To ensure the comprehensiveness and credibility of the analyzed data, the Web of Science (Core Collection) was chosen as the data source, with the indexes SCI-Expanded and SSCI selected. The search strategy employed was: “TS = (osteoporosis OR osteopenia OR osteoporotic OR bone loss OR low bone mass OR low bone density) AND TS = (Mitochondrion OR Mitochondria OR Mitochondrial).” The search was conducted within the time frame of January 1, 2014, to November 5, 2024. The search was restricted to articles and reviews published in English, while other types of publications, such as meeting abstracts, conference papers, and editorial materials, were excluded. The screening process was independently conducted by two authors to ensure the reliability of the included publications. Any discrepancies between the authors were resolved through discussion and consensus. The full records and cited references of the included publications were exported in plain text format. The specific search strategy and screening process are illustrated in Figure 1.

To conduct bibliometric analysis, three software tools—CiteSpace, VOS viewer, and the “Bibliometrix” package—are utilized. Each of these tools has its own strengths in the field of bibliometric analysis.

CiteSpace is adept at creating visual maps of scientific knowledge, which intuitively present the knowledge structure and development trends within a particular field. The core functions of CiteSpace include generating unique co-citation networks composed of multiple document co-citation networks, as well as automatically producing related analytical results. Each network corresponds to a specific time slice, revealing the overall structure of the network, clustering within the network, associations between clusters, key nodes, and pathways, among other features.

VOS viewer excels in generating any type of textual map and offers a variety of charts and visualizations to assist researchers in analyzing, visualizing, and understanding academic literature, knowledge networks, collaborative relationships, and research hotspots. It is particularly useful for its clear and intuitive graphical representations that can facilitate the interpretation of complex data.

The “Bibliometrix” package is an R-based software package for bibliometric analysis and scientific visualization. It provides a suite of tools for the quantitative study of scientific literature, enabling researchers to perform in-depth analyses of publication patterns, citation distributions, and other bibliometric indicators. This package supports a wide range of bibliometric studies by offering comprehensive functionalities for data processing, statistical analysis, and visualization.

The 780 articles used in this study were authored by 5,071 researchers from 1,171 organizations across 60 countries, published in 328 journals, and cited 42,976 references from 4,454 different journals. Figure 2 shows the temporal distribution of publications related to mitochondrial dysfunction and osteoporosis. Overall, the number of publications in this field has shown an upward trend. Notably, there was a significant increase in the number of publications after 2016, with annual publication output surpassing 100 articles since 2022. This phenomenon indicates that this field has garnered escalating scholarly interest in recent years, becoming a hot topic within the fields of osteoporosis and bone metabolism.

By conducting a bibliometric analysis of the authors of these articles, it is possible to identify representative scholars and core research forces in the field. Table 1 and Figure 3A show the top 10 most productive authors in terms of publication output within this research field. According to the well-known scholar Derek J. de Solla Price, in any given research field, approximately half of the articles are authored by a group of highly productive authors. The size of this group is roughly equal to the square root of the total number of authors in the field, i.e.,

n (X) denotes the number of authors writing X articles, I = n_max denotes the number of articles of the most productive authors in the field, N denotes the total number of authors, and m denotes the minimum number of publications of core authors.

The statistical information shows that in this research field, n_max = 7. According to Price’s Law, authors who have published more than 3 articles are considered core authors. In total, there are 176 core authors who have collectively published 664 articles, accounting for 85.1% of the total number of publications. This meets the criteria proposed by Price, indicating that a relatively stable group of collaborating authors has been established in this field. However, among the top 10 authors who contributed to the publications in the field of mitochondrial and OP research, the top 10 authors accounted for 12.8% of the total number of publications. This level of concentration may imply a “Matthew effect” in academic resource allocation, where a small number of high-output authors dominate the research direction. And there is insufficient participation of emerging scholars, resulting in the slow development of new research topics due to inadequate authoritative support. In this field, the proportion of authors with more than one publication also conforms to Lotka’s Law (Figure 3B). Among them, Almeida has the highest number of publications. From January 2004 to November 2024, he published 11 papers, which received a total of 803 citations, with an average of approximately 73 citations per paper. Nevertheless, the core authors’ collaboration network is primarily based on domestic cooperation, with only 21% of the collaboration being international. This “localised” cooperation pattern may hinder the innovation of cross-cultural research design.

All 780 articles were published across 328 journals. After analyzing the publication counts and citation frequencies of all journals, we found that the journal with the highest number of publications is Scientific Reports, followed by International Journal of Molecular Sciences, with 24 and 20 articles, respectively (Table 2 and Figure 4A). Both of these journals are open-access, indicating that the development of open-access journals has significantly contributed to research progress in this field. This also reflects the growing acceptance among scholars of the principle of free access to research findings. But it also raises concerns about the quality of papers. Some journals’ fast-track reviews may come at the cost of rigour.

The 780 articles in this study collectively cited references from 4,454 different journals. Among these, the journals that contributed more than 900 cited references are Journal of Biological Chemistry, Journal of Bone and Mineral Research, and Nature (Figure 4B). The high number of cited articles from these journals reflects their authority in the field, indicating that the research published in these journals is widely recognized and referenced by scholars. Therefore, we conclude that the research findings published in these three journals are of significant interest to researchers in this field. But since journals are mostly dominated by western countries, their review preferences may indirectly shape the research paradigm in the field.

Meanwhile, in our bibliometric analysis of journals, we applied Bradford’s Law to describe the distribution of publications across different journals. We identified 21 core journals, which are considered the primary journals preferred by researchers in this field (Figure 4B). Additionally, we analyzed the annual publication output of the top 10 core journals and found that the number of publications in these journals has shown an upward trend over the years. This trend aligns closely with the overall increase in the annual number of publications in the field, reflecting that research on the mechanisms of mitochondrial dysfunction in osteoporosis has become a significant focus for scholars (Figure 4C). Notably, among core journals, only Frontiers in Endocrinology and Oxidative Medicine and Cellular Longevity explicitly focus on clinical translation, indicating a disconnection between basic and clinical research. This suggests that researchers need to pay more attention to interdisciplinary cooperation to better link basic scientific research with clinical practice.

To identify which countries have made the most significant contributions to research on mitochondrial dysfunction and osteoporosis, we conducted a visual analysis of publication counts from 60 countries. In Figure 5A, darker colors indicate a higher number of publications. China leads with the highest number of publications, totaling 421 articles, followed by the United States with 173 articles. This geographical distribution highlights the uneven global allocation of scientific resources. China’s high output likely stems from its strategic investments in biomedicine, an aging population, and a growing OP disease burden. The United States, a traditional research powerhouse, excels in interdisciplinary collaboration and mature translational medicine platforms, with high-impact journals like the Journal of Bone and Mineral Research making significant contributions. Next, we performed a visual analysis of the collaboration network between countries. The results show a highly uneven distribution of publications, with a pronounced top-heavy effect, where the majority of publications are authored by scholars from a few countries (Figure 5B). This “top-heavy effect” might also result in a narrow research perspective. Current research mainly focuses on European, American, and East Asian populations, while neglecting the unique genetic diversity and environmental factors of regions like Africa and South America, which are crucial for understanding OP pathology. This limits the generalizability of the research outcomes. In terms of international collaboration, there is relatively close cooperation between countries (Figure 5C). Overall, a cooperative network centered around China and the United States has been established (Figures 5D,E). However, the relatively low participation of developing countries has intensified regional imbalances, hindering resource-limited regions from effectively addressing the public health challenge of OP. Nevertheless, India and Portugal have emerged as rising nations in this field in recent years. They are expected to achieve greater growth in the future, make up for the current research deficiencies, and become new research hubs (Figure 5F) (see Table 3).

We conducted a statistical analysis to identify the most prominent research organizations contributing to the field of mitochondrial dysfunction and osteoporosis. The authors of all articles come from 1,171 research organizations. Among these, Shanghai Jiao Tong University has the highest publication count with 46 articles, followed by China Medical University and Zhejiang University, each with 23 articles (Table 4 and Figure 6A). The top three institutions in terms of publication output are all from China, highlighting China’s central role in this research field. However, this concentration can also lead to homogenization of research topics and insufficient exploration of emerging directions.

Subsequently, we performed a visual analysis of the collaboration network between research institutions. The results show that there is very close collaboration between organizations, forming a mature and well-established network, which is particularly evident in China (Figure 6B).

Furthermore, we conducted an association analysis of the leading countries, institutions, and authors in this field. The results indicate that most research outcomes are associated with institutions and authors from China and the United States. The relationships between countries, institutions, and authors are complex (Figure 6C), suggesting that international cooperation and academic exchanges in this field are highly developed. This robust international collaboration has significantly boosted the vitality and progress of the field, driving its advancement and development. However, the participation of institutions in other regions is extremely low. This “core-periphery” structure may intensify geographical bias in knowledge production. Also, the insufficient collaboration on clinical translation highlights a disconnect between industry and academia.

The 780 articles in this study collectively cited references from 4,454 different journals. The top three journals with the highest number of cited articles are Journal of Biological Chemistry, Journal of Bone and Mineral Research, and Nature (Table 5). The volume of cited articles reflects the authority of these journals in the field, indicating that the research published in these journals is widely recognized and referenced by scholars. Therefore, we conclude that the research findings published in these three journals are of significant interest to researchers in this field.

Subsequently, we conducted a cluster analysis of the cited journals. The cluster analysis diagram, through its layout of nodes and edges, clearly illustrates the citation relationships and disciplinary distributions among different scientific journals. This helps to understand the interactions and influence of various journals within scientific research. The cited journals can be distinctly divided into three clusters (green, blue, and red). The green cluster includes journals such as Science, Nature, and Cell, which have strong influence in the biological sciences. The blue cluster includes journals such as Journal of Bone and Mineral Research and Bone, which have significant influence in the fields of medicine and orthopedics. And the red cluster includes journals such as Autophagy, Cell Death & Disease, Frontiers in Immunology, and Redox Biology, representing journals in the fields of biology, immunology, cell biology, and oxidative stress (Figure 7A).

The 780 articles in this study collectively cited 42,976 references. After analyzing the top 10 most frequently cited references, we found that the majority of these references are research articles, with content primarily focused on the mechanisms of mitochondrial dysfunction in the pathogenesis of osteoporosis (Table 6). We also observed that review articles from high-impact journals tend to attract significant attention, leading to higher citation counts. Subsequently, we conducted a cluster analysis of the references. The references can be clearly divided into three main clusters (red, green, and blue). Among them, the articles on red clustering focus on the fields of stem cell biology and cell death, while the articles on green clustering mainly include the fields of natural medicine and basic research, while the articles on blue clustering mostly play an important role in the fields of cell biology and molecular biology (Figure 7B).

The dual-map overlay in CiteSpace is a powerful tool that not only helps us better understand the structure and evolution of citation patterns in academic literature but also provides researchers with deep insights into the dynamic changes within a specific field. In the dual-map overlay, the red labels on the left represent the research areas of the journals where the published papers are from, while the blue labels on the right represent the research areas of the journals where the cited papers are from. It is evident that most of the published papers fall within the fields of Molecular Biology and Immunology, whereas papers in the field of Molecular Biology and Genetics have the highest citation frequency (Figure 7C).

We believe that promoting interdisciplinary research in future studies will further advance the development of research on osteoporosis and mitochondrial dysfunction. By fostering cross-disciplinary collaboration, we can integrate knowledge and methodologies from different fields, leading to more comprehensive and innovative findings.

Through the statistical analysis of keywords and key terms, we can intuitively show the research hotspots in this field and reflect the research trend. Through the analysis of the frequency of keywords, we found that the keywords with high frequency in this field are oxidative stress (177 times, 8%), differentiation (140 times, 7%), expression (102 times, 5%), osteoporosis (100 times, 5%), activation (90 times, 4%). It can be seen that the role of oxidative stress and cell differentiation in the pathogenesis of osteoporosis has always been a hot spot in this field (Figures 8A,B). Then we use the burst words tool of CiteSpace to analyze the most frequently cited keywords. We found the time distribution of burst words was very close, indicating the field has been in an explosive development stage with rapid research hotspot iteration (Figure 8C). The most popular keywords are mitochondrial transfer (3.36), osteoblast (2.88), stem cells (3.22), promot (3.62), health (2.71) (Figure 8B). The longest duration of the burst word is “induced oxidative stress,” which shows that the relationship between mitochondrial-mediated oxidative stress and osteoporosis has been the focus of scholars for a long time. From the timeline map of keywords, it is clear that research themes such as “mitochondrial biogenesis,” “antioxidants,” “mitochondrial function,” and “programmed cell death” have received widespread attention (Figure 8D). Emerging hotspots in the field of mitochondrial dysfunction and osteoporosis include topics like “ferroptosis” and “SIRT1 protein.” These phenomena reflect the future popular research directions in this field (Figure 8E).

This study retrieved literature on mitochondrial dysfunction and OP from the WoSCC database between 2014 and 2024 for the first time, and visualized it using bibliometric analysis tools CiteSpace and VOSviewer. By statistically analyzing and visualizing highly productive countries, research institutions, authors, journals, references, and keywords from the included 780 papers, we combed through the current status and trends in mitochondrial dysfunction research in osteoporosis over the past decade. The findings show that the annual number of publications in this field has grown overall in the past decade, with a more significant increase since 2016, indicating extensive scholarly attention. The journals with the most references, such as the “Journal of Biological Chemistry, ““Journal of Bone and Mineral Research,” and “Nature,” highlight their authority in this field. Moreover, bibliometric analysis based on Bradford’s Law identified 21 core journals, which are considered the primary choice for researchers in this field. Further statistics show that the annual number of publications in core journals is on the rise, consistent with the overall growth trend in the field, indicating that mitochondrial research in OP has become a hot topic. At the national and institutional levels, we analyzed the number of publications from 60 countries and found that China ranked first with 421 publications, followed by the United States with 173. Analysis of the international cooperation network shows that research distribution in this field is extremely uneven, with a few countries contributing most of the publications. China and the United States have become cooperation centers in this field, while India and Portugal, as emerging countries, are expected to become new research centers in the future. In terms of research institutions, Shanghai Jiao Tong University ranked first with 46 publications, followed by China Medical University and Zhejiang University with 23 each, highlighting China’s core position in this field. Analysis of the cooperation network among research institutions shows that cooperation is close and a mature network has been formed, especially in China. Further correlation analysis indicates that research results in this field are mainly associated with institutions and authors from China and the United States. The complex relationships among countries, institutions, and authors reflect the maturity of international cooperation and academic exchange in this field. This international collaboration has injected strong vitality into the development of the field, promoting its rapid progress.

Through the statistical analysis of keywords and key terms in 780 relevant publications, this study has unveiled the core hotspots and developmental trends in the field of OP research related to mitochondrial dysfunction. Oxidative stress emerged as the most representative research focus, with a keyword frequency of 177 occurrences, accounting for 8% of the total. The formation of multiple dense clusters in the co-citation network further confirmed its central role in the pathogenesis of OP. Additionally, “induced oxidative stress” as the longest-lasting burst term, further highlighted the key role of mitochondrial dysfunction in regulating oxidative stress in the pathological process of OP. Apoptosis, another important mechanism in OP research, had a keyword frequency of 90 occurrences, accounting for 4%. Its co-citation network was significantly associated with literature on oxidative stress and mitochondrial autophagy, suggesting that apoptosis may act as a downstream event of oxidative stress in the regulation of osteocyte fate. In recent years, the research on mitochondrial autophagy has shown a significant upward trend, with a 35% increase in keyword frequency compared to earlier periods. The research primarily focuses on mitochondrial quality control in osteoblasts and osteoclasts, and the interactions of its antioxidant pathways have provided new insights for the treatment of OP. As an emerging mechanism of intercellular communication, mitochondrial transfer has seen a 40% increase in keyword frequency since 2020. On one hand, the transfer of mitochondria from bone lineage cells to myeloid cells can inhibit osteoclast differentiation and regulate hormone-related osteoporosis. On the other hand, abnormal mitochondrial transfer between macrophages and mesenchymal stem cells can affect osteoblast differentiation and exacerbate bone metabolic imbalance. The discovery of these dual mechanisms has highlighted the unique potential of mitochondrial transfer in the regulation of the bone microenvironment.

In this study, emerging research hotspots in the field of mitochondrial dysfunction and osteoporosis were identified through multidimensional bibliometric indicators, including keyword frequency, co-occurrence patterns, citation trends, and institutional output. Ferroptosis and SIRT family proteins were recognized as emerging hotspots. Ferroptosis, a form of iron-dependent lipid peroxidation-induced cell death, has seen a significant increase in keyword frequency from a low level in 2018 to 32 occurrences in 2023, with a notable burst strength. Co-citation network analysis revealed that research in this area has formed an independent cluster, involving the intersection of mechanisms related to mitochondrial function regulation, oxidative stress, and bone metabolic imbalance. The research interest in SIRT family proteins was reflected by the increasing keyword frequency and highly cited literature. Family members such as SIRT1 and SIRT3, through their deacetylase activity, regulate mitochondrial antioxidant pathways and apoptosis. The citation frequency of related literature has significantly increased over the past 5 years. The institutional collaboration network showed that research teams from China and the United States have taken the lead in the field of SIRT family and bone metabolism regulation. Their research content includes the protective effects of SIRT1 activators on osteoblast function and the mechanistic dissection of SIRT3 in mitochondrial quality control.

Based on long-term systematic research on the pathogenesis of OP related to mitochondrial dysfunction, the core hotspots and emerging research areas in this field have gradually shifted from mechanism exploration to therapeutic strategy development. Zhang et al. (97) demonstrated that C1q tumor necrosis factor-related protein 3 (CTRP3) can protect OB from oxidative stress injury and promote bone formation by activating the AMPK/SIRT1/Nrf2 signaling pathway, thereby inhibiting the progression of OP. The team led by Wang et al. (98) also pointed out that SIRT1 can enhance the transcriptional activity of Nrf2 through deacetylation, thereby activating the expression of downstream antioxidant genes. This interaction is crucial for protecting cells from oxidative damage. Ling et al. (99) successfully reversed mitochondrial dysfunction caused by Sirt3 deficiency and excessive bone resorption mediated by estrogen deficiency, as well as bone loss in mice. These findings indicate that therapeutic strategies targeting oxidative stress hold significant research importance and potential application value. Studies have shown that vitamin K2 (VK2) can restore bone mass and enhance the expression of SIRT1, GPX4, and osteogenic markers in the distal femur by inhibiting bone loss and ferroptosis mediated by long-term high glucose (HG). VK2 achieves this by activating the AMPK/SIRT1 signaling pathway to ameliorate type 2 diabetes-associated osteoporosis (T2DOP) and suppress ferroptosis (100). Additionally, a novel active vitamin D derivative, eldecalcitol (ED-71), has been shown to prevent bone loss caused by osteoporosis by inhibiting cellular senescence of BMSCs in ovariectomized rats through the regulation of the SIRT1-Nrf2 signaling pathway, demonstrating promising efficacy in in vivo experiments (101). However, most current studies are based on cell experiments and animal models, lacking large-scale clinical trials in humans to verify the effectiveness and safety of these interventions for treating osteoporosis and osteonecrosis in different populations (102). Challenges remain in translating these research findings into clinical applications. However, clinical studies have confirmed that zoledronic acid and melatonin can inhibit oxidative stress via the Sirt3/SOD2 pathway, accelerate osteogenesis of BMSCs, and delay the progression of OP, demonstrating potential for treating bone loss (103, 104). These preliminary clinical results not only provide strong support for therapeutic strategies targeting oxidative stress but also point the way for the development and clinical application of related drugs in the future. Some plant-derived peptides, which can be obtained from natural and climate-friendly sources, are increasingly attracting attention in new drug development due to their various biological activities, including antioxidant properties (105). For example, Ginkgo biloba leaf extract can improve OP by influencing the SIRT3/NF-κB axis in OC and promoting M2 polarization in macrophages (106). Salvianolic acid A (SAL-A) protects osteoblasts from H₂O₂-induced oxidative stress by scavenging free radicals, enhancing osteoblast viability, mineralization, and differentiation, and inducing oxidative stress in rat osteoblasts (107). Curculigoside, a natural product widely found in plants, has shown significant positive effects in animal models by inhibiting inflammatory responses, antagonizing oxidative stress, and regulating various signaling pathways, as well as modulating the differentiation and function of osteoblasts (108). Lycium barbarum polysaccharides (LBP), a potential bone-enhancing agent, can improve cell viability and osteogenic differentiation. It alleviates the inhibitory effect of cadmium (Cd) on osteogenesis in BMSCs by stimulating the autophagy process and promoting the formation of autophagosomes and autolysosomes (109). In recent years, several novel therapeutic approaches have shown significant therapeutic potential in the field of OP and related bone defect repair. Kang et al. (110) developed a calcium phosphate cement (CPC) modified with α-ketoglutarate (α-KG) polyester microspheres (CPC/α-KG). This material enhances osteogenic differentiation and biomineralization capabilities by inhibiting inflammation and oxidative stress via the PI3K/AKT pathway, thereby improving the osteogenic microenvironment. Chen et al. (111) constructed a microenvironment-responsive coordination nanoparticle composed of salvianolic acid B, catechol-conjugated chitosan, and Ca²⁺, which was immobilized on the surface of titanium implants. The nanoparticles remain stable under physiological conditions and can moderately regulate immune responses. However, under acidic and oxidative pathological conditions, they rapidly decompose to achieve ROS scavenging, anti-inflammatory effects, and bone induction, thereby remodeling the pathological microenvironment into a regenerative microenvironment. Additionally, nanovesicles extracted from carrot juice by the extrusion method remain structurally stable at pH 7.4 but aggregate at pH 4.0. These vesicles can passively target osteoporotic bone and effectively reduce bone loss by alleviating oxidative stress, restoring mitochondrial function, and promoting osteoblastogenesis (112). The emergence of these novel therapeutic approaches not only enriches the treatment options for osteoporosis and related bone defect repair but also provides new ideas and directions for the development of more efficient and targeted therapeutic methods in the future.

Using bibliometrics, this study performed an in-depth analysis of the relationship between mitochondrial dysfunction and osteoporosis during the period from 2014 to 2024. It emphasizes the critical role of mitochondrial dysfunction in the pathogenesis of osteoporosis and offers a novel perspective for future prevention and treatment strategies. Nevertheless, certain limitations exist in this study. The analysis was restricted to English-language literature within the WoSCC core collection, potentially overlooking relevant studies in other languages or databases. Additionally, the research predominantly relied on bibliometric methods, which are effective for macro-level analysis of academic output and research trends but may lack qualitative assessments to complement the quantitative findings. While the study integrates knowledge from multiple disciplines, such as biology and medicine, it may fall short in achieving deeper interdisciplinary collaboration. Consequently, its direct implications for clinical application are somewhat limited. Future research should aim to incorporate literature from diverse languages and databases to achieve a more comprehensive research framework. Furthermore, integrating qualitative analysis methods could enhance understanding of key issues and provide clearer guidance for future research directions. Based on the established connection between mitochondrial dysfunction and osteoporosis, we propose the development of innovative therapeutic strategies.