To investigate whether tibiofemoral alignment influences early knee osteoarthritis (OA). We hypothesized that varus overload exacerbates early degenerative osteochondral changes, and that valgus underload diminishes early OA. Normal, over- and underload were induced by altering alignment via high tibial osteotomy in adult sheep (n = 8 each). Simultaneously, OA was induced by partial medial anterior meniscectomy. At 6 weeks postoperatively, OA was examined in five individual subregions of the medial tibial plateau using Kellgren-Lawrence grading, quantification of macroscopic OA, semiquantitative histopathological OA and immunohistochemical type-II collagen, ADAMTS-5, and MMP-13 scoring, biochemical determination of DNA and proteoglycan contents, and micro-computed tomographic evaluation of the subchondral bone. Multivariate analyses revealed that OA cartilaginous changes had a temporal priority over subchondral bone changes. Underload inhibited early cartilage degeneration in a characteristic topographic pattern ( ≥ 0.0983 vs. normal), in particular below the meniscal damage, avoided alterations of the subarticular spongiosa ( ≥ 0.162 vs. normal), and prevented the disturbance of otherwise normal osteochondral correlations. Overload induced early alterations of the subchondral bone plate microstructure towards osteopenia, including significantly decreased percent bone volume and increased bone surface–to–volume ratio (all ≤ 0.0359 vs. normal). The data provide high-resolution evidence that tibiofemoral alignment modulates early OA induced by a medial meniscus injury in adult sheep. Since underload inhibits early OA, these data also support the clinical value of strategies to reduce the load in an affected knee compartment to possibly decelerate structural OA progression.

中文翻译：

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羊胫股骨重新排列对早期骨关节炎的调节


探讨胫骨股骨排列是否影响早期膝骨关节炎 (OA)。我们假设内翻超负荷会加剧早期退行性骨软骨变化，而外翻负荷不足会减少早期骨关节炎。通过成年羊胫骨高位截骨术改变排列来诱导正常、超载和欠载（每只 n = 8）。同时，通过部分内侧前半月板切除术诱导 OA。术后 6 周，使用 Kellgren-Lawrence 分级、宏观 OA 定量、半定量组织病理学 OA 和免疫组织化学 II 型胶原、ADAMTS-5 和 MMP-13 评分、生化测定，检查内侧胫骨平台的五个单独分区的 OA DNA 和蛋白多糖含量，以及软骨下骨的显微计算机断层扫描评估。多变量分析显示，OA 软骨变化在时间上优先于软骨下骨变化。欠负荷抑制了特征性地形模式的早期软骨退化（≥ 0.0983 与正常），特别是在半月板损伤下方，避免了关节下海绵体的改变（≥ 0.162 与正常相比），并防止了其他正常骨软骨相关性的干扰。过载导致软骨下骨板微观结构发生骨质减少的早期改变，包括骨体积百分比显着下降和骨表面与体积之比增加（与正常相比，全部≤0.0359）。这些数据提供了高分辨率证据，表明胫股骨排列可调节成年羊内侧半月板损伤引起的早期骨关节炎。由于负荷不足会抑制早期 OA，因此这些数据也支持减少受影响膝关节室负荷以可能减缓结构性 OA 进展的策略的临床价值。