Vitamin D status associates with skeletal muscle loss after anterior cruciate ligament reconstruction

Abstract Objective We evaluated associations between vitamin D status and skeletal muscle, strength, and bone mineral density (BMD) outcomes after ACL reconstruction (ACLR) in an observational study. Methods Serum measures included 25-hydroxyvitamin D (25(OH)D; free and total), vitamin D binding protein (DBP), and 1,25-dihydroxy vitamin D (1,25(OH) 2 D) at baseline, 1 week, 4 months, and 6 months post-ACLR. Vastus lateralis biopsies were collected from the healthy and ACL-injured limb of 21 young, healthy participants (62% female; 17.8 [3.2] yr, BMI: 26.0 [3.5] kg/m 2 ) during ACLR and the injured limb only at 1 week and 4 month follow ups. RNA and protein were isolated from biopsies and assessed for vitamin D receptor [ VDR ], and vitamin D-activating enzymes. Quadriceps fiber cross-sectional area (CSA) was determined with immunohistochemistry. BMD of femur and tibia were determined at baseline and 6 months post-ACLR; strength was assessed with an isokinetic dynamometer. Results 1,25(OH) 2 D decreased from baseline to one week after ACLR (21.6 [7.9] vs. 13.8 [5.5] pg/mL; p<0.0001). VDR and 25-hydroxylase transcript abundance and VDR and DBP proteins were elevated one week after ACLR compared with baseline (FDR<0.05; p<0.05). Participants with an average total 25(OH)D <30 ng/mL showed significant decreases in CSA 1 week and 4 months after ACLR (p<0.01; p=0.041 for time x D status interaction), whereas those with total 25(OH)D ≥30ng/mL showed no significant differences (p>0.05 for all comparisons). BMD and strength measures were lower at follow up but did not associate with vitamin D status. Conclusion ACLR promotes vitamin D pathways in the quadriceps and low status is associated with loss of skeletal muscle both 1 week and 4 months after ACLR. Summary Box What is already known on this topic – Quadriceps muscle atrophy, strength loss, and reduced bone mineral density persist for many years after ACL tear and reconstruction (ACLR) leading to poorer function and long term knee health outcomes. Circulating 25-hydroxyvitamin D concentrations ≥30ng/mL (75nmol/L) have been associated with reduced risk of stress fracture and injury and greater strength, but it is not known how vitamin D status, which is easily modified with supplementation, may affect ACLR outcomes. What this study adds – Our work shows that ACLR surgery reduces biologically active vitamin D in circulation and promotes vitamin D receptor and activating enzyme expression in skeletal muscle one week after surgery. Circulating concentrations of 25(OH)D <30 ng/mL associate with greater loss of quadriceps fiber CSA both one week and 4 months after ACLR. How this study might affect research, practice or policy – Results suggest that correcting vitamin D status prior to ACLR may support retention of skeletal muscle size in recovery, which should be tested in a randomized clinical trial to begin to establish vitamin D cut points optimizing recovery from ACL tear and reconstruction.