Is ‘frozen shoulder’ a genetic condition? NY study finds links to specific genes

Research by orthopedists in New York City points to specific genes associated with an increased risk of this condition.

 People crowd into 7th Avenue at 42nd street in Manhattan in 2015.  (photo credit: REUTERS/MIKE SEGAR)
People crowd into 7th Avenue at 42nd street in Manhattan in 2015.
(photo credit: REUTERS/MIKE SEGAR)

Giving someone the cold shoulder means ignoring them, but the medical condition “frozen shoulder,” or adhesive capsulitis, cannot be ignored by the sufferer.

A common cause of shoulder pain and immobility, it was given that name because the more pain the person feels, the less likely the shoulder will be used. This lack of use causes the shoulder capsule to thicken and become tight, making the shoulder even more difficult to move and “freezing” its position.

It is not clear why some people develop it, but some groups are more at risk. It happens more often in women than in men, and you are more likely to get it if you are between the ages of 40 and 60. Your risk might also go up if you are in the process of recovering from a medical condition, such as a stroke, or surgery, such as a mastectomy, that keeps you from moving your arm. Smokers also have higher risk, as do patients with diabetes, heart, thyroid or Parkinson’s disease.

But now, research by orthopedists in New York City points to specific genes associated with an increased risk of this condition. Their findings have just been published in The Journal of Bone & Joint Surgery under the title “Genome-Wide Association Study of Adhesive Capsulitis Suggests Significant Genetic Risk Factors.”

The risk genes are associated with nearly a six-fold increase in the odds of developing frozen shoulder – a stronger association for most known clinical risk factors, according to the new research led by Dr. Mark Langhans of the Hospital for Specialty Surgery in Manhattan. The authors believe their findings may lend new insights into the causes, prevention and treatment of adhesive capsulitis.

Frozen shoulder occurs when the strong connective tissue surrounding the shoulder joint called the shoulder joint capsule becomes thick, stiff and inflamed. The joint capsule known as the ball-and-socket joint contains the ligaments that attach the top of the upper arm bone to the shoulder socket, firmly holding the joint in place. Treatment usually involves pain-relief methods until the initial phase passes.

 People line up at a COVID-19 testing site in Times Square during the coronavirus disease pandemic in the Manhattan borough of New York City, New York, US, December 17, 2021. (credit: REUTERS/CARLO ALLEGRI/FILE PHOTO) People line up at a COVID-19 testing site in Times Square during the coronavirus disease pandemic in the Manhattan borough of New York City, New York, US, December 17, 2021. (credit: REUTERS/CARLO ALLEGRI/FILE PHOTO)

What happens if the problem persists?

If the problem persists, therapy and surgery may be needed to regain motion if it does not return on its own. If surgery is required, full anesthesia is given, during which the orthopedist forces movement of the shoulder, causing the joint capsule to stretch or tear to loosen the tightness and increase the range of motion.

Since the risk is also higher in people with affected relatives, Langhans and his team thought there could be a genetic predisposition for the condition. They studied a large British database called the UK Biobank, performing a genome-wide association study to identify specific genes that might be related to the risk of frozen shoulder.

Out of the 500,000 patients in the database, they found 2,142 with adhesive capsulitis and identified three significant loci for frozen shoulder. The strongest association was found for gene variants located at a site called WNT7B. Weaker associations were also found for two genetic loci located near genes for POU1F1 and MAU2.

Their findings could bring new insights into the development of adhesive capsulitis, the authors suggested. In particular, genes located at WNT7B have been shown to be expressed in bone-forming cells (osteoblasts) and to be involved in regulating fibrosis, along with a wide range of other functions.

The two newly reported loci, POU1F1 and MAU2, are involved with cell division, which might provide clues to the cellular mechanism by which frozen shoulder develops.