) Lafeber et alUnloading joints to treat osteoarthritis, including joint distraction. Curr Opin Rheumatol (2006); 18(5): 519–525.

https://www.ncbi.nlm.nih.gov/pubmed/16896294

(2D) Verkerke et al. Knee Orthosis for Cartilage Repair. Knee Orthosis for Cartilage Repair (October 2014); 32-33.

doi 10.13140/2.1.2702.6244

https://www.researchgate.net/publication/270879215_Knee_Orthosis_for_Cartilage_Repair

(2E) Ramsey & Russell. Unloader Braces for Medial Compartment Knee Osteoarthritis. Sports Health (Sept 2009); 1(5): 416–426.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3445170/

(2F) van der Woude et al. Five-Year Follow-up of Knee Joint Distraction: Clinical Benefit and Cartilaginous Tissue Repair in an Open Uncontrolled Prospective Study. Cartilage (July 2017); 8(3): 263–271.

(2G) van der Woude et al. Knee Joint Distraction Compared to Total Knee Arthroplasty for Treatment of End Stage Osteoarthritis: Simulating Long-Term Outcomes and Cost-Effectiveness. (12 May 2016); 11(5): e0155524.

(2H) van der Woude et al. #885 – Six Weeks of Knee Joint Distraction: Sufficient for Cartilage Tissue Repair. Abstracts / Osteoarthritis and Cartilage 24 (2016); S63eS534

 

https://www.oarsijournal.com/article/S1063-4584(16)00958-4/pdf

(2I) Ornetti et alClinical effectiveness and safety of a distraction-rotation knee brace for medial knee osteoarthritis. Annals of Physical and Rehabilitation Medicine (June 2015); 58(3): 126-131.

(2J) Mastbergen, S. SP0166 Joint Distraction and Cartilage Regeneration – What is the Basis for Structural Repair? Ann Rheum Dis (2013); 72(Suppl 3).http://dx.doi.org/10.1136/annrheumdis-2013-eular.166

https://ard.bmj.com/content/72/Suppl_3/A38.2

 

(2K) McGonagle et al. Native joint-resident mesenchymal stem cells for cartilage repair in osteoarthritis.  (Dec 2017); 13(12): 719-730.

doi 10.1038/nrrheum.2017.182.

https://www.ncbi.nlm.nih.gov/pubmed/29118440

(2L) Centeno, CJ. Can an Aggressive Knee Surgical Implant Regrow Cartilage? Regenexx (5 Sept 2013).

https://www.regenexx.com/blog/regrow-cartilage/

 

(2M) Intema et al. Tissue structure modification in knee osteoarthritis by use of joint distraction: an open 1-year pilot study. Ann Rheum Dis (12 May 2011); 70: 1441–1446.

doi 10.1136/ard.2010.142364

(2N) Wiegant et al. Sustained clinical and structural benefit after joint distraction in the treatment of severe knee osteoarthritis. Osteoarthritis Cartilage (Nov 2013); 21(11): 1660-7.
doi 10.1016/j.joca.2013.08.006.
(2O) Eustice, Carol. Relieve pain and improve stability with an unloader knee brace for osteoarthritis. Braceworks (22 Oct 2018).

https://www.braceworks.ca/2018/11/26/health-tech/relieve-pain-and-improve-stability-with-an-unloader-knee-brace-for-osteoarthritis/

(2P) Mistry et al. An Update on Unloading Knee Braces in the Treatment of Unicompartmental Knee Osteoarthritis from the Last 10 Years: A Literature Review. Surg J (N Y) (2 Jul 2018); 4(3): e110–e118.

 

(2Q) Lee et al. Unloading knee brace is a cost-effective method to bridge and delay surgery in unicompartmental knee arthritis. BMJ Open Sport Exerc Med (31 Jan 2017); 2: e000195.

 

(2R) Thoumie et al. Effect of unloading brace treatment on pain and function in patients with symptomatic knee osteoarthritis: the ROTOR randomized clinical trial. Sci Rep (12 Jul 2018); 8(1): 10519.

doi 10.1038/s41598-018-28782-3

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6043544/pdf/41598_2018_Article_28782.pdf 

(2S) Kirane et al. Offloading strategies for knee osteoarthritis. ler magazine (Sept 2010).

https://lermagazine.com/article/offloading-strategies-for-knee-osteoarthritis

OTHER

(3) Vincent et al. The Pathophysiology of Osteoarthritis: A Mechanical Perspective on the Knee Joint. PM R (May 2012); 4(5 Suppl): S3–S9.

doi:10.1016/j.pmrj.2012.01.020.

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‘Off-Label’ Use of Epidiolex (Cannabidiol; CBD) and Tilray 2:100 for Pain?

Feature Image of Epidiolex (cannabidiol; CBD) bottles sourced from:

https://www.bloomberg.com/news/photo-essays/2018-10-31/gw-pharmaceuticals-s-epidiolex-cannabis-based-epilepsy-drug

Dear Pain Matters readers,

Epidiolex (Cannabidiol; CBD)

Overview

An oral solution called Epidiolex (cannabidiol; CBD) was approved on 25 June 2018 by the US Food and Drug Administration (FDA).  Made by GW Pharmaceuticals, Epidiolex may be used for the treatment of epileptic seizures in patients with Lennox-Gastaut syndrome and Dravet syndrome aged 2 and above.

Epidiolex is the first FDA-approved drug that is based on a molecule (i.e. CBD) derived from marijuana (in this instance, CBD-rich cannabis).  Contrary to tetrahydrocannabinol (THC) that may lead to a ‘high’, the CBD molecule does not exert psychoactive effects.

For more information about CBD and pain, please visit my blog post called:

Cannabidiol (CBD) – ‘Cannabis With the Fun Bit Taken Out’ – For Severe Chronic Pain

Possible ‘Off-Label’ Use of Epidiolex (Cannabidiol; CBD) for Pain

Given that:

  • Cannabidiol (CBD) may offer pain relief; and
  • Epidiolex virtually is CBD,

‘off-label’ use of Epidiolex for pain may be warranted (Anson, 2018; Urits et al, 2019).

Thus, while specifically approved for the treatment of certain epileptic conditions, ‘off-label’ prescription by doctors for Epidiolex for pain may be possible.

Tilray 2:100

Tilray 2:100 (that is comparable to Epidiolex) is now available in Canada for patients with epilepsy.  Tilray 2:100 offers a target concentration of 100 mg/ml of CBD and 2 mg/ml of THC (Henriques, 2019; Tilray, 2018).

Similar to Epidiolex, ‘off-label’ prescription by doctors for Tilray 2:100 for pain may be warranted.

Summary

You may ask yourself,

‘Why would anyone request an ‘off-label’ prescription for Epidiolex or Tilray 2:100 when one could simply buy CBD for pain online (where legal)?’

According to Kyle Varner, MD, Internal Medicine Specialist in Washington:

‘CBD oil has tremendous therapeutic potential.  Epidiolex is just CBD— but sold at a price tag of over $30,000 per year’ (Tapp, 2019).

The answer is that many CBD products sold online are mislabeled and unregulated.  This may lead to ineffective treatments and/or side effects (Bonn-Miller et al, 2017).

As such, Epidiolex and Tilray 2:100 may be prescribed ‘off-label’ for pain in the US and Canada, respectively (in addition to, or instead of, CBD).

This is great news!  Now there are more treatment options available for pain!

Please forward to anyone who may benefit from this blog post.

Sabina Walker

Blogger, Pain Matters (in WordPress)

REFERENCES

Epidiolex

(1) Urits et al. An Update of Current Cannabis-Based Pharmaceuticals in Pain Medicine. Pain Ther (5 Feb 2019).

doi: 10.1007/s40122-019-0114-4.

https://www.ncbi.nlm.nih.gov/pubmed/30721403

(2) Anson, Pat. FDA Approves First Marijuana-Based Prescription Drug. Pain News Network (25 June 2018).

https://www.painnewsnetwork.org/stories/2018/6/25/fda-approves-first-marijuana-based-prescription-drug

(3) van der Walt, Eddie & Dawson, Rob.America’s First Cannabis-Based Medicine Is Made in England. Bloomberg (31 

https://www.bloomberg.com/news/photo-essays/2018-10-31/gw-pharmaceuticals-s-epidiolex-cannabis-based-epilepsy-drug

(4) FDA. FDA approves first drug comprised of an active ingredient derived from marijuana to treat rare, severe forms of epilepsy. FDA (25 June 2018).

https://www.fda.gov/newsevents/newsroom/pressannouncements/ucm611046.htm

(5) Tapp, Fiona. Businesses envision a boom in CBD, the non-intoxicating oil from hemp. Boston Globe (24 Jan 2019).

https://www.bostonglobe.com/news/marijuana/2019/01/24/businesses-envision-boom-cbd-non-intoxicating-oil-from-hemp/TQhuB0EErYvrpNxpTXTXxJ/story.html

Tilray 2:100

(1A) Henriques, Carolina. Tilray Launches New High-CBD Cannabis Oil for Seizure Treatment in Canada. Dravet Syndrome News (29 May 2019).

https://dravetsyndromenews.com/2018/05/29/tilray-launches-new-high-cbd-cannabis-oil-seizure-treatment-canada/

(1B) Tilray Introduces New High-CBD Extract. Tilray (06/19/2018).

https://www.tilray.ca/en/blog/post/tilray-introduces-new-high-cbd-extract/

Labelling Accuracy of Cannabidiol Available Online

(1A) University of Pennsylvania School of Medicine. Nearly 70 percent of cannabidiol extracts sold online are mislabeled, study shows. Science Daily (7 Nov 2017).

https://www.sciencedaily.com/releases/2017/11/171107112244.htm

(1B) Royal Queen Seeds. The Recent Approval of Epidiolex and its Implications. 

https://www.royalqueenseeds.com/blog-the-recent-approval-of-epidiolex-and-its-implications-n1014

(1C) Bonn-Miller et al. Labeling Accuracy of Cannabidiol Extracts Sold Online. JAMA (2017); 318(17): 1708.

doi: 10.1001/jama.2017.11909

https://jamanetwork.com/journals/jama/fullarticle/2661569

The Woman with No Pain

Feature Image of Jo Cameron sourced from:

https://www.abc.net.au/news/2019-03-28/scientists-discover-genetic-mutation-that-blocks-pain/10950380

Dear Pain Matters readers,

Jo Cameron

A Scottish woman named Jo Cameron (71), a retired teacher, has never felt pain, fear nor anxiety.  In her words,

‘I was just a happy soul who didn’t realise there was anything different about me.

Recently, pain geneticists helped unravel the mystery why this was so. They found that Jo was born with 2 genetic mutations.

The first mutation is common and causes decreased FAAH activity.  A second mutation is rare and involves an as-of-yet undiscovered pseudogene dubbed FAAH-OUT that affects FAAH expression (Habib et al, 2019).  (Don’t you just love a scientist’s warped sense of humour?  i.e. FAAH OUT, for ‘far out’??)

Due to these mutations, Jo’s body is constantly flooded with a natural cannabinoid called anandamide.

Jo may have inherited these 2 genetic mutations from her father.  In her words:

‘[He] had little requirement for painkillers’.

Jo found it enlightening that after 65 years, she finally found out why she reacted so differently to certain events than others might.

This was because she feels no pain!

Furthermore, Jo does not feel anxiety, stress, depression nor fear.  Jo has never had a panic attack during a dangerous or scary incident.

In Jo’s words,

I knew that I was happy-go-lucky, but it didn’t dawn on me that I was different … I didn’t know anything strange was going on until I was 65.”

There is a lot of truth to the saying:

‘What you don’t know, you don’t miss.’ 

In Jo’s case, she did not know pain.  Therefore, she did not ‘miss’ pain.

Jo had many injuries throughout her life including cuts, burns, broken bones and numerous surgeries, all without pain.  At times, she would accidentally iron herself.  At other times, she would smell her own burning flesh before noticing that anything was amiss.

The good news is that Jo’s wounds always healed very quickly with very little scarring.

Following complex double hand surgery, her doctor found out that Jo did not require painkillers.  Stunned, he checked her medical history only to learn that she had never requested painkillers.

Jo clarified:

‘If you don’t need [painkillers], you don’t question why you don’t … you are what you are … until someone points it out.’

Referring to a hip replacement surgery, Jo stated (quoting):

‘I didn’t know my hip was gone until it was really gone.  I physically couldn’t walk with my arthritis.’

‘I’d not had a twinge.’

Jo added:

‘It would be nice to have warning when something’s wrong.’

Two years ago, a young driver cut in front of her by mistake, causing Jo’s car to flip onto its roof in a ditch.  Instead of panicking, Jo calmly got out of her car and walked over to comfort the shaking driver.

Many years earlier, Jo found childbirth ‘quite enjoyable really’.  (OMG! Really???)

Jo enjoyed eating hot chili peppers, saying that they left her with a brief ‘pleasant glow’ in her mouth (Habib et al, 2019; Judd, 2019; Sample, 2019).

For more details, please see References that include a 2-minute video called:

Die Frau, die keine Schmerzen fühlt.  [The woman who feels no pain.]  Spiegel Online (29.03.2019).

http://www.spiegel.de/video/seltene-gen-mutation-jo-cameron-fuehlt-keinen-schmerz-video-99026124.html

Ashlyn Blocker

Whilst rare, Jo Cameron is not the only person who can not feel pain.  Amongst others who do not know pain is a teenage girl from Georgia, US, named Ashlyn Blocker.

Ashlyn was diagnosed with congenital insensitivity to pain with reduced ability to sweat.  Gene testing revealed that Ashlyn was born with 2 novel SCN9A (Nav1.7 sodium channel) mutations.

Given that this blog focuses on stories about people living with pain, and not on those who do not know pain, curious readers can find further details about Ashlyn Blocker (whose gene mutations block pain … pardon the pun) in the References below.

 

In closing, wouldn’t it be great if not feeling pain was an option for as long as desired?

Sabina Walker

Blogger, Pain Matters (in WordPress)

REFERENCES

Jo Cameron

Media

(1) Judd, Bridget. Scientists discover genetic mutation that helps block pain and improve healing. ABC News (28 March 2019).

https://www.abc.net.au/news/2019-03-28/scientists-discover-genetic-mutation-that-blocks-pain/10950380 

NB Above link only works if you ‘copy and paste’ manually.

(2) Sample, Ian. Scientists find genetic mutation that makes woman feel no pain. The Guardian (28 March 2019).

https://www.theguardian.com/science/2019/mar/28/scientists-find-genetic-mutation-that-makes-woman-feel-no-pain

Peer-Reviewed Paper

(3) Habib et al. Microdeletion in a FAAH pseudogene identified in a patient with high anandamide concentrations and pain insensitivity. BJA (2019).

doi.org/10.1016/j.bja.2019.02.019

https://bjanaesthesia.org/article/S0007-0912(19)30138-2/fulltext

Video (in German, Subtitled in English)

(4) Spiegel Online. Seltene Genmutation – Die Frau, die keine Schmerzen fühlt. [The Woman Who Feels No Pain.] Spiegel Online (29.03.2019).

http://www.spiegel.de/video/seltene-gen-mutation-jo-cameron-fuehlt-keinen-schmerz-video-99026124.html

Ashlyn Blocker

Media

(1) Agresz, Patrick. The Girl Who Has Never Felt Pain. Patrick’s Case Studies (31/10/2017).

https://patrickscasestudies.wordpress.com/2017/10/31/the-girl-who-lives-without-pain/

(2) Heckert et al. The Hazards of Growing Up Painlessly. The New York Times (15/11/2012).

(3) Associated Press. Rare disease makes girl unable to feel pain. NBC News (11/1/2004).

http://www.nbcnews.com/id/6379795/ns/health-childrens_health/t/rare-disease-makes-girl-unable-feel-pain/#.XKYH0S2B1Z1

Peer-Reviewed Paper

(4) Staud et al. Two Novel Mutations of SCN9A (Nav1.7) are Associated with Partial Congenital Insensitivity to Pain. Eur J Pain (2010);15(3):223–230.

doi:10.1016/j.ejpain.2010.07.003

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2978801/

 

 

Transplantation of One’s Own Knee Cartilage – Is this ‘The Bee’s Knees’ for Painful Knees?

Feature Image showing healthy cartilage being extracted for cultivation in a laboratory.

Source:  https://mobil.stern.de/gesundheit/medizin/knie–knorpel-im-knie-sind-so-kostbar-wie-kaum-ein-anderes-gewebe-7645258.html

Another ‘bone-on-bone’ knee-related post is here:

https://painmatters.wordpress.com/2019/04/14/should-unloader-knee-braces-be-prescribed-for-osteoarthritis-knee-pain-before-total-knee-replacement

OVERVIEW

Dear Pain Matters readers,

There is a lot of truth in the saying, ‘You don’t know what you have until it’s gone.’

We often take our health for granted.  This includes the health of our articular cartilage, a layer of hyaline cartilage that covers the surface of our bones where they connect.

One day out of the blue, a person may suddenly feel pain and swelling in a knee joint.  Diagnostic tests may confirm damaged cartilage tissue in an otherwise normal knee joint.

Who would have thought that something as benign and nondescript as knee cartilage could cause so much pain and agony following its damage?

Healthy versus Defective Cartilage

Healthy articular knee cartilage helps to reduce shock and friction during movement at the synovial joints in the knees, ankles, hips, elbows and shoulders.  Knee cartilage is avascular (no blood vessels), aneural (no nerves) and alymphatic (no lymphatic vessels).  

Primarily consisting of cartilage cells (chondrocytes****) and an extracellular matrix, cartilage tissue comprises up to 80% water and proteins.  Chondrocytes exchange nutrients and waste via cellular diffusion.

While cartilage may be up to 6 mm thick in active people, its volume may be reduced as much as 25% in adults who led a sedentary life during childhood (Schneider, 2017).

When cartilage is injured, raw or simply worn down, ‘bone-on-bone’ knee pain may result during movement.  This may become severely arthritic if untreated resulting in the risk of total knee replacement.

Due its avascular and aneural nature, many believe that articular cartilage is unable to regenerate once injured or diseased (Huey et al, 2012).

Others say that while articular cartilage may regenerate in vivo, this can only occur in an anti-inflammatory, chondrocyte-friendly environment (Lyu et al, 2011; Tiku & Sabaawy, 2015) (more in an upcoming blog post).

Autologous osteochondral transfer may be an option if less than 2 cm² cartilage is damaged in an otherwise healthy knee joint (details to follow).

Cultivation of autologous cartilage cells ex vivo may promote regeneration and transplantation.  Requiring 2 minimally-invasive operations, this procedure is performed ~4,500 times annually in Germany (discussed below).

Articular cartilage paste grafting may also be an option for some patients (details below).

TREATMENT OPTIONS

OVERVIEW

Autologous osteochondral transfer or autologous cartilage transplantation may benefit patients whose cartilage defects are less than 2cm² or 10cm², respectively.

Furthermore, the defect area must be completely surrounded by healthy cartilage tissue. This is because autologous chondrocytes will only bind with, and grow into, intact and healthy cartilage tissue – not diseased, inflamed and broken cartilage tissue – post-transplantation.  As such, chondrocytes will not survive if transplanted into an arthritic knee joint.

Another procedure called an articular cartilage stem cell paste graft (aka paste graft) involves the use of a patient’s own bone marrow-derived stem cells and cartilage to repair both acute and chronic (arthritic) defects in the knee joint.  Furthermore, the paste graft is an integral part of the ‘BioKnee’ (more below).

Finally, if most or all of the cartilage tissue is injured, worn out or affected by arthritis, partial or total knee replacement (arthroplasty) may be the only remaining option.

DETAILS

Autologous Osteochondral Transfer

If less than 2 cm² cartilage is damaged, autologous osteochondral transfer may be done via minimally-invasive surgery.

Specifically, autologous cartilage-bone (osteochondral) cylinders are extracted from a non-weight-bearing part of the knee joint and transferred into the defective area.

See patient story by Elke Greis for details.

Autologous Cartilage Transplantation*

Thanks to regenerative medicine and cartilage tissue engineering, autologous cartilage cells can now be cultivated ex vivo in a laboratory.

First, small samples of healthy cartilage and underlying bone are taken from a non-weight-bearing part of the knee joint.  These samples are forwarded to a laboratory for isolation, incubation, manipulation and propagation into newly cultivated chondrocytes.

NB Chondrocytes reside in, and are isolated and cultivated from, cartilage.

After 3 to 6 weeks, cultivated cartilage cells are harvested and forwarded to the patient’s doctor.

A 2nd minimally-invasive surgery involves the transplantation of newly cultivated autologous chondrocytes into the defect site.

All the defective cartilage must first be removed prior to transplantation.  This may be done during the 1st or 2nd surgery, depending on the doctor’s preference.

See below for highlights of a study by Peterson et al as well as 2 patient stories.

Articular Cartilage Stem Cell Paste Graft 

Developed by Kevin R. Stone, MD, at The Stone Clinic in San Francisco, a procedure called an articular cartilage stem cell paste graft (paste graft) involves the use of a patient’s own:

  • Cartilage; and
  • Bone marrow (that includes stem cells, in particular, mesenchymal stem cells (MSC’s), being the progenitor of chondrocytes)

to repair traumatic and/or arthritic defects in the knee joint.

The aforementioned ‘basic ingredients’ (i.e. cartilage and its underlying bone) are removed from a non-weight-bearing part of the knee called the intercondylar notch$.

The extracted tissue samples are ground into a paste via a ‘bone graft smasher’ and subsequently pressed deep into the defect area (i.e. the base of the prepared lesion).

Pain relief, reduced swelling and improved function may result in the knee following a successful paste graft that stimulates the regeneration of articular cartilage inside a joint.

Due to paste graft requiring single step outpatient surgery only, it may be more cost effective than autologous cartilage transplantation that requires cell cultivation in a laboratory.    

In support of the paste grafting treatment, Chinese researchers reported that new cartilage grown via paste grafting resembled normal cartilage more than microfracture-induced new cartilage.  This likely occurred because stem cells were also included in the paste graft, together with extracellular matrix and chondrocytes (Xing et al., 2013).

Additional details are available in the following 6-minute and 1-minute YouTube videos by Dr Stone called Articular Cartilage Paste Graft Surgical Technique and Biologic Joint Replacement: Cartilage Paste Grafting, respectively:

 

More details are available here:

https://www.stoneclinic.com/search/node?keys=articular+cartilage+paste+grafting

See below for an overview of a study by Stone et al, an animal study and the ‘BioKnee’. 

Partial or Total Knee Replacement (Arthroplasty)

If one of the first 2 options are available, it may be possible to defer partial or total knee replacement for many years.

On the other hand, if cartilage damage due to trauma, injury, knee surgery or disease is excessive, partial or total knee replacement (arthroplasty) may be the only available options.

AUTOLOGOUS CARTILAGE (CHONDROCYTE) TRANSPLANTATION

A STUDY BY PETERSON AND COLLEAGUES

A study reviewed 94 patients who underwent autologous cultured chondrocyte transplantation of the knee 2 to 9 years earlier.  This treatment was offered for patients with large (1.5cm² to 12cm²) full thickness, large cartilage defects in the knee.

Good to excellent results were observed in:

  • 92% of patients with isolated femoral condyle defects;
  • 67% of patients with multiple lesions in the cartilage;
  • 89% of patients with osteochondritis dissecans;
  • 65% of patella patients; and
  • 75% of patients with femoral condyle defects and anterior cruciate ligament repair (Peterson et al, 2000). 

TWO PATIENT STORIES

Autologous chondrocyte transplantation may be a promising intervention for the repair of cartilage defects in an otherwise healthy knee joint.  Two patient stories are described below:

PATIENT 1 – TANJA DICHT

Overview

Tanja Dicht (48), a senior carer in Hamburg, Germany, was plagued with left knee pain for years.  Despite a meniscus operation in 2012, her knee pain persisted.

Magnetic resonance imaging in May 2017 revealed 4th grade cartilage damage on the upper joint surface of her medial (inner) left knee.  Specifically, 10 square cm of cartilage was destroyed right to the bone.

knie-4.jpg

Tanja Dicht, Left Knee Patient

Source:  https://mobil.stern.de/gesundheit/medizin/knie–knorpel-im-knie-sind-so-kostbar-wie-kaum-ein-anderes-gewebe-7645258.html

Dr Matthias Buhs, Orthopaedic Surgeon near Hamburg, suggested that Tanja’s damaged knee cartilage be restored via a 2-step process involving knee cartilage autotransplantation.

knie-2.jpg

Tanja’s Orthopaedic Surgeon, Dr Matthias Buhs

Tanja’s Autologous Knee Cartilage Transplantation and Repair

In July 2017, Tanja underwent minimally-invasive keyhole surgery called arthroscopy.  This involved a small incision on each side of her kneecap.

Two small samples of healthy cartilage no bigger than grains of rice and some underlying bone were removed from the upper, non-weight-bearing parts of Tanja’s knee joint (i.e. from her distal femur).

Nicknamed white gold, these cartilage samples plus 200ml blood were sent to a laboratory in Berlin called CO.DON.**  This laboratory specialises in the cultivation of hyaline articular cartilage cells.

After isolation in the laboratory, Tanja’s cartilage cells were placed via pipette into a bottle that contains a cell culture.  Tanja’s bottle was then placed inside an incubator at an ambient temperature of 37°C.

There are 84 incubators in total, enabling bottles for up to 84 patients to be incubated.

Andreas Eberle of CO.DON simplified the cell incubation process as follows (translated):

‘Just imagine an oven … First, you open the door.  You place the bottles inside.  Then you close the door.’ 

During incubation, Tanja’s cartilage cells were soaked with her own donated blood serum every 2 days.

Once the bottom of the bottle was covered with newly cultivated cells, they were harvested and transferred onto microplates that contain 96 small ‘wells’ or depressions.***

A ball comprising ~200,000 chondrocytes will grow inside each well after 5 to 8 weeks of incubation.  These balls are sometimes called chondrospheres, chondrocyte spheroids and/or spherical aggregates of chondrocytes (or ‘Spherox’).

Following maturation, Tanja’s microplate including 96 chondrospheres was sent to Dr Matthias Buhs for transplantation.

 

knie-3.jpg

A monitor displaying a ball of cartilage cells (chondrosphere), post-transplantation

Source:  https://mobil.stern.de/gesundheit/medizin/knie–knorpel-im-knie-sind-so-kostbar-wie-kaum-ein-anderes-gewebe-7645258.html

Exactly 58 days after removal of healthy cartilage samples, Tanja returned for her second minimally-invasive surgery involving autologous cartilage (chondrosphere) transplantation.

First, Tanja’s defective cartilage had to be cleaned to the bone to make way for the newly cultivated chondrospheres.

Thereafter, each ball of chondrocytes was gently transplanted into the gap.  Care was taken to ensure that ‘chondrosphere overcrowding’ did not occur.

Dr Buhs watched the repaired tissue area for 20 minutes to ensure that the transplanted cell balls grew into the gap.

After the chondrospheres ‘rose like yeast dumplings’, Dr Buhs closed the incisions in Tanja’s left knee.

Thereafter, Tanja remained in bed for 3 days to enable the new chondrospheres to integrate into the native cartilage.

Summary

While non-weight-bearing gentle movements were allowed, Tanja had to avoid bearing weight on her left knee for 6 weeks.

After 6 weeks, Tanja was allowed to bear normal weight on her left knee for 6 months.  Thereafter, she was able to go on walks and pursue light activities.

In Dr Buhs’ opinion, there was a 90% to 95% chance that Tanja’s left knee would be fully healed after 9 to 12 months.

On 27 March 2019, Dr Matthias Buhs confirmed that Tanja’s left knee was 100% pain free and functional.

For more details, see:

Transplantation von Knorpelgewebe – Weißes Gold: Warum Knorpel im Knie so kostbar sind. [Translated: Cartilage Tissue Transplantation – White Gold: Why knee cartilage is so precious.] (in German).

http://mobil.stern.de/gesundheit/medizin/knie–knorpel-im-knie-sind-so-kostbar-wie-kaum-ein-anderes-gewebe-7645258.html

PATIENT 2 – STEPHANIE OSTERLOH

Overview

As an operations nurse, Stephanie is constantly on her feet.  However, her knee was painful and swollen with limited mobility.

Stephanie first started having knee problems when she was 15 after playing handball almost daily.

Prof Dr Karl-Dieter Heller, Orthopaedic Surgeon in Braunschweig, confirmed that her cartilage was damaged and that there was too much friction.

Given the size of Stephanie’s defective cartilage site, Dr Heller recommended that she undergo autologous cartilage transplantation.

Stephanie’s Autologous Cartilage Transplantation and Repair

The first step involved removal of the damaged cartilage pieces, being the source of her knee pain.  The underlying bone remained untouched.

The next step involved the extraction of a small piece of healthy cartilage and its underlying bone.  This sample was sent to a laboratory for the cultivation of new cartilage cells.

The tissue sample was cut into little pieces and placed into a nutrient solution by laboratory technicians.  New cartilage cells grew onto a specialised chondrocyte matrix within 3 to 6 weeks.

The cultivated cartilage cells were sent to Dr Heller who then transplanted them into Stephanie’s defective cartilage site.  Once the defective site was filled, the newly cultivated cartilage cells grew into its surroundings.

Summary

According to Dr Heller (quoting; translated):

‘This treatment can only work:

  • If the defect is not too large; and 
  • If the surrounding cartilage is completely healthy. 

Otherwise it makes no sense.’

Good news!  Stephanie’s treatment was a success!  Her knee feels good and she can finally return to work without restriction.

After one year, Stephanie’s transplanted cartilage cells will (likely) offer the same weight-bearing capacity as her original cartilage.

For more details, see:

Walker, Niels. Knorpel defekt: Wann hilft Transplantation? [Translated: Cartilage defect: When does transplantation help?] NDR.de (10.12.2018) (in German).

https://www.ndr.de/ratgeber/gesundheit/Transplantation-bei-Knorpelschaden-im-Knie,knorpel104.html

(Includes links to two 5-minute YouTube videos, both in German)

AUTOLOGOUS OSTEOCHONDRAL TRANSFER

ELKE GREIS  

Elke Greis, an artist, suffered limited mobility due to knee pain including stabbing pain.

Given that Elke injured her knee during an accident when she was 16, she was worried that 41 years later, she would need a total knee replacement.

Prof Dr Jürgen Bruns of Hamburg put Elke’s mind at ease by saying that her knee pain was due to damaged cartilage.  Part of her bone was completely devoid of cartilage while another part resembled a ‘frayed, well-worn floor mat’ [translated].  Furthermore, Elke’s cartilage was damaged in a weight-bearing area.  If left untreated, this could lead to arthritis.

Dr Bruns recommended that her damaged cartilage be repaired via autologous osteochondral transfer.

Lasting around 3 hours, the operation replaced Elke’s damaged cartilage with autologous (i.e. her own) healthy osteochondral tissue.

The 1st step involved removing all of Elke’s damaged cartilage.

Thereafter, a slightly larger cylindrical piece of cartilage and its underlying bone was taken from a healthy, non-weight-bearing part of Elke’s knee.  The resulting hole was filled with artificial tissue while the healthy piece was seamlessly pressed into place in the defective area.

According to Dr Bruns, one cannot build a door without a door frame.  In other words, one cannot transfer healthy cartilage without its underlying bone.

For optimal results, the following criteria must be met:

  • There must be adequate healthy cartilage available; and
  • This cartilage must match the characteristics and form of the intact cartilage near the defect area.

This is difficult to do in a joint with many curves, as in a knee.

In one year, Elke’s transferred cartilage had settled in nicely inside the defective site.  Elke was now able to concentrate on her art for 1 or 2 hours at a time.  Thereafter, Elke was able to walk effortlessly down the stairs.  She was no longer limited by knee pain.

 

For more details, see:

Walker, Niels. Knorpel defekt: Wann hilft Transplantation? [Translated: Cartilage defect: When does transplantation help?] NDR.de (10.12.2018) (in German).

https://www.ndr.de/ratgeber/gesundheit/Transplantation-bei-Knorpelschaden-im-Knie,knorpel104.html

(Includes links to two 5-minute YouTube videos, both in German)

ARTICULAR CARTILAGE STEM CELL PASTE GRAFT AND THE ‘BIOKNEE’ (DEVELOPED BY DR STONE)

A 2- TO 12-YEAR FOLLOW-UP OF PASTE GRAFTING TO DEFECTIVE KNEE CARTILAGE

Dr Stone and his team followed up 125 knee patients(136 procedures; 34% female, 66% male; aged between 17 to 73) who were treated with an articular cartilage paste graft for Outerbridge grade IV arthritic chondral defects+.  The authors reported that 85% of 125 knee patients enjoyed 1 grade of improvement or better following paste graft treatment.

Positive results were also observed in regenerated cartilage biopsies done via second-look arthroscopy in 66 patients.  Specifically, the articular surfaces had regenerated in 42 of 66 (63.6%) biopsies.  Furthermore, there was development of cartilage in 18 of 66 (27.3%) biopsies.

The authors concluded that paste grafting via minimally-invasive surgery may be a cost-effective arthroscopic treatment for patients with chronic Outerbridge classification grade IV chondral lesions.

Thus, patients with painful chondral defects in arthritic and/or traumatically-injured knees may benefit from paste graft treatment that may offer lasting pain relief, restored function and potential cartilage tissue regeneration (Stone et al, 2006).

THE ‘BIOKNEE’ (DEVELOPED BY DR STONE)

The paste graft technique is the cornerstone of Dr Stone’s ‘BioKnee’ (a possible alternative to total knee replacement).

Specifically, the ‘BioKnee’ was developed by Dr Stone for patients who have an arthritic knee that no longer has load-bearing cartilage in the knee joint nor meniscus@ tissue.

The ‘BioKnee’ involves:

  • An articular cartilage paste graft; plus
  • meniscus transplantation (based on donor meniscus tissue).

More details about the ‘Bioknee’ are available here:

https://www.stoneclinic.com/bioknee

https://www.stoneclinic.com/video/Biologic-Knee-Replacement-Program-Meniscus-Transplant-and-Articular-Cartilage-Paste-Grafting

 

OTHER INTERESTING POINTS

AUTOLOGOUS CARTILAGE SOURCED ELSEWHERE  

Sometimes cartilage tissue is harvested for cultivation from other autologous sources such as the nose or a rib.  A Swiss study involving 20 patients obtained autologous cartilage tissue from the nose.  The nasal chondrocytes were isolated, cultivated and subsequently transplanted to repair defective knee cartilage in an otherwise healthy knee joint (Caluori, University of Basel).  Prof. Dr Karl-Heinz Frosch once sourced cartilage from a patient’s rib to repair defective cartilage in the same patient’s knee joint.

MESENCHYMAL STEM CELLS (MSC’s)

The progenitor of chondrocytes, being MSC’s, originate and reside in peri-articular bone marrow and subchondral bone.  Mesenchymal stem cells are also present in cartilage, synovium, synovial fluid, infrapatellar/sub-synovial fat pad and adipose tissue (Mastbergen, 2013; McGonagle et al, 2017).

 

Recent research shows that stable cartilage tissue may also be generated from adult MSC’s following manipulation (Occhetta et al, 2018; University of Basel, 2018; University of Basel, 2018, in German).  

 

A question: 

Could adult MSC’s be a source of cultivated chondrocytes (in addition to, or instead of, healthy cartilage)?

SUMMARY

Tanja, Stephanie and Elke had positive experiences following autologous chondrocyte transplantation or autologous osteochondral transfer.  These minimally-invasive options were possible because their damaged cartilage tissues were small.  Therefore, their cartilage defects were repaired before severe arthritis set in.

Furthermore, 85% of 125 knee patients enjoyed 1 grade of improvement or better following articular cartilage stem cell paste graft treatment by Dr Stone at The Stone Clinic in San Francisco.

Finally, using autologous (i.e. one’s own) cartilage tissue ensures nil risk of rejection by the immune system.

 

I hope that these patient stories offer hope to people with knee pain due to defective cartilage in an otherwise healthy knee joint. 

Sabina Walker

Blogger, Pain Matters (in WordPress)

Please forward to anyone who may benefit from this information.

KEY

* Autologous cartilage cell transplantation (aka Autologous chondrocyte transplantation) = Where the patient uses his/her own knee cartilage for propagation ex vivo and transplantation.

NB Cartilage cells are also called chondrocytes.

** CO.DON specialises in the cultivation  of autologous cartilage cells for minimally-invasive repair of defects in knee cartilage tissue.

 

http://www.codon.de/home.html?L=1

Other tissue engineering companies including Tetec also offer this service.

https://www.tetec-ag.com/en.html

*** Microplates, also called microtiter plates, are flat plates with many small ‘wells’ (depressions, or hollows).

 

**** Chondrocytes are the cartilage-producing cells in the body (more simply, cartilage cells).

# Microfracture surgery involves making small holes in the bone(s) of a knee joint to create bleeding and release marrow cells into defective cartilage.  This may induce a healing response and the growth of new cartilage.  

@ The meniscus is C-shaped cartilage tissue that acts as a shock absorber between the shin bone (tibia) and thigh bone (femur).

$ The intercondylar notch of femur is a depression between the posterior surfaces of the medial and lateral epicondyle of the thigh bone at the knee joint.

+ Outerbridge grade IV chondral defects are cartilage lesions (or erosions) right to the underlying subchondral bone.

REFERENCES

Media

(1) Buhs, Matthias. Cartilage Center of Northern Germany

https://www.cartilagecenter.de/dr-matthias-buhs/

(2A) NICE. Autologous chondrocyte implantation using chondrosphere for treating symptomatic articular cartilage defects of the knee. NICE (7 March 2018).

https://www.nice.org.uk/guidance/TA508/chapter/1-Recommendations

(2B) Spherox – Spheroids of human autologous matrix-associated chondrocytes. European Medicines Agency
https://www.ema.europa.eu/en/medicines/human/EPAR/spherox

(3A) Washington University Orthopedics. Autologous Chondrocyte Implantation (ACI). Washington University.

https://www.ortho.wustl.edu/content/Patient-Care/2888/Services/Sports-Medicine/Overview/Knee/Autologous-Chondrocyte-Implantation.aspx

(3B) Keeffe, Patrick. Knee Surgeries Could Soon Be More Successful Thanks to New Technique. Healthline (14 October 2018).

https://www.healthline.com/health-news/new-technique-can-help-people-under-55-who-are-having-knee-surgery#Success-elsewhere

(4A) Caluori, Reto. From nose to knee. University of Basel.

 

(5A) Stone, KR. Study proves stem cell paste graft therapy critical to rebuilding cartilage. The Stone Clinic.

https://www.stoneclinic.com/stem-cell-cartilage-study

(Above link includes 2 short videos called Articular Cartilage Paste Graft and Articular Cartilage Paste Graft Surgical Technique.)

(5B) Stone, KR. Why Microfracture Fails. The Stone Clinic (7 Feb 2015).

https://www.stoneclinic.com/blog/why-microfracture-fails

Media (in German)

(1) Schneider, Mathias. Transplantation von Knorpelgewebe – Weißes Gold: Warum Knorpel im Knie so kostbar sind. [Translated: Cartilage Tissue Transplantation – White Gold: Why knee cartilage is so precious.] Der Stern (7 October 2017); 80-84.

http://mobil.stern.de/gesundheit/medizin/knie–knorpel-im-knie-sind-so-kostbar-wie-kaum-ein-anderes-gewebe-7645258.html

(2) Walker, Niels. Knorpel defekt: Wann hilft Transplantation? [Translated: Cartilage defect: When does transplantation help?] NDR.de (10.12.2018) (in German).

https://www.ndr.de/ratgeber/gesundheit/Transplantation-bei-Knorpelschaden-im-Knie,knorpel104.html

(Includes links to two 5-minute YouTube videos, both in German)

(3) University of Basel. Züchtung von Knorpel aus Stammzellen gelungen. aerzteblatt.de (18/4/18).

https://www.aerzteblatt.de/nachrichten/93534/Zuechtung-von-Knorpel-aus-Stammzellen-gelungen

Peer-Reviewed Papers

(1) Piñeiro-Ramil et al. Cell Therapy and Tissue Engineering for Cartilage Repair. IntechOpen (20 Dec 2017).

doi: 10.5772/intechopen.70406

https://www.intechopen.com/books/cartilage-repair-and-regeneration/cell-therapy-and-tissue-engineering-for-cartilage-repair

(2A) Occhetta, Paola et al. Developmentally inspired programming of adult human mesenchymal stromal cells toward stable chondrogenesis. 

(2B) University of Basel. Cultivating cartilage from stem cells. Science Daily (16 April 2018).

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