In April, researchers at the University of Colorado Boulder, Duke, and Columbia University announced successes in separate, major federally funded efforts to regrow cartilage and bone to solve the problem of knee osteoarthritis.

Knee osteoarthritis is a huge and costly problem. About 40% of people will deal with knee osteoarthritis at some point, and it affects about one-third of people in their 60s and older.

Doctors do 800,000 knee replacements each year in the United States alone. These surgeries have high success rates, but the rehabilitation regimens are arduous, and patients face limitations to minimize wear and tear on artificial joints.

Over the past two decades, treatment options for knee osteoarthritis have expanded beyond traditional medications and corticosteroid injections. Established nonsurgical options now include hyaluronic acid and platelet-rich plasma injections, alongside emerging technologies such as shockwave and laser therapies.

Which treatment approaches work, and how well? How does lifestyle figure in? How far along are scientific efforts to regenerate knee cartilage? And what actually causes knee osteoarthritis in the first place? (It’s not just wear and tear.) To get up to speed on knee osteoarthritis, what people can do about it now and what might be coming soon, we reached out to UCHealth orthopedic surgeon Dr. Rachel Frank, who is also a professor of orthopedics at the University of Colorado Anschutz School of Medicine and specializes in joint preservation and cartilage restoration.

What is knee osteoarthritis?

Knee osteoarthritis is a condition in which the cartilage in the knee wears away. This leaves the bones at the knee grinding together rather than gliding over the cartilage on the bottom of the femur (thighbone), the top of the tibia (shinbone), and the thick meniscus cartilage that acts as a bumper between them.

What causes knee osteoarthritis with age?

Until a few years ago, the prevailing belief was that knee osteoarthritis was mechanical wear and tear with age. That belief is outmoded, Frank said.

“One of the most important advances in our understanding of osteoarthritis is recognizing that it is not simply cartilage wearing out over time,” she said.

Osteoarthritis is a disease of the entire joint, including cartilage, the underlying bone, the joint lining (synovium), surrounding soft tissues and “complex interactions among inflammatory and metabolic pathways,” she said.

A recent study found that those interactions appear to be consistent among people with knee osteoarthritis.

“Previous injuries, abnormal alignment, obesity and repetitive loading can all contribute to osteoarthritis, and, often, can trigger biological responses within the joint, including inflammation, changes in cartilage metabolism and alterations in the cells responsible for maintaining healthy tissue,” Frank said. “That helps explain why two patients with similar-looking X-rays can have very different symptoms, and why some patients develop progressive arthritis after an injury while others do not.”

The work to understand the biological causes of knee arthritis continues.

“We may eventually be able to intervene earlier and slow or prevent progression, rather than simply treating pain after significant joint damage has occurred,” Frank said.

Does walking or running cause osteoarthritis? Is it bad for knees with osteoarthritis?

Former elite athletes have higher rates of knee osteoarthritis than the general population, and that’s also true for those who have undergone an ACL reconstruction. But recent studies show that walking and recreational running are good for the knees for most people—including those with knee osteoarthritis.

One study found that 1,212 participants who walked for exercise had less-arthritic knees and less new knee pain than those who didn’t.

Another study found that older adults who walk about 6,000 steps a day have fewer functional limitations, such as difficulty walking or climbing stairs, than those who walk less.

Those studies aligned with a study that found runners over 50 have less new knee pain and no worsening knee pain or cartilage-loss progression on scans. Another — a review of MRI imagery — found that cartilage rebounds completely after running-related compression. Yet another found that marathoners have, on average, lower rates of knee osteoarthritis than age-adjusted peers.

It’s important to note that cartilage in healthy knees can regenerate and heal despite having no direct blood supply. The synovial fluid that lubricates the knees also delivers nutrients. But synovial fluid can also deliver inflammatory immune system proteins that hurt rather than help knee cartilage.

What are the best treatments for knee osteoarthritis?

Frank said the most effective treatments for knee osteoarthritis are a combination of exercise, physical therapy, weight management and medications or injections to manage symptoms. Treatments will differ based on the severity of arthritis, the patient’s activity level, and their goals, she said.

Exercise is one of the most important interventions to reduce pain and improve function, including strength training focused on the thighs, hips, and core, she said.

Weight loss can also help by reducing the load the knee bears and minimizing inflammation that can affect the knee and impair cartilage’s ability to maintain itself.

Oral acetaminophen and oral or topical NSAIDs such as ibuprofen or Voltaren can diminish pain. In the case of NSAIDs, inflammation and corticosteroid injections can also provide relief, but doctors can only use them intermittently. Knee braces that take pressure off the parts of the knee with worn cartilage also provide relief.

Corticosteroid injections can provide short-term relief of pain and inflammation, particularly during symptomatic flares. However, their benefits are generally temporary, and concerns about potential adverse effects on cartilage with repeated injections limit their long-term use, Frank said.

Hyaluronic acid (HA) injections, sometimes referred to as viscosupplementation, are another established option that may improve pain and joint function in selected patients, she said.

Platelet-rich plasma (PRP) injections, which use concentrated components of the patient’s own blood, have also demonstrated meaningful improvements in pain and function in multiple clinical studies. Some studies suggest that PRP may provide more sustained symptom improvement than corticosteroid or hyaluronic acid injections, although results vary depending on the PRP formulation, patient characteristics, and severity of arthritis.

“Importantly, the goal of these injections is to improve symptoms and function, not to regrow cartilage or cure arthritis,” Frank said. “We individualize treatment based on the patient’s needs, recognizing that no single injection is the best option for every patient.”

And at some point, when the pain becomes unbearable, there’s knee arthroplasty.

“For patients with advanced arthritis who continue to experience significant pain and disability despite nonsurgical treatment, knee replacement remains one of the most effective treatments available,” Frank said.

Do shockwave and laser therapies work for knee osteoarthritis?

There’s a long list of knee osteoarthritis treatments with what Frank and colleagues at the American Association of Orthopedic Surgeons describe as having limited evidence, including laser treatment, manual therapy, massage, acupuncture, transcutaneous nerve stimulation, percutaneous nerve stimulation and extracorporeal shockwave therapy.

Frank also notes advances in joint-preservation surgery, “including cartilage-restoration  procedures, meniscus transplant procedures and osteotomies to correct abnormal alignment in carefully selected patients.”

“These approaches are not appropriate for every patient with arthritis, but they can help certain patients maintain their native knee longer,” Frank said.

Could regenerating knee cartilage lead to a cure for osteoarthritis?

The Advanced Research Project Agency-Health, or ARPA-H, is providing more than $100 million to three research projects that have shown progress in regenerating cartilage and even bone in arthritic knees. The aim of the program, called Novel Innovations for Tissue Regeneration in Osteoarthritis, or NITRO, is to speed the transition from lab discovery to commercialization.

One team is led by the University of Colorado Boulder in collaboration with University of Colorado Anschutz and Colorado State University faculty. The $33.5 million project has repurposed an already-approved medication as an injectable that has, in animals with arthritic joints in injuries, healed the cartilage in four to eight weeks with a single injection into the joint. The team has launched Renovare Therapeutics to speed commercialization; they aim to start human clinical trials in the next year or so.

A Duke University-led team succeeded in healing animal joints with a combination of shots that makes cartilage cells grow and helps bone that can get misshapen with arthritis to remodel into a healthier form. And Columbia University’s NOVAKnee program is developing a complete, 3D-printed human knee, created with a biodegradable scaffolding material infused with stem cells.

“We seem to be entering one of the most exciting periods in osteoarthritis research,” Frank said. “What is especially encouraging is that these researchers are approaching this problem from several different directions, including regenerative therapies, tissue engineering, and treatments that target the biological pathways responsible for joint regeneration.”

But regenerating cartilage in a lab or with an animal model is still a long way from proving that it can “reliably reduce pain, improve function and potentially prevent joint replacement in humans,” she said.

“I remain optimistic that disease-modifying treatments will eventually become part of our clinical practice,” she said. “However, none of these emerging regenerative approaches should currently be viewed as a proven cure for osteoarthritis.”