In a new theory on the long-lasting impact of lead on health, University of Rochester scientists say exposure to the metal interferes with bone formation and increases the risk of osteoporosis later in life.
If verified, the theory would have significant implications for those in the baby boom generation, especially women, who may have been exposed to lead as they grew up in the 1950s and 1960s, when lead levels in the environment were higher than they are today.
As these women reach menopause, lead from their past, which has been stored in bone for decades, is released, the scientists say. The lead could accelerate the decline in bone density and increase the risk of fractures -- both symptoms of osteoporosis -- and also inhibit normal fracture healing.
Exposure to lead has not been considered a risk factor for osteoporosis. But UR scientists think it should be.
"We predict an increase in lead-related osteoporosis in the next decade," said Edward Puzas, UR professor of orthopaedics. "This really changes the way we view people who have been exposed to lead."
The UR scientists have based their theory on a decade of research at the cellular level and in animals. Much of the work has been published in peer-reviewed journals.
As part of the research, UR is now studying Rochester children who have been exposed to lead to determine whether lead prevents them from attaining peak bone density, a key element in the researchers' osteoporosis theory.
UR also has applied to the National Institute of Environmental Health Sciences for a grant that would provide $5 million to define the role of lead toxicity in bone.
"Their preliminary studies have provided a basic science foundation and compelling evidence for their theory," said Dr. Howard Hu, associate professor at the Harvard Schools of Medicine and Public Health. "Their proposed project will go a long way in assessing that theory."
Dangers of lead
Lead is toxic in the human body. The major sources of lead exposure are deteriorated paint in older housing and dust and soil contaminated with lead from old paint and emissions of leaded gasoline.
Lead exposure can create a lifetime of physical and mental problems. It is a major environmental threat to children. Even at low levels, lead can damage the nervous system, interfere with growth, lower IQ scores and make learning difficult. In severe cases, lead causes retardation.
More than a dozen UR scientists -- including Puzas; Dr. Randy Rosier, chairman of the UR department of orthopaedics; Dr. Regis O'Keefe, UR professor of orthopaedics; and Edward M. Schwarz, an assistant professor at UR's Center for Musculoskeletal Research -- are involved in the research.
At least 10 million Americans have the painful and often debilitating disease. The estimated annual expenditure in hospitals and nursing homes for treatment of osteoporosis and related fractures is $13.8 billion.
The evidence
The UR scientists do not link lead to all cases of osteoporosis. Other risk factors include a family history of the disease, a lifelong low-calcium diet, lack of exercise, smoking and drinking excess alcohol. Determining the percentage of cases actually related to lead exposure will take much more research, the UR scientists say.
But the scientists point to an array of findings that suggests lead is a culprit in the disease. Exposure to lead causes low bone density in lab animals such as mice, the UR scientists say. Fractures in mice with lead-induced osteoporosis also do not heal properly.
Lead alters the pathways bone cells use to transmit or regulate actions, the scientists found. This could explain limited bone growth in children and adolescents exposed to lead.
"Kids who have lead poisoning are small in stature and have abnormalities in bone growth," Rosier said. "The dramatic effects we are seeing in our studies of cell cultures are caused by lead levels that are relevant. They are levels you would find in the environment from paint and gasoline."
The researchers also report that lead interferes with a specific gene called TRIP that directs osteoblasts, cells that play a major role in the building of bone. UR has applied for a patent on the gene as a potential drug target to stimulate bone growth or as a possible gene therapy that could be applied to artificial implants or to fractured bone to enhance healing.
Despite a ban that removed lead from house paint in 1978 and from gasoline in the mid-1980s, lead remains a problem in the air, soil, walls and woodwork of many houses. A 1995 study found that 37.5 percent of Rochester children younger than 6 had elevated lead levels.
Puzas, the new president of the national Orthopaedic Research Society, said "osteoporosis starts when you are a kid... . If you are exposed to lead, you don't make as much bone and the structure is compromised. If you haven't made enough bone and then more comes out as you age, then you are really behind the eight ball."
Most of the lead that is not excreted from the body gets stored in bone, locked away for many years.
The body's changes
Throughout life, for a variety of reasons, bone changes. Old bone is broken down and removed by cells called osteoclasts. New bone replaces the old, a building job performed by the osteoblasts.
During menopause, the balance between breaking down and building new bone is altered because of a decline in the production of the estrogen hormone.
Women then begin to lose bone rapidly.
Although less prevalent, hormonal changes also can increase bone loss and the risk of osteoporosis in men.
As bone loss increases, the lead in the bone is released, according to UR scientists and other researchers. The lead again interferes with the bone formation process.
The reappearance of the lead could cause other problems, such as kidney dysfunction, high blood pressure and mental impairments.
"It might be that people are being repoisoned by the lead," Rosier said.
The proposed UR research project would examine the impact of lead at the cellular and molecular levels in bone and its effect on fracture healing. The scientists also want to study whether current drug treatments for osteoporosis are effective in containing lead in bone.
If the theory is verified, those exposed to lead should follow the best practices aimed at reducing the chance of osteoporosis, including weight-bearing exercise and a diet rich in calcium and Vitamin D.
A decision on the federal grant by NIEHS is expected by summer.
"One of the chief challenges with lead toxicity is that it affects all sort of things: enzyme systems, cell growth, DNA expression," said Harvard's Hu. "The challenge is not only to quantify that but also to figure out whether the effects that might be seen in the laboratory ultimately have health implications."
|
If you have come to this page from an outside location click here to get back to mindfully.org |