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Campbell, J. R., & Auinger, P. (2007). The association between blood lead levels and osteoporosis among adults-Results from the Third National Health and Nutrition Examination Survey (NHANES III). Environmental Health Perspectives, 115(7), 1018-1022.
Osteoporosis is a reduction in bone mass sufficient to increase the risk of fractures. 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 and bone strength. In addition, in vitro studies have reported that lead exposure inhibits the function of chondrocytes and osteoblasts, the cells that manufacture bone.
Human studies on the relationship between lead exposure and decreased bone density are very limited. The authors present and critically discuss studies that do not show the hypothesized inverse relationship between lead exposure and decreased bone density. They also present several studies that found the hypothesized relationship. In a study of children, no association between bone density and lead exposure was found. Here, the authors argue that because the children were examined at a very young age (18-47 months), there was insufficient time for the adverse effects on the bone to become manifest. In a cross-sectional study of 1,021 adults, aged 16-81 years, no association was found between lead exposure and BMD. Here, the authors argue that the mean blood lead level was low among the subjects studied (3.1 mg/dl), suggesting that the lack of an association may be attributable to low exposure. In an epidemiologic study on whether postmenopausal bone resorption was associated with elevated blood lead levels, an inverse association was found between blood lead levels (geometric mean blood lead level, 2.9 mg/dl among postmenopausal women) and BMD. In a study of former workers from a lead smelting facility, an inverse association was found between the log of the current blood lead level and spine BMD.
As recently as the late 1970s, 78% of the U.S. population had blood lead levels of 10 mg/dl or more, the current threshold of concern defined by the Centers for Disease Control and Prevention. Bone is the repository for 90%-95% of the total body burden of lead and harbors it for years after initial exposure. Thus, a high proportion of adult Americans may currently have elevated bone lead levels. The objective of this study was to conduct a secondary analysis of the national database to explore the association between lead exposure and osteoporosis in a large number of adults.
Data for the study was the Third National Health and Nutrition Examination Survey (NHANES III). The survey was a national-probability, cross-sectional survey of noninstitutionalized Americans. Multistage, nonrandom sampling techniques were used, and thus results were weighted to be representative of the U.S. population. Personal household interviews and physical examinations of about 40,000 people 2 months or older were conducted between 1988 and 1994. The Household Adult Questionnaire was administered to subjects 17 years or older, who were asked an extensive series of questions about their health. Questions included the presence and location of back pain and history, location, and mechanism of fractures. Blood levels were assessed in all subjects 1 year or older. BMD measurements were conducted for all men and nonpregnant women 20 years or older who underwent the physical examination.
The study sample consisted of 8,654 subjects 50 years or older who completed the Household Adult Questionnaire. From this group, subjects were excluded if they did not take part in the blood level and/or BMD measurement (n 5 2,430) or if they had an ethnicity other than non-Hispanic African American or non-Hispanic White (n 5 115), or if they were nonpostmenopausal women. The remaining 4,689 subjects constituted the primary study sample.
Blood lead levels collected at the time the subjects were interviewed by the NHANES survey were used for assessment. At that time, their blood was screened for background lead contamination. The researchers performed duplicate blood analyses on each sample. Blood lead levels below the detection limit were assigned a value of 0.7 mg/dl.
NHANES survey BMD measurement sites were limited to the hip: the femoral neck, trochanter, intertrochanter, Ward's triangle, and total hip. The researchers limited their analyses to the total hip because the BMD of the hip subregions is highly correlated to the BMD of the total hip.
Two clinical outcomes were defined: the presence of back pain and whether the subject had an osteoporotic-related fracture. Subjects were classified as having had a fracture due to osteoporosis if they had a hip, wrist, or vertebral fracture at age 50 years or older that occurred because of a fall from a standing height or less. In adjusted analyses, several confounders, that is, age, race, sex, body mass index, menopausal status, tobacco use, alcohol use, physical activity, calcium intake, chronic medical conditions, use of certain medications, and socioeconomic status (educational level), were considered.
Analyses of the data included analyzing the association between current blood lead level and total hip BMD among four groups (non-Hispanic White women, non-Hispanic White men, African American men, and African American women). To identify covariates for adjusted analysis, bivariate analysis (for each of the previously mentioned groups) was performed between these variables and the total hip BMD. For continuous covariates, the Pearson correlation coefficient was calculated and for categorical covariates the t test was used. The significant covariates were introduced into an analysis of covariance to determine the independent association between BMD of the total hip and the blood lead level tercile. In the unadjusted analysis of the clinical outcomes for each of the four groups, the researchers calculated the proportion of subjects with lower back pain and with fractures due to osteoporosis as a function of blood lead level tercile. The study results revealed a significant inverse association between lead exposure and BMD but only among White subjects.
Because Asian women are a population at risk and the researchers did not identify such individuals in their study, it can be assumed that there were too few individuals in the NHANES survey to test, although that was not stated by the authors. The statistical results seem to be inadequately described. The Pearson correlation coefficient is generally defined for discrete, not continuous, data. A rationale for grouping the actual blood level measures into terciles was not offered; one should have been provided as the procedure reduces the precision of the data. Nonetheless, the study does support previous research on adults linking blood lead levels with an increased risk of osteoporosis and fracture.
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