Association between Blood Lead Levels and Markers of Calcium Homeostasis: A Systematic Review and Meta-Analysis

Abstract

Introduction: Lead (Pb), on chronic exposure is associated with various systemic illness and some of its toxicity effects is posited to involve calcium metabolism and hypothesis pathways. Present study aims to comprehensively evaluate the association between chronic lead exposure and markers of calcium homeostasis markers by executing systematic review, to improve the current insights on Pb-Calcium metabolism interaction. Methods: Observational studies documenting the changes in calcium homeostasis markers (i.e. serum calcium, parathyroid hormone, vitamin D & calcitonin) among chronically (occupational) Pb exposed individuals as compared to control (individuals without obvious lead exposure) were systematically searched from Pubmed, Scopus and Embase digital databases since inception to September 24, 2020 (partly updated on March17, 2021). The systematic review adhered to PRISMA (Preferred Reporting Items of Systematic reviews and Meta-Analysis) guidelines during the execution. The mean differences of calcium homeostasis markers between Pb exposed and control groups were pooled using random-effects model. Heterogeneity was assessed by I2 statistic and Cochran-Q test. Risk of bias among the included studies was performed using Newcastle Ottawa Scale. Sub-group, sensitivity and meta-regression analyses were performed where data permitted. Results: The systematic search identified eleven studies, including 837 occupationally Pb exposed and 739 control participants. Chronically (i.e. Occupationally) Pb exposed individuals exhibited mean 36.13 (95% CI 25.88 to 46.38) µg/dl blood lead level (BLL) higher than controls. The Pb exposed group exhibited significantly lower serum calcium (-0.72 mg/dl, 95% CI -1.07 to -0.36), and trend of higher parathyroid levels (37.97 pg/ml, 95% CI -14.36 to 90.29) and lower vitamin D levels (-12.26 ng/ml, 95% CI -25.36 to 0.84) as compared to control group. The studies exhibited high levels of heterogeneity. Subgroup analysis exploring the influence of simultaneous exposure to other heavy metals did not alter the results. Conclusion: The pooled results show inverse relationship between chronic lead exposure and calcium homeostasis markers, particularly serum calcium. Present observations should caution the policymakers drafting regulations, to incorporate these (calcium homeostasis related parameters) investigations mandatory during the periodic examination (along with BLL) of individuals with chronic lead exposure (e.g. occupational lead exposure).