Underlying mechanisms contributing to the imbalance in bone turnover during osteoporosis remain only partially explained. Reduced sensory nerve function may contribute to this imbalance, as sensory neuropeptides affect the activity of osteoblasts and osteoclasts in vivo, especially during bone adaptation. In this study, we investigated bone adaptation in mice following two weeks of tibial compression (peak magnitude 3 N or 7 N). To induce decreased sensory nerve function, mice were treated with capsaicin as neonates. We hypothesized that decreased sensory nerve function would diminish the adaptation of bone to mechanical loading, assessed with μCT and dynamic histomorphometry. We found that tibial compression induced significant changes in cortical microarchitecture that depended on compression magnitude and location along the length of the tibia; in contrast, there was no effect of loading on trabecular bone of the tibial metaphysis. Tibial compression significantly increased periosteal, and decreased endosteal, bone formation. Contrary to our initial hypothesis, capsaicin-treated mice generally displayed a similar, if not larger, adaptive response to mechanical loading, including greater increases in bone mineral content and mineral apposition rate. To integrate mechanical loading of bone with sensory nerve activation, we examined whether concentration of the neuropeptides calcitonin gene-related peptide (CGRP) and substance P (SP) in bone were affected following 1 or 5 days of 5 N tibial compression or hindlimb unloading. We found that 1 day of tibial compression significantly increased CGRP concentrations in bone, and hindlimb unloading also exhibited a trend toward increased CGRP in bone. These results may suggest a role of sensory nerves in the bone adaptation response to the mechanical environment, though this remains unclear.

Osteophytes are a typical radiographic finding during osteoarthritis (OA). Osteophytes are thought to form in response to joint instability, however the time course of osteophyte formation and joint stabilization following joint injury is not well understood. In this study, we investigated the time course of osteophyte formation and joint function following non-invasive knee injury in mice. We hypothesized that initial joint instability following knee injury would initiate osteophyte formation, which would in turn restabilize the joint and reduce range of motion (ROM). Mice were subjected to non-invasive anterior cruciate ligament (ACL) rupture. Anterior-posterior (AP) joint laxity, ROM, and chondro/osteophyte formation were measured immediately after injury, and 2, 4, 6, and 8 weeks post-injury. Chondrophyte areas at each time point were measured with histology, while mineralized osteophyte volume was determined using micro-computed tomography. Immediately after ACL rupture, AP joint laxity was increased 2-fold, while ROM was increased 11.7%. Chondrophytes appeared by 2 weeks post-injury, corresponding with a decrease in AP joint laxity and ROM. By 8 weeks post-injury, considerable osteophyte formation was observed around the joint, AP joint laxity returned to control levels, and joint ROM decreased to 61% of control values. These data support a role for chondro/osteophytes in joint restabilization after injury, and provide crucial insight into the time course and pathology of joint degeneration during OA development in the mouse.