The most potent dioxin, known as TCDD (2,3,7,8-Tetrachlorodibenzodioxin), is a carcinogen that is present in the tar of cigarette smoke and also in the bodies of chronic smokers. Some studies have shown that TCDD inhibits bone formation in vitro.


Published 9/1/2012
Catherine Rategan

Preventing Bone Healing from Going up in Smoke

OREF grant recipient hopes to reverse the effects of dioxin

Dioxins are highly toxic chemical by-products of combustion. Perhaps best known as a contaminant in the defoliant Agent Orange used during the Vietnam War, dioxin caused health problems in millions of people who were exposed to it during that conflict. A dioxin was used to poison Ukrainian president Viktor Yushenko in 2004.

Many people, however, may not be aware that dioxins are also present in cigarette smoke. Smoking has been shown to inhibit bone healing in a range of orthopaedic procedures, including spine fusion and fracture treatment. But the exact way in which cigarette smoke interferes with bone healing is still unclear. Although some researchers have postulated that nicotine content prevents bone healing, clinical studies have yet to prove this hypothesis.

Wellington K. Hsu, MD
© Copyright 2010 Northwestern Memorial Hospital. All rights reserved. Used with permission.

“It’s not yet clear how and why cigarette smoke inhibits bone healing,” said Wellington K. Hsu, MD, assistant professor in the department of orthopaedic surgery at Northwestern University’s Feinberg School of Medicine. “In our lab, we’re conducting an in vivo study to see whether TCDD, a prevalent dioxin, inhibits spine fusion in rats. If it does, we’re prepared to treat those research subjects with a substance called resveratrol that reverses the effects of TCDD and can perhaps diminish the negative effects of this toxin.”

The Orthopaedic Research and Education Foundation (OREF) has awarded a Young Investigator Grant to Dr. Hsu for his study “Characterization of the Inhibitory Effects of Dioxin on Bone Healing.”

Smoking and surgery
Dr. Hsu points out that up to 25 percent of patients who require orthopaedic care are smokers. “Those patients are less likely to be offered a surgical option because smoking is a negative risk factor,” he said. “That’s one reason orthopaedic surgeons encourage all patients to stop smoking. But if we can find a way to mitigate the negative effects of smoking, it could open a door to additional treatment options.”

He also points to a subset of the patient population who are not smokers but have high TCDD levels. These patients may live in areas with high levels of the contaminant or consume large amounts of red meat containing TCDD that eventually deposits into their systems.

The most potent dioxin, known as TCDD (2,3,7,8-Tetrachlorodibenzodioxin), is a carcinogen that is present in the tar of cigarette smoke and also in the bodies of chronic smokers. Some studies have shown that TCDD inhibits bone formation in vitro.
Members of Dr. Hsu’s laboratory (from left to right): Darlene Whittington, Joseph Nicolas, Rehan Riaz, Tim Wang, Dr. Hsu, David Nelson, Vladimir Ilievski, Erin Hsu, Jason Ghodasra Courtesy Wellington K. Hsu, MD

“If we can improve fusion rates or bone healing rates among smokers and other patients with high levels of TCDD, we could significantly lessen the burden on the healthcare system, leading to fewer revisions and complications,” continued Dr. Hsu. “Smokers may also experience many wound complications, such as infections. Although we’re not looking at immunologic effects in this particular study, the effects of smoking are much more far-reaching than just bone healing.”

Balancing the lab and the clinic
Dr. Hsu’s co-investigator on this project is his wife, Erin L. K. Hsu, PhD, a molecular toxicologist at Northwestern. She discovered a pathway in which TCDD affects the metastasis of breast cancer cells, and together they’re now looking at the same pathway as it applies to bone healing.

“We’re partners in life and in work,” said Dr. Hsu, who’s also a surgeon, a clinician, and an administrator. “We don’t work together in the lab each day, but having that relationship certainly enhances the efficiency of the work we do.”

Dr. Hsu points to the clinical applicability of his study. “For 80 percent of my week, I see patients in the clinic and, at certain times, operate on patients who smoke. I spend the remaining 20 percent of my time on research, such as studying the effects of smoking in an animal model, and I hope my findings will lead to treatment options that I can offer to the patients I see during my clinical hours. That’s the most rewarding part for me—that I could actually implement the findings of this research when the time is right.”

In addition to his position in theorthopaedic department, Dr. Hsuis an assistant professor in the department of neurological surgery. He is widely recognized for treating cervical and lumbar spinal disorders. Other aspects of his research focus on regenerative technologies for bone graft substitutes, including stem cell therapy, nanotechnology, and osteoinductive growth factors. He also directs “The Professional Athlete Spine Initiative” and is widely recognized as an expert on the outcomes of professional athletes after spine surgery.

Dr. Hsu contends that without support from OREF, he and other researchers would never be able to get off the ground. “A foundation such as OREF is the only way we can keep research by clinician scientists within the orthopaedic realm at a high level. And 5 to 10 years from now, the importance of OREF to researchers at all levels will be even more critical.”

Catherine Rategan is a contributing writer for OREF. She can be reached at