What We Don’t Know About PRP and Joint Injections
Injections into injured joints and tissues have exploded in the last decade. Though they all seem to work, here is some of what we don’t know.
Joint injections used to be either cortisone or sugar-based injections (prolotherapy). Cortisone shuts down cell metabolism and activity in an inflamed joint where the living cells are overproducing fluid, providing relief of swelling and pain. The downside was that steroids did nothing to help heal. It also weakened the surrounding tissues, led to tendon ruptures, and was associated with a significantly higher infection rate if surgery was performed in the weeks or even months after a joint was injected.
Prolotherapy injects sugar-based fluids into joints and tissues. It induced inflammation, which caused cells to lay down new collagen — usually in the form of scar tissue. It was widely used around the spine, as it was believed that the excess motion of spinal segments led to pain, and new scar tissue would stabilize the joints.
In the 1970s, after it was noted that hyaluronic acid (HA) was the primary lubricant of all animal joints, HA injections became widely used. Various forms of HA were manufactured, each of which varied in the length of time the HA stayed within the joint. Injections in horses and humans were temporarily effective, but lasted variable amounts of time and had no direct effect on healing tissues.
Platelet-rich plasma (PRP) was initially used in the 1940s but popularized in orthopaedics in the 1990s. The fractions of blood containing platelets were concentrated, and the bioactive factors in the platelets released in various tissues. Multiple positive attributes were noted. These included anti-inflammatory, anti-fibrotic (scarring), immunomodulatory (influence the immune response), antibiotic, and anabolic effects on injured and arthritic tissues. There appears to be no downside. Studies conducted at The Stone Clinic and elsewhere showed that, when combined with HA injections, the beneficial effects of PRP lasted longer.
One problem in studying PRP, however, is that the product derived from the patients’ platelets varied by time of day, by hematocrit, by fluid status, and by a host of other unknown causes. Blood is not a static product, and the outcomes vary widely. Some patients with bone-on-bone arthritis and horrible-looking X-rays would come in and say “Doc, I am not letting you operate on my knee until those injections stop working”…18 months after the last one and other patients got no relief at all.
Injecting mesenchymal stem cells (MSCs) from the patients’ own fat or bone marrow (or grown in culture) became popular in the 2000s with broad claims of efficacy made without great science behind them. The concept was clear: Cells direct healing, stem cells are pluripotent, and therefore the more the better. Since they are “immune-privileged,” even cells from other donors can work. Needles were placed into body parts to harvest these cells, and some patients traveled to the Caymans, Mexico, and other places for various unapproved sources of cells. One problem was that it was not clear how long these injected mesenchymal stem cells lived within the joints — and no studies demonstrated convincingly that the effect of the cells was any better than the effect of PRP plus hyaluronic acid alone.
Birth tissues, primarily Wharton’s Jelly, have had enthusiastic followers since various assessments showed that they have sixty times the growth factor concentrations of PRP and that they potently recruit the body’s own stem cells to the site of injury. Membranes of amniotic tissues were used widely for diabetic ulcers and other severe wounds for decades before these injections started with dramatic and easily observed positive effects. The FDA, however, restricted birth tissues use as injectables in joints until more data through controlled trials is obtained.
The body has billions of stem cells living on the walls of blood vessels, even in older people. Intuitively, the most potent injections will be those that have an immediate local effect (like hyaluronic acid and PRP) combined with a vigorous recruitment of the body’s own cells. We, at Stone Research Foundation, and others are currently focusing on these recruitment factors. The Sirens’ call is to not just treat but to regenerate and improve the injury. We don’t yet know the best way but we surely know that just removing tissues is not the answer.
