Mechanical loading is important for maintaining bone mass, and researchers from Science Tokyo have found that sensory nerves inside the bone play a key role in this process. In mice, sensory nerve abundance changed in response to mechanical unloading and reloading, and removing these nerves prevented bone recovery. The findings reveal a link between mechanical loading, sensory nerves, and bone recovery and could support sensory nerve-targeted therapies and rehabilitation strategies for osteoporosis and fragility.
Bones may look like a static, unchanging structure, but they are a dynamic tissue that is constantly broken down and rebuilt through bone remodeling. This process helps maintain bone mass and strength in response to the forces being applied to the bones and the body. When these forces decrease due to prolonged inactivity or bed rest, the balance can shift toward bone loss and weakening of bones. Recent research shows that sensory nerves, part of the body's system for detecting physical sensations, help regulate bone metabolism and respond to changes in mechanical loading. However, it has remained unclear how these nerves change when the forces acting on bone are reduced or restored.
To address this question, researchers from Institute of Science Tokyo (Science Tokyo), Japan, investigated the effects of mechanical unloading and reloading in mice, focusing on how these changes affected sensory nerves and their role in maintaining bone health.
The study, published in Volume 14 of the journal Bone Research on August 28, 2026, was led by Associate Professor Shingo Sato, Professor Toshitaka Yoshii, and graduate student Shohei Tsujino, all affiliated to the Department of Orthopaedic Surgery, Science Tokyo. The team also included Researcher Hiroki Ochi of the National Rehabilitation Center for Persons with Disabilities, currently at Saitama Medical University, Japan; Professor Masafumi Muratani of the University of Tsukuba, Japan; and Professor Chihiro Akazawa of Juntendo University Graduate School of Medicine, Japan.
"Mechanical loading is crucial for maintaining bone mass, and understanding how bone remodels in response to changes in mechanical loading is essential for treating musculoskeletal disorders including osteoporosis," says Sato.
The space environment provides a unique setting for investigating the effects of mechanical loading on bone. The researchers examined the effects in mice housed in the "Kibo" Japanese Experiment Module on the International Space Station, where microgravity greatly reduces mechanical loading. They also used two ground-based models: tail suspension and hindlimb immobilization, which are widely used to reduce mechanical loading on the hind limbs. In these experiments, the researchers measured changes in bone and the nerve abundance inside the bones. They also investigated what happens when mechanical loading is restored.
The researchers found that reducing mechanical loading caused mice to lose bone mass and sensory nerves inside their bones. This occurred in both mice exposed to microgravity and those in the ground-based unloading models. When mechanical loading was restored, bone mass and sensory nerve abundance also recovered.
Moreover, the research team found that sensory nerves inside bone help maintain bone health in response to changes in mechanical loading. These nerves release signaling molecules called neuropeptides, which interact with bone cells and influence bone metabolism. When the researchers administered one of these neuropeptides, calcitonin gene-related peptide (CGRP), to mice during tail suspension, the mice lost much less trabecular bone than control mice who were administered saline. The CGRP-treated mice also had higher activity of osteoblasts, the cells that build new bone, than the control mice. The researchers further found that removing sensory nerves using surgical or genetic techniques prevented the normal recovery of trabecular bone after mechanical loading was restored.
"These findings demonstrate that sensory nerves inside bone play a critical role in regulating bone homeostasis. We also found that when sensory nerve projection into the bone is impaired, applying mechanical loading fails to increase bone mass," says Sato.
Reduced physical activity and aging can contribute to bone loss and conditions such as osteoporosis, in which bones become weaker and more prone to fractures. The findings of this study may help inform new strategies for preventing or treating bone loss caused by reduced mechanical loading, including prolonged inactivity, bed rest, or even long-term space travel. Additionally, these findings, when translated into clinical practice, could reduce the medical and socioeconomic burden related to conditions such as osteoporosis, and increase healthy life expectancy.
