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Dr. Wolf (right) hopes information obtained from her study will lead to a way to prevent thumb CMC arthritis. Also pictured are (l-r) Jason Stoneback, MD, and Melissa Munkwitz, PA-C.
Courtesy of the University of Colorado, Denver

AAOS Now

Published 3/1/2003
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Amy Kile

Getting a grip on thumb arthritis

Clinician-Scientist Award recipient wants to know why

Writing a note. Twisting the lid off a jar. Unlocking and opening a door. Simple, everyday tasks become painful activities for patients who have thumb carpometacarpal (CMC) arthritis.

“People are surprised by how much they use even their nondominant hand,” said Jennifer M. Wolf, MD, a hand surgeon and assistant professor at the University of Colorado School of Medicine, department of orthopaedics.

According to Dr. Wolf, some statistics show that the incidence of hand osteoarthritis is second only to knee arthritis in the United States. In addition, thumb CMC arthritis occurs nearly 10 times more often in women than in men. With the help of an Orthopaedic Research and Education Foundation (OREF) Clinician-Scientist Award, funded by the Dr. Zachary and Mrs. Kathleen Friedenberg Endowment Fund, Dr. Wolf plans to learn why.

“Dr. Wolf proposed an interesting hypothesis regarding the role of gender in understanding how a specific molecule might explain the predilection of women for a joint abnormality associated with laxity leading to arthritis of the thumb,” said Thomas A. Einhorn, MD, OREF vice chair, grants. “The findings from this research could explain other gender-associated differences in joint disorders and how prevention and treatment strategies may need to be adapted to women and men.”

“OREF understands how difficult it is for clinicians to focus on research,” Dr. Wolf said. “Its greatest strength is supporting young scientists. This study will provide the preliminary data I need to apply for federal funding such as a National Institutes of Health grant.”

The role of relaxin
Dr. Wolf thinks that the level of relaxin serum—the hormone that prepares the female body for childbirth by softening the pelvic ligaments and cervix—may be part of the reason more women than men have thumb CMC arthritis. Some relaxin is also found in men, as well as women who are not pregnant, but its possible role in the development of arthritis is not yet understood.

“We’re trying to learn more about the relationship between relaxin and ligament laxity that may play a role in the development of osteoarthritis,” she said. One theory is that relaxin up-regulates matrix metalloproteases (MMPs) 1 and 3, enzymes that break down connective tissue.

Dr. Wolf hypothesized that the higher level of relaxin serum and up-regulated MMP1 and MMP3 are responsible for increased joint laxity, leading to abnormal joint forces and arthritis. With Institutional Review Board approval, Dr. Wolf is recruiting volunteers who have never injured their thumbs or been treated for thumb pain. She will study three age groups: 18–39, 40–59, and 60 and older. Age groups, men and women, and a subgroup of women at different points in their menstrual cycles will all be compared.

Dr. Wolf (right) hopes information obtained from her study will lead to a way to prevent thumb CMC arthritis. Also pictured are (l-r) Jason Stoneback, MD, and Melissa Munkwitz, PA-C.
Courtesy of the University of Colorado, Denver
Jennifer M. Wolf, MD, operates on a patient with thumb CMC arthritis.
Courtesy of the University of Colorado, Denver

Blood draws will be used to see whether serum relaxin levels correlate with laxity shown in radio­graphs. Dr. Wolf will also look at volunteers’ responses to questions about prior injuries or problems with their thumbs and, among the women volunteers, menstrual and pregnancy history. She will also measure body mass index to see if it affects joint laxity. Degree of laxity will be measured through both a radiographic stress test and the Beighton-Horan Joint Laxity Index test.

A surgical cohort
Dr. Wolf will then perform these same tests and analyses on patients undergoing surgery for thumb CMC arthritis. Although most surgical patients are age 60 or older, Dr. Wolf will still be able to compare men and women. She will also compare patients with the normal volunteers.

“During surgery, we will remove a piece of the patients’ anterior oblique ligament,” Dr. Wolf explained. “We’ll analyze it for the presence of relaxin, relaxin receptor, MMP1, MMP3, and tissue inhibitors of the metalloproteases.” Using molecular markers, Dr. Wolf will compare the levels of these hormones and enzymes to learn the differences between the normal volunteers and surgical patients as well as differences between men and women. She would also like to know whether relaxin is present at any age or found only in younger individuals.

From the results, Dr. Wolf hopes to develop further studies that could lead to treatments that prevent thumb CMC arthritis, especially in women.

“Is there a way to keep people from attenuating or stretching out their thumb ligaments? I think an intra-articular blockade or prevention at the molecular level is the most attractive solution,” she said. “I’d like to use the information from this study to focus on a molecular target and see how we can change the molecular environment to prevent the problem.”

Preventing the problem
Preventing the problem could mean a lot to thumb CMC patients, who are often unable to work and therefore affected economically as well as physically.

“Our goal should be to enable people to live as they want,” Dr. Wolf said. “We shouldn’t be telling them that they have to modify their activities so severely because they have this problem. As a woman, I want to find a solution so I don’t have to worry about thumb CMC arthritis later in life so I can continue to perform surgery and do all of the things I like to do. Our goal should be to give patients solutions.”

Amy Kile, OREF publications manager, can be reached at kile@oref.org

The Origin of OREF’s Clinician-Scientist Awards
Inspired by his experiences as an orthopaedic surgeon in a teaching hospital and hoping for a way to encourage young orthopaedists to take their real-world experiences into the laboratory, Zachary B. Friedenberg, MD, and his wife, Kathleen Friedenberg, established an endowment in 2002 to fund the first OREF Clinician-Scientist Award.

Soon after, Dr. Dane A. and Mrs. Mary Louise Miller and The Journal of Bone and Joint Surgery agreed to provide support annually for additional awards. All OREF Clinician-Scientist Awards provide $100,000 per year for 3 years, allowing recipients to spend at least 40 percent of their time in the laboratory.