Researchers Warn of Escalation in Osteoporosis in Younger Women

NIH Funds Comprehensive Study to Determine Link Between Lead and Osteoporosis

April 09, 2003

Researchers at the University of Rochester Medical Center’s Musculoskeletal Research Unit believe that by the year 2005, when the majority of the female baby boomer generation begins entering menopause, more women than ever thought possible will begin to suffer from osteoporosis at a younger age due to high levels of lead exposure in their childhood. The early data indicate that as much as 10 percent of low bone density, the primary symptom of the disease, may be explained by lead in the skeleton.

A four-year, $3.8 million grant from the National Institutes of Health will allow scientists at the University’s Musculoskeletal Research Unit to explore the idea that lead can cause osteoporosis. The research program will also determine if lead slows down the bone’s ability to heal itself after fractures, as well as its role in skewing bone density mass test results. The four-year grant is the largest ever awarded to the University’s orthopaedic department, a leader in creating the osteotoxicology research field, which studies the relationship between toxins and their effect on bone metabolism.

Osteoporosis is a metabolic bone disease that predominantly occurs in women, affecting one in three American women over the age of 65. It is characterized by low bone mass and bone tissue deterioration that eventually can lead to fractures, mostly of the hip and vertebrae. These fractures can be life-threatening; experts say that more women die each year from hip fractures than from cancer of the ovaries, cervix and uterus combined. Close to $14 billion dollars is spent each year treating osteoporosis and related fractures.

According to Edward Puzas, Ph.D., the Donald and Mary Clark Professor of Orthopaedics and director of the Musculoskeletal Research Unit, research studies over the past four decades have consistently found that high levels of lead in the bloodstream can have adverse effects on bone growth and development. He and his team are expanding on this finding by trying to uncover the mechanism that explains this phenomenon and its relationship to osteoporosis.

"For decades, we have been aware that the human skeleton is a repository for people who were exposed to high levels of environmental lead in their childhood. Most have thought this storage of lead in the bones to be benign," Puzas said. "Recently, we have shown that the opposite is true—that high levels of lead in the bone will in fact stunt bone growth and decrease peak bone mass, and most importantly, contribute to bone loss at a greater rate once a woman enters menopause. The result will be that more women will be diagnosed with osteoporosis and suffer bone fractures while still in their 50s."

In addition, Puzas’ research leads him to believe that lead skews results from DEXA scans, the major diagnostic tool used to measure bone density and predict if a person has osteoporosis. It appears that lead makes a person’s bone mass look more dense than it actually is. Preliminary findings show that DEXA overestimates bone density by 4 to 11 percent—enough for a normal diagnosis, when in reality, the patient may have osteoporosis.

"The real tragedy here is that unlike a decade ago, today there are treatments for osteoporosis. So it’s frustrating to think that we could be helping people with osteoporosis, but we’re not because the lead in their bones is masking the disease," Puzas said.

Puzas’ study will attempt to develop a new DEXA scan standard that takes into account environmental lead exposure.

Troubling Demographics

In the 1950s and 1960s, when the baby boomer generation was growing up, exposure to environmental lead was a frequent occurrence, from lead in gasoline and in the plumbing, to paint on the walls and in the soil. Puzas says evidence suggests that this early lead exposure impairs several key bone-building mechanisms throughout a person’s lifetime:

  • Lead Stunts Skeletal Growth: At the heart of this theory is the bone’s growth plate, which determines the peak skeletal density achieved in adolescent and young adulthood. Puzas’ prior research shows that lead adversely affects the normal maturation of the growth plate. Thus, children exposed to lead will be relatively short in stature, but more importantly, will not achieve peak bone mass. Later in life, as all adults begin to lose bone mass, this becomes a big issue.

"If you are exposed to lead as a child, you don’t make as much bone an you normally should and the skeletal architecture may be compromised. If children do not reach a high peak level of bone in adolescence, they will be at higher risk for fractures later in life when we all lose bone." Puzas said.

  • Increased Bone Loss Rate: Previous studies have shown that lead-exposed individuals—especially females—lose bone at a faster rate than normal individuals. Throughout a lifetime, a person’s skeleton continually "turns over," where old bone is replaced with new bone. The rate of this turnover—or bone resorption and formation—is determined by a person’s age, genetics, diet, and physical activity, but for most people, the amount of new bone that is created equals the amount of bone resorbed by the body up until the age of 45. Then, as part of the natural aging process, both men and women begin to lose more bone than is replaced. Because estrogen is linked to the bone building process, the rate at which women lose bone greatly increases as they enter menopause.

Puzas’ preliminary works shows that lead creates an imbalance in resorption and formation, so that even more bone than usual is lost than replaced. That means lead-exposed individuals will lose more bone than normal, impacting a person’s bone mass.

  • Decreased Fracture Healing Rate: Building on prior research, Puzas said that significant lead levels in the skeleton will prevent normal fracture healing. The data to support this finding was derived from an experimental animal model and has not yet been proven to occur in humans, but Puzas believes future research will validate the findings.

The key investigators on Dr. Puzas’ team are Drs. Regis J. O’Keefe, Edward M. Schwarz, Randy N. Rosier, Michael J. Zuscik and James Campbell. He and his team will begin the research this year, and expect to complete it within a four-year period. At the same time, the team is also creating the methodology for a clinical trial that would conclusively confirm lead as an osteoporosis risk factor. If all goes well, Puzas hopes to have funding in hand to begin this research by 2003.

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