The pathogenesis of osteoporosis is closely related to the imbalance of oxidative stress. Currently, gas molecules and related factors such as hydrogen sulfide, nitric oxide, and hydrogen have shown great potential in the field of bone metabolism due to their unique redox regulatory properties. However, there is a lack of a systematic review regarding the development trajectory, emerging hotspots, and future trends in this area of research. Using bibliometric analysis methods, this study aims to provide a comprehensive view of the evolution of gas molecules and related factors in osteoporosis research from 2001 to 2025. It clarified the shifting patterns of research hotspots in this field and predicted future development directions. We conducted a literature search in the Web of Science Core Collection database to investigate the role of gas molecules and related factors in osteoporosis research. A total of 387 relevant articles published between 2001 and 2025 were included. We utilized bibliometric tools such as Citespace 6.4.R2, VOSviewer 1.6.20, and Bibliometrix (R-4.5.2) to perform a multidimensional visual analysis of the 387 articles, focusing on publication trends, scientific time span, contributions by countries/institutions, journal distribution, keyword co-occurrence, emerging hotspots, and highly cited papers. We found that: (1) The annual publication volume in this field shows a fluctuating upward trend, peaking in 2024, indicating that the field has entered a relatively mature development phase. (2) China and the United States constitute the first tier, with Harvard University leading globally in publication volume. (3) The most frequently used keywords include "osteoporosis" (112 occurrences), "osteoclasts" (48 occurrences), "osteoblasts" (40 occurrences), "reactive oxygen species" (33 occurrences), "oxidative stress" (31 occurrences), and "nitric oxide" (30 occurrences). (4) Keyword analysis indicates that gas molecules, by regulating the core pathological mechanism of "oxidative stress/ reactive oxygen species," have become a key hub connecting various pathological processes in osteoporosis. Nitric oxide, hydrogen sulfide, and hydrogen represent different stages of development. Nitric oxide is an early classic theme, with a median year of 2012; hydrogen sulfide is a current research hotspot, with a median year of 2020, actively transitioning to therapeutic applications; while hydrogen represents an emerging frontier, with a median year of 2023, indicating the latest exploratory direction. Overall, the research focus on gas molecules and related factors shows a relay-style evolution from nitric oxide to hydrogen sulfide to hydrogen, continuously deepening in conjunction with the core mechanism of "reactive oxygen species/oxidative stress." (5) The results of the literature analysis indicate that current evidence generally identifies oxidative stress, particularly related to reactive oxygen species, as a key pathological mechanism in the development of osteoporosis, with the nuclear factor erythroid 2-related factor 2-related pathway recognized as an important target for intervention. Inducible nitric oxide synthase produces excessive nitric oxide, which is involved in inflammatory bone loss. Studies from 2001 to 2019 establish nitric oxide as a common mediator of various bone protective agents. Emerging research from 2020 to 2025 demonstrates that hydrogen and hydrogen sulfide have confirmed bone-protective effects, primarily through their strong antioxidant and anti-inflammatory actions, which alleviate oxidative stress damage to bone cells. The recent surge in research on nanocarriers and smart materials is becoming a breakthrough for clinical translation in this field. Findings from this article show that: (1) From 2001 to 2025, the role of gas molecules and related factors in osteoporosis research has transitioned from investigating basic mechanisms to focusing on innovative targeted therapies, with basic research now entering a relatively mature development phase. (2) The most prominent gas molecules and related factors in this field are nitric oxide, hydrogen sulfide, and hydrogen, each representing different stages: exploration of mechanisms, optimization of delivery, and translational application. (3) Future research should focus on the delivery of gas molecules and related factors using new materials while also enhancing studies on the synergistic effects of various gas molecules and the precise spatiotemporal regulation of gas release. This approach will accelerate the clinical translation of gas molecules and related factors in the field of osteoporosis research. JOURNAL/mgres/04.03/01612956-990000000-00094/figure1/v/2026-04-11T111231Z/r/image-tiff
Zhao et al. (Sat,) studied this question.