Novel therapeutic approaches targeting biomechanical pathway alterations in bone diseases

Bone is a living tissue that undergoes continuous remodelling. This process is regulated not only by hormones and nutrients but also by biomechanical forces such as load, pressure, strain, and stress. These forces are sensed through molecular pathways in a process known as mechanotransduction. Osteocytes act as the main mechanosensors, triggering pathways including integrins, Wnt/β-catenin, ion channels, and prostaglandins. Their activation increases osteoblast activity and reduces osteoclast-mediated bone resorption, helping to maintain skeletal strength and integrity. When these biomechanical pathways are disrupted, bone diseases such as osteoporosis, osteoarthritis, etc., can develop. Current treatments rely largely on anti-resorptive and anabolic drugs, which improve bone turnover but do not correct the underlying mechanosensory defects. This makes targeting biomechanical pathways an exciting and novel therapeutic direction that could provide more effective and longer-lasting results. This review will explore how biomechanical regulation shapes bone biology, the consequences of altered mechanotransduction, and the recent advances in therapies designed to harness or restore these pathways. By drawing together knowledge from molecular biology, biomechanics, and clinical research, it aims to offer a broader perspective on improving bone disease management beyond traditional treatment approaches.