Changes in Bone Mineral Density of the Femur and Tibia Before Injury to 2 Years After Anterior Cruciate Ligament Reconstruction in Division I Collegiate Athletes.

BACKGROUND: Osteoarthritis (OA) is a significant long term concern after anterior cruciate ligament (ACL) reconstruction (ACLR). A low bone mineral density (BMD), particularly in the subchondral region, has been associated with the development of OA and is evident at the knee in patients long after ACLR. It is unknown if persistent BMD deficits are present in high level collegiate athletes. PURPOSE/HYPOTHESIS: The purpose of this study was to evaluate bilateral changes in the BMD of the femur and tibia from before the injury to 24 months after ACLR in collegiate athletes. We hypothesized that the BMD of both the distal femur and the proximal tibia would be significantly reduced within the surgical limb initially postoperatively but return to preinjury levels by 24 months after ACLR. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: A total of 33 Division I collegiate athletes were identified between 2010 and 2021 (13 female) who underwent total body dual-energy X-ray absorptiometry (DXA) before sustaining an ACL injury. DXA was repeated at 6, 12, and 24 months after ACLR. Linear mixed effects models assessed differences in the BMD at 5%, 15%, and 50% of the femur's length (F5, F15, F50) and at 5%, 15%, and 50% of the tibia's length (T5, T15, T50) within each limb from before the injury to 24 months after ACLR, reported as Tukey-adjusted P values. RESULTS: Compared with before the injury, the BMD at F5 of the surgical limb was reduced by 0.15 g/cm2 (SE, 0.02 g/cm2) at 6 months (P < .001). The BMD at F15 of the surgical limb was reduced by 0.06 g/cm2 (SE, 0.01 g/cm2), 0.09 g/cm2 (SE, 0.01 g/cm2), and 0.09 g/cm2 (SE, 0.01 g/cm2) at 6, 12, and 24 months, respectively (all P < .001). The BMD at T5 of the nonsurgical limb was reduced by 0.07 g/cm2 (SE, 0.02 g/cm2) at 12 months (P = .02) and 0.10 g/cm2 (SE, 0.02 g/cm2) at 24 months (P = .001). The BMD at T15 of the surgical limb was reduced by 0.07 g/cm2 (SE, 0.01 g/cm2) at 6 months and 0.08 g/cm2 (SE, 0.02 g/cm2) at 12 months (P < .001). CONCLUSION: BMD deficits at F15 of the surgical limb persisted out to 24 months (-7.1%) after ACLR compared with before the injury in collegiate athletes. The BMD at F5 and T15 of the surgical limb was reduced at 6 and 12 months but not at 24 months compared with preinjury levels. For the nonsurgical limb, no significant differences were detected, except for the T5 region at 12 months (-5.1%) and 24 months (-7.2%). The BMD at F50 and T50 of both limbs was not significantly different than preinjury levels at any time after ACLR.

An in silico analysis of primary and secondary structure specificity determinants for human peptidylarginine deiminase types 2 and 4.

Human peptidylarginine deiminases (hPADs) are a family of five calcium-dependent enzymes that facilitate citrullination, which is the post-translational modification of peptidyl arginine to peptidyl citrulline. The isozymes hPAD2 and hPAD4 have been implicated in the development and progression of several autoimmune diseases, including rheumatoid arthritis and multiple sclerosis. To better characterize the primary and secondary structure determinants of citrullination specificity, we mined the literature for protein sequences susceptible to citrullination by hPAD2 or hPAD4. First, protein secondary structure classification (α-helix, ß-sheet, or coil) was predicted using the PSIPRED software. Next, we used motif-x and pLogo to extract and visualize statistically significant motifs within each data set. Within the data sets of peptides predicted to lie in coil regions, both hPAD2 and hPAD4 appear to favor citrullination of glycine-containing motifs, while distinct hydrophobic motifs were identified for hPAD2 citrullination sites predicted to reside within α-helical and ß-sheet regions. Additionally, we identified potential substrate overlap between coil region citrullination and arginine methylation. Together, these results confirm the importance and offer some insight into the role of secondary structure elements for citrullination specificity, and provide biological context for the existing hPAD specificity and arginine post-translational modification literature.