Published 3/10/2025
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Rebecca Araujo
Researchers from Kyoto University found residual proinflammatory cytokine gene expressions after under-correction following medial open wedge high tibial osteotomy (MOWHTO). These findings will be presented as a poster at the AAOS 2025 Annual Meeting by Kohei Nishitani, MD, PhD, assistant professor of medicine at Kyoto University.
MOWHTO is surgical correction of lower-limb alignment from varus to valgus and is often performed in patients with medial knee osteoarthritis. According to Dr. Nishitani and colleagues, “While biomechanical studies have demonstrated that MOWHTO decreases medial compartment loading, it remains unclear whether optimizing knee alignment affects joint inflammation in the biological microenvironment.” The authors cited previous studies that have reported reduced proinflammatory cytokines and chemokines following MOWHTO, along with shifts in synovial macrophage polarity from M1 to M2 in synovial tissues. However, they noted, “The relationship between alignment correction and synovial gene expression has not been fully elucidated.” They undertook this study to assess how pre- and postoperative knee alignment are related to synovial gene expression and identify a cutoff value for postoperative knee alignment that is associated with improvement in inflammatory gene expression.
Thirty-six patients were included in the analysis. All patients underwent MOWHTO for medial compartment osteoarthritis between 2018 and 2020. MOWHTO was performed with a target weight-bearing line ratio (WBLR) of 60 to 62.5 percent. Follow-up was conducted until the time of plate removal following bone healing, which occurred around 1 year postoperatively. Clinical outcomes were captured with the Knee Injury and Osteoarthritis Outcome Score (KOOS) at baseline and at plate removal. WBLR was utilized for radiographic assessment of alignment, and hip-knee-ankle angle (HKAA) was measured via anteroposterior whole-leg standing radiography.
Synovial tissues were harvested from the suprapatellar pouch via arthroscopic examination. Relative gene expression was determined in each sample by real-time polymerase chain reaction. Spearman rank correlations were used to identify relationships between lower-limb alignment and synovial gene expression, and a receiver operating characteristic (ROC) curve analysis was used to determine WBLR cutoff values.
The mean preoperative HKAA was 8.3 degrees varus, which was corrected to 0.6 degrees valgus postoperatively. The preoperative WBLR was 14.6 percent, corrected to 51.4 percent postoperatively. The researchers found that postoperative HKAA correlated with interleukin-1 beta (IL-1B; P = 0.004) and interleukin-6 (IL-6; P = 0.01). Postoperative WBLR was also correlated with IL-1B (P = 0.008) and IL-6 (P = 0.01), which indicated that “knees with postoperative under-correction [were] associated with high expression of proinflammatory cytokines,” the authors noted. According to ROC curve analysis, the area under the ROC curve for postoperative WBLR to postoperative improvement of IL-1B and IL-6 expressions were 0.62 (P = 0.27) and 0.74 (P = 0.03), respectively.
WBLR of 52 percent was identified as the cutoff value for predicting IL-6 improvement. The authors noted that postoperative proinflammatory cytokine gene expressions were significantly different between patients with WBLR above and below 52 percent. Additionally, patients with WBLR below 52 percent tended to have inferior postoperative KOOS scores compared with patients with WBLR above the cutoff. In a subgroup of 30 patients with preoperative WBLR of >0 percent, postoperative WBLR >52 percent was achieved in 19 cases. However, no patients with preoperative WBLR <0 percent (n="6)" achieved postoperative wblr above the cutoff value (>P = 0.006).
“From this study, relationships between knee alignment and gene expressions were observed after MOWHTO, and patients with under-correction tended to have insufficient improvement of proinflammatory cytokine expressions,” the authors concluded. To predict improvement of IL-6 gene expression, they advised a postoperative alignment of WBLR to 52 percent, “which was considered as the minimum postoperative alignment for biological improvement,” they noted.
Poster P075 will be on display during Limb Deformity Poster Session 1, Monday and Tuesday in OrthoLive.
Dr. Nishitani’s coauthors of “Under-Correction Associated with Residual Proinflammatory Cytokine Gene Expressions after High Tibial Osteotomy” are Shinichi Kuriyama, MD, PhD; Shinichiro Nakamura, MD, PhD; and Shuichi Matsuda, MD.
Rebecca Araujo is the managing editor of AAOS Now. She can be reached at raraujo@aaos.org.