Tibial Bone Co-Morbidities Following Volumetric Muscle Loss Injury and Physical Inactivity

Abstract

Volumetric muscle loss (VML) injuries are a traumatic loss of muscle, limiting regenerative potential and resulting in chronic loss of function. In isolation the bone adjacent to the VML injury is often overlooked, but known association between the tissues are important to long-term health and function. Recent work suggests decrements in both bones and muscles of VML-injured limbs, as well as a distinct relationship between VML and bone health. The clinically injured VML population is expected to undergo considerable periods of physical inactivity or a long-term sedentary lifestyle, and thus decreased loading, after VML. Our objective was to investigate the concomitant impact of VML on the adjacent bone, with and without the restriction of physical activity (reduced ~50% of daily ambulation). We hypothesized that with restriction of physical activity, the tibia adjacent to the VML would have functional impairments greater than those with normal physical activity (daily ambulation >1km). Adult male C57BI/6J mice (n=41) underwent unilateral VML to the posterior hindlimb compartment or served as uninjured age-matched controls, then were randomized to standard or restricted activity cages for 8-wks. Terminally (age 20-wks), mice underwent in vivo muscle function testing. Adjacent tibia were assessed for strength, mid‐diaphysis cortical geometry, and intrinsic material properties, and the metaphyseal trabecular bone structure was evaluated by microcomputed tomography and three‐point bending. A subset of tibias was saved for histologic staining (H&E, TRAP). Data were evaluated by two-way ANOVA. There were no absolute or normalized functional muscle deficits following 8-wks of inactivity. That said, there were significant VML-functional deficits (~42% of uninjured) that are not exacerbated by inactivity (p<0.001). Cortical geometric changes in the bone were primarily a result of physical inactivity, with thickness and cross-sectional moment of inertia both diminished independent of injury (p≤0.018). However, there were no differences in cortical bone volume, diameter, or cross-sectional area (p≥0.056). Trabecular bone mineral density was lower in all VML-injured tibias compared to uninjured (p=0.003). While there was no difference across groups for trabecular spacing (p>0.397), there was a reduction in bone mineral density across all VML-injured, compared to uninjured tibias (p=0.003). The functional capacity of the tibia to resist fracture (i.e., ultimate load during 3‐point bending) was ~21% lower with inactivity (p=0.018), while there was only a trend for VML injury to impact resistance to fracture. Stiffness was calculated during the onset to ultimate load and ~15% less in the VML injured and inactivity VML tibias (p=0.016). Tibia of VML injured and inactive groups appear to have greater lipid accumulation compared to uninjured tibias. While discordant with muscle function, physical activity restriction with and without VML injury impairs adjacent tibia. Inactivity alone had the greatest impact on the cortical bone properties, while VML with and without physical inactivity impacted trabecular tibia properties. This study demonstrates the impact of VML with and without physical inactivity on the tibia, furthering the complexity of traumatic injury on the musculoskeletal system. W81XWH‐20‐10885 (JAC & SMG); S10OD025177. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.