Bone is a multifaceted organ that performs a myriad of functions beyond providing structural support and protection for vital organs; it facilitates movement, mineral ion regulation, physiological acid-base balance, and hematopoiesis [1], [2], [3]. Bone is not merely static; with research advancements, we now understand that it encompasses dynamic metabolic processes known as bone remodeling [4].

Bone remodeling, which occurs during growth and development, involves adaptive changes influenced by the balance between bone formation and bone resorption [4], [5]. Despite bone mass appearing relatively stable in adulthood, a small but significant portion of bone undergoes constant reconstruction, approximately 3–5 % annually, to sustain metabolic vitality and structural integrity. Consequently, bone should be considered a metabolically active tissue [6], [7].

In the context of bone metabolism, bone growth and development are tightly regulated processes that involve various types of bone cells with distinct functions. Aberrant bone remodeling can lead to metabolic bone disorders, such as osteoporosis and osteopetrosis [8]. A multitude of factors, including genetic predispositions, hormonal fluctuations, nutrition, and inflammatory and mechanical stress, can influence bone remodeling. It is worth noting that in the environment of bone metabolism under inflammatory conditions, inflammatory cells and cytokines affect bone metabolism through direct or indirect ways and are important coordinators of bone remodeling. At the same time, bone cells, including osteoblasts and osteoclasts, also influence immune cells, affecting their cellular functions and underlining the interplay between inflammation and bone health [8], [9], [10], [11].

Bone tissue comprises various cell types, including osteoprogenitor cells, osteoblasts, osteocytes, and osteoclasts. The body employs a range of mechanisms to regulate the activities of osteoblasts and osteoclasts, ensuring that bones assume a specific shape in line with an individual's overall growth and development. Osteoclasts are specialized migratory cells responsible for bone resorption, originating from hematopoietic stem cells. These cells develop from monocytes that migrate to bone tissue, undergoing a complex, multifactorial activation process [12].

The degradation of mineralized bone by osteoclasts is crucial for not only the normal growth and development of bones but also for maintaining skeletal integrity, facilitating calcium metabolism through remodeling, and ensuring internal homeostasis and repair. The functional dynamics of osteoclasts can be significantly influenced by external factors, including inflammatory stimuli and cytokine-mediated changes, which can sometimes result in pathological bone resorption [13].

Immune cells play a crucial role in the inflammatory process, including the regulation of bone metabolism and osteoclast function [1], [14]. These immune cells mainly consist of T cells, B cells, and macrophages, which participate in the formation and progression of inflammatory pathological changes in various disease scenarios [15], [16]. Studies have shown that during inflammation, immune cells become activated and secrete inflammatory cytokines, which further regulate the metabolic activity of tissue cells [17]. For example, Croes et al. found that T cells and interleukin-17 (IL-17) under inflammatory conditions could stimulate osteoblast differentiation [17], [18]. In addition, osteoclasts are also influenced by immune cells, leading to alterations in bone resorption function [19].

In chronic inflammatory diseases, such as rheumatoid arthritis and inflammatory bowel disease, immune cells and inflammatory cytokines play a pivotal role in the imbalance of bone metabolism [17]. Research indicates that in the context of inflammation, immune cells can orchestrate the metabolic functions of tissue cells, including osteoclasts, primarily through the action of inflammatory cytokines. This interaction plays a crucial role in disrupting bone metabolic equilibrium and, consequently, impacts skeletal health [7]. As another example, in rheumatoid arthritis (RA), activated T cells, B cells and macrophages produce specific cytokines to promote inflammatory response and induce osteoclasts to promote bone destruction [20].

In this review, we have summarized various immune cells and their pathways in affecting bone metabolism in different disease contexts. We will elaborate on how they influence the process of osteoclastogenesis and their specific mechanisms under pathological states of inflammation. Our goal is to further reveal the underlying mechanisms, explore the patterns, and provide insights into the future prospects of immune cell regulation of bone metabolism. In summary, this manuscript delves into the pivotal roles of osteoclasts and immune cells within the bone metabolism framework, underscoring their significance in both homeostasis and disease. Following this introduction, we will explore several key areas: Section 2 provides a detailed examination of osteoclast biology and its regulation, emphasizing recent discoveries in their function and interaction with immune cells. Section 3 focuses on the diverse roles of immune cells in bone metabolism, highlighting how they contribute to bone health and pathology. In Section 4, we discuss the impact of dysregulated osteoclast activity and immune cell function on bone-related diseases, with a particular focus on therapeutic targets and interventions. Finally, Section 5 offers a comprehensive review of current challenges and future directions in the study of bone metabolism, aiming to pave the way for novel research avenues and treatment strategies. By structuring our manuscript in this manner, we aim to provide readers with a coherent roadmap that facilitates a deeper understanding of the complex interplay between osteoclasts, immune cells, and bone metabolism.