Urinary calcium: a promising predictive biomarker for early recognition of environmental lead exposure in children

Abstract

Background: In the continuous search for accessible, reliable and sensitive biomarkers for early detection of environmental lead exposure, authors determined the interaction between blood lead level (BLL), the conventional marker of lead exposure, and the indices of calcium and bone metabolism in children.Methods: This cross-sectional study involved 309 apparently healthy children from eight public primary schools in Ibadan, Nigeria who were classified as Elevated BLL (EBLL) and control based on standard cut-off for childhood BLL. BLL, serum Ca (tCa), phosphate, magnesium (Mg), 25-hydroxy-Vitamin D, alkaline phosphatase (ALP), urinary calcium (uCa) and urinary deoxypyridinoline (uDPD) were determined using AAS, HPLC and ELISA as appropriate. Bone-specific ALP (B-ALP) and ionized calcium (iCa) were calculated using standard formulae. Data analyses involved Student’s t-test, Pearson correlation and multivariate regression analysis. p<0.05 was considered statistically significant.Results: BLL and 25-OH-Vitamin D levels were increased in EBLL (0.4±0.1 µmol/L and 60.1±10.7 mmol/L) compared with control (0.2±0.0 µmol/L and 55.1±14.3 mmol/L) p <0.05. No significant differences existed in the levels of ALP, B-ALP, uCa, uDPD, tCa, iCa, phosphate and Mg in both groups (p>0.05). BLL had significant positive correlation with uCa (r=0.176, p=0.002) (p<0.05) but no significant correlation with uDPD, ALP, B-ALP, tCa, iCa, phosphate, Mg and 25-OH-Vitamin D (p>0.05). BLL could be accounted for by uCa by applying the equation, BLL=0.329+0.324uCa.Conclusions: Urinary calcium could be a promising predictive biomarker for early recognition of significant environmental lead exposure in children.

Blood lead levels, calcium metabolism and bone-turnover among automobile technicians in Sagamu, Nigeria: Implications for elevated risk of susceptibility to bone diseases

“…The increased BLL in the automobile technicians was noted to be significantly negatively associated with reduced tCa and iCa levels. This finding reflects perturbation in calcium metabolism and suggests compromised calcium bioavailability, which may occur at the expense of bone, when bone calcium is mobilised to restore the extracellular calcium level (Anetor et al, 2005(Anetor et al, , 2007Nwobi et al, 2019). However, it is interesting to note that the finding of no significant changes in the levels of phosphate, Mg and albumin could imply that these factors may not be contributory to the reduced calcium levels.…”

“…However, reports have shown that compared to calcium, lead has larger ionic radius, greater electronegativity and irregular charge distribution in the electron cloud (Garza et al, 2006). These unique ionic characteristics allow lead to bind with greater affinity than calcium to the protein binding sites, resulting in interference with closely regulated calcium functions (Nwobi et al, 2019;Toscano and Guilarte, 2005).…”

Positive and inverse correlation of blood lead level with erythrocyte acetylcholinesterase and intelligence quotient in children: implications for neurotoxicity

“…However, the mechanism by which lead alters AChE activity is still incompletely understood as this enzyme does not contain free thiol groups in its structure to which Pb could bind (Rosenberry & Soggin, 1984;Ademuyiwa et al, 2007). However, the mechanism may be dependent on calcium, a nutritionally essential element involved in the regulation of many neurological processes, with which Pb competes at protein binding sites (Florea et al, 2013;Brini et al, 2014;Nwobi et al, 2019). Calcium norrmally activates Protein Kinase C (PKC), a phospholipid-dependent enzyme that is found in high concentrations in neuronal tissues where it participates in several signal transduction cascades by regulating neurotransmitter release and neuronal ion channels such as calcium channels involved in cholinergic neurotrassmission (Hwang et al, 2002;Brini et al, 2014).…”

“…Lead (Pb) is a naturally occurring ubiquitous toxic metal whose uncontrolled use in multiple industrial, domestic, agricultural, medical and technological applications has brought about its wide environmental distribution, widespread human exposure and subsequent serious health and intellectual concerns particularly in children in developing countries and Nigeria is not an exception (Ogunseitan & Smith 2007;WHO, 2013;Anetor et al, 2016;Nwobi et al, 2019).…”

“…Consequently, the US Centers for Disease Control and Prevention (CDC) since 2012 has identified BLL ≤5 µg/dl as acceptable and BLL >5 µg/dl as elevated blood lead level (EBLL) that should prompt further medical investigation in children (CDC, 2012). However, the use and interpretation of BLL for the early detection of LIN is not generally accepted owing to its short half-life of about 30 days and its ability to reflect primarily recent exposures without possibility of accurately assessing long term risk which has more insidious impact (Sommar et al, 2014;Nwobi et al, 2019).…”