Behind the hype surrounding regenerative medicine in orthopaedics

Look up “regenerative medicine” online and you’d be forgiven for thinking it’s a quick fix for almost any orthopaedic condition.

That’s because many in the medical profession are now touting the almost unlimited benefits of this new medicine. For example, it’s now common to see clinics splash on their websites the powerful effects that both stem cell and platelet-rich plasma (PRP) treatments — the two most common regenerative techniques in orthopaedics — can have on a host of problems ranging from Achilles tendinitis, arthritis of the joints, hip, knee, and shoulder pain to ligament sprains, degenerative disc disease, nonunion fractures, and nerve injuries.

Regenerative medicine is said to be able to regenerate cartilage in the joints and disc tissue in the spine, reduce knee pain, and heal nonunion fractures and inflammation in the Achilles tendon at the back of the ankle. In some instances, PRP is hailed as a potential alternative to surgery to treat rotator cuff tears and shoulder arthritis.

While some claims may be true, many are profoundly misleading because they tend to portray regenerative therapies as established approaches that can work effectively on their own to fix a host of orthopaedic problems. Others are outright false.

“In general, there’s too much exuberance about what regenerative therapies can do right now,” Dr Shane Shapiro, a medical orthopaedist and director of the Regenerative Medicine Therapeutics Program at the Mayo Clinic in Florida, told Global Health Asia-Pacific.

In his view, a minority of patients with orthopaedic conditions could definitely benefit from either PRP or stem cells therapies, but by and large these are still new treatments that can’t replace older ones. “In general, thinking that regenerative medicine is a distinct alternative to conventional standard of care would be incorrect in the current time,” he said.

The basic idea behind regenerative medicine is to use human cells and tissues to treat diseases, or “turning the body into its natural drug store,” in Dr Shapiro’s words. In orthopaedics, this translates into injecting platelets (blood components involved in clotting) and adult stem cells (special human cells that can generate multiple types of cells) into diseased joints and tissues to help them heal.

In fact, platelets are thought to contain growth factors, or substances needed for cells to grow, that might contribute to cellular regeneration, inflammation reduction, or overall health in the joints, the structures that connect different bones in the body. The problem is that these effects are not consistent across the board, meaning that just some orthopaedic issues can be treated with regenerative techniques, and in most instances are far from curative or even well-researched.

“The most important thing to recognise is that regenerative medicine is still a field of translational research. Even if we can use some of the treatments in clinical practice, most of it still needs more study, and that’s what we, who work in this field, are focused on,” said Dr Shapiro.

He explained that the term itself can be confusing because not every regenerative treatment actually regenerates tissues. That’s why in the orthopaedic community many experts refer to these as ‘orthobiologics’ to highlight that they are simply biologic products useful in treating some orthopaedic problems. While experts can debate terminology, what most agree on is that it’s an addition to the orthopaedist’s toolbox but in no way a one-size-fix-all therapy that can reverse tissue degeneration with quick injections.

When patients are injected with their own biologic products without any manipulation, regenerative medicine has shown to be safe, explained Dr Shapiro. But he also cautioned that patients have been harmed after receiving orthobiologics from unknown cell sources and banked cells.

Regenerative medicine at its best

The good news is that short-term research suggests that a couple of orthopaedic conditions could be cured by regenerative treatments.

Lateral epicondylitis, commonly known as tennis elbow, is one example. Caused by overuse of the elbow muscles, the condition leads to pain and difficulty extending the arm but can be effectively treated with PRP, which in this specific case regenerates the inflamed tendon, thus improving its health and often sparing patients the discomfort of long-term medications or surgery.

Similarly, stem cells have managed to fix avascular necrosis of the hip, where the bone cells in the hip joint die due to a lack of blood supply often triggered by the use of steroid medications. In such cases, the diseased bone is cut out and the injected stem cells can repair and stabilise it, avoiding the need for a hip replacement.

“Those are two examples where the orthobiologic treatments that we have available to us right now are actually curative,” said Dr Shapiro.

But since these are relatively new therapies, more studies are still needed to confirm the promising results in the long term.

Orthobiologics are complements, not magic bullets

In the vast majority of cases, orthobiologics are combined with other treatments to improve overall outcomes.

“In most of the things we treat, orthobiologics are not curative nor regenerative, but they are used to relieve pain and maybe alter the natural course of orthopaedic disease,” explained Dr Shapiro.

Osteoarthritis of the knee, an age-related problem that causes pain due to the wear and tear of the cartilage tissue, is a good case in point. Half of the patients who present with the condition usually end up having a knee replacement, a major surgery to cut away damaged bone and cartilage to replace them with metal and plastic implants.

PRP in particular has pushed the envelope in treating knee osteoarthritis, one of the most studied conditions when it comes to orthobiologics, perhaps because it affects about 30 million Americans and 240 million people worldwide.

“Our patients are getting one to two years of pain relief from their knee arthritis, and that’s a lot more than we usually see from a cortisone or hyaluronic acid injections, which are the standard of care,” he stressed.

Though the therapy triggers no tissue regeneration and has to be repeated regularly, it can dramatically help patients by sparing them knee replacement, but only if it’s complemented by physical therapy, knee bracing, or over-the-counter pain relievers like Tylenol. In other cases, it can put off surgery until patients are old enough to benefit from it.

“For a lot of people in their 50s, PRP can provide a number of years of solid treatment to delay a costly and invasive surgery until their late 60s or early 70s,” he said. This is the age group that usually undergoes knee replacement since the implant has a variable shelf life and needs to be replaced after wearing out.

Although in lab experiments stem cells have shown an even stronger therapeutic potential than PRP in relieving pain, there’s not as much evidence of their effect in patients to support their use against knee osteoarthritis with a similar degree of confidence.

“If you’re making a recommendation to the patient, you would always say, ‘we have 10 years of experience studying PRP and we know that works and what it does,’ therefore it’s a good recommendation to tell patients to try that. When it comes to stem cell treatments, it’s harder to make that recommendation because they’ve not been studied as much,” he acknowledged.

Another condition where orthobiologics can play a role is the rotator cuff tear, a common injury to the muscles and tendons of the shoulder joint that in about 25 percent of cases requires surgery.

Some studies have shown that adding PRP or stem cells to the site of the injury during surgery speeds up healing of the tendons and lowers the rate of retear in the future. Patients usually face three to four months of recovery and won’t be able to play sports for at least eight months, but orthobiologics can reduce healing time in the order of a month or so as well as the risk of retear by 15 to 20 percent.

“Even a month faster is real value to people,” stressed Dr Shapiro, who nonetheless cautioned that PRP didn’t prove to be an effective standalone approach for the condition. “PRP is not commonly used for a torn rotator cuff without surgery because it’s not an adequate treatment — another example showing that orthobiologics are not a magic cure but are used to complement standard treatments.”

But in addition to tennis elbow, there is another condition where PRP can also help avoid surgery altogether, for example, when a patient has a ligament injury to the connective tissue that connects bones to each other. Lots of baseball pitchers, for instance, get their elbow ligament injured and may require a surgical fix taking almost a year to recover. But PRP, when followed by physical therapy, can promote repairing of a partial ligament tear that has previously failed to heal and get patients back to doing sports in a matter of weeks or months.

“That’s an example of orthobiologics that has revolutionised sports medicine,” said Dr Shapiro, noting that the approach has not yielded the same results in treating all ligament injuries. Ankle sprains, for example, are a common problem that’s not responded well to PRP.

Similarly, not all tendon injuries have improved with orthobiologics. “We haven’t seen any great benefit for Achilles tendinitis, so we don’t use either PRP or stem cells to treat it,” he said.

The road ahead for orthobiologics

More research is required to strengthen the evidence backing up current regenerative treatments and expand the pool of conditions that can be treated with them.

“There are many people who are still sceptical about orthobiologics and for good reasons,” acknowledged Dr Shapiro. “We test vaccines on thousands of patients and these orthobiologics sometimes have only be tested on 25 or 50 patients — that’s not good enough evidence.”

Putting together data from multiple studies, he added, will make a stronger case for the use of orthobiologics, thus allowing them to gain more traction.

One successful example is the use of PRP during rotator cuff surgery. “Initially, all the studies were negative and it looked like it didn’t work, and it was only after researchers were able to combine larger numbers of patients, up to a thousand, that allowed the statisticians to determine that there was an actual benefit,” he said.

What this means is that we’re going to need specific studies to determine which orthopaedic condition is potentially amenable to which orthobiologic treatment before jumping to conclusions about what works against certain diseases.

“We have a stem cell study for shoulder arthritis because most of the research has gone into looking at knee arthritis, and then you just assume that everything that works for knee arthritis also works for the hip and the shoulder, but that’s not actually the case,” explained Dr Shapiro. “The orthopaedic community needs to conduct the same clinical trials in the shoulder, the hip, the wrist, and the ankle as we do in the knee, so we’re working on that for the shoulder.”

Another goal pursued by many researchers is to use orthobiologics to regrow knee cartilage, a breakthrough that could potentially help millions of people improve their mobility, decrease pain, and avoid knee replacement procedures.

One study at the Mayo Clinic looks promising, said Dr Shapiro, with early results hinting that patients’ stem cells that have been expanded in the lab (a technique not currently used in the clinic) can plug small defects in knee cartilage.

If successful, this approach could treat people who have signs of early cartilage degeneration before they reach a point where the knee joint is compromised and the only option is to replace it through surgery.

Dr Shapiro believes this prospect is not far-fetched.

“This trial just goes to show you that the treatments we’re using right now are our first effort at using cells to cure orthopaedic disease, but we anticipate, with better research, more trials, and novel therapies, we’ll be able to do even better.”