(P29-024-24) Genetic Predictors of Bone Density Loss After Anterior Cruciate Ligament Reconstruction

Objectives: Adolescence and early adulthood are crucial life stages for achieving peak bone mineral density (BMD) and minimizing later-life fracture risk. Youths undergoing anterior cruciate ligament reconstruction (ACLR) show BMD reductions in the femur of the operative limb of 10-50% six months post-ACLR. Considering certain single nucleotide polymorphisms (SNPs) are linked to lower bone mineral and vitamin D deficiencies, this study investigates if 11 SNPs related to vitamin D metabolism could predict BMD changes in ACLR patients. Identifying those at risk may warrant preventive interventions for these at-risk patients.

Methods: Healthy participants (n=16, mean ± standard deviation; 18 ± 4 years of age; BMI: 25 ± 3 kg/m; 75% female, 25% male; 62% non-Hispanic white, 38% Black) with recent ACL injury were evaluated at the University of Kentucky within 1 week before and six months after ACLR. BMD of the distal femur was measured with dual-energy X-ray absorptiometry (Lunar iDXA, GE Healthcare). The analysis focused on BMD percentage loss, using stepwise regression to identify predictive SNPs while accounting for race and sex. Principal component analysis (PCA) further categorized SNPs into principal components (PC) based solely on genotype data. Participants were then divided into groups based on a positive or negative score for PC1 and PC2 to determine if the PCs created based on genotype analysis predicted participants’ changes in femur BMD.

Results: T-tests comparing the top two PCs showed significant differences in BMD loss between participants high and low on PC2 (-31% for PC2 >0 and -20% for PC2 < 0; p=0.026), with significant contributions from rs10741657, rs2060793, rs731236, and rs1544410. The regression model highlighted female sex and the rs731236 G allele as significant predictors of reduction in BMD, achieving an adjusted R² of 0.520 (p=0.008).

Conclusions: This study underscores potential genetic influences on BMD resilience or vulnerability post-ACLR, meriting further investigation.

Funding Sources: NIH/NIAMS R01AR072061