Risk factor analysis of vertebral fractures requiring surgery in patients with ankylosing spondylitis.

OBJECTIVES: This study aimed to determine the risk factors for vertebral fractures requiring surgery in patients with ankylosing spondylitis (AS). METHODS: We included 60 patients with AS diagnosed by using the modified New York criteria and who were treated in our department from April 2004 to March 2019. We evaluated age, sex, disease duration, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), ankylosed sacroiliac joint, bamboo spine, number of ankylosed vertebrae, and treatment (nonsteroidal antiinflammatory drugs (NSAIDs)), prednisolone (PSL), conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), biological disease-modifying antirheumatic drugs (bDMARDs), spine surgery for vertebral fracture) at the final follow-up of the nonsurgical group and the preoperative follow-up of the surgical group. RESULTS: At the final follow-up, the mean age was 49 years, 46 patients (75%) were male, and the mean disease duration was 27 years. Additionally, 8 (13.3%) and 43 patients (71%) underwent surgical and medical treatments, respectively. The group of surgery for vertebral fracture had significantly higher CRP levels, which was also significantly associated with vertebral fracture surgery by multivariate analysis. CONCLUSIONS: CRP was identified as a risk factor for vertebral fractures requiring surgery. Control of systemic inflammation in patients with AS may reduce the risk of vertebral fractures requiring surgery.

Small change in the arithmetic hip-knee-ankle angle during unicompartmental knee arthroplasty improves early postoperative functional outcomes.

INTRODUCTION: The optimal lower-limb alignment after unicompartmental knee arthroplasty (UKA) remains controversial. This study aimed to investigate the optimal lower-limb alignment for functional improvement in the early post-UKA period. We hypothesized that a small change (Δ) in the arithmetic hip-knee-ankle (aHKA) angle during surgery would result in better postoperative knee function. MATERIALS AND METHODS: This single-centered, retrospective study analyzed 91 patients (91 knees) who underwent UKA from April 2021 and December 2022. Preoperative and postoperative standing whole-leg radiographs were used to evaluate the mechanical HKA angle and aHKA angle. The aHKA angle was calculated from the medial proximal tibial angle (MPTA) and lateral distal femoral angle (LDFA). We defined restored aHKA angle as a postoperative aHKA angle within ± 3° of the preoperative aHKA angle. Functional improvement was evaluated using the preoperative and one-year postoperative Knee Society Scoring 2011 (KSS 2011). A multivariate regression analysis was performed to investigate the optimal lower-limb alignment for functional improvement. RESULT: Postoperative restored aHKA angle (p = 0.020) was the only significant factor for improved KSS 2011 scores. Postoperative restored aHKA angle was obtained in 64 patients (70%). ΔMPTA (p < 0.001) and ΔLDFA (p = 0.037) were significant factors associated with a postoperative restored aHKA angle. CONCLUSIONS: UKA restores the native knee, including resurfacing constitutional alignment and medial collateral ligament tension. Minimal change in the aHKA angle during UKA improves the functional outcomes of the knee during the early postoperative period, consistent with the minimally invasive surgical concept of UKA.

Synovial-tissue resident macrophages play proinflammatory functions in the pathogenesis of RA while maintaining the phenotypes in the steady state.

Synovial tissue-resident macrophages (STRMs) maintain normal joint homeostasis in a steady state. However, it is unclear whether STRMs still play homeostatic roles or change the functions in the joint of rheumatoid arthritis (RA), where infiltrating peripheral blood monocyte-derived macrophages (PBMoMs) play proinflammatory roles. In the present study, we examined changes in the phenotypes and functions of STRMs in response to RA-related stimuli in vitro. STRMs were prepared from non-inflammatory osteoarthritis (OA) joint synovium, which is histologically indistinguishable from normal joint synovium. PBMoMs were prepared and used for comparison. After stimulation with plate-bound IgG, which mimics anti-citrullinated protein antibody immunocomplex formed in RA joints, or with combinations of RA-related inflammatory mediators, namely tumor necrosis factor-α (TNF-α) and prostaglandin E2 or interferon-γ, PBMoMs downregulated surface markers and genes associated with anti-inflammatory macrophages, and upregulated cytokine and marker genes of proinflammatory macrophages in RA. On the other hand, STRMs hardly changed the expression of surface molecules and marker genes but altered the pattern of cytokine gene expression after stimulation like PBMoMs. Furthermore, in vitro stimulated STRMs promote proinflammatory functions of cocultured synovial fibroblasts. Thus, STRMs might play proinflammatory roles in RA joints, while maintaining their phenotypes in the steady state.

"Grand-piano sign" as a femoral rotational indicator in both varus and valgus knees: a simulation study of anterior resection surface in total knee arthroplasty.

PURPOSE: The "Grand-piano sign" is a popular indicator of the appropriate rotational alignment of the femoral component during total knee arthroplasty (TKA). The aim of the study was to investigate the shape of the anterior femoral resection surface of varus and valgus knees. METHODS: A cohort of 80 varus knees and 40 valgus knees (hip-knee-ankle angle > 2° for varus and < - 2° for valgus knees) matched for age, sex, height, body weight, and KL grade was made using propensity score matching. Virtual TKA was performed using 3 patterns of components (anterior flange flexion angles of 3°, 5°, and 7°). The anterior femoral resection surface was evaluated for 3 patterns of rotational alignments: parallel to the surgical epicondylar axis (NR, neutral rotation), 3° internal rotation (IR), and 3°external rotation (ER) relative to the surgical epicondylar axis. In each anterior femoral resection surface, the vertical height of medial and lateral condyles was measured, and the ratio of the medial to the lateral height (M/L ratio) was evaluated. RESULTS: The M/L ratio in NR for both varus and valgus knees was 0.57 to 0.64, with no significant difference between the cohorts (p value > 0.05). The M/L ratio showed a similar pattern of increasing at IR and decreasing at ER in both varus and valgus knees. The variation in the M/L ratio with malrotation in valgus knees was smaller than in varus knees. CONCLUSION: During TKA, the anterior femoral resection surface was similar in varus and valgus knees; however, the variation with malrotation was smaller in valgus knees than in varus knees. TKA for valgus knees requires precise surgical technique and careful intraoperative assessment. LEVEL OF EVIDENCE: IV, Case series.

Similar short-term KOOS between open-wedge high tibial osteotomy and total knee arthroplasty in patients over age 60: A propensity score-matched cohort study.

OBJECTIVES: The purpose of the present study was to evaluate improvement in the Knee Injury and Osteoarthritis Outcome Score (KOOS) after open-wedge high tibial osteotomy (HTO) in comparison with total knee arthroplasty (TKA) in cohorts over age 60 matched by pre-operative age, gender, body mass index (BMI), hip-knee-ankle angle (HKAA), KOOS sub-scores, and osteoarthritis (OA) grade. METHODS: Propensity score matching was performed between 162 HTO patients and 134 TKA patients. When calculating the propensity score by multivariate logistic regression analysis, the following pre-operative confounders were included: age, gender, BMI, HKAA, KOOS sub-scores, and OA grade. Consequently, a total of 55 patients were included in each group. The Student's t-test was used to analyse differences in the post-operative KOOS sub-scores between groups. RESULTS: After propensity score matching, all matched pre-operative valuables were identical, with no significant differences between the HTO and TKA groups. None of the post-operative KOOS sub-scores at 1 year after surgery showed a significant difference between the HTO and TKA groups. Both groups demonstrated significant and comparable post-operative improvement in every KOOS sub-score. CONCLUSIONS: In patients over age 60, there was no significant difference in short-term pain relief and improvements in activity and quality of life between HTO and TKA after propensity score matching including pre-operative age, KOOS sub-scores, and OA grade. HTO is a joint preservation procedure that is valid for knee OA even in individuals over age 60.

Preoperative Virtual Total Knee Arthroplasty Surgery Using a Computed Tomography-based 3-dimensional Model With Variation in Reference Points and Target Alignment to Predict Femoral Component Sizing.

Background: The purpose of this study was to investigate the size differences of 19 different femoral component placements from the standard position in total knee arthroplasty using 3-dimensional virtual surgery. Methods: Three-dimensional bone models were reconstructed from the computed tomography data of 101 varus osteoarthritic knees. The distal femoral bone was cut perpendicular to the femoral mechanical axis (MA) in the coronal plane. Twenty different component placements consisting of 5 cutting directions (perpendicular to MA, 3° and 5° extension relative to MA [3°E-MA and 5°E-MA, respectively], and 3° and 5° flexion relative to MA [3°F-MA and 5°F-MA, respectively]) in the sagittal plane, 2 rotational alignments (clinical epicondylar axis [CEA] and surgical epicondylar axis [SEA]), and 2 rotational types of anterior reference guide (central [CR] and medial [MR]) were simulated. Results: The mean anteroposterior dimension of femur ranged from 54.3 mm (5°F-MA, SEA, CR) to 62.5 mm (5°E-MA, CEA, MR). The largest and smallest differences of anteroposterior dimension from the standard position (3°F-MA, SEA, and CR) were 7.1 ± 1.3 mm (5°E-MA, CEA, and MR) and -1.2 ± 0.2 mm (5°F-MA, SEA, and CR), respectively. Multiple regression analysis revealed that flexion cutting direction, SEA, and CR were associated with smaller component size. Conclusions: The femoral component size can be affected easily by not only cutting direction but also the reference guide type and the target alignment. Our findings could provide surgeons with clinically useful information to fine-tune for unintended loose or tight joint gaps by adjusting the component size.

Fluvastatin promotes chondrogenic differentiation of adipose-derived mesenchymal stem cells by inducing bone morphogenetic protein 2.

BACKGROUND: Adipose-derived mesenchymal stem cells (ADMSCs) are a promising source of material source for medical regeneration of cartilage. Growth factors, including transforming growth factor-ß (TGFß) subfamily members and bone morphogenetic proteins (BMPs), play important roles in inducing and promoting chondrogenic differentiation of MSCs. However, these exogenous growth factors have some drawbacks related to their cost, biological half-life, and safety for clinical application. Several studies have reported that statins, the competitive inhibitors of 3-hydroxy-2-methylglutaryl coenzyme A (HMG-CoA) reductase, induce the expression of BMP2 in multiple cell types as the pleotropic effects. The objective of this study was to investigate the effects of fluvastatin during chondrogenic differentiation of human ADMSCs (hADMSCs). METHODS: The effects of fluvastatin were analyzed during chondrogenic differentiation of hADMSCs in the pellet culture without exogenous growth factors by qRT-PCR and histology. For functional studies, Noggin, an antagonist of BMPs, mevalonic acid (MVA) and geranylgeranyl pyrophosphate (GGPP), metabolites of the mevalonate pathway, ROCK inhibitor (Y27632), or RAC1 inhibitor (NSC23766) were applied to cells during chondrogenic differentiation. Furthermore, RhoA activity was measured by RhoA pulldown assay during chondrogenic differentiation with or without fluvastatin. Statistically significant differences between groups were determined by Student's t-test or the Tukey-Kramer test. RESULTS: Fluvastatin-treated cells expressed higher levels of BMP2, SOX9, ACAN, and COL2A1 than control cells, and accumulated higher levels of glycosaminoglycans (GAGs). Noggin significantly inhibited the fluvastatin-mediated upregulation of ACAN and COL2A1. Both MVA and GGPP suppressed the effects of fluvastatin on the expressions of BMP2, SOX9, ACAN, and COL2A1. Furthermore, fluvastatin suppressed the RhoA activity, and inhibition of RhoA-ROCK signaling by Y27632 increased the expressions of BMP2, SOX9, ACAN, and COL2A1, as well as fluvastatin. CONCLUSIONS: Our results suggest that fluvastatin promotes chondrogenic differentiation of hADMSCs by inducing endogenous BMP2, and that one of the mechanisms underlying the effects is inhibition of RhoA-ROCK signaling via suppression of GGPP. Fluvastatin is a safe and low-cost compound that holds promise for use in transplantation of hADMSCs for cartilage regeneration.

Factors affecting patient satisfaction related to cost and treatment effectiveness in rheumatoid arthritis: results from the multicenter observational cohort study, FRANK Registry.

BACKGROUND: To further improve rheumatoid arthritis (RA) treatment, it is necessary to understand each RA patient's satisfaction and to identify the factors affecting their satisfaction. Despite the rise in medical costs for RA, little is known about the factors that influence patient satisfaction with the cost of treatment in RA patients. METHODS: This is a multicenter observational study of Japanese RA patients from the FRANK Registry with data analyzed from March 2017 to August 2020. We collected data on demographic characteristics, clinical data, quality of life which was evaluated using the EuroQol 5-dimensional questionnaire (EQ5D), and patient satisfaction. The four categories of patient satisfaction were evaluated individually (i.e., cost, treatment efficacy, activities of daily living [ADL], and global treatment satisfaction). We analyzed the factors that affected each patient's satisfaction, such as age, sex, EQ5D, disease duration, disease activity, and treatment. RESULTS: This study included 2235 RA outpatients (406 males, 1829 females). In RA patients, "very satisfied" and "satisfied" were given for nearly half of each satisfaction aspect (cost 49%; efficacy 72%; ADL 58%; global treatment 66%) at the time of the initial registration. To investigate the factors influencing each satisfaction, multivariate analysis has revealed that the use of b/tsDMARDs increased satisfaction of treatment effect (odds ratio [OR] 0.66) and ADL (OR 0.78) but decreased cost satisfaction (OR 2.21). Age (50-64 years; OR 0.91; 65-74 years, 0.55: ≥ 75 years, 0.35), female (OR 0.81), and history of musculoskeletal surgery (OR 0.60) all increased cost satisfaction. Patients with lower disease activity and higher EQ5D scores had higher levels of satisfaction in all areas. CONCLUSIONS: In this study, patient satisfaction in terms of cost, treatment effect, ADL, and overall treatment was generally higher, but some patients were dissatisfied. The cost of satisfaction increased with age and a history of musculoskeletal surgery, while it decreased with a lower EQ5D score and the use of b/tsDMARDs.

C10orf10/DEPP activates mitochondrial autophagy and maintains chondrocyte viability in the pathogenesis of osteoarthritis.

Osteoarthritis (OA), the most prevalent joint disease, is characterized by the progressive loss of articular cartilage. Autophagy, a lysosomal degradation pathway, maintains cellular homeostasis, and autophagic dysfunction in chondrocytes is a hallmark of OA pathogenesis. However, the cause of autophagic dysfunction in OA chondrocytes remains incompletely understood. Recent studies have reported that decidual protein induced by progesterone (C10orf10/DEPP) positively regulates autophagic functions. In this study, we found that DEPP was involved in mitochondrial autophagic functions of chondrocytes, as well as in OA pathogenesis. DEPP expression decreased in human OA chondrocytes in the absence or presence of pro-inflammatory cytokines, and was induced by starvation, hydrogen peroxide (H2 O2 ), and hypoxia (cobalt chloride). For functional studies, DEPP knockdown decreased autophagic flux induced by H2 O2 , whereas DEPP overexpression increased autophagic flux and maintained cell viability following H2 O2 treatment. DEPP was downregulated by knockdown of forkhead box class O (FOXO) transcription factors and modulated the autophagic function regulated by FOXO3. In an OA mouse model by destabilization of the medial meniscus, DEPP-knockout mice exacerbated the progression of cartilage degradation with TUNEL-positive cells, and chondrocytes isolated from knockout mice were decreased autophagic flux and increased cell death following H2 O2 treatment. Subcellular fractionation analysis revealed that mitochondria-located DEPP activated mitochondrial autophagy via BCL2 interacting protein 3. Taken together, our data demonstrate that DEPP is a major stress-inducible gene involved in the activation of mitochondrial autophagy in chondrocytes, and maintains chondrocyte viability during OA pathogenesis. DEPP represents a potential therapeutic target for enhancing autophagy in patients with OA.

Transverse osteotomy closer to tibial plateau is associated with larger postoperative change in valgus laxity after open-wedge high tibial osteotomy.

PURPOSE: To identify the factors impacting changes in valgus laxity between before and after open-wedge high tibial osteotomy (OW-HTO) using quantitative valgus stress radiographs. METHODS: A total of 40 knees from 38 patients who underwent OW-HTO were assessed. The study population comprised 14 men and 24 women, with a mean age of 61.5 years. Valgus stress radiographs before and 1 year after OW-HTO were performed using a Telos device. The difference between pre- and postoperative joint line convergence angle (JLCA) was expressed as ΔJLCA (post-pre). As indicators of the proximal detachment of superficial medial collateral ligament (sMCL) on radiographs, two distances were defined: the distance from the level of the osteotomy starting point to the tangent line of the proximal tibial plateau (Distance A), or to the medial edge of the proximal tibial plateau (Distance B). Correlations between ΔJLCA and radiographic parameters or KOOS sub-scores were assessed using Spearman's rank correlation coefficient analysis. Receiver operator curves were generated to evaluate the predictive strength of the significant factor for an increase in ΔJLCA > 1°. RESULTS: Pre-operative OA severity consisted of Kellgren-Lawrence grade 2 (n = 18), 3 (n = 16), and 4 (n = 6). The average ΔJLCA (post-pre) was 0.5°, and ranged from - 1.4° to + 3.0°. The maximum systemic measurement error and limits of agreement were 0.07° and 0.20°, respectively. There were significant correlations between ΔJLCA and Distance A (36.9 ± 3.9 mm, R = - 0.46, p = 0.002), between ΔJLCA and Distance B (39.9 ± 4.0 mm, R = - 0.49, p = 0.001). The cut-off value for Distance A was determined to be 35 mm below the tibial plateau; the AUC was 0.804, with a sensitivity of 0.75 and a specificity of 0.82. Distance B correlated strongly with Distance A (R = 0.96, p < 0.001). There was no significant correlation between ΔJLCA and KOOS sub-scores 1 year after OW-HTO. CONCLUSIONS: Transverse osteotomy closer to tibial plateau was associated with larger valgus joint laxity postoperatively. This finding implies that sMCL proximal detachment, which was related to the level of the osteotomy starting point on the proximal tibia, potentially affected postoperative valgus laxity. LEVEL OF EVIDENCE: IV.

Effect of osteoarthritis severity on survival and clinical outcomes after high tibial osteotomy.

BACKGROUND: This study aimed to evaluate the effect of osteoarthritis severity on clinical outcomes using the 2011 Knee Society Score (KSS2011) and survival rates after closed wedge high tibial osteotomy (CWHTO). METHODS: In this retrospective study, KSS2011 questionnaires were mailed to patients who had undergone CWHTO between January 1991 and December 2011. The completed questionnaires returned by the patients were analyzed. Preoperative osteoarthritis severity was evaluated by Kellgren-Lawrence (K-L) grade. KSS2011 was compared between the K-L grade groups. To determine the effect of K-L grade for revision surgery, Kaplan-Meier survival curves were created using the need for total knee arthroplasty (TKA) as the endpoint to estimate the probability of failure. RESULTS: There were 16, 81, and 47 knees with preoperative K-L 2, 3, and 4, respectively. Among the KSS2011 sub-scores, the symptom score showed significant differences between the groups (p = 0.006). However, no significant difference was found regarding satisfaction, expectation, and functional activity scores. No significant difference in the symptom score was found between the K-L 2 and 3 groups (p > 0.05). Eighteen knees were treated with TKA at a mean of 9 years after CWHTO. Using the Kaplan-Meier survival estimates, the K-L 4 group showed a significantly higher rate of total knee arthroplasty conversion than the K-L 2 and 3 groups (p < 0.001). CONCLUSIONS: Osteoarthritis severity affects clinical outcomes and survival rates during long-term follow-up after CWHTO. Surgeons should consider the preoperative osteoarthritis grade for long-term outcomes when considering CWHTO for patients with varus knees.

Axial But Not Sagittal Hinge Axis Affects Posterior Tibial Slope in Medial Open-Wedge High Tibial Osteotomy: A 3-Dimensional Surgical Simulation Study.

PURPOSE: The purpose of this 3-dimensional (3D) surgical simulation study was to investigate the effects of axial and sagittal hinge axes (hinge axes in the axial and sagittal planes) on medial and lateral posterior tibial slope (PTS) in medial open-wedge high tibial osteotomy (OWHTO), and evaluate the quantitative relationship between hinge axis and PTS change. METHODS: Preoperative computed tomography data from patients with varus knee deformity were collected. A standard hinge axis (0°) and 12 different hinge axes (6 axial hinge axes and 6 sagittal hinge axes: ±10°, ±20°, and ±30°) were defined in a 3D surgical simulation of OWHTO using a bone model. The differences between before and after simulation surgery in medial and lateral PTS, medial proximal tibial angle, opening gap, and opening wedge angle were measured. RESULTS: In total, 93 varus knees in 93 patients were included for study. Compared with the standard hinge axis, axial hinge axis significantly affected medial and lateral PTS (P < .001). In contrast, sagittal hinge axis had no significant effect on medial and lateral PTS (P > .05). Every 10° change in axial hinge axis with a mean coronal valgus correction of 10° might result in approximately 1.6° of alteration in PTS. Stepwise regression analysis showed that axial hinge axis is the most significant factors affecting PTS (ß coefficient = 0.78, P < .001), followed by opening wedge angle (ß coefficient = 0.36, P < .001) and gap ratio (ß coefficient = 0.12, P < 0.001). CONCLUSION: Based on our findings of 3D OWHTO simulation, axial hinge axis significantly influences medial and lateral PTS in OWHTO, but sagittal hinge axis has no effect on change in PTS. Every 10° change of axial hinge axis with a 10° coronal valgus correction caused approximately 1.6° change of PTS. CLINICAL RELEVANCE: Hinge axis in the axial plane significantly affects PTS, but hinge axis in the sagittal plane has no effect on PTS. To maintain PTS, surgeons should make hinge axis at the true lateral position of the tibia in the axial plane. To intentionally alter PTS, an anterolateral axial hinge axis could be used to decrease PTS or a posterolateral axial hinge axis could be used to increase PTS. Opening wedge angle or gap ratio is also useful for intentional modification of PTS.

Does Preparation of the Subtalar Joint for Primary Union Affect Clinical Outcome in Patients Undergoing Intramedullary Nail for Rheumatoid Arthritis of the Hindfoot and Ankle?

This study aimed to evaluate whether preparation of the subtalar joint affects the clinical outcomes after tibiotalocalcaneal arthrodesis using an intramedullary nail with fins for rheumatoid ankle/hindfoot deformity. Fifty-three joints in 51 patients who underwent tibiotalocalcaneal arthrodesis using an intramedullary nail with fins for rheumatoid arthritis at 2 institutions were included. Ten patients were male and 41 were female, with a mean age at surgery and follow-up period of 61.3 years and 71.6 months, respectively. Radiographic bone union was evaluated at the most recent visit. Univariate and multivariable analyses were performed to determine the risk factors associated with nonunion. The mean postoperative Japanese Society for Surgery of the Foot ankle/hindfoot scale was 65.3 (range, 5-84). The tibiotalar nonunion rate was 0%, whereas the subtalar nonunion rate was 43.3% (23 joints). Revision surgery was performed in 5, all of which were due to painful subtalar nonunion. Absence of subtalar curettage and earlier postoperative weightbearing were significantly associated with subtalar nonunion (p = .0451 and p = .0438, respectively). Subtalar nonunion after tibiotalocalcaneal arthrodesis for rheumatoid hindfoot is associated with higher revision rate. To decrease the risk of subtalar nonunion after tibiotalocalcaneal arthrodesis with an intramedullary nail in rheumatoid patients, curettage for the subtalar joint should be performed, and full weightbearing should be delayed until at least 26 days postoperatively.

Distal tuberosity osteotomy in open-wedge high tibial osteotomy does not exacerbate patellofemoral osteoarthritis on arthroscopic evaluation.

PURPOSE: The purpose of the present study was to use arthroscopy to evaluate the effect of distal tuberosity osteotomy (DTO) in open-wedge high tibial osteotomy (OW-HTO) on patellofemoral (PF) cartilage degradation. METHODS: Between 2012 and 2017, 46 knees underwent DTO in OW-HTO, and 65 knees underwent conventional OW-HTO (cOW-HTO). To assess changes in patellar height, the Blackburne-Peel (BP) ratio and the Caton-Deschamps (CD) index were measured. Arthroscopic evaluation on the PF joint was performed at the initial osteotomy and at the second-look procedure 1 year later. Statistical analyses were performed to compare difference between the DTO and the cOW-HTO group. RESULTS: In the cOW-HTO group, the mean BP ratio and CD index decreased significantly from 0.81 and 0.89 preoperatively, respectively, to 0.69 and 0.76 postoperatively, respectively (p < 0.001). In contrast, the DTO group maintained a consistent patellar height; the mean BP ratio and CD index were 0.77 and 0.83 preoperatively, respectively, and 0.73 and 0.80 postoperatively, respectively. Upon arthroscopic evaluation, 39 of 46 patients (84.8%) in the DTO group showed no progression of PF cartilage degradation at the second look; indeed, five of 46 patients (10.9%) even demonstrated improvement. In contrast, 21 of 65 patients (32.3%) in the cOW-HTO group exhibited increased PF cartilage degradation. There was a significant difference in progression of PF cartilage degradation between DTO and cOW-HTO (p < 0.001). CONCLUSION: DTO in OW-HTO maintained the preoperative patellar height, which could help prevent progression of cartilage degeneration in the PF joint after surgery. In respect of the biplanar osteotomy direction in OW-HTO, the DTO, rather than cOWHTO, is the preferred technique for the treatment of varus knee osteoarthritis to avoid progression of PF cartilage degradation. LEVEL OF EVIDENCE: III.

Patient-specific prediction of joint line convergence angle after high tibial osteotomy using a whole-leg radiograph standing on lateral-wedge insole.

PURPOSE: To assess the usefulness of a whole-leg radiograph standing on lateral-wedge insole (LWI) for predicting the change in joint line convergence angle (JLCA) before vs. after high tibial osteotomy (HTO). METHODS: Forty knees with medial osteoarthritis underwent open-wedge HTO. Pre-operatively, all patients had whole-leg radiographs taken in three different conditions: supine, standing, and standing on LWI inclined at 20°. A standing whole-leg radiograph was also obtained post-operatively. Radiological measurements including JLCA and percentage of mechanical axis (%MA) were compared. Using pre-operative radiographs, correction angles were calculated with the target %MA at 62.5%. Correlations between the difference in calculated correction angle among the three pre-operative conditions and the change in JLCA before vs. after HTO were assessed. RESULTS: In the pre-operative standing conditions, the mean JLCA of 3.8° was significantly decreased to 3.2° using LWI, which did not differ from post-operative JLCA of 3.1°. Mean %MA significantly shifted laterally from 20.6 to 24.8% using LWI, and was strongly correlated with the change in JLCA (coefficient, 0.83). Calculated correction angles differed significantly among the three pre-operative conditions. The difference in calculated correction angle between standing with and without LWI was strongly correlated to the change in standing JLCA before vs. after HTO (coefficient, 0.73). CONCLUSION: Larger differences in calculated correction angles between pre-operative radiographs standing with and without LWI predicted larger changes in JLCA after HTO. Whole-leg radiograph standing on LWI is a promising modality for correct pre-operative planning considering patient-specific changes in JLCA before vs. after HTO. LEVEL OF EVIDENCE: IV.

FOXO1 transcription factor regulates chondrogenic differentiation through transforming growth factor ß1 signaling.

The forkhead box O (FOXO) proteins are transcription factors involved in the differentiation of many cell types. Type II collagen (Col2) Cre-Foxo1-knockout and Col2-Cre-Foxo1,3,4 triple-knockout mice exhibit growth plate malformation. Moreover, recent studies have reported that in some cells, the expressions and activities of FOXOs are promoted by transforming growth factor ß1 (TGFß1), a growth factor playing a key role in chondrogenic differentiation. Here, using a murine chondrogenic cell line (ATDC5), mouse embryos, and human mesenchymal stem cells, we report the mechanisms by which FOXOs affect chondrogenic differentiation. FOXO1 expression increased along with chondrogenic differentiation, and FOXO1 inhibition suppressed chondrogenic differentiation. TGFß1/SMAD signaling promoted expression and activity of FOXO1. In ATDC5, FOXO1 knockdown suppressed expression of sex-determining region Y box 9 (Sox9), a master regulator of chondrogenic differentiation, resulting in decreased collagen type II α1 (Col2a1) and aggrecan (Acan) expression after TGFß1 treatment. On the other hand, chemical FOXO1 inhibition suppressed Col2a1 and Acan expression without suppressing Sox9 To investigate the effects of FOXO1 on chondrogenic differentiation independently of SOX9, we examined FOXO1's effects on the cell cycle. FOXO1 inhibition suppressed expression of p21 and cell-cycle arrest in G0/G1 phase. Conversely, FOXO1 overexpression promoted expression of p21 and cell-cycle arrest. FOXO1 inhibition suppressed expression of nascent p21 RNA by TGFß1, and FOXO1 bound the p21 promoter. p21 inhibition suppressed expression of Col2a1 and Acan during chondrogenic differentiation. These results suggest that FOXO1 is necessary for not only SOX9 expression, but also cell-cycle arrest during chondrogenic differentiation via TGFß1 signaling.

Degenerative changes in cartilage likely occur in the medial compartment after anterior cruciate ligament reconstruction.

PURPOSE: Magnetic resonance imaging with T1ρ mapping is used to quantify the amount of glycosaminoglycan in articular cartilage, which reflects early degenerative changes. The purposes of this study were to evaluate early degenerative changes in knees after anterior cruciate ligament (ACL) reconstruction by comparing T1ρ values before and 2 years after surgery and investigate whether surgical factors and clinical outcomes are related to differences in T1ρ values. METHODS: Fifty patients who underwent unilateral primary ACL reconstruction were evaluated using T1ρ mapping before and 2 years after surgery. Three regions of interest (ROIs) were defined in the cartilage associated with the medial (M) and lateral (L) weight-bearing areas of the femoral condyle (FC) (anterior: MFC1 and LFC1, middle: MFC2 and LFC2, and posterior: MFC3 and LFC3). Two ROIs associated with the tibial plateau (T) were defined (anterior: MT1 and LT1, and posterior: MT2 and LT2). T1ρ values within the ROIs were measured before and 2 years after surgery and compared using the paired t test. Correlations between the difference in T1ρ values at these two time points and patient characteristics, presence of a cartilaginous lesion, graft type, and postoperative anteroposterior laxity were also evaluated using Pearson's and Spearman's correlation coefficients. RESULTS: There was a significant increase in T1ρ before versus 2 years after surgery in the MT1, MT2, LFC1, and LT1 areas, and a significant decrease in the LFC3 and LT2 areas. There was a significant correlation between postoperative anterior-posterior laxity and a postoperative increase in T1ρ values in the MFC3 (r = 0.37, P = 0.013) and MT2 (r = 0.35, P = 0.021) areas. Increases in T1ρ values in the MFC2 area were negatively correlated with KOOS symptoms (ρ = - 0.349, P = 0.027) and quality of life (ρ = - 0.374, P = 0.017) subscale scores. CONCLUSION: Early degenerative changes in medial articular cartilage were observed with T1ρ mapping at 2 years after ACL reconstruction. Postoperative anterior-posterior laxity is correlated with an increase in T1ρ values in the posteromedial femur and tibia. An increase in T1ρ values in the central medial femoral condyle was associated with knee symptoms. LEVEL OF EVIDENCE: III.

Patient reported outcomes after high tibial osteotomy show comparable results at different ages in the mid-term to long-term follow-up.

BACKGROUND: Few studies have evaluated the impact of age on patient-reported outcomes in the long-term follow-up after high tibial valgus osteotomy (HTO). The purpose of this study is to assess the association between age at surgery and patient-reported clinical outcomes in the mid-term to long-term follow-up of HTO. MATERIALS AND METHODS: We mailed the 2011 Knee Society score (KSS) questionnaires to 234 consecutive patients (295 knees) who had undergone closing-wedge HTO, and 158 patients (202 knees, 68.5%) returned a completed questionnaire. The cohort was divided into two groups depending on the age at the time of surgery, and pairs matched the follow-up period and sex was created. The mean follow-up period was approximately 12 years. KSS scores at the final follow-up were compared between two groups using the Student t test and chi-square test, and the survival rates were calculated using Kaplan-Meier survival curves. RESULTS: The symptom, satisfaction, and expectation scores were not significantly different between the ≤64-year-old patients and ≥65-year-old patients. The functional activities score was significantly lower in older patients than in younger patients. The overall survival rates of HTO were 99.1 ± 0.4% at 5 years, 94.4 ± 1.2% at 10 years, and 84.6 ± 2.7% at 15 years. There was no significant difference in the survival rate after HTO between the two groups divided by the age (p = 0.602). CONCLUSIONS: Pain relief and satisfaction after HTO in older patients were comparable to those in younger patients in the mid-term to long-term follow-up, although the functional activity was affected by age.

Bony landmarks with tibial cutting surface are useful to avoid rotational mismatch in total knee arthroplasty.

PURPOSE: The purpose of this study was to define various anteroposterior axes of the tibial component as references and to evaluate their accuracy and variability using virtual surgery. It was hypothesized that (1) Akagi's Line could result in high accuracy and low variability in varus osteoarthritic knees; (2) anteroposterior axes defined by using the tibial bony cutting surface as a landmark might be good substitutes for Akagi's Line; and (3) extra-articular bony landmarks might influence the variability of the anteroposterior axis. METHODS: Three-dimensional bone models were reconstructed from the preoperative computed tomography data of 111 osteoarthritic knees with varus deformities. Seven different anteroposterior axes of the tibial component were defined: Akagi's Line, Axis MED, Axis 1/6MED, Axis 1/3MED, Axis of Oval Shape, Axis of Anterior Crest, and Axis Second Metatarsus. The rotational mismatch angle was measured between the tibial anteroposterior axis and the line perpendicular to the transepicondylar axis projected on the cutting surface (positive value: external rotation of the tibial anteroposterior axis). RESULTS: The average rotational mismatch angles (referring to the projected anatomical/surgical epicondylar axes) were - 2.7° ± 5.8°/1.0° ± 6.0° (Akagi's Line), - 4.2° ± 7.7°/- 0.5° ± 7.8°, 2.9° ± 7.2°/6.6° ± 7.2°, 9.8° ± 7.0°/13.5° ± 6.8° (Axis MED, Axis 1/6MED, Axis 1/3MED), - 5.1° ± 7.9°/- 1.4° ± 7.8° (Axis of Oval Shape), and 19.3 ± 9.5°/23.0° ± 9.6°, - 2.0° ± 11.3°/1.7° ± 11.4° (Axis Anterior Crest, Axis Second Metatarsus), respectively. CONCLUSIONS: Akagi's Line provided the best accuracy and least variability in varus osteoarthritic knees. Axis 1/6MED and Axis MED are good substitutes for Akagi's Line due to the difficulty of identifying the attachment site of the posterior cruciate ligament after the proximal tibia has been cut. Extra-articular bony landmarks should not be used for alignment due to their high variability. This study will aid surgeons in choosing the proper anteroposterior axis of the tibial component to reduce rotational mismatch and thus achieve good clinical knee outcomes. LEVELS OF EVIDENCE: III.

Medial soft tissue contracture does not always exist in varus osteoarthritis knees in total knee arthroplasty.

PURPOSE: To evaluate preoperative soft tissue balance for total knee arthroplasty (TKA), varus/valgus stress radiographs has been used in previous studies. While the joint line of femur and tibia is almost parallel in healthy and postoperative knees, osteoarthritis (OA) knees exhibit articular cartilage wear that causes the joint line tilting even in a non-stress condition. Therefore, the exact angle of the joint line might mislead to understand the joint laxity in OA knees. The purpose of this study was to evaluate soft tissue balance in varus OA knees using preoperative stress radiographs under three different constant loads, taking the articular cartilage wear into consideration. METHODS: One hundred and eighteen varus-deformed OA knees in 102 patients were investigated before primary TKA. Preoperative knee radiographs were obtained in the anteroposterior view with no stress (defined as the neutral condition) and with varus and valgus stresses (5, 10, and 15 kg) in extension. Two different types of joint line angle (JLA), the absolute JLA (an exact angle of joint line) and the relative JLA (the absolute JLA minus the JLA in the neutral condition), were compared for the same load with the paired t test. RESULTS: The absolute JLA was 7.9 ± 1.2°/- 1.5 ± 2.2° under varus/valgus 15 kg stress, 6.7 ± 2.4°/- 0.3 ± 2.1° under varus/valgus 10 kg stress, and 4.7 ± 2.4°/1.1 ± 2.2° under varus/valgus 5 kg stress. Significant differences in the numerical values of the absolute JLA were observed between varus and valgus stresses for each load. The neutral JLA was 3.2 ± 2.0°. The relative JLA was 4.8 ± 2.1°/- 4.7 ± 1.8° under varus/valgus 15 kg stress, 3.5 ± 2.0°/- 3.5 ± 1.8° under varus/valgus 10 kg stress, and 1.5 ± 1.9°/- 2.1 ± 1.8° under varus/valgus 5 kg stress. No significant differences in the numerical values of the relative JLA were observed between varus and valgus stresses for each load. CONCLUSIONS: Consideration of cartilage wear allowed knee laxity to be evaluated more precisely in this study than in previous reports. It was shown that medial soft tissue contracture did not always exist, even in varus OA knees. Regarding clinical relevance, surgeons should be aware that underestimating medial soft tissue laxity due to reliance on the absolute JLA might lead to excessive medial tissue release and result in postoperative instability and lower patient satisfaction. LEVEL OF EVIDENCE: IV.