Environmental Lead Exposure Disproportionately Disrupts Bone Metabolism in Non-Occupational Settings: A Systematic Review and Meta-Analysis

Abstract

<title>Abstract</title> Background Lead exposure remains a persistent public health concern with well-established neurotoxic effects, yet comprehensive quantitative synthesis of its effects on bone metabolism across diverse populations is lacking. Previous studies have yielded inconsistent findings regarding associations between lead exposure and bone turnover biomarkers, particularly across different exposure contexts. Methods We conducted a systematic review and meta-analysis, searching PubMed, Web of Science, Scopus, Embase, and Chinese databases (CNKI, Wanfang, VIP) from inception through October 2025. We included observational studies examining associations between lead exposure and bone metabolism markers (bone alkaline phosphatase [BALP], 25-hydroxyvitamin D3 [25-OH-D3], osteocalcin). Random-effects meta-analyses were performed using Hedges' g as the effect size measure. Comprehensive heterogeneity exploration included Baujat plots, Galbraith plots, and multi-dimensional subgroup analyses stratified by population type (occupational versus non-occupational exposure), study quality, sample size, and geographic region. Results 19 studies comprising 3,301 participants (2,090 exposed; 1,211 controls) were included. Lead exposure significantly elevated bone alkaline phosphatase (pooled g = 0.821, 95% CI: 0.407–1.234, p = 0.003, I² = 88.7%), reduced 25-hydroxyvitamin D3 levels (g = − 1.106, 95% CI: −2.207 to − 0.004, p = 0.047, I² = 97.7%), and showed a trend toward reduced osteocalcin (g = − 0.360, 95% CI: −0.737 to 0.018, p = 0.055). Critically, non-occupational environmental exposure demonstrated substantially larger effects compared to occupational exposure for both BALP (2.4-fold larger: g = 1.273 versus 0.530) and osteocalcin (7.4-fold larger: g = − 0.719 versus − 0.097), despite typically involving lower exposure concentrations. Comprehensive publication bias assessment using Egger's regression, trim-and-fill analysis, fail-safe N, and selection models supported validity of BALP findings (fail-safe N = 115, robust across bias scenarios) while indicating caution for 25-OH-D3 under adverse bias assumptions. Conclusions Lead exposure significantly disrupts multiple bone metabolism markers through dysregulated bone remodeling and impaired calcium-vitamin D axis regulation. The striking finding that non-occupational environmental exposures produced equal or larger effects than occupational exposures—challenging conventional dose-response assumptions—underscores the critical importance of environmental lead remediation and protection of vulnerable populations including children, pregnant women, and chronically exposed communities from chronic low-level environmental lead exposure.

Affiliated Institutions

• Shahid Beheshti University of Medical Sciences IR
• Shahid Sadoughi University of Medical Sciences and Health Services IR
• Iran University of Medical Sciences IR
• Iranshahr University IR
• Medical University of Ilam IR
• Tehran University of Medical Sciences IR
• Miami University US
• Shiraz University of Medical Sciences IR
• Imam Hossein Hospital IR

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