Salamanna Francesca, Di Martino Alberto, Contartese Deyanira, Faldini Cesare, Giavaresi Gianluca, Fini Milena
Surgical Sciences and Technologies, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy.
1st Orthopedic and Traumatologic Department, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy.
Front Med (Lausanne). 2025 Jul 21;12:1584022. doi: 10.3389/fmed.2025.1584022. eCollection 2025.
Spontaneous osteoclastogenesis, a phenomenon characterized by the unregulated differentiation and activation of osteoclasts in the absence of exogenous stimulatory factors, plays a central role in osteoporosis. While conventionally attributed to an imbalance between osteoclast and osteoblast activity, as well as to factors they release and/or produce, and to the involvement of T cells, emerging evidence suggests that platelets may contribute to this process beyond their established role in hemostasis. In this opinion, we propose that platelet activation and the subsequent release of cytokines, growth factors, and chemokines, including PDGF, IL1β, TGFβ, MIP-1α, TNFα, CXCL12 (SDF1), and CCL5 (RANTES), create a pro-inflammatory and osteoclastogenic microenvironment. These mediators may enhance RANKL production, recruit osteoclast precursors, and disrupt osteogenic signaling, indirectly fostering spontaneous osteoclastogenesis. Additionally, platelet interactions with endothelial cells, macrophages, and immune populations could further amplify inflammatory responses and sustain chronic bone resorption, contributing to the stimulation of spontaneous osteoclastogenesis. Although direct evidence linking platelets activation to spontaneous osteoclastogenesis is not yet available, existing literature supports the plausibility of this interplay. Exploring this underrecognized platelet-bone axis could provide new insights into osteoporosis pathophysiology and open avenues for novel diagnostic and therapeutic strategies. These hypotheses may be assessed in clinical practice to develop innovative approaches for the screening, diagnosis, monitoring and treatment of osteoporosis.
自发性破骨细胞生成是一种在无外源性刺激因子情况下破骨细胞不受调控地分化和激活的现象，在骨质疏松症中起核心作用。传统上认为这归因于破骨细胞与成骨细胞活性之间的失衡，以及它们释放和/或产生的因子，还有T细胞的参与，但新出现的证据表明血小板可能在这一过程中发挥作用，且超出了其在止血方面已确定的作用。在本观点中，我们提出血小板激活以及随后细胞因子、生长因子和趋化因子（包括血小板衍生生长因子、白细胞介素1β、转化生长因子β、巨噬细胞炎性蛋白1α、肿瘤坏死因子α、CXC趋化因子配体12（基质细胞衍生因子1）和CC趋化因子配体5（调节激活正常T细胞表达和分泌因子））的释放会创造一个促炎和成骨细胞生成的微环境。这些介质可能会增强核因子κB受体活化因子配体的产生，募集破骨细胞前体，并破坏成骨信号，间接促进自发性破骨细胞生成。此外，血小板与内皮细胞、巨噬细胞和免疫群体的相互作用可能会进一步放大炎症反应并维持慢性骨吸收，从而促进自发性破骨细胞生成。虽然将血小板激活与自发性破骨细胞生成联系起来的直接证据尚不可得，但现有文献支持这种相互作用的合理性。探索这一未被充分认识的血小板-骨轴可能会为骨质疏松症的病理生理学提供新的见解，并为新的诊断和治疗策略开辟道路。这些假设可在临床实践中进行评估，以开发用于骨质疏松症筛查、诊断、监测和治疗的创新方法。
