Glutamine Promotes Rotator Cuff Healing by Ameliorating Age-Related Osteoporosis

Background: Age-related osteoporosis complicates rotator cuff tear (RCT) treatment, undermining the integrity of surgical anchor fixation during rotator cuff repair (RCR). This study aimed to investigate whether supplementation with glutamine, an intrinsic amino acid crucial in cell metabolism, can enhance rotator cuff healing by ameliorating age-associated osteoporosis. Methods: Forty-eight female Sprague-Dawley rats were divided into 4 groups: (1) young control (sham surgery), (2) aged control (sham surgery), (3) aged-RCT (RCR with fibrin), and (4) aged-RCT-Gln (RCR with glutamine-enriched fibrin). RCR was performed bilaterally on rats in the RCT groups, with subsequent application of the respective fibrin gel at the tendon-bone interface. Evaluations included micro-computed tomography (CT) for bone quality, histology and immunohistochemistry for tissue integrity, and biomechanical testing for tendon-bone complex strength. Results: Micro-CT revealed worse bone quality at the proximal humerus in the aged rats compared with the young rats, confirming spontaneous osteoporosis occurring with age. Glutamine supplementation improved bone quality in the aged-RCT-Gln group compared with the aged-RCT group, with significantly higher mean bone volume/total volume fraction (BV/TV) (28.69% ± 3.1% compared with 21.13% ± 3.9%), trabecular number (Tb.N) (1.88 ± 0.18 compared with 1.55 ± 0.21 mm −1 ), and trabecular thickness (Tb.th) (0.15 ± 0.03 compared with 0.12 ± 0.02 mm) and lower trabecular separation (Tb.sp) (0.19 ± 0.03 compared with 0.22 ± 0.03 mm). Histological and immunohistological analysis demonstrated enhanced bone regeneration and a more organized tendon-cartilage-bone interface in the aged-RCT-Gln group. Biomechanical analysis also revealed a more resilient tendon-bone complex after glutamine supplementation. Conclusions: Osteoporosis occurred spontaneously at the proximal humerus with age. Glutamine supplementation effectively mitigated age-related osteoporosis and enhanced RCR in elderly rats. These findings support the potential of glutamine, the most abundant amino acid in the body, as a valuable therapeutic intervention for improving RCT outcomes in the aging population, warranting further investigation in clinical settings. Clinical Relevance: Glutamine supplementation may be a novel therapeutic strategy to enhance RCR in elderly patients with osteoporosis.