Special Poster Session 50th International Society for the Study of the Lumbar Spine Annual Meeting 2024

INTRODUCTION Age-related skeletal muscle atrophy of specific muscle groups appears to develop differently. From the review by Masatoshi Naruse et al., the paraspinal muscles (0.47%/year) and psoas (0.58%/year) have higher annual decline rate than the limb muscles such as soleus (0.13%/year) [1]. The TSC1mKO mouse model has muscle-specific knockout of TSC1 gene, leading to the upregulation of mTORC1. From our previous study on TSC1mKO mice undergoing exercise, two-month treadmill exercise can significantly improve grip test and endurance but  not the Cobb angle. This study suggests that the atrophy of core muscles such as erector spinae, multifidus and psoas may be harder to treat than the limb muscles. The aim of study is 1) To investigate whether myopathy-induced kyphosis can be reversed at the late-stage life cycle under rapamycin treatment. 2) To examine the difference in the central nucleus density pattern between the core muscles (erector spinae (ES), multifidus (MF) and psoas) and limb muscles (extensor digitorum longus (EDL) and soleus (SOL).

METHODS Twelve female 9-month-old TSC1mKO mice were divided into two groups: 1) TSC1mKO mice with no treatment (n=7), 2) TSC1mKO mice treated with 8mg/kg rapamycin (n=5). All the Cobb angles of the mice were measured by live micro-CT before treatment and three months after treatment. The endurance of the mice muscle was also evaluated using the treadmill before and after treatment. Myopathic changes in the harvested core muscles (erector spinae, multifidus and psoas) and limb muscles (extensor digitorum longus and soleus) were examined via WGA/DAPI stain.

RESULTS Thoracolumbar kyphosis was partially reversed after three months of rapamycin treatment (Pre: 99.14° ± 4.35° vs Post: 90.90° ± 5.07°, p=0.06) while the untreated group showed no improvement in the Cobb angle (Pre: 112.2° ± 6.0° vs Post 111.1° ± 9.0°) (Fig 1). Treadmill endurance was significantly improved in rapamycin-treated TSC1mKO mice from 11.0 ± 1.0m/min to 18.2 ± 3.8m/min while untreated mice declined from 14.1 ± 4.5m/min to 13.0 ± 2.2m/min.

From the WGA/DAPI histology images, the rapamycin treatment restored the fibre size to normal level in both core and limb muscles. The central nucleus density of the core muscles in both rapamycin-treated (ES: 19.14 ± 4.76%, MF: 17.32 ± 10.40%, Psoas: 17.13 ± 5.07%) and untreated TSC1mKO mice (ES: 24.19 ± 6.84%, MF: 16.17 ± 5.83%, Psoas: 30.03 ± 7.14%) were higher than the limb muscles of the mice counterparts (TSC1mKO treated with rapamycin EDL: 8.43 ± 3.62%, SOL: 5.86 ± 2.94%, untreated TSC1mKO mice EDL 8.04 ± 1.73%, SOL 9.86 ± 4.99%) (Fig 2).

DISCUSSION Rapamycin fails to restore myopathy-induced kyphosis in the late-stage life cycle of TSC1mKO mice. The underlying reason may be loss of intervertebral disc height and vertebral shape change. The central nucleus density of the core muscles is higher than the limb muscles of the mice counterparts, suggesting higher degeneration in the core muscles compared to the limb muscles. The lower degree of degeneration in the limb muscles may explain why general exercise is effective on limb muscles but not core muscles.