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New Research Offers Promise for Treating Arthrofibrosis

August 27, 2019
A hormone produced during pregnancy might be an effective treatment for frozen shoulder and arthrofibrosis of other joints as well.

With Jason Hsu, MD, Jaqueline Brady, MD, and Edward K. Rodriguez, MD, PhD

Arthrofibrosis, also known as adhesive capsulitis, of the joints affects 3 to 6% of the general population, and up to 20% in those with diabetes.1 The condition, which is most common in the shoulders, knees, wrists, and ankles, may be idiopathic, but is often post-traumatic—from an accident or a complication of surgery. It tends to occur when excessive formation of scar tissue interferes with the mobility of a joint. The condition tends to be painful and treatment is costly and time-consuming.

“Some people have really exuberant scar tissue formations,” explained Jason Hsu, MD, assistant professor of medicine at the University of Washington Medical Center in Seattle. Arthrofibrosis may lead to significant disability, making it difficult for individuals to work or perform their daily tasks. The condition is particularly common in the shoulder, where it is sometimes referred to as “frozen shoulder.” Shoulder arthrofibrosis may be self-limiting, resolving within one to three years.1 However, as many as 50% of patients continue to have problems for up to 10 years.2

First-line treatment is usually physical therapy, although debates exist over the best approach and technique.Some evidence shows that aggressive (high-grade) physical therapy is not as effective as gentler (low-grade) approaches, while other studies have found both modalities as equally effective.1 “If you have a skilled therapist and a motivated patient, physical therapy can be successful,” said Jaqueline Brady, MD, an assistant professor of orthopedics and rehabilitation at the Oregon Health & Science University School of Medicine in Portland. “However, it is hard work and painful.”

In some cases, manipulation under anesthesia is needed, where surgical removal of some of the scar tissue may be warranted. However, recent research3 from the Beth Israel Deaconess Medical Center in Boston, MAindicates shows promising results to better treating this problem.

A hormone produced during pregnancy could be beneficial for post-surgical arthrofibrosis. (Source: 123RF)

Lessons from Mom

Edward K. Rodriguez, MD, PhD, chief of orthopedic trauma in the Department of Orthopedic Surgery at Beth Israel Deaconess Medical Center in Boston, noted an interesting pattern when treating a few patients recovering from joint surgery. Some years ago, he saw three young female patients presenting with broken elbows. While he was able to repair the damage, all three patients suffered a significant loss of motion. A few years later, Dr. Rodriguez was surprised to find that all three patients had regained full motion. All three had also given birth since their treatment, which caught Dr. Rodriguez’s attention.

“Pregnant women’s joints get loose; they [tend to] walk wobbly,” he explained. This loosening of the joints is due to the production of a hormone called relaxin, which helps the mother’s body prepare for labor and delivery. However, after seeing how his patients regained mobility in their joints after pregnancy, Dr. Rodriguez saw a potential for new adaptation: “Can we make this work in other joints? In people who are not pregnant?”

Dr. Rodriguez teamed with researchers at his hospital to study an immobilization of the shoulders of female rats in order to induce arthrofibrosis and then treat them with relaxin-2 (a particular version of the hormone responsible for loose joints during pregnancy). “The half-life of relaxin is only a matter of hours,” said Dr. Rodriguez, “so we had to give them frequent injections.”

The results were impressive. The relaxin, by down-regulating the expression of collagen, reduced scar formation and produced significant and lasting improvement in range of motion in the subjects, compared to controls.

Next Challenges

The team’s next goals are to find a way to improve the delivery of the hormone relaxin to prevent frequent injections, and to figure out how the therapy could be tweaked to be effective in males, said Dr. Rodriguez. “If it becomes useful, could you overdo it and make the shoulder too loose?” he considered.

Added Dr. Hsu, “This therapy might be useful for that small set of patients who have post-surgical arthrofibrosis. [However], you’d need to be very aware of possible safety issues. Anytime you inject something into a joint, there’s the possibility of infection. Also, there’s always the possibility of unintended consequences.”

Agreed Dr. Brady, “It wouldn’t be for everyone. In problems that involve laxity, such as when reconstructing ligaments in knee surgery, it would be unpredictable and might even cause more problems. However, it could be very useful for rotator-cuff surgeries, after which patients are often plagued by stiffness and therefore take a long time to recover.”

However, where Dr. Rodriguez’s findings might be a real game changer, said Dr. Brady, is in those with diabetes. “Diabetics are at a higher risk for frozen shoulder, but you don’t want to use steroids because they can interfere with glucose levels and carry a risk of infection. This could be very beneficial for [them].”

More research is needed before the therapy becomes a reality. However, the researchers are hopeful that this well-tolerated hormone may prevent a common complication of surgery. “All knee and shoulder surgeries require physical therapy. This could avoid that,” said Dr. Rodriguez.

Last updated on: August 29, 2019
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