The Association between Blood Lead Levels and Osteoporosis - NHANES III
The Association between Blood Lead Levels and Osteoporosis - NHANES III
Background: Osteoporosis is a reduction in bone mass sufficient to increase the risk of fracture. Lead exposure during childhood may be a risk factor for low bone mineral density (BMD). Basic-science research demonstrates that lead exposure is associated with a decrease in BMD in animals. However, human studies are limited.
Objective: Our objective was to conduct a secondary analysis of a national database to explore the association between lead exposure and osteoporosis in adult humans.
Methods: In this study we used data from the Third National Health and Nutrition Examination Survey (NHANES III). We analyzed subjects who were ≥ 50 years of age. A concurrent venous blood lead level defined lead exposure. The primary outcome variable was the BMD of the total hip. We conducted analyses on four groups: non-Hispanic white men, non-Hispanic white women, African-American men, and African-American women. We conducted bivariate analyses between covariates known to be associated with bone density (i.e., age, body mass index, calcium intake, ethanol/tobacco consumption, physical activity, socioeconomic status) and the total hip BMD. The significant covariates were introduced into analysis of covariance to determine the association between BMD and blood lead level tercile.
Results: The adjusted mean total hip BMD among non-Hispanic white males with a blood lead level in the lowest tercile versus the highest tercile was 0.961 g/cm and 0.934 g/cm, respectively (p < 0.05). We also found a similar association among white females, but the difference was marginally significant (0.05 < p < 0.10).
Conclusions: We found a significant inverse association between lead exposure and BMD, but only among white subjects. However, because of the cross-sectional design of NHANES, we cannot make inferences about the temporal sequence of this association. With the large number of adults who had lead exposure in the past and the morbidity associated with osteoporosis, further inquiry is necessary on the possible casusal association between lead exposure and osteoporosis in humans.
Osteoporosis is a reduction in bone mass sufficient to increase the risk of fractures (Krane and Holick 1998), and is a common and serious affliction of the elderly (Chandler et al. 2000; Looker et al. 1995; Melton et al. 1992). Lead exposure may be a risk factor in the development of osteoporosis. Animal studies report that increased lead exposure is associated with a decrease in bone density (Escribano et al. 1997; Gruber et al. 1997; Puzas et al. 1999) and bone strength (Ronis et al. 2001). Additional in vitro studies report that lead exposure inhibits the function of chondrocytes (Hicks et al. 1996) and osteoblasts, the cells that manufacture bone (Klein and Wiren 1993; Puzas et al. 1999; Ronis et al. 2001).
Human studies on this association are limited. In a study of children, Laraque et al. (1990) found no association between bone density and lead exposure. However, because the children were examined at a young age (range, 18-47 months), sufficient time may not have elapsed for the adverse effects on the bone to become manifest. In a cross-sectional study of 1,021 adults age 16-81 years, Alfvén et al. (2002) also found no association between lead exposure and bone mineral density (BMD). However, the mean blood lead level was low among the subjects studied [3.1 μg/dL (Alfvén T, personal communication)]–suggesting that the lack of an association may have been attributed to low exposure. In contrast, an epidemiologic study on whether postmenopausal bone resorption is associated with elevated blood lead levels found an inverse association between blood lead level (geometric mean blood lead level, 2.9 μg/dL among postmenopusal women) and BMD (Nash et al. 2004). In a study of former workers from a lead smelting facility, there was an inverse association between the log of the current blood lead level and spine BMD [regression coefficient -0.039; 95% confidence interval (CI), -0.060 to -0.019; p < 0.0002] (Potula et al. 2006).
As recently as the late 1970s, 78% of the U.S. population had blood lead levels ≥ 10 μg/dL (Mahaffey et al. 1982), the current threshold of concern defined previously by the Centers for Disease Control (CDC 1991). Bone is a repository for 90-95% of the total body burden of lead (Wedeen 1992), and harbors it for years after initial exposure (Gulson et al. 1995). Thus, a high proportion of adult Americans may currently have elevated bone lead levels. With this many who were exposed to lead when younger, and the morbidity associated with osteoporosis, it is important to investigate whether an association exists between lead exposure and osteoporosis in humans. Our objective was to conduct a secondary analysis of a national database to explore the association between lead exposure and osteoporosis in a large number of adults.
Abstract and Introduction
Abstract
Background: Osteoporosis is a reduction in bone mass sufficient to increase the risk of fracture. Lead exposure during childhood may be a risk factor for low bone mineral density (BMD). Basic-science research demonstrates that lead exposure is associated with a decrease in BMD in animals. However, human studies are limited.
Objective: Our objective was to conduct a secondary analysis of a national database to explore the association between lead exposure and osteoporosis in adult humans.
Methods: In this study we used data from the Third National Health and Nutrition Examination Survey (NHANES III). We analyzed subjects who were ≥ 50 years of age. A concurrent venous blood lead level defined lead exposure. The primary outcome variable was the BMD of the total hip. We conducted analyses on four groups: non-Hispanic white men, non-Hispanic white women, African-American men, and African-American women. We conducted bivariate analyses between covariates known to be associated with bone density (i.e., age, body mass index, calcium intake, ethanol/tobacco consumption, physical activity, socioeconomic status) and the total hip BMD. The significant covariates were introduced into analysis of covariance to determine the association between BMD and blood lead level tercile.
Results: The adjusted mean total hip BMD among non-Hispanic white males with a blood lead level in the lowest tercile versus the highest tercile was 0.961 g/cm and 0.934 g/cm, respectively (p < 0.05). We also found a similar association among white females, but the difference was marginally significant (0.05 < p < 0.10).
Conclusions: We found a significant inverse association between lead exposure and BMD, but only among white subjects. However, because of the cross-sectional design of NHANES, we cannot make inferences about the temporal sequence of this association. With the large number of adults who had lead exposure in the past and the morbidity associated with osteoporosis, further inquiry is necessary on the possible casusal association between lead exposure and osteoporosis in humans.
Introduction
Osteoporosis is a reduction in bone mass sufficient to increase the risk of fractures (Krane and Holick 1998), and is a common and serious affliction of the elderly (Chandler et al. 2000; Looker et al. 1995; Melton et al. 1992). Lead exposure may be a risk factor in the development of osteoporosis. Animal studies report that increased lead exposure is associated with a decrease in bone density (Escribano et al. 1997; Gruber et al. 1997; Puzas et al. 1999) and bone strength (Ronis et al. 2001). Additional in vitro studies report that lead exposure inhibits the function of chondrocytes (Hicks et al. 1996) and osteoblasts, the cells that manufacture bone (Klein and Wiren 1993; Puzas et al. 1999; Ronis et al. 2001).
Human studies on this association are limited. In a study of children, Laraque et al. (1990) found no association between bone density and lead exposure. However, because the children were examined at a young age (range, 18-47 months), sufficient time may not have elapsed for the adverse effects on the bone to become manifest. In a cross-sectional study of 1,021 adults age 16-81 years, Alfvén et al. (2002) also found no association between lead exposure and bone mineral density (BMD). However, the mean blood lead level was low among the subjects studied [3.1 μg/dL (Alfvén T, personal communication)]–suggesting that the lack of an association may have been attributed to low exposure. In contrast, an epidemiologic study on whether postmenopausal bone resorption is associated with elevated blood lead levels found an inverse association between blood lead level (geometric mean blood lead level, 2.9 μg/dL among postmenopusal women) and BMD (Nash et al. 2004). In a study of former workers from a lead smelting facility, there was an inverse association between the log of the current blood lead level and spine BMD [regression coefficient -0.039; 95% confidence interval (CI), -0.060 to -0.019; p < 0.0002] (Potula et al. 2006).
As recently as the late 1970s, 78% of the U.S. population had blood lead levels ≥ 10 μg/dL (Mahaffey et al. 1982), the current threshold of concern defined previously by the Centers for Disease Control (CDC 1991). Bone is a repository for 90-95% of the total body burden of lead (Wedeen 1992), and harbors it for years after initial exposure (Gulson et al. 1995). Thus, a high proportion of adult Americans may currently have elevated bone lead levels. With this many who were exposed to lead when younger, and the morbidity associated with osteoporosis, it is important to investigate whether an association exists between lead exposure and osteoporosis in humans. Our objective was to conduct a secondary analysis of a national database to explore the association between lead exposure and osteoporosis in a large number of adults.
