Relationship of Blood Lead Levels to Incident Nonspine Fractures and Falls in Older Women: The Study of Osteoporotic Fractures

Abstract

Lead is stored in the skeleton and can serve as an endogenous source for many years. Lead may influence the risk of fracture, through direct effects on bone strength or indirectly by disturbing neuromuscular function and increasing the risk of falls. The objective of this analysis is to test the hypothesis that women with higher blood lead levels experience higher rates of falls and fracture. This was a prospective cohort study of 533 women 65-87 yr of age enrolled in the Study of Osteoporotic Fractures at two U.S. research centers (Baltimore, MD; Monongahela Valley, PA) from 1986 to 1988. Blood lead levels (in microg/dl) were measured in 1990-1991 by atomic absorption spectrophotometry and classified as "low" (<or=3; lower 15th percentile, referent); "medium" (4-7); or "high" (>or=8; upper 15th percentile). Total hip BMD was measured by DXA twice, 3.55 yr apart. Information on falls was collected every 4 mo for 4 yr. Incident nonspine fractures were identified and confirmed over 10 yr. Cox proportional hazards models were used to estimate the hazard ratio (HR) and 95% CI of fracture. Generalized estimating equations were used to calculate the incident rate ratio of falls (95% CI). The mean blood lead level was 5.3 +/- 2.3 (SD) microg/dl (range, 1-21 microg/dl). Baseline BMD was 7% lower in total hip and 5% lower in femoral neck in the highest compared with lowest blood lead group (p < 0.02). Hip bone loss tended to be greater in the high lead group, but differences were not significant. In multivariable adjusted models, women with high blood lead levels had an increased risk of nonspine fracture (HR = 2.50; 95% CI = 1.25, 5.03; p trend = 0.016) and higher risk of falls (incident rate ratio = 1.62; 95% CI = 1.07, 2.45; p trend = 0.014) compared with women with lowest lead level. Blood lead levels are associated with an increased risk of falls and fractures, extending the negative health consequences of lead to include osteoporotic fractures.

Association of lead and cadmium exposure with frailty in US older adults

“…Second, exposure to lead and cadmium has been related to a higher risk of several pathologic conditions that are also linked to frailty. Environmental exposure to lead in the elderly has been associated with cognitive decline (Bandeen-Roche et al 2009;Grashow et al 2013;Nordberg et al 2000;Power et al 2014;Shih et al 2006;van Wijngaarden et al 2011), impaired motor skills (Grashow et al 2013), increased blood pressure (Perlstein et al 2007), ischemic heart disease (Jain et al 2007), decreased renal function (Tsaih et al 2004), falls and fractures in women (Khalil et al 2008), hearing loss (Park et al 2010) and vision problems (Schaumberg et al 2004;Wu et al 2014). Cadmium, for which fewer studies have been conducted in the elderly, has also been associated with an increased risk of atherosclerotic plaques (Fagerberg et al 2012), peripheral artery disease (Tellez-Plaza et al 2013a), osteoporosis (Engstrom et al 2011;Gallagher et al 2008) and macular degeneration (Shiue 2013;Wu et al 2014).…”

“…Increasing evidence supports the contribution of environmental lead and cadmium to the development of several age-related chronic diseases, including cardiovascular disease (Navas-Acien et al 2007;Tellez-Plaza et al 2013b), chronic kidney disease (Navas-Acien et al 2009), and osteoporosis (Engstrom et al 2011;Gallagher et al 2008;Khalil et al 2008). Despite this evidence, and the established connection between these diseases and the frailty syndrome (Heuberger 2011), no previous studies have examined the association between lead or cadmium exposure and frailty.…”

Effects of thirty elements on bone metabolism

“…Lead accumulates in bones during fetal development, and adverse effects on bone metabolism present even after lowlevel of exposure [64,152,153]. Lead causes growth retardation by inhibiting endochondral ossification.…”

“…Lead causes growth retardation by inhibiting endochondral ossification. Increased bone turnover and reduced mineralization rates combine to decrease bone mineral density and mass, and, in the most severe cases, cause osteoporosis [153][154][155][156][157][158][159][160][161][162][163][164].…”

Inhibition of beta‐catenin signaling by Pb leads to incomplete fracture healing

“…We used a closed tibial model of healing to illustrate the effect of Pb on cellular and molecular aspects of bone repair. Khalil et al 30 published a study indicating that increased Pb exposure increases fracture risk by decreasing bone strength and decreasing neuromuscular control, i.e. chance of falling.…”