Exploring the Cellular and Molecular Mechanisms Underlying Heavy Metal-Induced Osteoporosis: The Role of Cadmium, Lead, and Zinc in Disrupting Bone Metabolism in Peromyscus leucopus
Cristina Reyes
Clarisse Mendoza
Abstract
Heavy metal exposure is a recognized risk factor for skeletal disorders, including osteoporosis. This study investigates the mechanisms by which cadmium, lead, and zinc contribute to osteoporosis in Peromyscus leucopus white-footed mouse, focusing on cellular and molecular disruptions that affect bone metabolism. Cadmium and lead, known toxicants, impair bone health through mechanisms such as inhibition of osteoblast activity, enhancement of osteoclast-mediated bone resorption, disruption of calcium homeostasis, and induction of oxidative stress. These metals interfere with essential signaling pathways, including RANK/RANKL/OPG, promoting an imbalance favoring bone resorption. Conversely, zinc, though beneficial at physiological levels, can exacerbate bone loss at higher concentrations due to oxidative stress induction and dysregulation of matrix metalloproteinases (MMPs). The study employs histological analysis, gene expression profiling, and biochemical assays to assess changes in bone structure, turnover markers, and cellular stress responses in metal-exposed mice. Findings indicate significant alterations in bone density and microarchitecture associated with elevated oxidative damage and impaired calcium metabolism. Heavy metal exposure also modulates critical regulatory pathways, shifting the balance between bone formation and resorption. These insights suggest that heavy metal exposure accelerates osteoporosis development through combined effects on osteoblast and osteoclast function, oxidative stress, and disrupted signaling pathways. Understanding the complex interactions between heavy metals and bone metabolism is essential for developing prevention and treatment strategies for heavy metal-induced osteoporosis. This research highlights the need for environmental and public health interventions to reduce exposure to harmful metals, thereby potentially decreasing the prevalence of osteoporosis in exposed populations.
