Abstract

Osteoporosis (OP) is a metabolic bone disease with a high incidence rate worldwide. Its main features are decreased bone mass, increased bone fragility and deterioration of bone microstructure. It is caused by an imbalance between bone formation and bone resorption. Ginsenoside is a safe and effective traditional Chinese medicine (TCM) usually extracted from ginseng plants, having various therapeutic effects, of which the effect against osteoporosis has been extensively studied. We searched a total of 44 relevant articles with using keywords including osteoporosis, ginsenosides, bone mesenchymal cells, osteoblasts, osteoclasts and bone remodeling, all of which investigated the cellular mechanisms of different types of ginsenosides affecting the activity of bone remodeling by mesenchymal stem cells, osteoblasts and osteoclasts to counteract osteoporosis. This review describes the different types of ginsenosides used to treat osteoporosis from different perspectives, providing a solid theoretical basis for future clinical applications.

Introduction

Osteoporosis (OP) is a metabolic bone disease characterized by decreased bone mass and destruction of bone tissue microstructure, leading to increased bone fragility and susceptibility to fractures ( Gopinath, 2023 ). A global epidemiological survey on osteoporotic vertebral fractures showed that one in three women and one in five men over the age of 50 will be directly affected by osteoporosis for the rest of their lives ( Laird et al., 2023 ). A study on the prediction of hip fractures in Asia estimated that by 2050, the direct cost of osteoporotic fractures in Asia alone may reach at least $15 billion per year ( Cheung et al., 2018 ). Therefore, early detection and treatment of osteoporosis is crucial for preventing fractures and reducing the burden on the global health care system.

Normal bone homeostasis in the human body is mainly maintained by osteoblasts differentiated from bone marrow mesenchymal stem cells (BMSCs) and osteoclasts produced by the fusion of monocytes and macrophages ( Guo et al., 2023 ; Kular et al., 2012 ), which participate in bone reconstruction and exert the sequential function of absorbing old bone and forming new bone ( Harris et al., 2023 ; Iantomasi et al., 2023 ) ( Fig. 1 ). The main cause of OP is aging, while secondary causes include genetic diseases, endocrine diseases, gastrointestinal diseases, blood diseases, neurological diseases, rheumatism and autoimmune diseases ( Patel and Wairkar, 2023 ). In addition, lifestyle changes, such as vitamin D and calcium deficiency, high salt intake, alcohol consumption, and smoking, also significantly increase the risk of osteoporosis. These factors can lead to an imbalance in bone cell activity and disrupt the dynamic cycle of bone formation and absorption, thereby affecting bone homeostasis and exacerbating OP ( Beekman et al., 2023 ).

Conclusion

In recent years, there has been increasing research on the treatment of osteoporosis with ginsenosides. Therefore, this review describes the possible mechanisms of different types of treatment for osteoporosis from three aspects, BMSCs, osteoblasts, and osteoclasts, and summarizes their specific signaling pathways or key factor mechanisms. However, this treatment method is still in the initial stage of clinical transformation, and there are still many obstacles between its experimental results and clinical application, such as in terms of combination therapy, drug delivery pathways, bioavailability, and combination with biochemical materials. With increasing attention given to the role of ginsenosides in bone reconstruction, ginsenosides may become a new drug for treating osteoporosis and promoting fracture healing and a powerful candidate for cytokines in tissue engineering bone.