Airborne contaminant exposure and bone development: a systematic review and meta-analysis

Air pollution, including particulate matter (PM10, PM2.5) and airborne metals (Cd, Hg, As, Pb) are a systemic health hazard, but osteotoxic effects remain underrecognized. We systematically synthesized human, animal, and in vitro evidence on airborne contaminants and outcomes to skeletal health. Following Office of Health Assessment and Translation (OHAT) guidance, we searched PubMed and Google Scholar (2014-2024; final search November 24, 2024) for English-language studies relating PM or airborne metals to skeletal outcomes, excluding studies limited to adult occupational exposures, age-related bone disease, or non-peer-reviewed reports. Studies were screened and data extracted in Covidence. Risk of bias was assessed using tools from the Quality Assessment and Risk of Bias Tool Repository, and certainty of evidence was graded with GRADE. We used a random-effects meta-analyses model to estimate relative risks (RRs) interpreted as directional consistency hazards for bone loss, impaired osteoblast differentiation, enhanced osteoclast activity, bone marrow adiposity, epigenetic changes, and altered bone microarchitecture. Fifty-three studies met the inclusion criteria. Across outcomes, meta-analyses showed higher hazard risk in exposed versus control groups, with RRs ranging from 7 to 10; for example, bone loss (RR 7.12, 95% CI 4.20-12.06) and altered bone microarchitecture (RR 10.28, 95% CI 4.67-22.61). Epidemiologic and experimental evidence may implicate oxidative stress, inflammation, and epigenetic dysregulation as key mechanisms. Overall certainty was low to moderate due to residual confounding, exposure misclassification, and heterogeneity. Growing evidence indicates that airborne PM and metals adversely affect bone health, particularly during critical developmental windows, underscoring the need to integrate skeletal endpoints into health assessment and policy.