Other Endocrine Disruptors
Compiled by Melissa Kaplan, 2000
Estrogen, Fracture Healing, Bone Formation
ROSEMONT, Ill.--Smoking impairs the health of muscles, bones and joints, according to the latest issue of the peer-reviewed Journal of the American Academy of Orthopaedic Surgeons (JAAOS).
"It decreases people's ability to form bone, putting them at risk for osteoporosis," said co-author Scott E. Porter, MD. "Nicotine also lessens the benefits of estrogen.'
Cigarette smoking accelerates the bone loss of osteporotic postmenopausal women, noted co-author Edward N. Hanley Jr., MD, chairman, department of orthopaedic surgery, Carolinas Medical Center, Charlotte, N.C.
"Women who smoke have significantly less bone mass, which may be due in part to nicotine's inhibition of estrogen," said Dr. Hanley. "Male smokers also are at increased risk of developing osteoporosis because smoking affects the production of bone cells."
For the study, the two orthopaedic surgeons conducted a literature review of scientific data on the relationship between smoking and musculoskeletal disease. Their findings, "The Musculoskeletal Effects of Smoking," are reported in the January/February 2001 JAAOS, an official publication of the American Academy of Orthopaedic Surgeons.
Each year, more than 500,000 deaths in the U.S. can be attributed to smoking. "The effects of smoking on a person's cardiovascular health are well documented," said Dr. Porter. Tobacco is linked to numerous cancers as well.
"What many smokers may not realize is that smoking also has a negative impact on musculoskeletal health," he said, noting that many people experiencing low back pain are smokers. "It is possible that heart disease, caused by smoking, can initiate low back pain symptoms because the lumbar discs may be malnourished from the lack of adequate blood supply."
Smoking may also be an indicator of poor health and lifestyle, which contribute to the development of low back pain. The JAAOS article also reported that smoking is associated with bone loss, hip fractures and decreased ability for bones and wounds to heal.
"Several studies showed that smokers who have wounds or surgical incisions often take longer to heal than non-smokers," said Dr. Hanley, explaining that smokers' tissues do not get enough oxygen to fully repair themselves. "As a result, it is more difficult for smokers to recover from breaking a bone. Cigarette smoking also slows the healing after orthopaedic surgical procedures. For example, it specifically decreases the rate of both healing and success after spinal fusion. This has huge economic impact."
In its 'Smoking and the Musculoskeletal System' Position Statement," the Academy states "People who smoke cigarettes during adult life can expect to live 7 to 10 years less than nonsmokers. Cigarette smoking not only affects the quantity of life, but also the quality of life, especially in later years."
The Academy strongly recommends avoidance of smoking due to the severe and negative impact on the musculoskeletal system-the bones, muscles, tendons and ligaments in the body.
"The risks and complications associated with smoking should be discussed with people who are receiving orthopaedic treatment," said Dr. Porter, the Harry Winkler Jr. orthopaedic surgery research fellow, department of orthopaedic surgery, Carolinas Medical Center. He urged patients to give a complete smoking history to their doctors.
"Tobacco smoking is the most preventable cause of morbidity and mortality in the United States," Dr. Hanley said. "Doctors should offer their patients assistance in smoking cessation."
The American Academy of Orthopaedic Surgeons (www.aaos.org or http://orthoinfo.aaos.org) is a not-for-profit organization that provides education programs for orthopaedic surgeons, allied health professionals and the public. An advocate for improved patient care, the Academy is participating in the Bone and Joint Decade (www.bonejointdecade.org), the global initiative in the years 2000-2010 to raise awareness of musculoskeletal health, stimulate research and improve people's quality of life.
Arsenic: A new type
of endocrine disrupter?
Hanover, NH A team of Dartmouth Medical School investigators has uncovered what may be a unique mechanism for the way chronic exposure to low levels of arsenic increases the risk of certain diseases. The work is described in the March issue of the journal Environmental Health Perspectives.
Arsenic at high doses has been known as the poison of choice since ancient times. Recently, it has become clear that decades of exposure to very low doses of arsenic such as levels found in drinking water in many areas of the United States may substantially increase the risk of vascular disease, diabetes and several types of cancer. Until now, little was known about how arsenic might contribute to these diseases, however.
Using cultured animal cells, a team led by toxicologist Joshua Hamilton, director of Dartmouth's Toxic Metals Research Program, found that exposure to very low concentrations of arsenic disrupts the function of the glucocorticoid receptor, a steroid hormone receptor that regulates a wide range of biological processes. Arsenic appears to suppress the ability of this critical receptor to respond to its normal hormone signal. Chemicals that disrupt steroid hormone receptor signaling are called endocrine disrupters. Arsenic, a metal, appears to act through a unique mechanism not previously shown for other endocrine disrupters such as pesticides.
"This is unlikely to be the only mechanism underlying diseases associated with low-level arsenic exposure, but we suspect it will be an important contributor," says Hamilton. The research was performed in Hamiltons laboratory in the Department of Pharmacology and Toxicology by former graduate student Ronald Kaltreider (now an assistant professor at York College in York Pa.) with the assistance of undergraduate student Alisa Davis and Research Assistant Jean Lariviere. The Toxic Metals group is one of the interdisciplinary research projects associated with the Center for Environmental Health Sciences at Dartmouth, which Hamilton also directs. The work is funded by a grant from the National Institute of Environmental Health Sciences and the Environmental Protection Agency through the Superfund Basic Research Program.
Glucocorticoids are steroid hormones in the same class as estrogen, progesterone and testosterone. Steroid hormones are chemical messengers secreted by glands into the bloodstream and carried to distant cells throughout the body where they help regulate the body's functions. Each hormone has a specific receptor it binds to in order to initiate its effects. Glucocorticoids, acting through their receptor, help regulate embryo development, stress, blood glucose levels, blood vessel function, and lung and skin development, and may also play a key role in suppressing cancer.
Prior to this study, endocrine disrupting chemicals were thought to act primarily in one of two ways. One way is by binding to a steroid receptor and mimicking the normal hormone, leading to an inappropriate activation of the receptor. The other way is by binding to the receptor and blocking the ability of the normal hormone to activate the receptor. Arsenic appears to act in a third way. Kaltreider's research demonstrated that arsenic does not inappropriately activate the glucocorticoid receptor, nor does it block its ability to bind hormone or be activated by hormone binding. Rather, in the presence of arsenic, the activated receptor is unable to stimulate the correct cascade of signals that usually results from hormone binding, particularly the ability to turn on certain hormone-responsive genes. Metals have not previously been shown to act as endocrine disrupters. Blocking the actions of the glucocorticoid receptor by arsenic in this unique way could explain, at least in part, many of the health effects observed in arsenic-exposed human populations.
Whether the effects observed in cultured cells also occur in animals or humans exposed to low doses of arsenic remains to be determined, and Hamilton's laboratory is actively pursuing that research. The researchers are also examining whether arsenic has a similar effect on the estrogen, progesterone and testosterone receptors, which could have further implications for arsenic's effects on human health.
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