Tobacco Smoke Toxins Shown to Cause Bone Degradation and Loss
Landmark Research Led by Mount Sinai Medical Center and the University of Pennsylvania Lays Groundwork to Prevent and Treat Osteoporosis
Two toxic compounds – benzo(a)pyrene (BaP) and 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) – have been shown to cause bone degradation and osteoporosis, in a landmark animal study titled "Smoke Carcinogens Cause Bone Loss Through the Aryl Hydrocarbon Receptor and Induction of Cyp1 Enzymes." Results of the study, led by a joint research team from The Mount Sinai Medical Center and the University of Pennsylvania, are published online June 17 in the Proceedings of the National Academy of Sciences of the United States of America.
"It has long been known that firsthand exposure to cigarette smoke has an adverse impact on the body's bone structure, putting chronic smokers at higher risk for bone fractures and osteoporosis. But until now, it was not entirely clear exactly how smoking caused bone loss," said Mone Zaidi, MD, PhD, Professor of Medicine, Endocrinology, Diabetes and Bone Disease at the Icahn School of Medicine at Mount Sinai and the Director of the Mount Sinai Bone Program, who led the study in collaboration with researchers at the University of Pennsylvania.
"Our study implicates a number of poly aryl hydrocarbons and dioxins found in tobacco smoke, and clarifies how those toxins enhance active bone breakdown to make the skeleton more fragile," Dr. Zaidi added. "It is our hope that these findings provide the conceptual framework for the design of novel therapies to help prevent and treat osteoporosis."
"It has been known from many epidemiological studies that smokers usually show bone loss, and their bone density is much lower than non-smokers' bone density," said Narayan Avadhani, PhD, Biochemistry Professor and Chair of the Department of Animal Biology at the University of Pennsylvania's School of Veterinary Medicine. "What we show here is that excessive formation of osteoclasts by cigarette chemicals causes bone loss."
As part of the body's natural processes, bone matter undergoes both removal and regrowth in what is known as bone remodeling. In this mouse study, researchers showed that two toxins found in tobacco smoke, BaP and TCDD, interacted with the subjects' aryl hydrocarbon receptors (AhR) to induce osteoclastic bone resorption through the activation of enzymes called cytochrome P450 1a/1b Cyp1. That is, the normal process through which bone is remodeled became unbalanced; more bone matter was being removed than was being created.
Overall, researchers found that the data identify both AhR and Cyp1 enzymes not only in the pathophysiology of smoke-induced osteoporosis, but also as potential targets for selective modulation by new therapeutics.
About Penn Vet
Penn Vet is one of the world's premier veterinary schools and is the only school in Pennsylvania graduating veterinarians. Founded in 1884, the school was built on the concept of Many Species, One MedicineTM. The birthplace of veterinary specialties, the school serves a distinctly diverse array of animal patients at its two campuses, from companion animals to horses to farm animals.
In Philadelphia, on Penn's campus, are the Matthew J. Ryan Veterinary Hospital of the University of Pennsylvania (Ryan Hospital) for companion animals; classrooms; research laboratories; and the School's administrative offices. The large-animal facility, New Bolton Center, in Kennett Square, PA, includes the George D. Widener Veterinary Hospital for large animals; diagnostic laboratories serving the agriculture industry; and research facilities to determine new treatment and diagnostic measures for large-animal diseases. For more information, visit http://www.vet.upenn.edu.
About The Mount Sinai Medical Center
The Mount Sinai Medical Center encompasses both The Mount Sinai Hospital and Icahn School of Medicine at Mount Sinai. Established in 1968, the Icahn School of Medicine at Mount Sinai is one of the leading medical schools in the United States. The Icahn School of Medicine is noted for innovation in education, biomedical research, clinical care delivery, and local and global community service. It has more than 3,400 faculty members in 32 departments and 14 research institutes, and ranks among the top 20 medical schools both in National Institutes of Health (NIH) funding and by U.S. News & World Report.
The Mount Sinai Hospital, founded in 1852, is a 1,171-bed tertiary- and quaternary-care teaching facility and one of the nation's oldest, largest and most-respected voluntary hospitals. In 2012, U.S. News & World Report ranked The Mount Sinai Hospital 14th on its elite Honor Roll of the nation's top hospitals based on reputation, safety, and other patient-care factors. Mount Sinai is one of just 12 integrated academic medical centers whose medical school ranks among the top 20 in NIH funding and by U.S. News & World Report and whose hospital is on the U.S. News & World Report Honor Roll. Nearly 60,000 people were treated at Mount Sinai as inpatients last year, and approximately 560,000 outpatient visits took place.