In recent years, global plastic production has exceeded 400 million tons annually, yet since 2012, the overall recycling rate has remained as low as 9% (1, 2). A significant portion of plastic waste ultimately enters the natural environment. For instance, in 2019, Europe generated approximately 25.9 million tons of plastic waste, the vast majority of which was inadequately treated (3). Over time, environmental weathering leads to the breakdown of plastics into microplastics (MPs, 1 µm–5 mm) and nanoplastics (NPs, <1 µm), collectively referred to as MNPs. Studies have shown that MNPs can enter the human body through various exposure routes, including dietary intake, drinking water, and airborne particles. It is estimated that the average person ingests approximately 0.1–5.0 grams of MNPs per week, equating to 74,000–121,000 particles annually (4, 5). Due to their widespread presence and potential toxicity in both ecosystems and the human body, MNPs have emerged as a pressing global public health concern (6). Accumulating evidence suggests that MNPs can activate multiple pathophysiological pathways associated with skeletal toxicity, affecting the function of chondrocytes, osteoblasts, and osteoclasts (7). These effects are often mediated through oxidative stress, inflammatory responses, and disruptions to bone homeostasis (8). Animal studies further support that MNPs exposure can lead to structural and metabolic abnormalities in bone tissue (9). To ensure a comprehensive and systematic synthesis of existing evidence, we performed database searches in PubMed, Web of Science, and Scopus from inception to June 2025. The primary search strategy was: (“microplastics” OR “nanoplastics”) AND (“osteotoxicity” OR “bone” OR “skeletal system” OR “osteoblast” OR “osteoclast” OR “bone microenvironment” OR “bone remodeling”). Only peer-reviewed articles published in English were considered. Inclusion criteria encompassed (i) original studies using in vivo mammalian models or in vitro mammalian cells, (ii) investigations directly assessing the effects of microplastics or nanoplastics on bone, bone marrow, or the skeletal muscle system, and (iii) availability of full text. Exclusion criteria were: (i) editorials, commentaries, conference abstracts, and case reports, (ii) studies not directly related to musculoskeletal outcomes, (iii) non-English publications, and (iv) studies lacking sufficient methodological detail or quantitative data relevant to the musculoskeletal system. The primary aim of this review is to synthesize the current scientific evidence on the effects of MNPs on the musculoskeletal system, with an emphasis on the emerging research landscape. It focuses on studies reporting the detection of MNPs within the musculoskeletal system and explores their potential associations with skeletal disorders. Finally, this review outlines future research directions necessary to elucidate the scientific basis of MNPs as an emerging risk factor for bone health.

Since the invention of plastic by Belgian chemist Leo Baekeland in 1909, the variety and applications of plastic materials have expanded rapidly. To meet diverse functional requirements, plastic products are commonly formulated with additives such as antioxidants, plasticizers, and flame retardants (10), which enhance their durability and render them persistent organic pollutants. Through biotic and abiotic degradation processes in natural environments and biological systems, plastics can break down into MNPs, classified by particle size into microplastics (MPs,1 µm–5 mm) and nanoplastics (NPs, <1 µm) (11). MNPs can be either primary—manufactured at microscopic sizes—or secondary, generated from the breakdown of larger plastic debris. They are widely found in personal care products, synthetic materials, and fragmented plastic waste (12). Common polymers such as polyethylene (PE), polypropylene (PP), polystyrene (PS), polyvinyl chloride (PVC), and polyethylene terephthalate (PET) account for approximately 90% of global plastic production (13). These polymers differ significantly in their environmental degradability, making complete elimination of plastic pollution particularly challenging. Recent studies have demonstrated that MNPs can be taken up by plants and transferred through the food chain to animals and humans, raising global concerns regarding their potential toxicity and health risks (14).

Given their near-ubiquitous presence across global ecosystems, MNPs have emerged as a growing environmental threat (15). Facilitated by wind, riverine systems, and ocean currents, MNPs can undergo long-range transport and are now distributed across aquatic systems, terrestrial soils, and the atmosphere (16). Research has shown that MNPs can enter organisms via inhalation, ingestion, or foliar absorption, potentially impairing reproductive and physiological health, and ultimately bioaccumulating in the human body through trophic transfer (14, 17, 18). Although larger particles are often excreted via feces, smaller MNPs are more readily absorbed and biologically active (19). Particles smaller than 150 μm can penetrate intestinal epithelial cells, while those under 20 μm may translocate via M cells or dendritic cells to distant organs such as the liver, kidneys, and muscles (20). Particles ranging from 0.1 to 10 μm in size have even been shown to cross the blood–brain barrier (21). Moreover, MPs can further degrade into nanoplastics capable of integrating into cellular membranes (22), and their accumulation in various human tissues has now been confirmed (23). Animal studies have also demonstrated that MNPs can enter the body via ingestion, inhalation, or dermal contact, triggering a range of health risks (24). Despite increasing evidence of MNP accumulation and toxicity in multiple human tissues, their behavior and effects within bone tissue remain poorly characterized. Given the structural complexity of the bone microenvironment and its essential roles in bone metabolism and immune regulation, elucidating how MNPs enter and impact this niche is critical to advancing our understanding of their biosafety and systemic health implications.

Although MPs and NPs often share similar environmental sources and exposure routes, their particle size–dependent physicochemical properties lead to notable differences in their in vivo distribution, biological effects, and toxicological characteristics. In terms of distribution, MPs—particularly those larger than 150 µm—are generally retained within the gastrointestinal tract or translocated to specific organs through lymphatic and circulatory pathways, whereas NPs can penetrate cellular membranes more readily, enter systemic circulation, and cross critical biological barriers such as the blood–brain barrier and placenta. Regarding biological effects, MPs tend to induce localized tissue irritation, chronic inflammation, and microbiome dysbiosis, while NPs, due to their higher surface area-to-volume ratio and reactivity, can directly interact with intracellular components, disrupt mitochondrial function, and alter organelle dynamics. In terms of toxicological characteristics, NPs generally exhibit higher bioavailability, stronger potential for biomolecular binding, and greater potency in inducing oxidative stress and apoptosis at lower doses compared with MPs. Nevertheless, both MPs and NPs are capable of perturbing bone homeostasis through mechanisms involving oxidative stress, inflammatory signaling, and dysregulation of key pathways such as NF-κB, MAPK, and BMP/Smad, ultimately leading to altered bone remodeling and skeletal integrity.” As summarized in Figure 1 , MNPs can enter the human body via ingestion, inhalation, or dermal absorption, and smaller particles penetrate biological barriers to reach distant tissues including bone marrow.”

The bone microenvironment refers to the intricate biological niche surrounding bone tissue, composed of osteoblasts, osteoclasts, bone marrow mesenchymal stem cells, as well as extracellular matrix components, vascular networks, cytokines, and signaling pathways (25). This specialized milieu not only supports bone formation, remodeling, and repair, but also plays crucial roles in immune regulation, hematopoiesis, and tumor metastasis (26). Emerging evidence indicates that MNPs can penetrate biological membranes and interact with cells (27).To date, MNPs have been detected in human colon, testis, endometrium, placenta, and lung tissues (28–32), suggesting that they can enter the body via inhalation, ingestion, or the circulatory system, accumulate in various organs, and exert potential toxicity on the reproductive, nervous, and digestive systems (33). These findings also imply that MNPs may target the bone microenvironment. Studies have identified nanoplastic particles composed of PET, PS, or PE in human peripheral blood, with an average concentration of 1.6 μg/mL (34). Moreover, bone marrow samples have been shown to contain PE, PS, polyvinyl chloride (PVC), polyamide-66 (PA66), and PP, with an average concentration of 51.29 μg/g (35). Given that bone tissue receives nutrients primarily through the dense vascular networks of the periosteum, subchondral bone, and endplate regions (36, 37) there exists a plausible anatomical basis for MNPS entry into the bone microenvironment. More importantly, polystyrene nanoparticles with diameters less than 100 nm have been shown to infiltrate the bone marrow, impair hematopoietic function, and disrupt the homeostasis of the bone marrow niche (35, 38). Recent human studies also suggest that MNPs may accumulate within the musculoskeletal system and contribute to various pathological processes (39). Collectively, these findings indicate that MNPs can access bone tissue via the circulatory system and may disturb the bone microenvironment through mechanisms including physical damage, chemical toxicity, inflammatory activation, and metabolic disruption, posing a potential threat to bone homeostasis and function.

The skeletal system and skeletal muscle are closely interconnected tissue systems that exhibit coordinated changes during development, growth, aging, and various pathological conditions. Skeletal muscle is not only one of the most abundant tissues in the human body—accounting for approximately 40–50% of total body weight in healthy adults—but also serves as a vital protein reservoir. In addition to regulating locomotor functions, skeletal muscle plays a fundamental role in respiration, feeding, energy metabolism, and the maintenance of glucose, amino acid, and lipid homeostasis, thereby being essential for overall health and quality of life (89).

Although studies have shown that MNPs can enter and accumulate in skeletal muscle tissue through dermal absorption or trophic transfer, current research on their impact on muscle structure and function is primarily limited to in vitro experiments and animal models, and the underlying mechanisms remain incompletely understood. For instance, Pause et al. (90)demonstrated that 100 nm polystyrene nanoparticles could penetrate granulosa cells in bovine oocytes and porcine myocytes, indicating their membrane-crossing capability. Similarly, Yang et al. (91) reported that feeding piglets with 150 mg/kg PS-MPs led to upregulation of THBS1 expression, which suppressed angiogenesis and subsequently impaired skeletal muscle development and meat quality traits such as flavor and redness. In chickens, Chen et al. (92) found that oral administration of PS-MPs for 21 consecutive days significantly increased microplastic accumulation in the pectoralis muscle, while levels decreased in the leg muscle over time. In vitro experiments further revealed that PS-MPs promoted both proliferation and apoptosis of primary chicken myoblasts, while inhibiting their differentiation, suggesting that MPs may modulate gene networks involved in neural function and muscle development, thereby affecting skeletal muscle physiology.

In addition, studies using fish models have demonstrated that co-exposure to microplastics and emamectin benzoate (EMB) induces oxidative stress and disrupts the balance of mitochondrial fusion and fission. Specifically, co-exposure led to the downregulation of fusion-related genes (Mfn1, Mfn2, OPA1) and upregulation of the fission-related gene DRP1, resulting in elevated levels of ROS, reduced mitochondrial membrane potential, and impaired ATP synthesis, ultimately contributing to skeletal muscle atrophy (93). Notably, the extent of damage under combined exposure was more severe than that induced by either agent alone, and supplementation with the antioxidant N-acetylcysteine (NAC) effectively alleviated these toxic effects. Consistent findings have been reported in C2C12 myoblasts, where PS-NP exposure was shown to induce mitochondrial dysfunction in differentiated muscle cells, disrupt cellular homeostasis, and promote a premature aging phenotype (94). Further evidence has demonstrated that maternal exposure to PS-NPs (0.1 μm, 10 mg/L) via drinking water during pregnancy altered the expression of genes related to lipid metabolism and muscle development in fetal muscle tissue and even interfered with skin formation (95). In another study, PS-MPs of different particle sizes (1–10 μm and 50–100 μm) were directly injected into the tibialis anterior muscle of mice. While no significant effect on overall muscle growth was observed, smaller particles markedly impeded fibrotic tissue repair following muscle injury, suggesting that particle size is a critical determinant of microplastic toxicity (96).

MPs can infiltrate the skeletal muscle system via various exposure routes and accumulate in muscle tissues across different species, though their distribution appears to be tissue-specific. MPs disrupt muscle cell homeostasis through mechanisms including oxidative stress, mitochondrial dysfunction, and gene dysregulation, leading to imbalances in myoblast proliferation and differentiation, impaired muscle fiber repair, and even atrophy. Notably, MP-induced toxicity is both size-dependent and potentiated under co-exposure conditions. However, most existing studies are limited to in vitro systems or agricultural species. Future research should focus on elucidating the long-term and transgenerational effects of MPs on human skeletal muscle and exploring the mechanistic differences induced by MPs with varying physicochemical properties, thereby providing a theoretical basis for strategies aimed at preserving muscle health.

To provide a comprehensive overview, Table 1 consolidates the current evidence on how MNPs affect bone resorption, osteogenesis, oxidative stress, the bone marrow microenvironment, and skeletal muscle.”

MNPs have emerged as a global public health concern. Human exposure to microplastics through ingestion, inhalation, and dermal contact is increasing, posing a potential risk to the general population. Such exposure may occur continuously throughout the human lifespan—from infancy to adulthood. Although the long-term effects of microplastics on human bone and bone marrow have not yet been fully established, experimental studies have shown that even at relatively low concentrations in the microgram range (97), MNPs can accumulate in bone tissue and induce damage to bone marrow cells.

A notable limitation of this review lies in the current gaps and uncertainties in understanding the impact of MNPs on the bone microenvironment and skeletal muscle system. First, the dose–response relationship of long-term human exposure to MPs remains unclear. Most available data are derived from animal models or in vitro experiments, with a lack of large-scale, systematic epidemiological and clinical studies in humans. This limitation hampers a comprehensive assessment of the actual health risks posed by MPs. Moreover, the concentrations of MPs used in different studies often exceed levels typically encountered in daily life, as higher doses are frequently employed to predict potential toxic effects. This compromises the clinical translatability of such findings. Additionally, inconsistencies in exposure doses, particle types, experimental models, and endpoint indicators across studies contribute to considerable variability and controversy, thereby limiting the comparability and generalizability of the results.

Second, the underestimation of environmental MNPs exposure remains a major challenge. While humans are chronically exposed to microplastics, current assessments are largely based on dietary intake, often overlooking other critical exposure routes such as inhalation, dermal absorption, and inadvertent ingestion from presumed plastic-free sources. This narrow focus on estimated quantities inevitably results in an underestimation of the total exposure burden. Unlike short-term laboratory studies, real-world human exposure to microplastics is lifelong, beginning in the embryonic stage and extending into old age, raising growing concerns about their cumulative effects. Another often overlooked source of microplastic exposure involves unavoidable contact through medical, dental, and cosmetic procedures. The degradation behavior of microplastics within biological systems significantly influences their toxicity and bioaccumulation. However, the underlying degradation mechanisms and their implications for the selection of bone repair materials remain poorly understood. Degradation products of microplastics may alter the biocompatibility and mechanical properties of such materials, providing important considerations for the design and safety evaluation of biomedical implants.

Currently, research on the detrimental effects of micro- and nanoplastics (MNPs) on the musculoskeletal system has predominantly focused on elucidating toxicological mechanisms, while preventive and therapeutic strategies remain largely underexplored. Preliminary evidence (98) suggests that certain natural antioxidants, such as anthocyanins and quercetin derivatives, may mitigate MNPs-induced oxidative stress and inflammatory responses, indicating their potential in preventing MNPs-related skeletal damage. Moreover, interventions targeting key signaling pathways, including NF-κB, mTOR, and autophagy, have demonstrated restorative effects in experimental models (48, 59), providing a theoretical foundation for the development of targeted pharmacological approaches. Future studies should incorporate exposure models that more closely mimic physiological conditions in humans to systematically evaluate the efficacy and safety of such interventions. In addition, given its low metabolic turnover and high degree of mineralization, bone tissue may serve as a potential reservoir for MNPs accumulation. Recent findings have identified various polymeric microplastics in human bone and bone marrow (39), suggesting that bone may act as a “time capsule,” retaining a long-term record of environmental exposure in individuals or populations. However, the mechanisms governing the deposition, transport, and potential clearance of MNPs within bone tissue remain poorly understood. Whether MNPs can be gradually removed through bone remodeling, or instead persist indefinitely once deposited, has yet to be determined. If bone indeed exhibits high affinity for and retention of MNPs, it may represent a critical site for long-term bioaccumulation, with implications for environmental epidemiology, biomonitoring, and the design of bone repair materials. Therefore, future research should not only address the dose–response relationships, molecular mechanisms, and transgenerational effects of MNPs exposure on the skeletal and muscular systems, but also expand toward the development of individualized and population-level intervention strategies, while recognizing the unique role of bone tissue in toxicity assessment and retrospective exposure analysis.

Against this backdrop, the present review aims to summarize current evidence regarding the exposure and accumulation of MNPs and their effects on the human musculoskeletal system. Future research should focus on developing exposure models that more closely mimic physiological human conditions, and conducting long-term in vivo and in vitro studies using gradient dosing strategies to elucidate the dose–response relationship and potential transgenerational effects of MNPs. Moreover, there is a critical need to investigate the degradation processes and metabolic dynamics of MNPs with diverse physicochemical properties in bone tissue, to inform the development and application of biomaterials for bone repair. Integrating multi-omics approaches will also be essential to uncover the molecular mechanisms underlying the effects of MNPs on skeletal muscle and the bone microenvironment, ultimately providing a scientific foundation for prevention and therapeutic intervention.