Can Emerging Injectable Modalities Keep Athletes In The Game?

For those of us who work with collegiate and professional athletes, keeping our patients on the field of play can be a real challenge. We often need every imaginable modality possible. As with our surgical patients, it is a challenge to figure out which modality will work the best to keep athletes going.

I work with the ultimate professional athletes: military service members. For me, the most exciting aspect of treating them today is the ability to utilize a wide variety of injectables: non-steroidal anti-inflammatory drugs (NSAIDs), alcohol, platelet rich plasma (PRP), hyaluronic acid and/or stem cell therapy.  

Since 1989, ketorolac (Toradol, Roche) has been a mainstay for dealing with postoperative pain in every hospital and surgery center. Unfortunately, over the past 10 years, there have been national shortages and supply delays. You can thank the military. We have been stockpiling supplies of ketorolac to support American troops in Iraq and Afghanistan.  

Like the military, college and professional athletes have utilized ketorolac for decades.^1-3 Ironically, there have been growing concerns about repeated use of ketorolac in the National Football League (NFL) and Major League Baseball (MLB). Former NFL players have filed a lawsuit, claiming that league physicians used ketorolac to keep them playing.⁴ They claim this did not cure their injuries but actually prolonged their injuries, leading to shortened careers or career-ending injuries.  

Some have raised similar concerns about Major League Baseball as well. Many physicians have questioned the use of ketorolac amongst MLB pitchers. They have suggested that the number of shoulder and elbow injuries has risen steadily as a result of increased pitch counts because ketorolac use has allowed pitchers to throw longer and harder.⁴ More recently, the Nevada Boxing Commission denied Manny Pacquiao a ketorolac shot prior to his fight against Floyd Mayweather in May 2015.⁵  

There is a new injectable NSAID called Dyloject (diclofenac sodium) from the company Hospira. The initial studies for this modality compare very favorably to ketorolac.⁶ You can bet that professional athletes will be using it as soon as they can get their hands on it. I am sure the military will be trying it out as well.  

Even more exciting than injectable NSAIDs is the use of PRP and stem cell therapy. Unlike NSAIDs, which simply deal with inflammatory responses and assist with analgesia, PRP and stem cells can actually stimulate the healing response to pain and address the etiology of the pain. We can target the source of pain by injecting directly into the muscle, joint or bone. Early research has shown that these injectables are excellent adjuncts to surgery and, in some cases, can speed up recoveries significantly.^7-8 It was only a matter of time before physicians began to utilize both PRP and stem cells to assist with conditions earlier and earlier in the disease process. Not only are we seeing athletes use the therapies to stay in the game but they are also using them to delay surgery.

A Closer Look At The Potential Of Platelet Rich Plasma
Platelet rich plasma has become widely used by every specialty in medicine. Some of the kits and centrifuges for use in the clinic or operating room include Angel (Arthrex), GPS III (Biomet), Symphony II (Depuy), PRP Kit (Dr. PRP USA), SmartPrep (Harvest Technologies), MagellanPRP (Arteriocyte) and RegenKit (Regen Lab). Every company boasts that it provides the highest concentration of cells or cell counts or best cells. I have used many of the systems. Some are easier and some involve way too many steps, sometimes as many as 30 steps as outlined by their technique manuals. Search for PRP on the Internet and you will see that there are multiple companies that have come up with aftermarket collection vessels that assist in concentrating the PRP. Personally, I think what matters the most is a safe and simple delivery process.

As far as the results go, the scientific research is definitely mixed. For me, PRP has been a great adjunct for surgical cases and has become increasingly helpful in dealing with tendonitis, tendinosis and chronic pain in general.^9-11  

Unfortunately, the majority of insurance companies will not cover PRP treatment so PRP injections are a cash business. In regard to the clinical effectiveness and the science behind it, PRP is still a little sketchy. A Canadian meta-analysis conducted for insurance purposes concluded that PRP was more helpful than expected in orthopedic indications.¹²  

I suggest that you ignore the hype and the financial side of PRP. The process of drawing 10-30 mL of the patient’s blood and injecting it back into his or her painful tendon, joint, or muscle is very tolerable, and may help the patient get back into the game. The rewards are worth it, especially for athletes and soldiers whose paychecks depend on their performance.^13-14

Is Hyaluronic Acid Effective For Athletes?
The use of hyaluronic acid injections has been growing steadily despite some of the long-term data suggesting that it is no better than using an oral NSAID.¹⁵ These injections have allowed patients to relieve pain and delay surgery. Within the sports community, these injections have kept athletes playing. We all know that these injections were originally designed and approved for end-stage osteoarthritis of the knee, but they have been very helpful with grade II and III chondromalacia, especially in the ankle.^16-20 In the Army, we have patients with chronic ankle pain come in two weeks before their physical fitness  test. I have seen patients who could not run down the hallway, let alone two miles. Within days of an injection, they were able to run two miles in 15 minutes and pass their physical fitness test.  

There is no doubt that collegiate and professional athletes are using hyaluronic acid injections. At this point, they have replaced steroid injections in many of our practices as a precursor to surgery. In time, I believe research will show that repeated hyaluronic acid injections can actually convert Grade III (fibrillation) to Grade II and even down to Grade I chondromalacia.
     
Current Insights On The Use Of Stem Cells For Athletic Injuries
Even more exciting is the use of stem cell therapy. One can purchase stem cell therapy commercially or obtain it via bone marrow aspiration techniques. Many surgeons have already been using stem cells in surgery. Many of us have routinely used Trinity (Orthofix) and AlloStem (Allosource). Both modalities utilize stem cells mixed in a demineralized bone matrix. RTI Surgical recently came out with a new version called Map3. All three products are exclusively for bone grafting.    

At this point, our best option for obtaining stem cells is through bone marrow aspiration. Unfortunately, not every patient is a good candidate. Smokers as well as patients with osteoporosis and diabetes are more suited to commercially harvested stem cells. There are aspiration kits including Angel (Arthrex), BioCUE (Biomet), Retrieve (Globus Medical), BMAC Bone Marrow Aspirate Concentrate Kit (Harvest Technologies), Aspirex (Integra Life Sciences), Marrowmax (Medtronic) and Procure (Synthes). All of these modalities include a large bore needle or trephine for harvesting the aspirate from the hip, tibia or even the calcaneus. The RIA (reamer, irrigator and aspirator) System (Synthes) allows one to collect the reamings from the tibia or femur prior to a recon/intermetatarsal nailing.    

Surgeons have been utilizing bone marrow aspiration for bone grafting over the past decade. Interest has grown among the sports medicine community to utilize bone marrow aspiration for injecting joints and muscles.^21-26 Dwight Howard of the Houston Rockets had bone marrow aspiration to assist in repairing his meniscus last season. Surgeons have focused significant research on using bone marrow aspiration to heal cartilage, the meniscus, partial anterior cruciate ligament tears and even tendon ruptures.²⁷ Surgeons are utilizing bone marrow aspiration before and after surgeries to speed up the healing process.

Surgeons are also combining bone marrow aspiration with structural proteins that are commercially available in powder form via MatriStem MicroMatrix (ACell), which is derived from urinary bladder matrix, and Neox Flo (Amniox Medical), which is derived from amniotic tissue. One can hydrate both powders and inject them into the host tissue to improve angiogenesis while reducing the development of scar tissue. When one combines these structural proteins with bone marrow aspiration or PRP, they can provide a highly potent and effective number of mesenchymal stem cells. Their uses are expanding and have attracted attention within the orthopedic community. Surgeons have used the matrix products primarily for wound care and tissue repair. However, one could use the combination in bones, muscles or joints.

Do an Internet search and you will quickly see the rising popularity of stem cell therapy. As with anything new, we will see both promising results mixed with skeptical reviews. How can one not be skeptical when you see the outlandish promises that many “Internet” surgeons claim. Podiatry, like orthopedics, has our share of self-promoters claiming the ability to cure heel pain with a “single stem cell injection.” They say, “Three injections and you are cured, or your money back!” Stem cell therapy may become a miracle cure someday in the future but it surely will not be that for plantar fasciitis.    

In Conclusion
My hope for the future is that the quality of research will improve and the indications for use will become more clearly defined. Results will become more predictable. There clearly is a place for PRP, hyaluronic acid and stem cell therapy within sports medicine and our surgical practices. Right now, we need to use some healthy caution and restraint while assessing our patients and reviewing the literature. Inject wisely.

Dr. Spitalny is a staff podiatrist at General Leonard Wood Army Community Hospital in Ft. Leonard Wood, Mo. He is an Adjunct Faculty member for the Depaul Podiatric Surgical Residency in St. Louis. Dr. Spitalny is a Fellow of the American College of Foot and Ankle Surgeons.

References   

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