Varus malalignment increases the susceptibility of cartilage to mechanical overloading, which stimulates catabolic metabolism to break down the extracellular matrix and lead to osteoarthritis (OA). The altered mechanical axis from the hip, knee to ankle leads to knee joint pain and ensuing cartilage wear and deterioration, which impact millions of the aged population. Stabilization of the remaining damaged cartilage, and prevention of further deterioration, could provide immense clinical utility and prolong joint function. Our previous work showed that high tibial osteotomy (HTO) could shift the mechanical stress from an imbalanced status to a neutral alignment. However, the underlying mechanisms of endogenous cartilage stabilization after HTO remain unclear. We hypothesize that cartilage-resident mesenchymal stem cells (MSCs) dampen damaged cartilage injury and promote endogenous repair in a varus malaligned knee. The goal of this study is to further examine whether HTO-mediated off-loading would affect human cartilage-resident MSCs' anabolic and catabolic metabolism. This study was approved by IACUC at Xi'an Jiaotong University. Patients with medial compartment OA (52.75±6.85 yrs, left knee 18, right knee 20) underwent open-wedge HTO by the same surgeons at one single academic sports medicine center. Clinical data was documented by the Epic HIS between the dates of April 2019 and April 2022 and radiographic images were collected with a minimum of 12 months of follow-up. Medial compartment OA with/without medial meniscus injury patients with unilateral Kellgren /Lawrence grade 3–4 was confirmed by X-ray. All incisions of the lower extremity healed well after the HTO operation without incision infection. Joint space width (JSW) was measured by uploading to ImageJ software. The Knee injury and Osteoarthritis Outcome Score (KOOS) toolkit was applied to assess the pain level. Outerbridge scores were obtained from a second-look arthroscopic examination. RNA was extracted to quantify catabolic targets and pro-inflammatory genes (QiaGen). Student's t test for two group comparisons and ANOVA analysis for differences between more than 2 groups were utilized. To understand the role of mechanical loading-induced cartilage repair, we measured the serial changes of joint space width (JSW) after HTO for assessing the state of the cartilage stabilization. Our data showed that HTO increased the JSW, decreased the VAS score and improved the KOOS score significantly. We further scored cartilage lesion severity using the Outerbridge classification under a second-look arthroscopic examination while removing the HTO plate. It showed the cartilage lesion area decreased significantly, the full thickness of cartilage increased and mechanical strength was better compared to the pre-HTO baseline. HTO dampened medial tibiofemoral cartilage degeneration and accelerate cartilage repair from Outerbridge grade 2 to 3 to Outerbridge 0 to 1 compared to untreated varus OA. It suggested that physical loading was involved in HTO-induced cartilage regeneration. Given that HTO surgery increases joint space width and creates a physical loading environment, we hypothesize that HTO could increase cartilage composition and collagen accumulation. Consistent with our observation, a group of cartilage-resident MSCs was identified. Our data further showed decreased expression of RUNX2, COL10 and increased SOX9 in MSCs at the RNA level, indicating that catabolic activities were halted during mechanical off-loading. To understand the role of cartilage-resident MSCs in cartilage repair in a biophysical environment, we investigated the differentiation potential of MSCs under 3-dimensional mechanical loading conditions. The physical loading inhibited catabolic markers (IL-1 and IL-6) and increased anabolic markers (SOX9, COL2). Knee-preserved HTO intervention alleviates varus malalignment-related knee joint pain, improves daily and recreation function, and repairs degenerated cartilage of medial compartment OA. The off-loading effect of HTO may allow the mechanoregulation of cartilage repair through the differentiation of endogenous cartilage-derived MSCs

Knee joint distraction (KJD) has been associated with clinical and structural improvement and synovial fluid (SF) marker changes. However, structural changes have not yet been shown satisfactorily in regular care, since radiographic acquisition was not fully standardized. AI-based modules have shown great potential to reduce reading time, increase inter-reader agreement and therefore function as a tool for treatment outcome assessment. The objective was to analyse structural changes after KJD in patients using this AI-based measurement method, and relate these changes to clinical outcome and SF markers. 20 knee OA patients (<65 years old) were included in this study. KJD treatment was performed using an external fixation device, providing 5 mm distraction for 6 weeks. SF was aspirated before, during and immediately after treatment. Weight-bearing antero-posterior knee radiographs and WOMAC questionnaires were collected before and ~one year after treatment. Radiographs were analysed with the Knee Osteoarthritis Labelling Assistant (KOALA, IB Lab GmbH, Vienna, Austria), and 10 pre-defined biomarker levels in SF were measured by immunoassay. Radiographic one-year changes were analysed and linear regression was used to calculate associations between changes in standardized joint space width (JSW) and WOMAC, and changes in JSW and SF markers. After treatment, radiographs showed an improvement in Kellgren-Lawrence grade in 7 of 16 patients that could be evaluated; 3 showed a worsening. Joint space narrowing scores and continuous JSW measures improved especially medially. A greater improvement in JSW was significantly associated with a greater improvement in WOMAC pain (β=0.64;p=0.020). A greater increase in MCP1 (β=0.67;p=0.033) and lower increase in TGFβ1 (β=-0.787;p=0.007) were associated with JSW improvement. Despite the small number of patients, also in regular care KJD treatment shows joint repair as measured automatically on radiographs, significantly associated with certain SF marker change and even with clinical outcome

Introduction and Objective. To estimate the prevalence of acetabular ossifications in the adult population with asymptomatic, morphologically normal hips at CT and to determine whether the presence of labral ossifications is associated with patient-related (sex, age, BMI), or hip-related parameters (joint space width, and cam- and pincer-type femoroacetabular impingement morphotype). Materials and Methods. We prospectively included all patients undergoing thoracoabdominal CT over a 3-month period. After exclusion of patients with a clinical history of hip pathology and/or with signs of osteoarthritis on CT, we included a total of 150 hips from 75 patients. We analyzed the presence and the size of labral ossifications around the acetabular rim. The relationships between the size of labral ossifications and patient- and hip-related parameters were tested using multiple regression analysis. Results. The prevalence of labral ossifications in this population of asymptomatic, non-OA hips was 96% (95%CI=[80.1; 100.0]). The presence of labral ossifications and their size were correlated between right and left hips (Spearman coefficient=0.64 (95%CI=[0.46; 0.79]), p<0.05)). The size of labral ossifications was significantly associated with age (p<0.0001) but not with BMI (p=0.35), gender (p=0.05), joint space width (p≥0.53 for all locations) or any of the qualitative or quantitative parameters associated with femoroacetabular morphotype (all p≥0.34). Conclusions. Labral ossifications are extremely common in asymptomatic, non-osteoarthritic hips. Their size is not correlated with any patient-, or hip-related parameters except for the age. These findings suggest that the diagnosis of osteoarthritis or femoroacetabular impingement morphotype should not be made based on the sole presence of acetabular labral ossifications

Summary. In this study we validate that weight-bearing images are needed for accurate polyethylene liner wear measurement in total knee prostheses by measuring the difference in minimum joint space width between weight-bearing and non-weight-bearing RSA views. Introduction. Recent studies show that Model-based Roentgen Stereophotogrammetric Analysis is superior to the conventional in vivo measurements of polyethylene liner wear in total knee prostheses. Although it is generally postulated that weight-bearing (standing) views are required to detect liner wear, most RSA images are acquired in non-weight-bearing (supine) view for practical reasons. Therefore, it would be of interest to know if supine views would be sufficient for measuring TKA liner wear, defined as a change in minimum joint space width (mJSW). As a difference in mJSW between weight-bearing and non-weight-bearing RSA images has never been validated, the aim of this study is to compare the outcome of in vivo measurements of mJSW in total knee prosthesis when conducted with weight-bearing and non-weight-bearing RSA views. Method. We selected the first 16 patients with a Triathlon total knee prosthesis from a clinical study for which subsequently a weight-bearing eand a non-weight-bearing RSA image pair were acquired at one year follow up. For both images the mJSW and the corresponding contact point locations in terms of mediolateral (ML) and anterioposterior (AP) coordinates were measured. In addition, the ML stability was scored to assess knee laxity. The size of the mJSW difference between non-weight-bearing and weight-bearing views was determined and a regression analysis was conducted to investigate the effect of knee laxity to this difference, while correcting for differences between the contact point locations. Results. On average, the measured mJSW was 0.22 mm larger in the non-weight-bearing views (T-test, p < 0.05). The standard deviation of the difference was 0.22 mm. The regression analysis showed that a difference in the ML position of the contact location was an important covariate (beta = 0.255±0.054, Wald 95% CI). 13 patients had a high ML stability (< 5 deg) and three had a medium stability (5–10 deg). The regression analysis showed that on average patients with medium ML stability had a 0.17 mm larger difference in mJSW than patients with a high ML stability. Conclusion. The study shows that the mJSW is larger in non-weight-bearing views. The differences found are clinically relevant, as wear rates in practice are as small as 0.1 mm per year. Hereby it is validated that weight-bearing RSA images are more capable of detecting the mJSW in total knee prostheses. The size of the difference in mJSW between the views seems to be in relation with the knee laxity

Summary. The dGEMRIC index correlates more strongly with the pattern of radiographic joint space narrowing in hip osteoarthritis at five year follow-up than morphological measurements of the proximal femur. It therefore offers potential to refine predictive models of hip osteoarthritis progression. Introduction. Longitudinal general population studies have shown that femoroacetabular impingement increases the risk of developing hip osteoarthritis, however, morphological parameters have a low positive predictive value. Arthroscopic debridement of impingement lesions has been proposed as a potential strategy for the prevention of osteoarthritis, however, the development of such strategies requires the identification of individuals at high risk of disease progression. We investigated whether delayed Gadolinium-Enhanced MRI of Cartilage (dGEMRIC) predicts disease progression. This imaging modality is an indirect measure of cartilage glycosaminoglycan content. Patients and Methods. 34 asymptomatic individuals from a longitudinal cohort study (sibkids) were assessed at baseline with the collection of Patient Reported Outcome Measures (PROMs), anteroposterior and cross-table lateral radiographs, 3D morphological MRI, and dGEMRIC at 3T of their index hip. A dGEMRIC index was calculated as a ratio of the anterosuperior acetabular cartilage T1 relaxation time and the total femoral and acetabular cartilage T1 relaxation time. 29 individuals were followed up at 5 years for repeat assessment (average age 51 years and range 36 to 67). Radiological measurements were made by a single observer using in house Hipmorf software. Radiographic disease progression was assessed using minimum joint space width (JSW), lateral sourcil JSW, and medial sourcil JSW. These were measured on baseline and five year follow-up anteroposterior radiographs with an intra-observer ICC of 0.916. Alpha angle measurements were made by the same observer on radiographs and MRI radial slices with an intra-observer ICC of 0.926. Results. Mean minimum JSW for the cohort fell by 0.16mm over five years (p=0.024). Baseline dGEMRIC index did not correlate with change in minimum JSW (r=0.031 p=0.873). There was a moderate correlation between baseline dGEMRIC and the direction of JSW loss (change in JSW at the lateral sourcil minus change in JSW at the medial sourcil) (r=0.561 p=0.002). There was a weak correlation between the change in Non-Arthritic Hip Score and baseline dGEMRIC (r=0.256 P=0.180). Maximum alpha angle measured on baseline MRI radial slices did not correlate with change in minimum JSW and weakly correlated with the direction of JSW narrowing (r=0.273 p=0.160). Conclusion. A low dGEMRIC index indicates reduced glycosaminoglycan concentration in the anterosuperior acetabular cartilage compared with the total femoral and acetabular cartilage. This correlates with lateral JSW narrowing relative to medial JSW narrowing as osteoarthritis progresses. The dGEMRIC index correlates better with osteoarthritis progression than alpha angle measurements and offers the potential to refine a predictive model for osteoarthritis progression to aid patient selection for clinical trials

Objectives

We have previously investigated an association between the genome copy number variation (CNV) and acetabular dysplasia (AD). Hip osteoarthritis is associated with a genetic polymorphism in the aspartic acid repeat in the N-terminal region of the asporin (ASPN) gene; therefore, the present study aimed to investigate whether the CNV of ASPN is involved in the pathogenesis of AD.