Caring Medical - Where the world comes for ProlotherapyAlternative to cortisone shots

Ross Hauser, MD.

Cortisone and anti-inflammatory medications have damaged your joints. Can that damage be repaired?

If you are reading this article, you are likely looking for answers for your long time pain problems that may also offer some hope that you can avoid a joint replacement surgery. You have been on a long journey of degenerative disease, you may have been told joint replacement is the end of the line. Joint replacement can help a lot of people. But it may not be the type of help you are looking for right now.

You may find yourself in this situation because your joints and spine are breaking down slowly, steadily, and at a rate faster than your body can fix them. In an attempt to help manage you along, your pain management health care providers may suggest treatments that include anti-inflammatory medications and cortisone injections.

In this article, we will discuss new research including troubling findings which say that:

  • Corticosteroid triamcinolone acetonide increases knee cartilage destruction.
  • Cortisone injections increase the risk of joint surgery.
  • Cortisone injections increase the need for secondary surgery and possible higher risk for post-surgical infections in the joint.
  • Corticosteroids can alter the healing environment of the joint by effecting damage on the native stem cells in cartilage.

And we will look at the most recent research which suggests in its title: “Intra-articular Corticosteroid Injections in the Hip and Knee: Perhaps Not as Safe as We Thought?”

It is my opinion, the increase in the number of hip and knee replacements is a direct result of the injection of corticosteroids into these joints. This is an opinion now shared by many.

The title of the research above comes from a study with an October 2019 publication date. This paper, published in the medical journal Radiology (1) lists as its essential messages the following:

  • Adverse joint events after intra-articular corticosteroid (IACS) injection, including accelerated osteoarthritis progression, subchondral insufficiency fracture, complications of osteonecrosis, and rapid joint destruction with bone loss, are becoming more recognized by physicians, including radiologists, who may consider adding these risks to the patient consent.
  • Certain imaging findings and patient characteristics could potentially assist radiologists and other physicians in identifying which joints are at risk for complications after IACS injections combined with local anesthetics.
  • The radiology community should actively engage in high-quality research to further understand these adverse joint findings and how they possibly relate to IACS injections to prevent or minimize complications.

In other words, back to what the researchers titled their paper: “Intra-articular Corticosteroid Injections in the Hip and Knee: Perhaps Not as Safe as We Thought?”

The press information released by the Radiological Society of North America, the publishers of the journal Radiology, listed these important points:

  • “Steroid injections may lead to joint collapse or hasten the need for total hip or knee replacement.”
  •  Ali Guermazi, M.D., Ph.D., professor of radiology and medicine at Boston University School of Medicine, and lead researcher of the study, found that “corticosteroid injections may be associated with complications that potentially accelerate the destruction of the joint and may hasten the need for total hip and knee replacements. . . “We’ve been telling patients that even if these injections don’t relieve your pain, they’re not going to hurt you,” Dr. Guermazi said. “But now we suspect that this is not necessarily the case.”
  • In a review of existing literature on complications after treatment with corticosteroid injections, Dr. Guermazi and colleagues identified four main adverse findings: accelerated osteoarthritis progression with loss of the joint space, subchondral insufficiency fractures (stress fractures that occur beneath the cartilage), complications from osteonecrosis (death of bone tissue), and rapid joint destruction including bone loss.
  • “Physicians do not commonly tell patients about the possibility of joint collapse or subchondral insufficiency fractures that may lead to earlier total hip or knee replacement,” Dr. Guermazi said. “This information should be part of the consent when you inject patients with intra-articular corticosteroids.”

Cortisone InfographicThe fact that new research is pouring in on the detrimental effects of cortisone injections should not convince anyone that suddenly medicine is being alerted to the risk of corticosteroids.

The fact that new research is pouring in on the detrimental effects of cortisone injections should not convince anyone that suddenly medicine is being alerted to the risk of corticosteroids. The dangers of cortisone injections have long been known. But in eagerness by health professionals and the patients themselves to get instant relief, the dangers were accepted as part of the treatment, in other words, “let’s manage the pain until the patient is ready for joint replacement treatment.”

In 2009, I wrote in the Journal of Prolotherapy “It is my opinion that there is no doubt that the rise of osteoarthritis, as well as the number of hip and knee replacements, is a direct result of the injection of corticosteroids into these joints.”(2)

My evidence then was a summary of the effects of cortisone on articular cartilage which included:

  • a decrease of protein and matrix synthesis (the nutrient and healing bed that cells grow in),
  • mutation of (cartilage) cell shape
  • growth of new cartilage inhibited,
  • cartilage destruction risk and enhancement
  • cartilage surface deterioration including edema, pitting, shredding, ulceration and erosions, etc, etc.

In ten years since, the evidence has grown.

Cortisone can work in the short-term and make the problem worse in the long run

The idea that cortisone can cause damage was not an easy sell for some researchers. Corticosteroid injections have been used for a very long time. Their anti-inflammatory and pain relief properties made its use a common practice within the medical community. Further, they are effective.

Corticosteroid injections have been shown to be effective in decreasing the inflammation and pain of ligament injuries for up to 8 weeks; however, these same properties lead to the destruction of cartilage as mentioned above. Simply, the body heals via inflammation, cortisone inhibits inflammation and healing by disrupting the three characteristic phases: inflammatory, proliferative and remodeling.

Simply, healing comes in phases. The first phase, the inflammatory-reparative phase, sets the foundation for the other phases of healing including repairing and remodeling connective tissue. This inflammatory phase of healing is critically affected by treatment options chosen. These options can either block or stimulate the healing process. Cortisone, as it has been well shown, blocks and retards this initial healing phase. Cortisone is the “feet of clay” of which the whole healing structure crumbles upon.

Corticosteroid damaged knee cartilage and provided no significant pain relief after two years.

In 2017, doctors from Tufts Medical Center in Boston asked, “What are the effects of intra-articular injection of 40 mg of triamcinolone acetonide every 3 months on the progression of cartilage loss and knee pain in patients with osteoarthritis?”

Writing in the Journal of the American Medical Association, (JAMA) they published their answer:

“Among patients with symptomatic knee osteoarthritis, 2 years of intra-articular triamcinolone, compared with intra-articular saline, resulted in significantly greater cartilage volume loss and no significant difference in knee pain. These findings do not support this treatment for patients with symptomatic knee osteoarthritis.”(3)

  • Corticosteroid damaged knee cartilage and provided no significant pain relief after two years.

In other words, cortisone can either work or make the problem worse.

Cortisone disrupts natural healing and hurts native joint cells

Cortisone as well as other anti-inflammatories, and the RICE (rest, ice, compression, and elevation) protocol– which has very recently been rescinded by its author due to its detrimental effect on healing all are considered “non-healing,” and whose long-term usage will make the patient’s condition worse.

Cortisone disrupts and hurts healing cellsCortisone vs. Prolotherapy

Recent research from the Mayo Clinic says cortisone may hinder the native stem cells in cartilage. (Mesenchymal stem cells (MSCs) are the building blocks of cartilage other musculoskeletal tissue.) Cortisone threatens their innate regenerative capacity in exchange for temporary analgesia.(4)

It becomes perplexing then, that these medications continue to be routinely injected into people’s joints “therapeutically” for pain.  While corticosteroid and analgesic injections have the potential to temporarily relieve pain by shutting down the body’s inflammatory mechanisms, these medications are toxic to cartilage cells.  Results of bovine cartilage studies from the University of Pittsburgh School of Medicine revealed the following:

“A direct correlation between increased steroid concentration and increased chondrocyte apoptosis (cartilage death) as well as increased chondrocyte toxicity (cartilage poisoning) with increasing time of exposure to methylprednisolone. The addition of lidocaine to methylprednisolone significantly increased the rate of chondrocyte cell death.”(4)

In the American Journal of Sports Medicine, university medical researchers in Japan demonstrated a case history in which a patient received high-dose cortisone treatments for a case of Bell’s Palsy, the same patient was also a volunteer subject in a study to test a stem cell based Tissue Engineered Construct for cartilage and bone defect. Stem cells were harvested from the patient to “build a scaffold patch.”

  • At three weeks after the cortisone treatment, the patient’s stem cells could not help generate the construct needed for the cartilage/bone patch.
  • At seven weeks after steroid therapy the stem cells could, the stem cells had successfully withstood a direct attack from the cortisone, but it did take 7 weeks to recover.(5)

Cartilage cell counts decline with cortisone and exercise

This single piece of research published by French doctors in the journal Clinics in orthopedic surgery should be enough to convince anyone that cortisone makes healing with stem cells difficult. Patients seeing doctors who insist on cortisone first, should research this treatment decision.

  • “Following corticosteroid therapy in osteonecrotic patients, abnormalities have been demonstrated in the bone marrow of the iliac crest, with a decrease in the stem cell pool.”(6). 

It is the message over and over – When injected into joints, corticosteroids not only trigger cartilage cell death but also completely suppress healing by their innate mechanism of action, which is to suppress the immune system and block inflammation.

Cortisone injection risks, side effects, and tissue toxicity

Despite the research, the first trip to the joint pain specialist is usually a recommendation to cortisone. Shortly after doctors started injecting cortisone and other steroids into knee joints in the 1950s, researchers began noting severe problems of joint degeneration and so discouraged the use of cortisone injections. Today, despite the dangers, cortisone use remains widespread as a standard of care.

This is what cortisone does:

  • Cortisone has a harmful effect on soft tissue healing by inhibiting blood flow to the injured area, suppressing new blood vessel formation, suppressing growth of immune cells like leukocytes and macrophages, preventing protein synthesis, fibroblast proliferation and ultimately collagen formation.
  • Cortisone inhibits the release of growth hormone, which further decreases soft tissue and bone repair.
  • Cortisone weakens collagen and therefore soft tissue such as ligaments and tendons.

This is what research says about it:

  • Research 2013: Cortisone works well for some but not for others and no one seems to be able to identify why:
    • From the journal Seminars in Arthritis & Rheumatism: “Previous research has not identified reliable predictors of response to intraarticular corticosteroid injections, a widely practiced intervention in knee and hip osteoarthritis. Further studies are required if this question is to be answered.”(7)
  • The Journal of the American Academy of Orthopaedic Surgeons (2009) Researchers concluded that corticosteroids reduce knee pain for at least 1 week and that intra-articular corticosteroid injection is a short-term treatment of a chronic problem.(8)
    • (My comment, good for one week, damages stem cells for three weeks, referring to above research).
  • From the International Journal of Clinical Rheumatology, a paper entitled: “Future directions for the management of pain in osteoarthritis”. (2014) Dangers of cortisone injection include cartilage and joint destruction, especially in those with osteoarthritis of the joint. “Corticosteroid therapy, as well as NSAIDs, can lead to destruction of cartilage, suggesting that a positive effect on joint pain may also be associated with accelerated joint destruction, which is an extremely important factor in a chronic, long-term condition such as osteoarthritis.”(9)
    • (My comment: Cortisone is clearly not part of the Future directions for the management of pain in osteoarthritis).
  • In March 2017, Italian researchers publishing in the medical journal Expert Opinion in Drug Safety noted: local glucocorticoids injections have shown positive results in some tendinopathies but not in others. moreover, worsening of symptoms, and even spontaneous tendon ruptures have been reported. (10). 
    • The was a confirmation of a study that appeared 40 years earlier in 1977. Here Stanford University Medical Center and Kaiser-Permanente Medical Center researchers suggested that cortisone injections can lead to painful tendon and ligament ruptures. They compromise tendon and ligament strength, a scary finding considering that many athletes return to the game or the sport shortly after an injection.(11)
  • The evidence for the effectiveness of intraarticular epidural steroid injection for Sacroiliac joint dysfunction treatment is poor (12)

Cortisone injections can predispose a joint to infection. Patients have reported severe pain, including muscle pain, and burning after a cortisone injection.

In research from 2015, doctors at the University of Toronto (13) wrote of the problem of injection infection.

Intraarticular hip injections of corticosteroids and hyaluronic acid may be used to treat hip osteoarthritis. Although sterile technique is recommended to avoid infiltration of the joint with microorganisms normally found on the surface of the skin there remains a risk of infection. (All injections can carry the risk of infection, this includes our injection techniques of Prolotherapy PRP Prolotherapy and stem cell Prolotherapy)

HERE IS THE DIFFERENCE -Patients prior to hip replacement surgery may typically receive hip injections of corticosteroids and hyaluronic acid to manage their pain until surgery day.

Intraarticular hip injections of corticosteroids and hyaluronic acid may increase the risk of infection because of the immune system suppression characteristic of cortisone.

Therefore, in the setting of total hip replacement, preoperative receipt of a hip injection may increase the risk of infection, leading to early revision arthroplasty.

While the researchers were unable to determine what agent was injected into the joint prior to surgery, they concluded that the most likely therapies were corticosteroids and hyaluronic acid, with or without a local anesthetic.

As hyaluronic acid has no proven benefit for hip osteoarthritis, it is likely that most of the injections were of corticosteroids.

  • Corticosteroid joint injection may have local immunomodulatory effects that may increase the risk of infection following hip replacement.

If so, there may be a period of time required for these effects to be “cleared” before a hip replacement can be safely implanted into the joint. Regardless of the solution injected, intraarticular injections expose the joint to the external environment and may allow seeding by microbes, particularly when an improper sterile technique is used. Further research is warranted to determine whether the documented increased risk of infection following hip injection differs according to the solution used (corticosteroids versus hyaluronic acid).

Hyaluronic acid cannot repair cortisone induced cartilage damage

In new research, doctors in China released their findings on animal studies on the damaging effects of cortisone on cartilage and the ability of hyaluronic acid to repair this and other damage.

Here is what they said:

Intra-articular injection of corticosteroids is used to treat the inflammatory pain of arthritis and osteoarthritis, but (in their previous study) found a deleterious effect of these steroids on chondrocyte cells. Hyaluronic acid (HA) injection has been suggested as a means to counteract negative side effects through replenishment of synovial fluid that can decrease pain in affected joints…

Combinations of steroid and Hyaluronic acid treatments have not been completely understood or standardized and are still a matter of concern. We suggest that if this combined treatment cannot be avoided, then an appropriate treatment duration should be provided.(13)

You now become a pain management patient until such time as you can get a joint replacement

In our office, the first way is to fix the joint or spine by rebuilding and repairing damaged tissue with regenerative injections. We can accomplish this with Prolotherapy and Platelet Rich Plasma Injections used together.

  • Nature’s way is for chondrocytes (healing and rebuilding cells in our body) to repair the damage. Our therapies can assist in this process and accelerate healing.
  • During this healing, the body produces its own specialized inflammatory process that acts as a protective barrier to protect the new cartilage that is being built.
  • Once repair is complete, our body shuts down the inflammation. The inflammation is no longer needed.

Is the above scenario, the repair of the joint has shut down the inflammation. This is not so in the second scenario where medication and steroids are used to shut down inflammation.

The second way to shut down the inflammation does not involve healing or repair

  • The pharmaceutical industry has made billions and billions producing anti-inflammatories to try to get the inflammation to shut off.
  • The anti-inflammatories the industry produces simply attacks the natural inflammation, they do not repair or change the course of the disease.
  • Since the repair mechanism in your body has been shut off, you now become a pain management patient until such time as you can get a joint replacement.

The amazing chondrocyte cell. It makes cartilage. It is already in your joints. It can reverse years of your cortisone, anti-inflammatory and painkiller damage if you help it.

chondrocyte is a cell that makes cartilage. In the human body, the chondrocyte is the only cell type in cartilage. Your entire cartilage is a wall of chondrocytes.

If you can imagine the example of the brick wall above being the cartilage that covers the ends of your bones or being a meniscus in your knee or hip labrum or shoulder labrum. In degenerative joint disease, this wall starts developing holes or lesions. To have bone-on-bone part of this brick wall has to wear through.

Now imagine your body trying to repair this damage. How does it do it? Here comes the amazing chondrocyte and its repair forces.

  • The cartilage repairing chondrocyte is a very smart replacement brick.
  • The chondrocyte finds its own way to a portion of the wall that is damaged.
  • It then embeds itself into a lesion or hole.
  • Once in place, it secretes its own mortar and embeds itself into the damaged wall.
  • When you have many chondrocytes doing the same thing, they create a healing environment of positive, healing inflammation.

Now imagine this damage is too far gone and the chondrocytes cannot complete a repair 

  • When the chondrocytes cannot complete a repair of the damage, they do not stop trying.
  • The inflammation they are creating to protect their workspace does not shut off.
  • The “runaway” inflammation the chondrocytes are making turns into a toxic environment of oxidant stress wearing away at the entire joint.
  • As stated above, the pharmaceutical industry has made billions and billions producing anti-inflammatories to try to get the inflammation to shut off.
  • Medicine, therefore, has stopped trying to help the chondrocyte heal the joint damage and instead shuts down inflammation.
  • END RESULT? The same conclusion we reached above. Medicine manages people along until the final outcome, unavoidable joint replacement.

The damage of anti-inflammatories, cortisone, painkillers and no treatment – the answer to why there are so many joint replacements.

  • Imagine again the brick wall above. It is still damaged but it is no longer being repaired because cortisone and anti-inflammatories have shut down the repair process.
  • When you stop repairing a damaged brick wall, it will collapse. If this were your knee or hip, you are now bone-on-bone and at times your knee or hip will feel like it is collapsing under your weight.
  • This is when you get your pain, possibly severe at times. Painkillers will be prescribed.
  • Your mobility is limited. You will now become dependent on others.
  • You are being managed along until joint replacement can be scheduled.

When you stop repairing a damaged brick wall, it will collapse. If this were your knee or hip, you are now bone-on-bone and at times your knee or hip will feel like it is collapsing under your weight.

The bricks and mortar of healing – the stuff that inflammation does

So this time let’s imagine that your own healing cells have mobilized by treatment. In this case by simple dextrose injections or Prolotherapy. Let’s explore how Prolotherapy may work in this scenario.

Here we will present Prolotherapy as one possible option to cortisone.

Prolotherapy has been utilized in clinical practices for over 80 years. Standardized and reviewed in clinical application by Dr. George Hackett in the 1950s, Prolotherapy has been shown to be an effective treatment in patients who suffer from joint instability due to ligament damage and overuse and related musculoskeletal and osteoarthritis.

  • Prolotherapy is a nonsurgical regenerative injection technique that introduces small amounts of an irritant solution to the site of painful and degenerated tendon insertions (entheses), joints, ligaments, and in adjacent joint spaces during several treatment sessions to promote growth of normal cells and tissues.
  • Irritant solutions most often contain dextrose (d-glucose), a natural form of glucose normally found in the body

For the patient, the goal of Prolotherapy in chronic musculoskeletal pain and instability is the stimulation of body’s natural healing and regenerative processes in the joint that will facilitate the repair and regrowth of connective tissue, ligaments, tendons for tensile strength, and cartilage and other joint stabilizing structures such as labral tissue.

Prolotherapy removes damaged tissue and debris from the joint – clean up

Let’s go back to our collapsed brick wall example. At the base of the wall in the picture above are piles of damaged bricks. If you were to bring in a masonry crew to fix that brick wall, the first thing they would do is clean up the damaged bricks so they had a safe and clean work environment. Prolotherapy also helps with a clean and safe environment to work in too. When Prolotherapy is injected into the joint, it stimulates the production of leukocytes (an immune cell that absorbs and gets rid of diseased tissue) and macrophages. The term macrophage is from the Greek meaning, “Big Eaters.” They eat debris and damaged tissues in the joint.

Prolotherapy brings oxygen to the joint to help provide healing cells energy and a clean, safe work environment.

In a 2017 stem cell (stem cells are cells native in the body that help remodel damage tissue) study, Dr. Ming Pei of West Virginia University publishing in the medical journal Biomaterials (14suggests that while adult stem cells are a promising cell source for cartilage regeneration, they have a hard time in a harsh joint environment when hypoxia (the lack of oxygen) and inflammation have created a toxic soup for the stem cells to work in. As noted above healing cells, like your native stem cells, like a clean, safe work environment. Chronic inflammation slowly and steadily brings about a low oxygen environment in joints because the body feels that diseased tissue will die in a low oxygen environment. Oxygen deprivation is designed to be a short-term drastic measure to healing a wound. Byt chronic inflammation means a slow strangulation of the joint

Sometimes we forget the cells of the body obtain their energy via aerobic metabolism.  The primary substrates or substances that are needed for aerobic metabolism are oxygen and glucose. The body breathes to get oxygen and we eat to break down the food into sugar. Even if a person just eats protein, ultimately the body finds a way to break down the protein into individual amino acids and eventually into glucose. Without glucose, the cells and the body cannot live.

Prolotherapy feeds healing cells the food they like and helps make more of them

One important published paper on stem cell research from Purdue University confirmed the notion that dextrose, especially hypertonic (extra) dextrose is a significant factor in the ability of mesenchymal stem cells from bone marrow to proliferate. What is in a Prolotherapy injection? Hypertonic dextrose (15)

The mesenchymal stem cell consumption of glucose increased proportionally with the glucose concentration in the medium. (The more food the stem cells were given, the more they ate). The primary results note that the higher glucose and serum concentrations appear to produce higher stem cell populations over time.

Prolotherapy is an alternative and effective treatment to heal chronic musculoskeletal injuries. Comprehensive Prolotherapy involves the injection of natural substances (named orthobiologics) used to induce healing within the body. Dextrose is a heavily studied proliferant and is safe and effective in many cases. It can be used in high concentrations without threatening side effects. This allows us to treat multiple body parts on the same person during the same visit.

Comprehensive Prolotherapy stimulates, rather than interferes with, the normal healing process of inflammation. While corticosteroids inhibit the enzymes that block the production of prostaglandins and leukotrienes, which mediate the inflammatory process, Prolotherapy stimulates them.

In addition, the collagen that forms in ligaments and tendons treated with cortisone is disrupted and weaker, while that treated with Prolotherapy is stronger. Prolotherapy provides the stimulus that is needed to bring in healing fibroblasts and allow them to proliferate and lay down new collagen fibers. This causes the connective tissues, ligaments, and tendons to become thicker and stronger. Prolotherapy stimulates the normal inflammatory-reparative mechanisms of the body, encouraging normal collagen and extracellular matrix growth.

Comprehensive Prolotherapy and Platelet Rich Plasma. Comparisons to Cortisone

  • Patients with chronic gluteal tendinopathy for more than 4 months, diagnosed with both clinical and radiological examinations, achieved greater clinical improvement at 12 weeks when treated with a single PRP injection than those treated with a single corticosteroid injection.(16)
  • Autologous blood injection, a derivative of Platelet Rich Plasma where the blood is reintroduced without the platelet concentration improved pain and function patients with chronic lateral epicondylitis (Tennis elbow), who had not had relief with cortisone injection.(17)
  • Journal of clinical and diagnostic research, a 2015 study reveals PRP as a superior treatment option to cortisone in cases of tennis elbow.(18)
  • Doctors in Pakistan have shown the effectiveness of platelets rich plasma versus corticosteroids or the “tennis elbow steroid injection.” The doctors looked at 102 patients in the study and divided them into two groups of 51(50%) each.
    • In the patients in the cortisone group 53% improvement
    • In the patients in the PRP group 82%
    • Their conclusion: PRP is an effective alternative to corticosteroid in the treatment of lateral epicondylitis (tennis elbow).(19)
  • International orthopaedics (2012) Compared with cortisone injections, PRP showed significant clinical benefit for patellar tendinopathy. Additionally, the PRP benefit worked best when the patient did not have a PREVIOUS CORTISONE INJECTION.(20)
  • Doctors in the United Kingdom found that PRP is as effective as Steroid injection at achieving symptom relief at 3 and 6 months after injection, for the treatment of plantar fasciitis, but unlike Steroid, its effect does not wear off with time. At 12 months, PRP is significantly more effective than Steroid, making it better and more durable than cortisone injection.(21)

In summary, while cortisone shots weaken an injured area even further, Prolotherapy stimulates the body to repair it. Prolotherapy stimulates blood flow to the area, protein synthesis, fibroblast proliferation and ultimately collagen formation. The choice is simple: cortisone shots that lead to proliferative arthritis of joints or proliferative injections (Prolotherapy) that stimulate the repair of the injured tissue.

Do you have a question about finding an alternative to cortisone shots? Get help and information from our Caring Medical staff.

 References:

1 Kompel AJ, Roemer FW, Murakami AM, Diaz LE, Crema MD, Guermazi A. Intra-articular Corticosteroid Injections in the Hip and Knee: Perhaps Not as Safe as We Thought? Radiology, 2019; 190341 DOI: 10.1148/radiol.2019190341
2 Hauser RA The Deterioration of Articular Cartilage in Osteoarthritis by Corticosteroid Injections Journal of Prolotherapy. 2009;1(2):107-123. [Journal of Prolotherapy]
3 McAlindon TE, LaValley MP, Harvey WF, Price LL, Driban JB, Zhang M, Ward RJ. Effect of Intra-articular Triamcinolone vs Saline on Knee Cartilage Volume and Pain in Patients With Knee OsteoarthritisA Randomized Clinical Trial. JAMA. 2017;317(19):1967-1975. [Google Scholar]
4 Wyles CC, Houdek MT, Wyles SP, Wagner ER, Behfar A, Sierra RJ. Differential cytotoxicity of corticosteroids on human mesenchymal stem cells. Clinical Orthopaedics and Related Research®. 2015 Mar 1;473(3):1155-64.  [Google Scholar]
5 Yasui Y, Hart DA, Sugita N, Chijimatsu R, Koizumi K, Ando W, Moriguchi Y, Shimomura K, Myoui A, Yoshikawa H, Nakamura N. Time-Dependent Recovery of Human Synovial Membrane Mesenchymal Stem Cell Function After High-Dose Steroid Therapy: Case Report and Laboratory Study. The American journal of sports medicine. 2017 Dec 1:0363546517741307.  [Google Scholar]
6. Hernigou P, Trousselier M, Roubineau F, Bouthors C, Chevallier N, Rouard H, Flouzat-Lachaniette CH. Stem cell therapy for the treatment of hip osteonecrosis: a 30-year review of progress. Clinics in orthopedic surgery. 2016 Mar 1;8(1):1-8. [Google Scholar]
7 Hirsch G, Kitas G, Klocke R. Intra-articular corticosteroid injection in osteoarthritis of the knee and hip: factors predicting pain relief–a systematic review. Semin Arthritis Rheum. 2013 Apr;42(5):451-73. doi: 10.1016/j.semarthrit.2012.08.005. Epub 2013 Jan 29.  [Google Scholar]
8 Hepper CT, Halvorson JJ, Duncan ST, Gregory AJ, Dunn WR, Spindler KP. The efficacy and duration of intra-articular corticosteroid injection for knee osteoarthritis: a systematic review of level I studies. J Am Acad Orthop Surg. 2009 Oct;17(10):638-46.  [Google Scholar]
9. Sofat N. Kuttapitiya A. Future directions for the management of pain in osteoarthritis. Int J Rheumatol. Apr 2014; 9(2): 197–276.  [Google Scholar]
10. Abate M, Salini V, Schiavone C, Andia I. Clinical benefits and drawbacks of local corticosteroids injections in tendinopathies. Expert Opin Drug Saf. 2017 Mar;16(3):341-349. doi: 10.1080/14740338.2017.1276561. Epub 2016 Dec 28.  [Google Scholar]
11. Halpern AA, Horowitz BG, Nagel DA. Tendon ruptures associated with corticosteroid therapy. Western Journal of Medicine. 1977 Nov;127(5):378.  [Google Scholar]
12. Hansen H, Manchikanti L, Simopoulos TT, Christo PJ, Gupta S, Smith HS, Hameed H, Cohen SP. A systematic evaluation of the therapeutic effectiveness of sacroiliac joint interventions. Pain Physician. 2012 May-Jun;15(3):E247-78.  [Google Scholar]
13 Ravi B, Escott BG, Wasserstein D, Croxford R, Hollands S, Paterson JM, Kreder HJ, Hawker GA. Intraarticular hip injection and early revision surgery following total hip arthroplasty: a retrospective cohort study. Arthritis Rheumatol. 2015 Jan;67(1):162-8. doi: 10.1002/art.38886.  [Google Scholar]
14 Pei M. Environmental preconditioning rejuvenates adult stem cells’ proliferation and chondrogenic potential. Biomaterials. 2017 Feb 1;117:10-23. [Google Scholar]
15 Deorosan B, Nauman EA. The Role of Glucose, Serum, and Three-Dimensional Cell Culture on the Metabolism of Bone Marrow-Derived Mesenchymal Stem Cells. Stem Cell International. 2011;  Article ID 429187, 12 pages. Doi:10.4061/2011/429187 . [Google Scholar]
16 Fitzpatrick J, Bulsara MK, O’Donnell J, McCrory PR, Zheng MH. The Effectiveness of Platelet-Rich Plasma Injections in Gluteal Tendinopathy: A Randomized, Double-Blind Controlled Trial Comparing a Single Platelet-Rich Plasma Injection With a Single Corticosteroid Injection. The American Journal of Sports Medicine. 2017:0363546517745525.  [Google Scholar]
17. Massy-Westropp N, Simmonds S, Caragianis S, Potter A. Autologous blood injection and wrist immobilisation for chronic lateral epicondylitis. Adv Orthop. 2012;2012:387829. doi: 10.1155/2012/387829. Epub 2012 Dec 4.  [Google Scholar]
18 Yadav R, Kothari SY, Borah D.  Comparison of Local Injection of Platelet Rich Plasma and Corticosteroids in the Treatment of Lateral Epicondylitis of Humerus. J Clin Diagn Res. 2015 Jul;9(7):RC05-7. doi: 10.7860/JCDR/2015/14087.6213. Epub 2015 Jul 1.  [Google Scholar]
19 Khaliq A, Khan I, Inam M, Saeed M, Khan H, Iqbal MJ. Effectiveness of platelets rich plasma versus corticosteroids in lateral epicondylitis. J Pak Med Assoc. 2015 Nov;65(11 Suppl 3):S100-4. [Google Scholar]
20. Gosens T, Den Oudsten BL, Fievez E, van ‘t Spijker P, Fievez A. Pain and activity levels before and after platelet-rich plasma injection treatment of patellar tendinopathy: a prospective cohort study and the influence of previous treatments. Int Orthop. 2012 Sep;36(9):1941-6. doi: 10.1007/s00264-012-1540-7. Epub 2012 Apr 27 [Google Scholar]
21. Jain K, Murphy PN, Clough TM. Platelet rich plasma versus corticosteroid injection for plantar fasciitis: A comparative study. Foot (Edinb). 2015 Dec;25(4):235-7. [Google Scholar]

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9738 Commerce Center Ct.
Fort Myers, FL 33908
(239) 308-4701 Phone
(855) 779-1950 Fax Fort Myers, FL Office
Chicagoland Office
715 Lake St., Suite 600
Oak Park, IL 60301
(708) 393-8266 Phone
(855) 779-1950 Fax
We are an out-of-network provider.
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National Prolotherapy Centers specializing in Comprehensive Prolotherapy,
Stem Cell Therapy, and Platelet Rich Plasma.

Meet our Prolotherapy Doctors and check out our Prolotherapy research.