Effects of volumetric muscle loss injury on contractile function, and bone structure and functional capacity in male C57BL/6J mice

Skeletal muscles and bones are structurally and functionally linked, such that bone strength is primarily determined the frequency and magnitude of the mechanical strain derived from muscular contractions. Volumetric muscle loss (VML) injury results in a significant loss of muscle tissue and a non-recoverable loss of muscle strength. However, the extent to which limbs that sustain a VML injury have associated changes to bone structure and functional capacity is unknown. This study’s objective was to investigate whether VML injury affects the adjacent tibial bone structure and functional capacity in adult male C57BL/6J mice. At 12 weeks of age, mice (n=14) underwent a unilateral VML injury (4mm diameter muscle biopsy) to the left hindlimb plantar flexor muscles, while the right limbs served as uninjured controls. At 20 weeks of age (2 months post-VML injury), mice were bilaterally tested for in vivo peak-isometric plantarflexion torque. Post-mortem analyses of tibial bone structure and mechanical properties was assessed via μCT and 3-point bending tests, respectively, at the mid-diaphysis. Statistical analyses were performed between injured and uninjured limbs via paired t-test, with an α-level of 0.05. At 2 months post-injury, VML-injured limbs had significantly less gastrocnemius muscle mass (28%), and peak-isometric torque (35%) as compared to uninjured limbs (p<0.001). Tibial bone strength, as measured by ultimate load, demonstrated a trend in VML-injured limbs to be 3% lower than that in uninjured limbs (p=0.055). Most notably, the cross-sectional moment of inertia (CSMI), the principal structural determinant of the bone’s ultimate load was 9% smaller in VML-injured limbs as compared to uninjured limbs (p=0.035). Additional structural changes in cortical bone were detected: notably, less cortical bone thickness (4.5%), volume (6.6%), and cross-sectional area (4.9%) in VML-injured limbs as compared to the uninjured limb (p≤ 0.025). Bone-to-muscle functional ratio (i.e., ultimate load:peak-isometric torque) was 38% greater in VML-injured limbs compared to uninjured limbs (p<0.001) indicating the deficits in muscle far outweigh that of bone at 2 months post-injury. Future research directions include determining if more time post-VML injury has a greater effect on bone ultimate load and exploring the extent to which the uninjured limbs in VML-injured mice experience compensatory or related changes to bone structure and function. W81XWH-20-1-0885 to JAC and SMG This is the full abstract presented at the American Physiology Summit 2023 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.