Dose-dependent roles of aspirin and other non-steroidal anti-inflammatory drugs in abnormal bone remodeling and skeletal regeneration

Abstract

The failure of remodeling process that constantly regenerates effete, aged bone is highly associated with bone nonunion and degenerative bone diseases. Numerous studies have demonstrated that aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) activate cytokines and mediators on osteoclasts, osteoblasts and their constituent progenitor cells located around the remodeling area. These cells contribute to a complex metabolic scenario, resulting in degradative or synthetic functions for bone mineral tissues. The spatiotemporal effects of aspirin and NSAIDs in the bone remodeling are controversial according the specific therapeutic doses used for different clinical conditions. Herein, we review in vitro, in vivo, and clinical studies on the dose-dependent roles of aspirin and NSAIDs in bone remodeling. Our results show that low-dose aspirin (< 100 μg/mL), which is widely recommended for prevention of thrombosis, is very likely to be benefit for maintaining bone mass and qualities by activation of osteoblastic bone formation and inhibition of osteoclast activities via cyclooxygenase-independent manner. While, the roles of high-dose aspirin (150-300 μg/mL) and other NSAIDs in bone self-regeneration and fracture-healing process are difficult to elucidate owing to their dual effects on osteoclast activity and bone formation of osteoblast. In conclusion, this study highlighted the potential clinical applications of low-dose aspirin in abnormal bone remodeling as well as the risks of high-dose aspirin and other NSAIDs for relieving pain and anti-inflammation in fractures and orthopedic operations.

Keywords: Aspirin; Bone remodeling; NSAIDs; Osteoblast; Osteoclast.

Fig. 1

The roles of low-dose aspirin in the regulation of bone remodeling. Aspirin at low dosage might suppress the differentiation of osteoclasts and promotes the bone formation via osteoblastic cells. The solid red arrows indicate the promotion of cellular processes, and the solid green lines indicate inhibition of cellular processes. The dotted lines indicate that the mechanism has not been fully elucidated. HSC hematopoietic stem cells, MSC mesenchymal stem cells, T cell T lymphocytes, Pre-OC precursors of osteoclasts, Pre-OB precursors of osteoblasts, OPG osteoprotegerin

Fig. 2

Dual effects of high-dose aspirin on osteoclasts and osteoblasts activities. Aspirin at high dosage regulates osteoclast-mediated bone resorption and osteoblastic bone formation by activating or inhibiting molecules and target cells. High-dose aspirin has multiple roles in the regulation of osteoclasts and osteoblasts. The solid red arrows indicate the promotion of cellular processes, and the solid green lines indicate inhibition of cellular processes. HSC hematopoietic stem cells, MSC mesenchymal stem cells, T cell T lymphocytes, Pre-OC precursors of osteoclasts, Pre-OB precursors of osteoblasts