Purpose: Osteoarthritis (OA) is a common degenerative joint disease, with its etiology remaining poorly understood. Our study aims to explore the causal associations between immune cells and OA, with the goal of generating a new perspective for targeted intervention strategies. Methods: A bidirectional two-sample Mendelian randomization (MR) analysis was performed to estimate the causality between multiple circulating immune cells and different sites of OA. The immune cell traits analyzed included the counts of circulating white blood cells (WBC), lymphocytes, monocytes, neutrophils, eosinophils, and basophils, as well as certain subsets of T and B lymphocytes. The OA types included were OA at any site, knee OA, hip OA, spine OA, thumb OA, and hand OA. Inverse-variance weighted (IVW), MR-Egger, weight median and weight mode were used to evaluate causal effects, with IVW being the main analysis method. Sensitivity analyses were conducted to assess heterogeneity and pleiotropy. Results: Our findings indicated that resting regulatory T cell (Treg) absolute counts (AC) were causally associated with an increased risk for spine OA [odds ratio (OR), 1.051; 95 % confidence interval (CI), 1.018-1.086; P=0.0005, P-FDR=0.0350], and spine OA showed a positive causal relationship with the neutrophils count (OR, 1.104; 95 %CI, 1.032-1.181; P=0.0039, P-FDR=0.0233). Besides, OA at any site was correlated with a rise in circulating eosinophils count (OR, 1.05; 95 %CI, 1.021-1.079; P=0.0007, P-FDR=0.0041), while knee OA was associated with decreased total WBC (OR, 0.945; 95 %CI, 0.912-0.979; P=0.0016, P-FDR=0.0048) and monocytes counts (OR, 0.958; 95 %CI, 0.934-0.982; P=0.0007, P-FDR = 0.0041). No evidence of heterogeneity or horizontal pleiotropy was detected. Conclusions: Our study has demonstrated the causal associations between multiple immune cells and diverse joint OA. These results highlight the intricate interplay between immune cells and OA, suggesting potential targets for therapeutic interventions to manage disease progression and alleviate symptoms.

Purpose: The femoral trochlea axial orientation has been shown to be a better predictor of patellar dislocation than the femoral anteversion angle. However, no study has investigated the importance of the femoral trochlea axial orientation in the surgical treatment of patellar dislocation. It is aimed to explore the pathological threshold of the femoral trochlea axial orientation and its guiding implications for surgical interventions in the study. Methods: Sixty-four patients with patellar dislocation and 64 controls were included for measurement of the femoral trochlea axial orientation. The ability to predict the patellar dislocation and the pathologic threshold of the femoral trochlea axial orientation were evaluated using the receiver operating characteristic curve. One hundred patients with medial patellofemoral ligament reconstruction and 25 patients with derotational distal femur osteotomy were divided into two groups based on the femoral trochlea axial orientation cut-off value and their postoperative knee functions, and patellar tilt angles were compared. Results: There were significant differences in the femoral trochlea axial orientation (60.8 +/- 7.9 vs. 67.8 +/- 4.6, p < 0.05) between patients with patellar dislocation and the normal population. The sensitivity and specificity of the femoral trochlea axial orientation were 0.641 and 0.813, respectively, at the femoral trochlea axial orientation smaller than 63.8 degrees. Amongst patients having had isolated medial patellofemoral ligament reconstruction with decreased femoral trochlea axial orientation, knee function was poorer after surgery. The prognosis of patients with the femoral trochlea axial orientation correction in derotational distal femur osteotomy was better than that for patients without correction. Conclusions: The femoral trochlea axial orientation had good predictive efficiency for patellar dislocation. Isolated medial patellofemoral ligament reconstruction is not sufficiently effective for patients with patellar dislocation and decreased femoral trochlea axial orientation. Patients with a decreased femoral trochlea axial orientation can have better surgical outcomes after correction by derotational distal femur osteotomy.

To develop a comprehensive and validated personalized scoring system based on anatomical characteristics to predict the probability of failure to return to sport after medial patellofemoral ligament reconstruction in patients with patellar dislocation. 312 patients with medial patellofemoral ligament reconstruction in our hospital from 2013 to 2023 were included. Demographic and anatomical characteristics were collected retrospectively. A backward stepwise approach was used to identify independent predictors, and a nomogram was constructed to predict the probability of recurrence. The predictive performance was evaluated by receiver operating characteristic curves, calibration diagram and decision curve analysis. Multivariate analysis showed that increased tibial tubercle–trochlear groove (TT-TG) distance, trochlear dysplasia, increased femoral anteversion angle, and patellar alta were independent risk factors for failure of return to sport after medial patellofemoral ligament reconstruction. Validation of this column graph in the training cohort and validation cohort showed strong predictive power, with areas under the curve of 0.850 and 0.844, respectively. The nomogram has good calibration and good clinical practicability. The study developed a personalized predictive nomogram with 4 predictors (increased TT-TG distance, trochlear dysplasia, increased femoral anteversion angle, and patellar alta) that allowed surgeons to stratify the risk of failure to return to sport after medial patellofemoral ligament reconstruction and recommend skeletal surgery for patients with these factors. Level of Evidence: Level III.

Abstract Object Varus-valgus lower alignment is a risk factor for patellofemoral osteoarthritis, but malalignment alone affect not only the tibiofemoral joint but also the patellofemoral joint. The aim of the present study was to analyse the contact area of patellofemoral joint in varus alignment and valgus alignment of healthy subjects using magnetic resonance imaging. Methods Twenty-six healthy subjects with valgus lower limb alignment (Group I, n = 26) and twenty-six volunteers with varus lower limb alignment (Group II, n = 26) was performed. An MRI scan was used to capture and measure the patellofemoral joint articular cartilage contact area at different degrees of knee flexion (20°, 40°,60°) in passive movement. All subjects were categorized on the basis of the global limb alignment and mechanical alignment of the femur and tibia. Varus alignment is hip–knee–ankle angle ≥ 3°; and valgus alignment is hip–knee–ankle angle ≥ − 3°. To obtain medial facet contact area and lateral facet contact area for each slice, the length of each respective line of contact was multiplied by the 5 mm slice thickness. Results The overall joint contact area increased from 168.0 ± 20.5 mm2 at 20° knee flexion to 334.4 ± 30.5 mm2 at 60° knee flexion in group (I) The overall joint contact area increased from 178.0 ± 18.9 mm2 at 20° knee flexion to 328.9 ± 27.2 mm2 at 60° knee flexion in group (II) There was a significant difference in lateral facet contact area between group I and group II at 40° of knee flexion. There was significantly different in medial facet contact area between group I and group II at 20° and 40° of knee flexion. Conclusions Throughout the knee movement, the contact area on the lateral facet of the patellofemoral joint was greater in the valgus group. In the early phase of knee flexion, the contact area of the medial patellofemoral joint was larger in the varus group. Lower alignment is an important factor in patellofemoral joint degeneration.

PURPOSE:To develop a comprehensive and effective personalized scoring system on the basis of demographic and clinical characteristics for predicting recurrence probability in patients with primary lateral patellar dislocation (LPD). METHODS:Participants included 261 primary patients with LPD with 2-year minimum follow-up from our hospital across 2013 to 2020. Demographic and clinical characteristics were collected retrospectively. The backward stepwise method was performed to identify independent predictors and construct a nomogram to predict the probability of recurrence. The predictive performance was assessed by receiver operating characteristic curves, calibration plots, and decision curve analysis. RESULTS:After variables selection, 6 independent predictors of recurrence (skeletal maturity, trochlear dysplasia, tibial tuberosity-trochlear groove distance, mechanical axis deviation, Insall-Salvati index, and patellar tilt) were enrolled in our model. Validation of this nomogram in both training and validation cohort revealed powerful predictive ability, with an area under the curve of 0.962 and 0.977, respectively. The nomogram also showed great calibration and good clinical practicability. CONCLUSIONS:Our study presented a nomogram that incorporates 6 independent risk factors (skeletal maturity, trochlear dysplasia, tibial tuberosity-trochlear groove distance, mechanical axis deviation, Insall-Salvati index, and patellar tilt), which can be conveniently used to accurately predicts the risk of recurrence after primary LPD in individual cases. LEVEL OF EVIDENCE:Level III, retrospective comparative prognostic study.

Purpose To investigate the differences of patellofemoral joint pressure and contact area between the process of stair ascent and stair descent. Methods The finite element models of 9 volunteers without disorders of knee (9 males) to estimate patellar cartilage pressure during the stair ascent and the stair descent. Simulations took into account cartilage morphology from magnetic resonance imaging, joint posture from weight-bearing magnetic resonance imaging, and ligament model. The three-dimension models of the patella, femur and tibia were developed with the medical image processing software, Mimics 11.1. The ligament was established by truss element of the non-linear FE solver. The equivalent gravity direction (-z direction) load was applied to the whole end of femur (femoral head) according to the body weight of the volunteers, and the force of patella was observed. A paired-samples t -test or Wilcoxon rank sum test to make comparisons between stair ascent and stair descent. Statistical analyses were performed using SPSS 22.0 using a P value of 0.05 to indicate significance. Results During the stair descent (knee flexion at 30°), the contact pressure of the patella was 2.59 ± 0.06Mpa. The contact pressure of femoral trochlea cartilage was 2.57 ± 0.06Mpa. During the stair ascent (knee flexion at 60°), the contact pressure with patellar cartilage was 2.82 ± 0.08Mpa. The contact pressure of the femoral trochlea cartilage was 3.03 ± 0.11Mpa. The contact area between patellar cartilage and femoral trochlea cartilage was 249.27 ± 1.35mm 2 during the stair descent, which was less than 434.32 ± 1.70mm 2 during the stair ascent. The area of high pressure was located in the lateral area of patella during stair descent and the area of high pressure was scattered during stair ascent. Conclusion There are small change in the cartilage contact pressure between stair ascent and stair descent, indicating that the joint adjusts the contact pressure by increasing the contact area.

Purpose The molecular mechanism of patellar instability (PI) remains unknown. The purpose of this study was to explore the function of SOST/sclerostin in PI and examine the effect of sclerostin antibody (Scl-Ab). Materials and Methods We randomly divided 60 male 3-week-old C57Bl/6 mice into four groups: sham, PI, Scl-Ab intraperitoneal injection (Scl-Ab IP), Scl-Ab intraarticular injection (Scl-Ab IA). PI was established in the latter three groups. The Scl-Ab IP/IA groups were administered with an intraperitoneal/intraarticular Scl-Ab injection (100 mg/kg, 20 mu l), respectively, at 5-day intervals. Distal femurs were collected 30 days after the surgery. The SOST/sclerostin, beta-catenin, ALP, OPG and RANKL expression in distal femur were determined. Trochlear morphology and structural parameters of the trabecular and cortical bone compartments were determined by micro-CT. Further sub-regional analysis was performed. HE staining and Masson's trichrome staining were performed to evaluate cartilage changes. Results PI increased the expression of SOST/sclerostin and RANKL, and decreased beta-catenin, ALP and OPG levels, while Scl-Ab IP reversed these changes. Scl-Ab IP brought trochlear morphology closer to normality. Additionally, Scl-Ab IP significantly improved most of the bone parameters. Importantly, both PI and Scl-Ab IP acted mainly on trabecular bone. Histological analysis showed that Scl-Ab IP protected cartilage from degeneration. However, Scl-Ab IA did not protect against bone loss or cartilage degradation. Conclusions SOST/sclerostin plays an important role in PI and systemic Scl-Ab use promotes bone formation through the Wnt/beta-catenin signaling pathway in the femoral trochlear after PI.

Background: Osteoarthritis (OA) is the most prevalent chronic degenerative joint disease among the aged population. However, current treatments for OA are limited to alleviating symptoms, with no therapies that prevent and regenerate cartilage deterioration. Purpose: To assess the effects of platelet-derived exosomes (Plt-exos) on OA and then to explore the potential molecular mechanism. Study Design: Controlled laboratory study. Methods: Exosomes derived from human apheresis platelets were isolated and identified. The effects of Plt-exos in protecting chondrocytes under interleukin 1β stimulation were evaluated by analyzing the proliferation and migration in human primary chondrocytes. RNA sequencing was later performed in vitro for primary chondrocytes to reveal the underlying mechanisms of Plt-exo treatment. Anterior cruciate ligament transection was used to construct an OA mice model, and intra-articular injection of Plt-exos was given once a week for 6 weeks. Mice were sacrificed 4 weeks after the last injection. Histologic and immunohistochemistry staining and micro–computed tomography analysis were performed to assess alterations of articular cartilage and subchondral bone. Results: Plt-exos significantly promoted proliferation and migration of chondrocytes within a dose-dependent manner, as well as dramatically promoted cartilage regeneration and attenuated abnormal tibial subchondral bone remodeling, thus slowing the progression of OA. After being treated with Plt-exos, 1797 genes were differentially expressed in chondrocytes (923 upregulated and 874 downregulated genes). Functional enrichment results and hub genes were mainly involved in anti-inflammatory effects, mediating cell adhesion, stimulating cartilage repair, promoting anabolism, and inhibiting catabolism. Conclusion: Our results demonstrated that Plt-exos promoted chondrocyte proliferation and migration in vitro, as well as attenuated cartilage degeneration, improved the microarchitecture of subchondral bone, and retarded OA progression in vivo. Clinical Relevance: Our study illustrated that the administered Plt-exos could alleviate knee OA by attenuating cartilage degeneration and subchondral bone loss, possibly serving as a novel promising treatment for OA in the future.

Background: Increased femoral anteversion (FA) is reportedly associated with patellar dislocation (PD) and trochlear dysplasia (TD), and the increase in FA may occur at different segments of the femur. In addition, TD is associated with dysplasia of the posterior femoral condyle. Among patients with PD, whether FA is greater with or without TD remains unclear. Purpose: To explore differences in FA and torsion distribution at different femoral sections among patients with PD and TD, patients with PD and no TD, and sex- and age-matched controls and to investigate the association between FA and distal femoral morphology. Study Design: Cross-sectional study; Level of evidence, 3. Methods: This study involved 132 knees: 44 knees with PD and TD, 44 knees with PD but no TD, and 44 control knees. FA, proximal torsion (PT), middle torsion (MT), distal torsion (DT), and distal femoral morphology were measured. Differences were investigated by 1-way analysis of variance. Pearson correlation analysis was conducted to explore the association between FA and each parameter. Results: FA was significantly larger in the PD with TD group (25.4° ± 4.7°) than in the other groups (controls: 18.9° ± 5.6°; PD without TD: 19.9° ± 4.8°) ( P < .01). DT was significantly larger in the PD with TD group (15.8° ± 2.9°) than in the other groups (controls: 9.0° ± 4.3°; PD without TD: 8.8° ± 3.9°) ( P < .01). In all 3 groups, FA was strongly positively correlated with DT (control, PD without TD, and PD with TD, respectively: r = 0.76, 0.80, and 0.88; P < .01), strongly positively correlated with the posteromedial condylar length ( r = 0.48, 0.48, and 0.70; P < .01) and negatively correlated with the posterolateral condylar length ( r = −0.30, −0.35, and −0.78, respectively; P < .05). Conclusion: The increased FA in knees with TD was due mainly to DT rather than PT or MT, which may provide a reference for choosing the optimal position for femoral derotation osteotomy.

To investigate the changes in patellar morphology following soft tissue surgical correction of recurrent patellar dislocation in children with low-grade trochlear dysplasia. The prospective cohort study was performed between November 2007 and December 2012. Finally, 25 cases, with the mean age of 8.4 years (range from 7 to 10 years), were admitted to the study. All patients were diagnosed as bilateral recurrent patellar dislocation associated with femoral trochlear dysplasia. The knee that suffered injury or was dislocated was treated with medial patellar retinacular plasty (surgery group). The contralateral knee, which served as a control, was treated conservatively (conservative group). Axial CT scans were undertaken in all patients to assess the patellar morphological characteristics. The mean follow-up time was 60.8 months (range 48 to 75 months). Preoperatively, there were no statistically significant differences between the patellar morphology in the two groups ( P > 0.05). Many radiological parameters of patellar morphology were significantly different between the two groups at the final follow-up, including well-known parameters, such as the mean patellar width (surgery group, 40.58 mm [SD 1.26]; conservative group, 36.41 mm [SD 1.17]; P < 0.05), the mean patellar thickness (surgery group, 11.59 mm [SD 0.74]; conservative group, 9.38 mm [SD 0.56]; P < 0.05) and the mean Wiberg index (surgery group, 0.54 [SD 0.06]; conservative group, 0.72 [SD 0.08]; P < 0.05). There are also little-known parameters, such as the ratio of length of lateral patella to medial patella (surgery group, 1.26 [SD 0.17]; conservative group, 1.69 [SD 0.21]; P < 0.05), which was a measurement of facet asymmetry. However, the Wiberg angle was not significantly different between the two groups (surgery group, 128.63° [SD 9.05]; conservative group, 125.47° [SD 13.96°]; P > 0.05) at the final follow-up. No complications were found. The patellar morphology can be significantly improved by early soft tissue surgical correction in children with patellar instability associated with low-grade femoral trochlear dysplasia.

The femoral anteversion angle is considered to be the same as femoral torsion; however, the femoral anteversion angle is strongly influenced by the femoral posterior condylar morphology. It remains unclear whether the femoral anteversion angle and axial orientation of the femoral trochlea can predict patellar instability. This study aimed to redefine the femoral inherent torsion, verify whether the femoral anteversion angle reflects the femoral inherent torsion, and compare the validity and calculate the cut-off values of the femoral anteversion angle and femoral trochlear axial orientation for predicting patellar instability. Seventy-three patients with patellar instability and 73 matched controls underwent computed tomography to measure the femoral anteversion angle, femoral inherent torsion, and femoral trochlear axial orientation. Pearson’s product moment correlation coefficients and linear regression were calculated to determine correlations between measurements. Receiver operating characteristic curves and nomograms were plotted to evaluate the predictive validity of the femoral anteversion angle and femoral trochlear axial orientation for patellar instability. All measurements showed excellent intra- and inter-observer reliability. Compared with the control group, the patellar instability group had a significantly larger femoral anteversion angle (25.4 ± 6.4° vs. 20.2 ± 4.5°) and femoral inherent torsion (18.3 ± 6.7° vs. 15.8 ± 3.4°), and significantly smaller femoral trochlear axial orientation (58.1 ± 7.3° vs. 66.9 ± 5.1°). The femoral anteversion angle and femoral trochlear axial orientation had area under the receiver operating characteristic curve values of 79 and 84