Vitamin D status associates with skeletal muscle loss after anterior cruciate ligament reconstruction
Yuan Wen, Christine M. Latham, Angelique N. Moore, Nicholas T. Thomas, Brooke D. Lancaster, Kelsey A. Reeves, Alexander R. Keeble, Christopher S. Fry, Darren L. Johnson, Katherine L. Thompson, Brian Noehren, Jean L. Fry
Yuan Wen, Christine M. Latham, Angelique N. Moore, Nicholas T. Thomas, Brooke D. Lancaster, Kelsey A. Reeves, Alexander R. Keeble, Christopher S. Fry, Darren L. Johnson, Katherine L. Thompson, Brian Noehren, Jean L. Fry
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Clinical Research and Public Health Muscle biology

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

Abstract

BACKGROUND Although 25-hydroxyvitamin D [25(OH)D] concentrations of 30 ng/mL or higher are known to reduce injury risk and boost strength, the influence on anterior cruciate ligament reconstruction (ACLR) outcomes remains unexamined. This study aimed to define the vitamin D signaling response to ACLR, assess the relationship between vitamin D status and muscle fiber cross-sectional area (CSA) and bone density outcomes, and discover vitamin D receptor (VDR) targets after ACLR.METHODS Twenty-one young, healthy, physically active participants with recent ACL tears were enrolled (17.8 ± 3.2 years, BMI 26.0 ± 3.5 kg/m2). Data were collected through blood samples, vastus lateralis biopsies, dual energy x-ray bone density measurements, and isokinetic dynamometer measures at baseline, 1 week, 4 months, and 6 months after ACLR. The biopsies facilitated CSA, Western blotting, RNA-seq, and VDR ChIP-seq analyses.RESULTS ACLR surgery led to decreased circulating bioactive vitamin D and increased VDR and activating enzyme expression in skeletal muscle 1 week after ACLR. Participants with less than 30 ng/mL 25(OH)D levels (n = 13) displayed more significant quadriceps fiber CSA loss 1 week and 4 months after ACLR than those with 30 ng/mL or higher (n = 8; P < 0.01 for post hoc comparisons; P = 0.041 for time × vitamin D status interaction). RNA-seq and ChIP-seq data integration revealed genes associated with energy metabolism and skeletal muscle recovery, potentially mediating the impact of vitamin D status on ACLR recovery. No difference in bone mineral density losses between groups was observed.CONCLUSION Correcting vitamin D status prior to ACLR may aid in preserving skeletal muscle during recovery.FUNDING NIH grants R01AR072061, R01AR071398-04S1, and K99AR081367.

Authors

Yuan Wen, Christine M. Latham, Angelique N. Moore, Nicholas T. Thomas, Brooke D. Lancaster, Kelsey A. Reeves, Alexander R. Keeble, Christopher S. Fry, Darren L. Johnson, Katherine L. Thompson, Brian Noehren, Jean L. Fry

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Figure 6

Mean study 25(OH)D less than 30 ng/mL associates with cross-sectional area (CSA) reductions in the vastus lateralis muscle.

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Mean study 25(OH)D less than 30 ng/mL associates with cross-sectional ar...
(A) When comparing participants with low study vitamin D status [25(OH)D < 30 ng/mL] and those with adequate status [25(OH)D ≥ 30 ng/mL], the low vitamin D status group showed significant reductions in fiber CSA at 1-week and 4-month follow-ups when compared with baseline. At 4 months, the fiber CSA was significantly lower in participants having study 25(OH)D < 30 ng/mL (n = 10) when compared with participants who had 25(OH)D ≥ 30 ng/mL (n = 7). (B) Representative CSA IHC for a low-status participant. (C) Representative CSA IHC for an adequate-status participant. B and C are representative images for the experiment shown in A having 21 total participants at the baseline and 1-week time points and 17 participants at the 4-month mark. Scale bars: 200 μm. Full-factorial repeated-measures ANOVA with post hoc tests. The model showed an overall time × vitamin D status interaction effect P = 0.041; results of host-hoc tests on graph. **P < 0.01; ***P < 0.001; ****P < 0.0001.