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3X less muscle atrophy after ACL surgery if more than 40 ng of vitamin D – May 2022


Anterior Cruciate Ligament Reconstruction Upregulates Vitamin D Activating Pathways within the Quadriceps

FASEB J . 2022 May;36 Suppl 1. doi: 10.1096/fasebj.2022.36.S1.L7890. abstract of presentation
Jean L. Fry,Camille R. Brightwell,Christine M. Latham,Brooke D. Munson,Brian Noehren,Christopher S. Fry
Supported by NIH R01 AR072061, R01 AR071398-04S1, K23 AR062069

Anterior cruciate ligament (ACL) tears are prevalent sport-related injuries that result in protracted quadriceps atrophy and weakness despite surgical reconstruction and physical therapy. Vitamin D and its receptor are integral for skeletal muscle development and homeostasis. In addition, vitamin D status is positively associated with muscle size and strength. If the vitamin D receptor and related enzymes are upregulated with ACL injury and reconstruction, then overall vitamin D status may be an important effector of recovery. Concentrations of vitamin D needed to support optimal recovery may differ from typical clinical cut points used to diagnose vitamin D deficiency, which could have powerful therapeutic implications following ACL injury and reconstruction. This is especially important given recent research showing over 50% of athletes have vitamin D inadequacy. We hypothesized that subjects with circulating vitamin D sufficient to suppress parathyroid hormone secretion (≥ 40 ng/mL) would be better protected against quadriceps atrophy at the conclusion of rehabilitation. Muscle biopsies (vastus lateralis) were obtained from ACL-injured and Healthy limbs of 16 participants (6M,10F; 19±5yr, body mass index: 25.1±3.7kg/m2) prior to surgical reconstruction, 1 week following reconstruction (Recon), and following the completion of post-surgical rehabilitation (6 months following surgery, Post-Rehab). RNA was isolated from all quadriceps biopsies, followed by library construction, sequencing, and bioinformatics analysis. Transcript abundance of vitamin D activating pathway regulators (vitamin D receptor [VDR], and Cytochrome P450 2R1 [CYP2R1] and Family 27 Subfamily B Member 1 [CYP27B1]) was assessed following analysis using DESeq2 and false discovery rate (FDR) adjustment of p-values. Additionally, 25-hydroxy vitamin D (25(OH)D) was assessed in serum samples obtained at the time of reconstruction surgery. Quadriceps fiber cross-sectional area was measured via laminin immunohistochemistry. Recon (1 week post-surgery) muscle showed increased transcript abundance of the vitamin D receptor, VDR(elevated 7.8 fold, FDR<0.05), and vitamin D-activating pathway regulators CYP2R1 (elevated 1.5 fold, FDR<0.05) and CYP27B1 (elevated 2.6 fold, FDR<0.05) when compared to the Healthy limb.

Following the completion of rehabilitation at the 6-month follow-up, participants with 25(OH)D

  • above 40 ng/mL showed 6.4% atrophy of quadriceps fiber size compared to
  • 22.8% atrophy in participants with 25(OH)D below 40 ng/mL (p=0.06).

These findings provide evidence for surgically induced elevations in the vitamin D activating pathway within skeletal muscle. Upregulation of the vitamin D activating pathway may support quadriceps mitochondrial health and satellite cell activity and self-renewal capacity, both of which are compromised following ACL reconstruction. In addition, elevated vitamin D concentrations may protect against protracted quadriceps atrophy. Future research should investigate if manipulation of vitamin D concentrations can enhance quadriceps functional recovery following ACL reconstruction.


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Health problems often need >30 ng of Vitamin D

* Evolution of experiments with patients, often also need co-factors


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