Growing body of research links lead to osteoporosis

Bolstered by recent laboratory findings, researchers at the University of Rochester Medical Center are embarking on a National Institutes of Health-funded clinical study to better understand the deceptive role environmental lead exposure plays in bone maturation and loss. The clinical trial is the latest in a growing body of research that is putting yet one more notch in the belt of diseases attributed to lead, and this time, researchers say, its target is older adults at risk for osteoporosis.

For decades, scientists have known that the human skeleton is a repository for lead in people who were exposed to high levels of this environmental toxin in their childhood, but thought this storage to be benign. Recently, a growing body of research is showing that the opposite is true, and that lead in bone actually sets off a bizarre chain reaction, first accelerating bone growth, and then eventually limiting it so that a high peak bone mass is not achieved. Preventing a high peak bone mass will predispose a young person to osteoporosis later in life.

Now, researchers in the Center for Musculoskeletal Research at the University of Rochester Medical Center are set to embark on the next phase of a four-year, $5 million research project funded by the National Institute of Environmental Health Sciences with a clinical study aimed at better understanding the deceptive role lead initially plays in bone development, growth and loss – and how this all might lead to earlier onset of osteoporosis in those exposed to high levels of lead as a child.

A metabolic bone disease that predominantly occurs in women, osteoporosis affects one in three American women over the age of 65. It is characterized by low bone mass that eventually leads to fractures, mostly of the hip and vertebrae. These fractures can be life-threatening; experts say that more women die each year from hip fracture complications than from cancer of the ovaries, cervix and uterus combined. Close to $20 billion dollars is spent each year treating osteoporosis and related fractures.

An Ironic Growth Pattern

The pattern of growth in the skeleton determines the peak skeletal density of an individual, and this level is established by the time most people reach 20. Recent research completed at the University of Rochester Medical Center shows that lead adversely affects the normal maturation of the growth plate – but does so in an odd way.

"As a child, lead appears to accelerate bone development and maturation, so that lead-exposed children actually have a higher bone density than those not exposed to environmental lead," said James Campbell, M.D., M.P.H., associate professor of Pediatrics and a co-investigator of the study. "But, we believe this higher bone density effect is short-lived, and in fact, we believe it actually prevents these children from achieving an optimal peak bone mass later on in life."

J. Edward Puzas, Ph.D., professor of Orthopaedics and director of the overall project, added that limiting peak bone mass has dire consequences as a person begins to age.

"When everyone begins to lose bone mass starting at around age 50, lead-exposed individuals are at a higher risk for bone fractures and osteoporosis – and probably at an earlier age than the typical osteoporosis patient."

At what specific age lead-exposed individuals will plateau in bone growth, and at what age they will begin to lose more bone as older adults, is the focus of this clinical research. Puzas and Campbell have used their prior research to guesstimate when these two milestones occur, but are turning to sophisticated lead measurement devices to help them pinpoint exact timeframes.

"We believe that somewhere around age 20, we'll begin to see low-lead exposed individuals surpass high-lead exposed individuals in bone mass density," Campbell said. "Then, in the 50 to 60 age group – the age at which any individuals will begin to experience a natural loss of bone – we expect to see the high-lead exposed individuals losing more bone sooner."

An X-ray fluorescence spectrometer will be used to measure the bone lead levels in 500 people, separated into three age groups: 8-9 years old, 18-19 years old, and 50-60 years old. One of only a few installed machines worldwide, it provides a precise, noninvasive measurement of the historic accumulated exposure to lead, allowing researchers to place each of the research subjects into an either "low-lead exposure" or "high-lead exposure" category within their age groups. A DEXA-scan will then be used to measure bone density, and with these data in hand, the investigators will have a better sense of when lead-exposed individuals might begin to experience osteoporotic symptoms.