Next-Generation Regenerative Orthopedics
By bringing the comprehensive, cellular medicine approach we employ in our other service offerings to the typically slow-to-change field of orthopedics, we offer regenerative orthopedic consults and procedures aimed at helping you heal and strengthen in the long term (not just alleviating immediate pain).
BLI’s Regenerative Orthopedic Services
PLATELET RICH PLASMA (PRP) / PLATELET RICH FIBRIN MATRIX (PRFM)
PRP/PRFM are injections of a concentration of a patient’s own platelets to assist with the healing of injured tendons, ligaments, muscles, and joints.
AOD 9604 + HA
AOD9604 is a GH fragment which comprises the last 16 amino acids of the larger growth hormone molecule.
Alpha-2-Macroglobulin, more commonly referred to as A2M, is a master protease inhibitor that already exists in your blood and acts as a powerful inhibitor of cartilage breakdown.
Australian researcher and physician, Dr. Peter Ghosh from the University of Sydney has brought an old drug back into the light for arthritis sufferers.
Platelet Rich Plasma (PRP) / Platelet Rich Fibrin Matrix (PRFM)
PRP/PRFM are injections of a concentration of a patient’s own platelets to assist with the healing of injured tendons, ligaments, muscles, and joints. PRP/PRFM injections are prepared by taking anywhere from one to a few tubes of your own blood and running it through a centrifuge to concentrate the platelets. These activated platelets are then injected directly into your injured or diseased body tissue. This releases growth factors that stimulate and increase the number of reparative cells your body produces.
Owing to the high concentrations of growth factors, this product has been extensively used in musculoskeletal disorders to modulate progression of the inflammatory process and promote healing.
Osteoarthritis is a main cause of musculoskeletal disabilities – Platelet-rich plasma could offer a more practical and accessible option of biological therapy for osteoarthritis compared to other biological therapies. Furthermore, PRFM has been shown to be even more efficacious than PRP for joint repair.
AOD 9604 + HA
AOD9604 is a GH fragment which comprises the last 16 amino acids of the larger growth hormone molecule. Although originally studied for fat loss, further studies have transitioned its application for regenerative medicine. In combination with hyaluronic acid (HA), it is now being used to help regenerate hyaline cartilage and is showing strong efficacy in the treatment of osteoarthritis.
The combination acts to enhance the differentiation of adipose mesenchymal cells into bone, promote proteoglycan and collagen production in chondrocytes, and promote differentiation of myoblasts into C2C12 cells; all of which are essential for bone, cartilage, and muscle repair. These studies indicate that it has stronger therapeutic benefits compared to Bone Marrow Aspirate Concentrate (BMAC) and Platelet Rich Plasma (PRP) therapy, which have also been emerging as candidates for osteoarthritis medications. AOD9604 + HA has proceeded to human WOMAC trials which allow the combination to be investigated for on an osteoarthritis index which considers pain, stiffness, and functionality on a variety of scores.
Summer 2015;45(4):426-32 Effect of Intra-articular Injection of AOD9604 with or without Hyaluronic Acid in Rabbit Osteoarthritis Model Dong Rak Kwon, Gi Young Park
Alpha-2-Macroglobulin, more commonly referred to as A2M, is a master protease inhibitor that already exists in your blood and acts as a powerful inhibitor of cartilage breakdown. It is our body’s own defense mechanism. This special molecule works by binding to proteases that degrade the cartilage cells and tissue. However, it is too big and complex to enter the joint or disc space in large enough quantities. As a result, it is necessary to inject additional concentrated A2M into the affected area to restore balance and relieve pain. A patented and proprietary filtration process has been developed that can concentrate the naturally occurring A2M molecule from a patient’s own blood. This process allows therapeutic injections in concentrated dosages that:
- Boost natural healing by reducing the additional deterioration of cartilage and inflammation
- Support tissue growth with naturally occurring compounds from your own blood
Australian researcher and physician, Dr. Peter Ghosh from the University of Sydney has brought an old drug back into the light for arthritis sufferers. The drug is called pentosan polysulfate sodium (known in medical circles as PPS). To date, trials of the drug involving human patients have been proven highly successful. As PPS eliminates pain associated with arthritic disease by acting on bone marrow lesions that cause pain and cartilage degeneration. By controlling these lesions there is a reduction in symptoms and pain.
PPS is a very safe drug and has been successfully used for 70 years to treat urinary infections in women and is FDA-approved and used for the treatment of interstitial cystitis (or painful bladder syndrome) and deep vein thrombosis. The drug is neither an anabolic steroid nor an opioid-based pain reliever so is not considered to enhance performance.
How does Pentosan work?
In osteoarthritis, pentosan reduces the destruction of cartilage by affecting inflammatory mediators. It also increases the number of proteoglycans into the outer cell matrix. Proteoglycans are important because they allow tissues like collagen to withstand compression and swelling forces. Joint cartilage also contains Proteoglycans.
In the synovium, the part that surrounds the inner lining of your joint, pentosan increases both the production and the molecular weight of hyaluronan. Hyaluran or Hyaluronic acid is a compound that occurs naturally in your body, and it is responsible for attracting and retaining moisture. Pentosan also has another anti-inflammatory function due to its fibrinolytic activity. This activity improves the blood flow not only in the synovium but also in the subchondral bone.
Recently, Paradigm Pharmaceuticals, an Australian biotech company doing studies on Pentosan had reported greater than 50% reduction in chronic knee pain by a group of osteoarthritis patients being treated with its injectable Pentosan Polysulfate Sodium drug. Researchers hope that it may work as well in relieving pain in other parts of the body.
Paradigm Biopharmaceuticals also concluded a phase 2A clinical trials of Pentosan Polysulfate to treat viral arthritis caused by mosquito-borne alphavirus infections, including the debilitating Ross River virus (RRV) and chikungunya virus (CHIKV). The clinical trials passed both safety and efficacy measures amongst participants with chronic RRV-induced arthralgia who were treated with the injectable pentosan polysulfate sodium (PPS). At their three-month follow-up, 72.7% of the study participants treated with PPS showed near remission of symptoms in contrast to those participants who were administered with a placebo (14.3%).
Benefits of Pentosan
- Treats bone marrow edema lesions (BMLs)
- Limiting cartilage deterioration;
- Promoting new cartilage formation;
- Thickening the joint fluid – thus acting as a better lubricant;
- Improving blood supply to the joint, in turn helping it heal;
- By virtue of these actions, it provides pain relief for a much longer period of time
- Treats all joints of the body at the same time
- Inhibits in vitro replication of HIV and other enveloped viruses
Kenji Kumagai, Susumu Shirabe, Noriaki Miyata, Masakazu Murata, Atsushi Yamauchi, Yasuhumi Kataoka and Masami Niwa. Sodium pentosan polysulfate resulted in cartilage improvement in knee osteoarthritis – An open clinical trial. BMC Clin Pharmacol. 2010; 10:7. Published online 2010 Mar 28. doi: 10.1186/1472-6904-10-7. PMCID: PMC2873929. PMID: 20346179
Ghosh P, Edelman J, March L, Smith M. Effects of pentosan polysulfate in osteoarthritis of the knee: A randomized, double-blind, placebo-controlled pilot study. Current Therapeutic Research. 2005;66:552–571. doi: 10.1016/j.curtheres.2005.12.012.
Ghosh P. The pathobiology of osteoarthritis and the rationale for the use of pentosan polysulfate for its treatment. Semin Arthritis Rheum. 1999 Feb;28(4):211-67.
Takizawa M, Yatabe T, Okada A, Chijiwa M, Mochizuki S, Ghosh P, Okada Y. Calcium pentosan polysulphate directly inhibits enzymatic activity of ADAMTS4 (aggrecanase-1) in osteoarthritic chondrocytes. FEBS Letters. 2008;582:2945–2949. doi: 10.1016/j.febslet.2008.07.036.
Troeberg L, Fushimi K, Khokha R, Emonard H, Ghosh P, Nagase H. Calcium pentosan polysulfate is a multifaceted exosite inhibitor of aggrecanases. FASEB J. 2008;22:3515–3524. doi: 10.1096/fj.08-112680.
Munteanu SE1, Ilic MZ, Handley CJ. Calcium pentosan polysulfate inhibits the catabolism of aggrecan in articular cartilage explant cultures. Arthritis Rheum. 2000 Oct;43(10):2211-8.
Guangyong Ma, Jun-ichirou Yasunaga, Koichi Ohshima, Tadashi Matsumoto, Masao Matsuoka. Pentosan Polysulfate Demonstrates Anti-human T-Cell Leukemia Virus Type 1 Activities In Vitro and In Vivo. Journal of Virology Jul 2019, 93 (16) e00413-19; DOI: 10.1128/JVI.00413-19
Lara J. Herrero, Suan-Sin Foo, Kuo-Ching Sheng, Weiqiang Chen, Mark R. Forwood, RichardBucala, Suresh Mahalingam. Pentosan Polysulfate: a Novel Glycosaminoglycan-Like Molecule for Effective Treatment of Alphavirus-Induced Cartilage Destruction and Inflammatory Disease. Journal of Virology Jul 2015, 89 (15) 8063-8076; DOI: 10.1128/JVI.00224-15
Orthopedic Planning Consult
During this 30 minute appointment, you can discuss your challenges, concerns, and questions with the provider and gain guidance and recommendations on next steps or alternate approaches.
Only available to first time orthopedic clients
Orthopedic Imaging Review
30 minute appointment to review imaging related to your orthopedic issue or concern and get expert feedback and advice.
Only available to new clients or as follow-up to Planning Consult
Orthopedic General Consult
Opportunity to continue receiving expert guidance and care regarding your orthopedic concerns.
For returning clients/ongoing follow-ups
"Is regenerative medicine legitimate?"
The progression of modern medicine has created a bit of skepticism in things that sound new or futuristic. This skepticism leads many to wonder if regenerative medicine is even legitimate.
As functional medicine, which professed a “root cause” mentality, intertwined with holistic, naturopathic, and alternative medicines, a hesitancy developed about what seemed like a confused approach to looking at the issues with the systems causing symptoms.
Specializing in what it calls, “better medicine,” the Boulder Longevity Institute aims to eliminate the confusion by focusing on cutting edge, science-backed treatment options in a clinical environment.
A secondary challenge with regenerative medicine, making it seem less accessible, is the more detailed science and data driven nature of the field. While the data is proving invaluable as we get better at Cellular Medicine (the approach to healthcare that involves looking at the cellular pathways and behaviors that cross over multiple systems), it can feel overwhelming if not approached from a human first perspective.
The Boulder Longevity Institute aims to offer clients a legitimate, guidance based practice that leverages the most advanced knowledge while balancing the needs of each individual. By offering clients the latest science and research applied in a clinical setting, BLI weaves regenerative, cellular, and functional medicine into a comprehensive approach to optimizing health.
"How does pentosan work?"
Pentosan, also known as sodium pentosan polysulfate (PPS) has been used in humans for over six decades. Pentosan works as an anti-inflammatory and inhibits cartilage enzymatic breakdown.
Hitting the market as Elmiron, pentosan has been used as a treatment for the inflammatory ailment of the bladder called interstitial cystitis.
More recently, pentosan is being injected into patients suffering from knee osteoarthritis (OA) and the symptoms from the common lesions associated with OA. These patients are seeing pain relief and in some cases, cartilage regeneration.
Pentosan is not administered into the joint space, like most common treatments for knee OA. This has led researchers to investigate how Pentosan might shine light on osteoarthritis being a disease caused by systemic issues, versus the common approach believing OA is strictly related to knee trauma or wear and tear.
While Pentosan is showing great promise as a game changer in cartilage loss associated with OA, it is considered “off-label” for the purposes of osteoarthritis treatment. However, the United States FDA has fast-tracked the use of PPS (under the brand name Zilosul) for OA.
Clinical trials are ongoing but the chances of Pentosan becoming a treatment for OA look promising.
"What Is a Platelet-Rich Plasma (PRP) Injection?"
Platelet-rich plasma (PRP) is the liquid portion of blood (plasma) and platelets (a type of blood cell that helps with healing). A PRP injection is simply blood with more platelets than usual injected into the body. Platelet-rich Fibrin Matrix (PRFM) is similar to PRP, but often thought of as the next generation of PRP treatments. Similar to PRP treatments, PRFM uses injections of a concentration of a patient’s own platelets to assist with the healing of injured tendons, ligaments, muscles, and joints.
Most of us have heard of platelets because of their role in blood clotting. There is a therapeutic role for platelets to play, as well. Platelets contain growth factors that have various benefits including angiogenesis, encourage regeneration, and stimulate healing in an area of injury.
A PRP injection is actually a reinjection of your own blood! A sample is drawn and spun in a device called a centrifuge. The spinning causes the platelets to separate from the other components in the blood sample, gathering in the plasma.
Now that the PRP has been created, it can be loaded as an injection to be used therapeutically. Ideally, the injection is placed as closely to the injury site as possible. Many providers use ultrasound guidance to ensure the injection goes exactly where they determine it would be most useful.
Research shows that the buildup of growth factors found in the PRP could stimulate and expedite healing, leading to a faster recovery time overall. Furthermore, PRFM has been shown to be even more efficacious than PRP for joint repair.
“How long do PRP injections last?”
The length of the impact of a PRP injection is a little subjective but depending on the injury, there could be six to nine months of effect.
It is important to note that a PRP injection can provide pain relief but will ideally be combined with other therapies that will aid in recovery from the injury or chronic problem.
“Do PRP injections hurt?”
Many people say a PRP injection is about as painful as any other injection. Of course, every individual tolerates pain differently.
There is also some notable difference in pain level based on the location and extent of the injection. This is based on the site of the injury or chronic ailment.
“What is the success rate of PRP injections?”
There is no consensus on a firm success rate of PRP injections. Studies have shown a reduction in pain in a large portion of participants.
PRP injections are not typically considered a stand-alone treatment for pain. Ideally, PRP is used to improve your ability to heal while addressing rehabilitation from injury or inflammation causing chronic problems.
“How long does it take for PRP to start working?”
The PRP injection begins working immediately by concentrating platelets in the area of an injury or chronic damage. This allows the healing process to commence.
The noticeable results of pain relief typically hit their peak in the three to six week range. Importantly, PRP injections can continue to aid the healing process for up to nine months after the procedure.
“Is PRP a permanent solution?”
The results of a PRP injection are not permanent. Ideally, during the six to nine month timeframe that a PRP injection is effective, the body would be able to heal from whatever injury or chronic ailment. The goal of regenerative therapies like PRP is to not just be a band-aid but actually to restore tissue so the hope is results are long lasting!
There are cases where second PRP injections could be determined to be helpful. This would be at the discretion of your provider based on your circumstances.
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Hear What We Had to Say to Jeff
Meet Jeff, in his 40s with chronic pain.
Jeff was injured ten years ago and has suffered from chronic pain ever since. He misses biking with his buddies and is in a never ending circle of not being able to heal because he can’t exercise to get stronger.
Listen in as Dr. Yurth suggests areas that Jeff, a healthy male in his 40s, should keep on his radar.
Hear What We Had to Say to Katie
Meet Katie, 25, with an acute injury.
Katie was having a great day skiing the bumps, and the next thing she knew, she was being brought down the mountain in a sled.
Accidents happen, but what can Katie do to make sure she not only heals quickly, but prevents re-injury and avoids chronic pain later in life?
The key to healing long term is how you deal with inflammation, blood flow, and scar tissue. Listen in for suggestions Dr. Yurth would give Katie, or any healthy person in the age range of 20-35.