Senescence of endplate osteoclasts induces sensory innervation and spinal pain.

Spinal pain affects individuals of all ages and is the most common musculoskeletal problem globally. Its clinical management remains a challenge as the underlying mechanisms leading to it are still unclear. Here, we report that significantly increased numbers of senescent osteoclasts (SnOCs) are observed in mouse models of spinal hypersensitivity, like lumbar spine instability (LSI) or aging, compared to controls. The larger population of SnOCs is associated with induced sensory nerve innervation, as well as the growth of H-type vessels, in the porous endplate. We show that deletion of senescent cells by administration of the senolytic drug Navitoclax (ABT263) results in significantly less spinal hypersensitivity, spinal degeneration, porosity of the endplate, sensory nerve innervation, and H-type vessel growth in the endplate. We also show that there is significantly increased SnOC-mediated secretion of Netrin-1 and NGF, two well-established sensory nerve growth factors, compared to non-senescent OCs. These findings suggest that pharmacological elimination of SnOCs may be a potent therapy to treat spinal pain.

Enhancing Endogenous Hyaluronic Acid in Osteoarthritic Joints with an Anti-Inflammatory Supramolecular Nanofiber Hydrogel Delivering HAS2 Lentivirus.

Osteoarthritis (OA) management remains challenging because of its intricate pathogenesis. Intra-articular injections of drugs, such as glucocorticoids and hyaluronic acid (HA), have certain limitations, including the risk of joint infection, pain, and swelling. Hydrogel-based therapeutic strategies have attracted considerable attention because of their enormous therapeutic potential. Herein, a supramolecular nanofiber hydrogel is developed using dexamethasone sodium phosphate (DexP) as a vector to deliver lentivirus-encoding hyaluronan synthase 2 (HAS2) (HAS2@DexP-Gel). During hydrogel degradation, HAS2 lentivirus and DexP molecules are slowly released. Intra-articular injection of HAS2@DexP-Gel promotes endogenous HA production and suppresses synovial inflammation. Additionally, HAS2@DexP-Gel reduces subchondral bone resorption in the anterior cruciate ligament transection-induced OA mice, attenuates cartilage degeneration, and delays OA progression. HAS2@DexP-Gel exhibited good biocompatibility both in vitro and in vivo. The therapeutic mechanisms of the HAS2@DexP-Gel are investigated using single-cell RNA sequencing. HAS2@DexP-Gel optimizes the microenvironment of the synovial tissue by modulating the proportion of synovial cell subpopulations and regulating the interactions between synovial fibroblasts and macrophages. The innovative nanofiber hydrogel, HAS2@DexP-Gel, effectively enhances endogenous HA production while reducing synovial inflammation. This comprehensive approach holds promise for improving joint function, alleviating pain, and slowing OA progression, thereby providing significant benefits to patients.

Senescence of endplate osteoclasts induces sensory innervation and spinal pain.

Spinal pain affects individuals of all ages and is the most common musculoskeletal problem globally. Its clinical management remains a challenge as the underlying mechanisms leading to it are still unclear. Here, we report that significantly increased numbers of senescent osteoclasts (SnOCs) are observed in mouse models of spinal hypersensitivity, like lumbar spine instability (LSI) or aging, compared to controls. The larger population of SnOCs is associated with induced sensory nerve innervation, as well as the growth of H-type vessels, in the porous endplate. We show that deletion of senescent cells by administration of the senolytic drug Navitoclax (ABT263) results in significantly less spinal hypersensitivity, spinal degeneration, porosity of the endplate, sensory nerve innervation and H-type vessel growth in the endplate. We also show that there is significantly increased SnOC-mediated secretion of Netrin-1 and NGF, two well-established sensory nerve growth factors, compared to non-senescent OCs. These findings suggest that pharmacological elimination of SnOCs may be a potent therapy to treat spinal pain.

Irisin promotes fracture healing by improving osteogenesis and angiogenesis.

Background: Osteogenesis and angiogenesis are important for bone fracture healing. Irisin is a muscle-derived monokine that is associated with bone formation. Methods: To demonstrate the effect of irisin on bone fracture healing, closed mid-diaphyseal femur fractures were produced in 8-week-old C57BL/6 mice. Irisin was administrated intraperitoneally every other day after surgery, fracture healing was assessed by using X-rays. Bone morphometry of the fracture callus were assessed by using micro-computed tomography. Femurs of mice from each group were assessed by the three-point bending testing. Effect of irisin on osteogenic differentiation in mesenchymal stem cells in vitro was evaluated by quantitative real-time polymerase chain reaction (qRT-PCR), alkaline phosphatase staining and alizarin red staining. Angiogenesis of human umbilical vein endothelial cells (HUVECs) were evaluated by qRT-PCR, migration tests, and tube formation assays. Results: Increased callus formation, mineralization and tougher fracture healing were observed in the irisin-treated group than in the control group, indicating the better fracture callus healing due to Irisin treatment. The vessel surface and vessel volume fraction of the callus also increased in the irisin-treated group. The expression of BMP2, CD31, and VEGF in callus were enhanced in the irisin-treated group. In mouse bone mesenchymal stem cells, irisin promoted ALP expression and mineralization, and increased the expression of osteogenic genes, including OSX, Runx2, OPG, ALP, OCN and BMP2. Irisin also promoted HUVEC migration and tube formation. Expression of angiogenic genes, including ANGPT1, ANGPT2, VEGFb, CD31, FGF2, and PDGFRB in HUVECs were increased by irisin. Conclusion: All the results indicate irisin can promote fracture healing through osteogenesis and angiogenesis. These findings help in the understanding of muscle-bone interactions during fracture healing. The Translational Potential of this Article: Irisin was one of the most important monokine secreted by skeletal muscle. Studies have found that irisin have anabolic effect one bone remodeling through affecting osteocyte and osteoblast. Based on our study, irisin could promote bone fracture healing by increasing bone mass and vascularization, which provide a potential usage of irisin to promote fracture healing and improve clinical outcomes.

HKA Angle-A Reliable Planning Parameter for High Tibial Osteotomy: A Theoretical Analysis Using Standing Whole-Leg Radiographs.

High tibial osteotomy (HTO) is a recognized treatment for early-stage medial compartment knee osteoarthritis. Preoperative planning with standing whole-leg radiographs (WLRs) is essential for ensuring optimal postoperative alignment. The primary purpose of this study is to investigate the theoretical accuracy of the wedge opening required for two different preoperative planning parameters in open-wedge HTO. The second purpose is to theoretically determine which parameter is superior. Preoperative planning for HTO was performed with standing WLRs for 39 knees with isolated medial osteoarthritis. The Miniaci preoperative planning method was applied to correct the hip-knee-ankle (HKA) angle to 3to 6 degrees of valgus and the weight-bearing line (WBL) percentage within 60 to 70% of the width of the tibial plateau. To ensure that the HKA angle was between 3 and 6 degrees of valgus, the required accuracy window for the Miniaci angle was 3.25 ± 0.03 degrees (range, 3.20-3.30°). To ensure that the WBL percentage was between 60 and 70%, the accuracy window required for the Miniaci angle was 2.35 ± 0.13 degrees (range, 2.10-2.65°). This study suggests that to correct the HKA angle and the WBL percentage within the target range on two-dimensional WLRs, the Miniaci angle must be controlled to an accuracy of ± 1.63 and ± 1.18 degrees, respectively. Theoretically, the HKA angle is highly suitable as a preoperative planning parameter for HTO with a large permissible error and a small variability in the degree of change in the Miniaci angle (ΔMiniaci).

Abnormal subchondral trabecular bone remodeling in knee osteoarthritis under the influence of knee alignment.

OBJECTIVE: This study aimed to investigate the abnormal subchondral trabecular bone (STB) remodeling in knee osteoarthritis (OA) under the influence of knee alignment [hip-knee-ankle (HKA) angle]. DESIGN: Forty-one patients with knee OA underwent radiographic examination before total knee arthroplasty (TKA) for the measurement of HKA angle. Tibial plateau specimens obtained during TKA were used for histomorphometric analyses to assess STB remodeling and cartilage degradation. Tartrate-resistant acidic phosphatase (TRAP) staining was used to test osteoclast activity. Osterix, osteocalcin, and sclerostin expression in the STB were determined using immunohistochemistry. RESULTS: The interaction between HKA angle and side (medial vs lateral of tibial plateau) was the main significant influence factor for STB remodeling and microstructure. The STB with the deviation of the knee alignment was accompanied by obvious abnormal bone remodeling and microstructural sclerosis. Bone volume fraction (BV/TV) was the only significant influence factor for OARSI score, the larger the BV/TV of STB, the higher the OARSI score of cartilage. Moreover, the tibial plateau affected by alignment had more TRAP + osteoclasts, Osterix + osteoprogenitors, and osteocalcin + osteoblasts and fewer sclerostin + osteocytes. CONCLUSIONS: The variation of tibial plateau STB remodeling activity and microstructure was associated with HKA angle and cartilage degradation. Knee malalignment may cause abnormal STB remodeling and microstructural sclerosis, which may potentially affect load stress transmission from the cartilage to the STB, thus resulting in accelerated knee OA progression.

Associations of osteoclastogenesis and nerve growth in subchondral bone marrow lesions with clinical symptoms in knee osteoarthritis.

BACKGROUND/OBJECTIVE: Subchondral bone marrow lesions (BMLs) are common magnetic resonance imaging (MRI) features in joints affected by osteoarthritis (OA), however, their clinical impacts and mechanisms remain controversial. Thus, we aimed to investigate subchondral BMLs in knee OA patients who underwent total knee arthroplasty (TKA), then evaluate the associations of osteoclastogenesis and nerve growth in subchondral BMLs with clinical symptoms. METHODS: Total 70 patients with primary symptomatic knee OA were involved, then separated into three groups based on MRI (without BMLs group, n â€‹= â€‹14; BMLs without cyst group, n â€‹= â€‹37; BMLs with cyst group, n â€‹= â€‹19). Volume of BMLs and cyst-like lesions was calculated via the OsiriX system. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) questionnaire was used to assess clinical symptoms. Histology and immunohistochemistry were deployed to assess subchondral osteoclastogenesis and nerve distribution. Pearson's correlation coefficient was used to evaluate the associations between volume of BMLs and joint symptoms, and to assess the associations of osteoclastogenesis and nerve growth in subchondral BMLs with joint symptoms. RESULTS: In BMLs combined with cyst group, patients exhibited increased osteoclastogenesis and nerve distribution in subchondral bone, as shown by increased expression of tartrate resistant acid phosphatase (TRAP) and protein gene product 9.5 (PGP9.5). Volume of subchondral cyst-like component was associated with joint pain (p â€‹< â€‹0.05). Subchondral osteoclastogenesis and nerve distribution were positively associated with joint pain in BMLs with cyst group (p â€‹< â€‹0.05). CONCLUSION: The subchondral cyst-like lesion was an independent factor for inducing pain in OA patients; osteoclastogenesis and nerve growth in subchondral cyst-like lesions could account for this joint pain. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: Our results indicated that the increased osteoclastogenesis and nerve growth in subchondral cyst-like lesions could account for the pain of OA joints. These findings may provide valuable basis for the treatment of OA.

Subchondral Trabecular Microstructure and Articular Cartilage Damage Variations Between Osteoarthritis and Osteoporotic Osteoarthritis: A Cross-sectional Cohort Study.

Osteoporotic osteoarthritis (OP-OA) is a specific type of OA. In this study, we aimed to assess the subchondral plate and rod microstructural differences between OA and OP-OA patients by using an individual trabeculae segmentation (ITS) system and to analyze the relationships between subchondral microstructures and cartilage damage in OA and OP-OA patients. Overall, 31 femoral heads were included in this study, which included 11 samples with OA and 13 samples with OP-OA; the normal control (NC) group contained 7 healthy femoral heads. ITS was performed to segment the subchondral trabecular bone into plate and rod trabeculae based on microcomputed tomography (micro-CT) images. We compared the plate and rod trabeculae of the subchondral trabecular bone between OA and OP-OA patients. The Osteoarthritis Research Society International (OARSI) score was employed to evaluate cartilage damage based on histological observations. Pearson's correlation coefficient and linear regression analysis were applied to analyze the relationships between subchondral microstructures and articular cartilage damage. Results showed that several microstructural parameters, including bone volume fraction (BV/TV), plate bone volume fraction (pBV/TV), rod bone volume fraction (rBV/TV), plate trabecular number (pTb.N), rod trabecular number (rTb.N), junction density between rod and plate (R-P Junc.D), and junction density between plate and plate (P-P Junc.D), were significantly decreased in patients with OP-OA compared with those in patients with OA (p < 0.05). Histological observations indicated that cartilage damage was more serious in patients with OP-OA than that in patients with OA (p < 0.05). Moreover, BV/TV, pBV/TV, pTb.N, and pTb.Th were significantly related to the OARSI score in both OA and OP-OA patients. These results indicated that there were differences in the subchondral rod and plate trabeculae between OA and OP-OA patients. Subchondral decreased plate trabeculae (pBV/TV, pTb.N, and pTb.Th) might account for cartilage damage in the progression of OP-OA. This study provided new insights to research OA when it is combined with OP.

D-dimer for diagnosis of periprosthetic joint infection: A meta-analysis.

BACKGROUND: The D-dimer test is easily available to detect periprosthetic joint infection (PJI). This study aimed to estimate the diagnostic accuracy of the D-dimer test in PJI diagnosis and identify possible independent factors affecting the diagnostic value of this test. METHODS: MEDLINE and EMBASE databases identified literature until February 2020 that utilized the D-dimer test for PJI diagnosis. The pooled sensitivity, specificity, area under the curve (AUC), diagnostic odds ratio (DOR), positive likelihood ratio (PLR), and negative likelihood ratio (NLR) were calculated to evaluate the diagnostic accuracy of the D-dimer test. Meta-regression and subgroup analyses were performed to assess potential heterogeneity. RESULTS: The databases identified 243 records, and eight studies were included in the final analysis. The pooled sensitivity and specificity of the D-dimer test for PJI diagnosis were 0.78 (95% confidence interval [CI], 0.69-0.84) and 0.74 (95% CI, 0.85-0.99), respectively. The AUCs and DORs of the D-dimer test were 0.83 (95% CI, 0.79-0.86) and 10 (95% CI, 4-24), respectively. The PLR and NLR of the D-dimer test for PJI detection were 3.0 (95% CI, 1.9-4.8) and 0.30 (95% CI, 0.20-0.47), respectively. The results of the meta-regression and subgroup analyses indicated that studies that excluded patients with hypercoagulation disorder had higher sensitivity (0.85 vs 0.86) and specificity (0.83 vs 0.62). The sensitivity of the D-dimer test also improved in studies that excluded patients with inflammatory arthritis (0.81 vs 0.75). CONCLUSION: The D-dimer test is a practical method for PJI diagnosis, especially in patients without history of hypercoagulation disorder and inflammatory arthritis.

Association between knee alignment, osteoarthritis disease severity, and subchondral trabecular bone microarchitecture in patients with knee osteoarthritis: a cross-sectional study.

BACKGROUND: Knee osteoarthritis (OA) is a common disabling disease involving the entire joint tissue, and its onset and progression are affected by many factors. However, the current number of studies investigating the relationship between subchondral trabecular bone (STB), knee alignment, and OA severity is limited. We aimed to investigate the variation in tibial plateau STB microarchitecture in end-stage knee OA patients and their association with knee alignment (hip-knee-ankle, HKA, angle) and OA severity. METHODS: Seventy-one knee OA patients scheduled for total knee arthroplasty (TKA) underwent preoperative radiography to measure the HKA angle and Kellgren-Lawrence grade. Tibial plateaus collected from TKA were scanned using micro-computed tomography to analyze the STB microarchitecture. Histological sections were used to assess cartilage degeneration (OARSI score). Correlations between the HKA angle, OA severity (OARSI score, Kellgren-Lawrence grade), and STB microarchitecture were evaluated. Differences in STB microstructural parameters between varus and valgus alignment groups based on the HKA angle were examined. RESULTS: The HKA angle was significantly correlated with all STB microarchitecture parameters (p < 0.01). The HKA angle was more correlated with the medial-to-lateral ratios of the microarchitecture parameters than with the medial or lateral tibia plateaus. The HKA angle and all STB microarchitecture parameters are significantly correlated with both the OARSI score and Kellgren-Lawrence grade (p < 0.01). CONCLUSIONS: The STB microarchitecture is associated with the HKA angle and OA severity. With the increase of the knee alignment deviation and OA severity, the STB of the affected side tibial plateau increased in bone volume, trabecular number, and trabecular thickness and decreased in trabecular separation.

Irisin inhibits osteocyte apoptosis by activating the Erk signaling pathway in vitro and attenuates ALCT-induced osteoarthritis in mice.

Moderate exercise can alleviate symptoms of osteoarthritis (OA) such as pain, stiffness, and joint deformities that are associated with progressive cartilaginous degeneration, osteophyte formation, subchondral bone changes, and synovial inflammation. Irisin is an exercise-related myokine that reportedly plays a crucial role in bone remodeling. However, its role in OA remains unknown. This study aimed to determine whether irisin can attenuate OA progression and the mechanism of its therapeutic effect. Three-month-old male C57BL/6J mice were randomized to groups that underwent sham operation, and anterior cruciate ligament transection (ACLT) intraperitoneally injected with vehicle or irisin in vivo. Apoptosis was induced by stretching murine osteocyte-like MLO-Y4 cells in vitro. Irisin reduced wear, maintained the proportion of hyaline cartilage, a more complete cartilage structure, and lower Osteoarthritis Research Society International (OARSI) scores at 4 weeks after ACLT. Irisin reduced the expression of matrix metalloproteinase (MMP)-13 in cartilage and caspase 3 in the subchondral bone. Irisin exerted rescue effects in microstructural parameters of subchondral trabecular bone including bone volume fraction (BV/TV), trabecular number (Tb.N), connection density (Conn. D), and the structure model index (SMI) compared with ACLT-vehicle group. Bone histomorphometry showed that irisin increased subchondral bone remodeling. The decreasing ratio (%) of the eroded surface (ES/BS) was reversed by irisin in the ACLT+vehicle group. Staining with tartrate-resistant acid phosphatase showed a decreased number of osteoclasts. Irisin significantly increased the proliferation of osteocytes, protected them from apoptosis, and maintained cellular activity by regulating the expression of Bax, Bcl-2, and osteoprotegerin/receptor activator of nuclear factor (NF)-kB-ligand (OPG/Rankl). Irisin activated serine/threonine-selective protein kinases (Erk) and p38 signaling, and its anti-apoptosis function depended on the Erk signaling pathway. Irisin attenuated OA progression by decreasing osteocyte apoptosis and improving the microarchitecture of subchondral bone. Activation of the Erk pathway by irisin plays an important role in reducing osteocyte apoptosis in vitro.

Differences in subchondral trabecular bone microstructure and finite element analysis-based biomechanical properties between osteoporosis and osteoarthritis.

BACKGROUND/OBJECTIVE: The microstructure of the subchondral trabecular bone, including the composition and distribution of plates and rods, has an important influence on the disease progression and mechanical properties of osteoarthritis (OA) and osteoporosis (OP). We aimed to determine whether differences in plates and rods influence the variations in the quantities and qualities of the subchondral trabecular bone between OA and OP. MATERIALS AND METHODS: Thirty-eight femoral head samples [OA, n = 13; OP, n = 17; normal control (NC), n = 8] were collected from male patients undergoing total hip arthroplasty. They were scanned using microcomputed tomography, and subchondral trabecular structures were analysed using individual trabecular segmentation. Micro-finite element analysis (µFEA) was applied to assess the mechanical property of the trabecular bone. Cartilage changes were evaluated by using histological assessment. Analysis of variance was used to compare intergroup differences in structural and mechanical properties and cartilage degradation. Pearson analysis was used to evaluate the relationship between the trabecula microstructure and biomechanical properties. RESULTS: Compared with the OP and NC group, there was serious cartilage damage in the OA group. With respect to the microstructure results, the OA group had the highest plate and rod trabecular microstructures including number and junction density among the three groups. For the mechanical properties detected via µFEA, the OA group had higher stiffness and failure load than did the OP group. Pearson analysis revealed that compared with OP, OA had a higher number of microstructure parameters (e.g., rod bone volume fraction and rod trabecular number) that were positively correlated with its mechanical property. CONCLUSIONS: Compared with OP, the OA subchondral bone has both increased plate and rod microarchitecture and has more microstructures positively related with its mechanical property. These differences may help explain the variation in mechanical properties between these bone diseases. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: Our findings suggested that changes in the plates and rods of the subchondral trabecular bone play a critical role in OA and OP progression and that the improvement of the subchondral trabecular bone may be a promising treatment approach.

Different subchondral trabecular bone microstructure and biomechanical properties between developmental dysplasia of the hip and primary osteoarthritis.

OBJECTIVE: Developmental dysplasia of the hip (DDH) is recognized as a frequent cause of secondary osteoarthritis (OA). The purpose in this study was to compare structural and biomechanical properties of subchondral trabecular bone â€‹and its relationship with cartilage damage between patients with DDH and patients with primary hip OA. METHODS: Forty-three femoral head specimens obtained from patients who underwent total hip arthroplasty [DDH, n â€‹= â€‹17; primary OA, n â€‹= â€‹16; and normal control (NC), n â€‹= â€‹10] were scanned by microcomputed tomography and analyzed by individual trabecula segmentation to obtain the microstructural types of subchondral trabecular bone. The biomechanical properties were analyzed by micro-finite element analysis, and cartilage damage was evaluated by histology. The linear regression analysis was used to indicate the association between microstructures, biomechanical property, and articular cartilage. RESULTS: The DDH group showed the lowest total bone volume fractions (BV/TV) and plate BV/TV in the three groups (p â€‹< â€‹0.05). There were also different discrepancies between the three groups in plate/rod trabecular number, plate/rod trabecular thickness, trabecular plate surface area/trabecular rod length, and junction density with different modes (plate-plate, rod-rod, and plate-rod junction density). The micro-finite element analysis, histology, and linear regression revealed that the subchondral trabecular bone in the DDH group had inferior biomechanical properties â€‹and cartilage damage of patients with DDH was more serious with different subchondral trabecular bone microstructures. CONCLUSION: Our findings detected deteriorating subchondral trabecular bone microstructures in patients with DDH. The mass and type of subchondral trabecular bone play a key role in mechanical properties in DDH, which might be related to cartilage damage. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: Our findings suggested that changes of subchondral trabecular bone play a critical role â€‹in DDH progression and that the improvement on subchondral trabecular bone may be a sensitive and promising way in treatment of DDH.

Articular Cartilage Degradation and Aberrant Subchondral Bone Remodeling in Patients with Osteoarthritis and Osteoporosis.

Osteoarthritis (OA) and osteoporosis (OP) are two skeletal disorders associated with joint structures. Occasionally, OA and OP occur in the same patient. However, the effect of OP changes on OA progression in patients with osteoporotic OA (OP-OA) has not been reported, especially the potential association between subchondral bone and articular cartilage. Thus we investigated the alterations in the microstructure, biomechanical properties, and remodeling of subchondral bone as well as their association with cartilage damage in the hip joint of patients with OP-OA. Thirty-nine femoral head specimens were obtained from patients who underwent total hip arthroplasty (OA group, n = 19; OP-OA group, n = 20), and healthy specimens from cadaver donors were used (control group, n = 10). The microstructure and biomechanical properties of subchondral bone were evaluated by micro-computed tomography and micro-finite-element analysis. Histology, histomorphometric measurements, and immunohistochemistry were used to assess subchondral bone remodeling and cartilage damage. Linear regression analysis was performed to elucidate the relationship between subchondral bone and articular cartilage. In the subchondral bone of the OP-OA group, compared with that of the OA group, aberrant bone remodeling leads to an inferior microstructure and worsening biomechanical properties, potentially affecting transmission of loading stress from the cartilage to the subchondral bone, and then resulting in accelerated OA progression in patients with OP-OA. The results indicate that changes in subchondral bone could affect OA development and the improvement in subchondral bone with bone-metabolism agents may help mitigate OA progression when OP and OA coexist in the same patients. © 2019 American Society for Bone and Mineral Research.

The fibular shaft axis and medial cortex of the proximal fibula are reliable landmarks for the mechanical axis of the tibia in patients with knee osteoarthritis.

BACKGROUND: This study aimed to evaluate the validity of proximal fibular anatomic landmarks for measuring the coronal tibial mechanical axis in patients with knee osteoarthritis and to investigate individual factors associated with their reliability. METHODS: A total of 106 knees in 96 patients were retrospectively reviewed. The angles between the tibial mechanical axis and fibular shaft axis (TFA), medial cortex of the proximal fibular shaft (MTA), and lateral cortex of the proximal fibular shaft (LTA) were measured from full-leg standing digital anteroposterior radiographs. An angle within three degrees was considered reliable. The association between the above three angles and individual factors, such as age, sex, body mass index (BMI), and varus-valgus knee malalignment, was determined to investigate individual factors associated with their reliability. RESULTS: The median TFA, MTA, and LTA were 1.52°, 1.56°, and 2.62°, respectively. The reliability rates of TFA, MTA, and LTA were 73.6% (95% CI: 65.19-81.98%), 82.1% (74.77-89.38%), and 58.5% (49.11-67.87%), respectively. The reliability of TFA and MTA was not associated with individual variables. The reliability of LTA was associated with BMI. Among patients with BMI greater than 25.3 kg/m2, LTA was considered reliable in 65.7%; this rate was significantly higher than that among patients with BMI less than 25.3 kg/m2. CONCLUSIONS: The fibular shaft axis and medial cortex of the proximal fibular shaft are reliable landmarks of the mechanical axis of the tibia. However, the reliability of the lateral cortex of the proximal fibular shaft is less satisfactory, especially in patients with BMI less than 25.3 kg/m2.

Synovial fluid α-defensin in the diagnosis of periprosthetic joint infection: the lateral flow test is an effective intraoperative detection method.

BACKGROUND: Synovial fluid α-defensin is a valuable biomarker for periprosthetic joint infection (PJI). Its diagnostic value for PJI has been widely evaluated recently, but results are inconsistent, especially for different test methods. The objective of this study was to evaluate the diagnostic value of laboratory-based immunoassay and lateral flow testing for the detection of α-defensin against hip and knee PJI. METHODS: We systematically searched MEDLINE and EMBASE for articles on the diagnostic accuracy of α-defensin for PJI published up to September 2018. The pooled sensitivity, specificity, area under the curve (AUC), positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were calculated for the evaluation of the diagnostic value of α-defensin for PJI. RESULTS: Nineteen studies were included. Eleven evaluated laboratory-based immunoassay, and 10 evaluated the lateral flow test results. The pooled sensitivity, specificity, AUC, PLR, NLR, and DOR of laboratory-based immunoassays were 0.96 (95% confidence interval [CI] 0.90-0.98), 0.97 (95% CI 0.95-0.99), 0.99 (95% CI 0.98-1.00), 35.0 (95% CI 18.5-66.2), 0.04 (95% CI 0.02-0.11), and 811 (95% CI 220-2990), respectively. The pooled sensitivity, specificity, AUC, PLR, NLR, and DOR of the lateral flow test were 0.86 (95% CI 0.81-0.91), 0.96 (95% CI 0.93-0.98), 0.95 (95% CI 0.93-0.97), 21.2 (95% CI 11.7-38.5), 0.14 (95% CI 0.10-0.21), and 148 (95% CI 64-343), respectively. CONCLUSIONS: Laboratory-based immunoassay of α-defensin is highly accurate for the diagnosis of hip and knee PJI. The lateral flow test is less sensitive but still a useful intraoperative detection tool for PJI.

The effect of varus knee deformities on the ankle alignment in patients with knee osteoarthritis.

BACKGROUND: We evaluated the compensatory change in ankle alignment due to knee malalignment and its relationship with varus knee deformities, as well as sex differences in compensation. METHODS: From October 2016 to September 2017, 103 patients with end-stage knee osteoarthritis underwent primary total knee arthroplasty (TKA). Ninety-five knees (78 patients) were included. The hip-knee-ankle angle (HKA) and ankle alignment and tilt were evaluated with full-leg standing anteroposterior radiographs. The ankle alignment was estimated according to the tibiotalar angle, tibial anterior surface angle (TAS), and lateral distal tibial angle. The talar tilt angle (TT), anatomical talocrural angle, angle between the tibial plateau and distal tibial plafond, angles between the ground and distal tibial plafond, and angles between the ground and upper talus were measured to evaluate ankle tilt. The patients were separated into two sex-based groups; correlations between the HKA and ankle parameters were estimated. RESULTS: The mean HKA in men and women was 8.16 ± 4.36° and 7.69 ± 5.93°, respectively. The relative tilt of the talus and distal tibia plafond to the ground was increased when varus knee deformities progressed. In women, there was a positive correlation between the knee alignment and TAS (r = - 0.295, p = 0.016). As the knee mechanical axis became more varus, the distal tibia plafond became more valgus. In women, a negative correlation was observed between the HKA and TT (r = - 0.359, p = 0.003). Compensatory changes in the ankle alignment and TT to knee alignment were not observed in men. CONCLUSION: Compensatory ankle changes should be considered before TKA.

Association Between Knee Malalignment and Ankle Degeneration in Patients With End-Stage Knee Osteoarthritis.

BACKGROUND: The association between knee malalignment and ankle degeneration has not been well established. This study aimed at determining whether knee malalignment and compensatory ankle morphology to knee malalignment are associated with the development and progression of ankle osteoarthritis (OA) in patients with end-stage knee OA. METHODS: We retrospectively reviewed 96 patients (106 knees) who underwent total knee arthroplasty. The progression of ankle OA, knee alignment, and ankle morphology were evaluated based on digital radiographs. Alignment deformity of the lower extremity was evaluated with hip-knee-ankle angle and medial proximal tibial angle (MPTA). Ankle morphology was evaluated by the lateral distal tibial angle, talar tilt, tibial plafond inclination angle, and ankle joint line orientation angle. RESULTS: The incidence of radiological ankle OA was observed in 39 of 106 cases. The MPTA (odds ratio = 0.72, P = .0009) and hip-knee-ankle angle (odds ratio = 1.13, P = .0169) were significantly associated with ankle OA. Among patients with tibial varus deformity, 26 of 49 had ankle OA. Among patients with neutral tibial alignment, 13 of 57 had radiological findings of ankle OA. MPTA was the only parameter associated with the progression of ankle OA. No association was observed between compensatory change in ankle morphology and the severity of ankle OA. CONCLUSION: Tibial varus deformity is associated with the development and progression of ankle OA; however, it is unclear whether it causes ankle OA. Due to the high incidence of ankle OA in total knee arthroplasty patients, it is reasonable to consider routine evaluation of the ankle.