Clinical Relevance of Posterior Osteophyte Formation in Ultra-congruent Total Knee Arthroplasty: Midterm Radiographic Rollback and Impingement Analysis.

Background: Posterior femoral condylar osteophytes were frequently observed in patients with the ultra-congruent (UC) deep-dish design prosthesis. Therefore, the purpose of the present study was to verify the clinical relevance of osteophyte formation in the UC design. Methods: From March 2014 to February 2018, a comparative study was conducted on 96 knees using the UC design. They were divided into 2 groups (group 1: osteophyte +, group 2: osteophyte -). Intraoperative findings, indirect femoral rollback assessment using 30° flexion and active full flexion lateral radiographs, serial change of the osteophyte, and outcomes were compared. Results: The mean follow-up period was 49.35 ± 3.47 months in group 1 and 47.52 ± 3.37 months in group 2. Posterior component coverage was significantly different between the groups: group 1 exhibited more underhang and group 2 exhibited more overhang (p = 0.022). On the indirect assessment of the femoral rollback, there was a statistically significant difference in deep flexion and change in distance (p < 0.001 and p < 0.001, respectively). There was no statistical difference between the 2 groups in the American Knee Society knee and function score, and group 2 showed significant improvement in pain compared to group 1 in Western Ontario and McMaster University Arthritis Index pain score (p = 0.029). Conclusions: Posterior condylar osteophyte formation was related to posterior impingement. It was more frequently observed in the underhang of the femoral component and insufficient femoral rollback. In addition, it changed with time and caused negative effects, including a gradual decrease in flexion and more pain.

Disease-Modifying Effects of Lenvatinib, a Multiple Receptor Tyrosine Kinase Inhibitor, on Posttraumatic Osteoarthritis of the Knee.

Angiogenesis and vascular endothelial growth factor (VEGF) are involved in osteoarthritis (OA). We previously reported the inhibitory effect of bevacizumab in a rabbit model of OA. In the current study, we investigated the effects of lenvatinib, an angiogenesis inhibitor targeting the VEGF and fibroblast growth factor receptors, on synovitis, osteophyte formation, and cartilage degeneration in a rabbit OA model. Posttraumatic OA was induced by anterior cruciate ligament transection (ACLT) on one knee of each rabbit. Rabbits were placed into four groups according to the following lenvatinib doses: untreated control (n = 12), L0.3: 0.3 mg/kg/day (n = 15), L1.0: 1.0 mg/kg/day (n = 14), and L3.0: 3.0 mg/kg/day (n = 13) groups. We evaluated limb pain using the weight distribution ratio measured with an incapacitance tester, macroscopic osteophyte formation, and femoral condyle synovium and cartilage histology. For cartilage evaluation, the following distal sites of the femur were evaluated separately: femoral-tibial (FT), femoral-patellar (FP), and femoral corner (between FP and FT). The weight distribution ratio at 12 weeks after surgery was higher in the L0.3 and L1.0 groups than in the control group. Osteophyte formation and synovitis scores were significantly lower in the L0.3, L1.0, and L3.0 groups than in the control group. The Osteoarthritis Research Society International scores of the FT, corner, and FP sites in the L0.3 group were lower than in the control group. The cartilage thickness ratio at the FT and corner sites was significantly lower in the L0.3 group than in the control group. Krenn's grading system of cartilage synovitis showed that all lenvatinib-administered groups had significantly lower scores than the control group. MMP3 expression level in cartilage tissue was significantly lower in the L3.0 group compared with the other three groups. ADAMTS5 expression was lower in the L3.0 group compared with the control and L0.3 groups. Oral administration of lenvatinib inhibited synovitis, osteophyte formation, and cartilage degeneration and reduced pain in a rabbit ACLT model. Lenvatinib is an oral VEGF inhibitor that is easier to administer than other VEGF inhibitors and may have potential as a treatment of posttraumatic OA.

Osteophyte Cartilage as a Potential Source for Minced Cartilage Implantation: A Novel Approach for Articular Cartilage Repair in Osteoarthritis.

Osteoarthritis (OA) is a common joint disorder characterized by cartilage degeneration, often leading to pain and functional impairment. Minced cartilage implantation (MCI) has emerged as a promising one-step alternative for large cartilage defects. However, the source of chondrocytes for MCI remains a challenge, particularly in advanced OA, as normal cartilage is scarce. We performed in vitro studies to evaluate the feasibility of MCI using osteophyte cartilage, which is present in patients with advanced OA. Osteophyte and articular cartilage samples were obtained from 22 patients who underwent total knee arthroplasty. Chondrocyte migration and proliferation were assessed using cartilage fragment/atelocollagen composites to compare the characteristics and regenerative potential of osteophytes and articular cartilage. Histological analysis revealed differences in cartilage composition between osteophytes and articular cartilage, with higher expression of type X collagen and increased chondrocyte proliferation in the osteophyte cartilage. Gene expression analysis identified distinct gene expression profiles between osteophytes and articular cartilage; the expression levels of COL2A1, ACAN, and SOX9 were not significantly different. Chondrocytes derived from osteophyte cartilage exhibit enhanced proliferation, and glycosaminoglycan production is increased in both osteophytes and articular cartilage. Osteophyte cartilage may serve as a viable alternative source of MCI for treating large cartilage defects in OA.

Mild exercise expedites joint clearance and slows joint degradation in a joint instability model of osteoarthritis in male rats.

OBJECTIVE: Exercise remains a hallmark treatment for post-traumatic osteoarthritis (PTOA) and may maintain joint homeostasis in part by clearing inflammatory cytokines, cells, and particles. It remains largely unknown whether exercise-induced joint clearance can provide therapeutic relief of PTOA. In this study, we hypothesized that exercise could slow the progression of preclinical PTOA in part by enhancing knee joint clearance. DESIGN: Surgical medial meniscal transection was used to induce PTOA in 3-month-old male Lewis rats. A sham surgery was used as a control. Mild treadmill walking was introduced 3 weeks post-surgery and maintained to 6 weeks post-surgery. Gait and isometric muscle torque were measured at the study endpoint. Near-infrared imaging tracked how exercise altered lymphatic and venous knee joint clearance during discrete time points of PTOA progression. RESULTS: Exercise mitigated joint degradation associated with PTOA by preserving glycosaminoglycan content and reducing osteophyte volume (effect size (95% Confidence Interval (CI)); 1.74 (0.71-2.26)). PTOA increased hind step widths (0.57 (0.18-0.95) cm), but exercise corrected this gait dysfunction (0.54 (0.16-0.93) cm), potentially indicating pain relief. Venous, but not lymphatic, clearance was quicker 1-, 3-, and 6-weeks post-surgery compared to baseline. The mild treadmill walking protocol expedited lymphatic clearance rate in moderate PTOA (3.39 (0.20-6.59) hrs), suggesting exercise may play a critical role in restoring joint homeostasis. CONCLUSIONS: We conclude that mild exercise has the potential to slow disease progression in part by expediting joint clearance in moderate PTOA.

Classification of Osteophytes Occurring in the Lumbar Intervertebral Foramen.

BACKGROUND: Surgeons have limited knowledge of the lumbar intervertebral foramina. This study aimed to classify osteophytes in the lumbar intervertebral foramen and to determine their pathoanatomical characteristics, discuss their potential biomechanical effects, and contribute to developing surgical methods. METHODS: We conducted a retrospective, non-randomized, single-center study involving 1224 patients. The gender, age, and anatomical location of the osteophytes in the lumbar intervertebral foramina of the patients were recorded. RESULTS: Two hundred and forty-nine (20.34%) patients had one or more osteophytes in their lumbar 4 and 5 foramina. Of the 4896 foramina, 337 (6.88%) contained different types of osteophytes. Moreover, four anatomical types of osteophytes were found: mixed osteophytes in 181 (3.69%) foramina, osteophytes from the lower endplate of the superior vertebrae in 91 (1.85%) foramina, osteophytes from the junction of the pedicle and lamina of the upper vertebrae in 39 foramina (0.79%), and osteophytes from the upper endplate of the lower vertebrae in 26 (0.53%) foramina. The L4 foramen contained a significantly higher number of osteophytes than the L5 foramen. Osteophyte development increased significantly with age, with no difference between males and females. CONCLUSIONS: The findings show that osteophytic extrusions, which alter the natural anatomical structure of the lumbar intervertebral foramina, are common and can narrow the foramen.

Are enlarged peroneal tubercle and accessory anterolateral talar facet associated with calcaneal spur?

BACKGROUND: As the anatomical variations of the foot, enlarged peroneal tubercle (EPT) and accessory anterolateral talar facet (AALTF) have attracted the attention of foot surgeons in recent years. However, EPT and AALTF have not been examined for a relationship with calcaneus spur (CS) as a common osteophyte. METHODS: The subjects were 369 individuals who died in northeastern Thailand and were preserved as skeletal specimens. The authors examined for the presence of left and right EPT, AALTF, and calcaneus spur (CS). We divided the EPT (+) group with EPT and the EPT (-) group without it and also divided the AALTF (+) group with AALTF and the AALTF (-) group without it. The age at death and the presence of CS were compared statistically between the EPT (+) and EPT (-) groups and between the AATLF (+) and AALTF (-) groups. RESULTS: Out of the total 369 cases, EPT was found in 117 cases (31.7%), AALTF was positive in 91 cases (24.7%), and CS was found in 194 cases (52.3%). In comparison between EPT (+) and EPT (-) groups, CS was significantly higher (p < 0.0001) in the EPT (+) group, but there was no significant difference in age at death. In comparison between AALTF (+) and AALTF (-) groups, there was no significant difference in age at death or CS. CONCLUSION: This study showed a strong relationship between EPT and CS, and the prevalence of EPT and AALTF by age in Thailand was first reported. We believe it helps to know the pathogenesis and biomechanism of EPT and AALTF. TRIAL REGISTRATION: Not applicable.

Quantitative analysis and stochastic modeling of osteophyte formation and growth process on human vertebrae based on radiographs: a follow-up study.

Osteophytes are frequently observed in elderly people and most commonly appear at the anterior edge of the cervical and lumbar vertebrae body. The anterior osteophytes keep developing and will lead to neck/back pain over time. In clinical practice, the accurate measurement of the anterior osteophyte length and the understanding of the temporal progression of anterior osteophyte growth are of vital importance to clinicians for effective treatment planning. This study proposes a new measuring method using the osteophyte ratio index to quantify anterior osteophyte length based on lateral radiographs. Moreover, we develop a continuous stochastic degradation model with time-related functions to characterize the anterior osteophyte formation and growth process on cervical and lumbar vertebrae over time. Follow-up data of anterior osteophytes up to 9 years are obtained for measurement and model validation. The agreement test indicates excellent reproducibility for our measuring method. The proposed model accurately fits the osteophyte growth paths. The model predicts the mean time to onset of pain and obtained survival function of the degenerative vertebrae. This research opens the door to future quantification and mathematical modeling of the anterior osteophyte growth on human cervical and lumbar vertebrae. The measured follow-up data is shared for future studies.

[Effectiveness comparison of ultrasound-guided closed reduction and Kirschner wire fixation for different unstable humeral lateralcondylar fractures of children].

Objective: To compare the effectiveness of ultrasound-guided closed reduction and Kirschner wire fixation for different unstable humeral lateralcondylar fractures of children. Methods: The clinical data of 94 children with unstable humeral lateralcondylar fractures admitted to three medical centers between January 2021 and October 2022 were retrospectively analyzed. The children were divided into three groups according to the Song classification and whether the elbow joint was dislocated or not, including 42 cases of Song 4 type (group A), 38 cases of Song 5 type (group B), and 14 cases of elbow joint dislocation (group C). There was no significant difference in gender, age, side, cause of injury, and time from injury to operation among the three groups ( P>0.05). All children were treated with ultrasound-guided closed reduction and Kirschner wire fixation. The operation time and complications of the three groups were recorded and compared, and the failure of closed reduction was evaluated by ultrasound. X-ray examination was performed at last follow-up to measure the Baumann angle, condylar angle, carrying angle, and lateral osteophyte of the affected side; the extension, flexion, pronation, and supination range of motion of the affected elbow joint were measured; the function of the elbow joint was evaluated by Mayo score. Results: The operation time in group A was significantly longer than that in groups B and C ( P<0.05). There were 7, 2, and 5 cases of closed reduction failure in groups A, B, and C, respectively, and there was no significant difference in the incidence of the closed reduction failure ( P>0.05). All patients were followed up 6-28 months, with an average of 15.7 months. There was no significant difference in the follow-up time among the three groups ( P>0.05). Complications: in group A, there were 2 cases of delayed union, 4 cases of needle tract infection, 1 case of trochlear necrosis, and 39 cases of lateral osteophyte; in group B, there was 1 case of malunion, 5 cases of needle tract infection, 1 case of redisplacement, and 26 cases of lateral osteophyte; in group C, there were 2 cases of needle tract infection and 10 cases of lateral osteophyte. There was no significant difference in the incidence of complications among the three groups ( P>0.05). No cubitus varus or cubitus valgus deformity was found in all patients. At last follow-up, except that the condylar angle in group A was significantly greater than that in groups B and C ( P<0.05), there was no significant difference in other imaging indicators, elbow range of motion, or Mayo score between groups ( P>0.05). Conclusion: The Song type 4 of humeral lateralcondylar fracture treated with ultrasound-guided closed reduction and Kirschner wire fixation has a longer operation time, more postoperative complications, and is more prone to lateral osteophyte.

Distribution and analysis of subacromial spurs and the relationship with acromial classification and angle in healthy individuals.

BACKGROUND: Subacromial spurs are considered the one of the pathology underlying shoulder impingement syndrome. Furthermore, few studies have focused on the morphology of the subacromial spurs in normal Chinese people. This study aimed to study the spur distribution and to illustrate the morphology of spurs, which may help guide the extent of acromioplasty. METHODS: A total of 93 normal individuals were enrolled, and both shoulders of all enrolled individuals were analyzed. The subjects were divided and classified into three different groups by ages: group I = 18-40 years, group II = 41-60 years, and group III ≥ 61 years. The osteophyte distribution, osteophyte area, subacromial surface area and osteophyte area/subacromial surface area ratio were measured and illustrated using Mimics and 3-matic software. The shape of the acromion was classified according to the Bigliani and Morrison classification system. The acromial angle was also classified. Then, the relationship between osteophytes, acromial classification and acromial angle was analyzed. RESULTS: Type II (curved shape) was the most common type of acromion, and the hooked shape was a rare form. A significant increase in the left subacromial surface area in males was observed in group III compared with group I (P < 0.001) and group II (P = 0.004). The total spur/subacromial area ratio was significantly higher in group II than I. An obvious increase in the right subacromial area was observed in group III compared with group I (P = 0.004). Furthermore, there was a significant increase in the right spur area (P = 0.021) and total spur/subacromial area ratio (P = 0.006) in females in group II compared with group I. Fewer spurs were observed on the left than on the right side (p = 0.0482). One spur was most common among type II acromions (29/36) (80.56%) on the left side and the right side (34/52, 65.38%). CONCLUSIONS: Spurs osteophytes are mainly distributed with an irregular shape and mostly run through the medial and lateral sides of the subacromial surface in normal subjects. The characteristics of subacromial spurs are so diverse that a surgeon must conduct subacromial decompression completely based on the morphology of individual spurs.

[Dysphagia as the main symptom in anterior cervical spine osteophytes (Forestier disease and cervical spondylosis deformans). Case reports and literature review]. / Disfagiya kak osnovnoi simptom pri perednikh osteofitakh sheinogo otdela pozvonochnika (bolezn' Forest'e i tservikal'nyi deformiruyushchii spondilez): obzor literatury i analiz klinicheskikh sluchaev.

Anterior cervical osteophytes are a fairly common X-ray finding in people over 50 years old. Incidence of dysphagia in patients with anterior osteophytes varies from 1% in those aged 40-60 years to 10.6% in patients over 60 years old. The most common causes of anterior cervical hyperosteophytosis causing dysphagia are cervical spondylosis deformans and Forestier disease. We present 2 clinical cases of spondylogenic dysphagia in cervical spondylosis deformans and Forestier disease. The review is devoted to the causes and diagnostic methods for dysphagia caused by anterior cervical osteophytes, as well as surgical options for this pathology. CONCLUSION: Microsurgical resection of anterior osteophytes is an effective method for dysphagia after ineffective therapy for 3 months. Microsurgical osteophytectomy provides stable regression of dysphagia with low recurrence rate.

Reliability of an ultrasound imaging acquisition procedure for examining osteoarthritis in the first metatarsophalangeal joint.

OBJECTIVE: Given the ability of ultrasound imaging (USI) to depict tissue-specific morphological changes before the onset of pain and before the point of irreversible structural damage, USI could play a fundamental role in earlier detection and assessment of foot osteoarthritis (OA). The current guidelines require further refinement of anatomical landmarks to establish a standardized imaging procedure to improve the interpretability and reproducibility between studies evaluating the first metatarsophalangeal joint (MTPJ). The aims were to develop an USI acquisition procedure and grading system to examine OA features in the first MTPJ and to determine intra-examiner and inter-examiner reliability of a newly developed USI acquisition procedure. DESIGN: Thirty participants with first MTPJ OA confirmed radiographically with the use of the La Trobe Foot Atlas were included. An experienced sonographer applied a newly developed USI procedure to examine the following features: joint effusion, synovial hypertrophy, synovitis, joint space narrowing, osteophytes, and cartilage thickness. A semiquantitative grading system was applied to all features. A continuous measure was also examined for osteophyte size, joint space narrowing, and cartilage thickness. To determine the intra-examiner and inter-examiner reliability, an experienced radiologist and sonographer applied the developed grading system to the images acquired from two imaging sessions. Intra-examiner and inter-examiner reliability were calculated using intraclass correlation coefficients (ICCs). RESULTS: ICCs for intra-examiner between session reliability ranged from 0.58 to 0.92 for semiquantitative grading and 0.39 to 0.94 for continuous measures. Joint effusion and osteophytes achieved the highest intra-examiner reliability (ICC = 0.78-0.94). ICCs for session one inter-examiner reliability ranged from 0.61 to 1.0 for semiquantitative grading; all continuous measures had an ICC of 1. ICCs for session two inter-examiner reliability ranged from 0.55 to 1.0 for semiquantitative grading and 0.9 to 0.97 for continuous measures. Inter-examiner reliability was good for grading joint effusion (ICC = 0.55-0.62) and was excellent for all other USI features (ICC = 0.77-1.0). CONCLUSION: The USI acquisition procedure and grading system are reliable in evaluating first MTPJ OA features in participants with radiologically confirmed OA. The study will inform the methodological development of an ultrasound atlas for grading the degree of osteoarthritic change in the first MTPJ.

ILK inhibition reduces osteophyte formation through suppression of osteogenesis in BMSCs via Akt/GSK-3ß/ß-catenin pathway.

BACKGROUND: Osteophyte development is a common characteristic of inflammatory skeletal diseases. Elevated osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) participates in pathological osteogenesis. Integrin-linked kinase (ILK) positively regulates the osteoblastic differentiation of osteoprogenitors, but whether the ILK blockage prevents osteophytes and its potential mechanism is still unknown. Furthermore, the low-dose tumor necrosis factor-α (TNF-α) promotes osteogenic differentiation, but a lack of study reports on the relationship between this cytokine and ILK. OSU-T315 is a small ILK inhibitor, which was used to determine the effect of ILK inhibition on osteogenesis and osteophyte formation. METHODS AND RESULTS: The osteogenesis of BMSCs was evaluated using Alizarin red S staining, alkaline phosphatase, collagen type I alpha 2 chain, and bone gamma-carboxyglutamate protein. The expression and phosphorylation of protein were assessed through western blot. Immunofluorescence was employed to display the distribution of ß-catenin. microCT, hematoxylin-eosin, and safranin O/fast green staining were utilized to observe the osteophyte formation in collagen antibody-induced arthritis mice. We found that ILK blockage significantly declined calcium deposition and osteoblastic markers in a dose- and time-dependent manner. Furthermore, it lowered osteogenesis in the TNF-α-induced inflammatory microenvironment by diminishing the effect of ILK and inactivating the Akt/ GSK-3ß/ ß-catenin pathway. Nuclear ß-catenin was descended by OSU-T315 as well. Finally, the ILK suppression restrained osteophyte formation but not inflammation in vivo. CONCLUSIONS: ILK inhibition lowered osteogenesis in TNF-α-related inflammatory conditions by deactivating the Akt/ GSK-3ß/ ß-catenin pathway. This may be a potential strategy to alleviate osteophyte development in addition to anti-inflammatory treatment.

Pathological Priors Inspired Network for Vertebral Osteophytes Recognition.

Automatic vertebral osteophyte recognition in Digital Radiography is of great importance for the early prediction of degenerative disease but is still a challenge because of the tiny size and high inter-class similarity between normal and osteophyte vertebrae. Meanwhile, common sampling strategies applied in Convolution Neural Network could cause detailed context loss. All of these could lead to an incorrect positioning predicament. In this paper, based on important pathological priors, we define a set of potential lesions of each vertebra and propose a novel Pathological Priors Inspired Network (PPIN) to achieve accurate osteophyte recognition. PPIN comprises a backbone feature extractor integrating with a Wavelet Transform Sampling module for high-frequency detailed context extraction, a detection branch for locating all potential lesions and a classification branch for producing final osteophyte recognition. The Anatomical Map-guided Filter between two branches helps the network focus on the specific anatomical regions via the generated heatmaps of potential lesions in the detection branch to address the incorrect positioning problem. To reduce the inter-class similarity, a Bilateral Augmentation Module based on the graph relationship is proposed to imitate the clinical diagnosis process and to extract discriminative contextual information between adjacent vertebrae in the classification branch. Experiments on the two osteophytes-specific datasets collected from the public VinDr-Spine database show that the proposed PPIN achieves the best recognition performance among multitask frameworks and shows strong generalization. The results on a private dataset demonstrate the potential in clinical application. The Class Activation Maps also show the powerful localization capability of PPIN. The source codes are available in https://github.com/Phalo/PPIN.

Deep learning based detection of osteophytes in radiographs and magnetic resonance imagings of the knee using 2D and 3D morphology.

In this study, we investigated the discriminative capacity of knee morphology in automatic detection of osteophytes defined by the Osteoarthritis Research Society International atlas, using X-ray and magnetic resonance imaging (MRI) data. For the X-ray analysis, we developed a deep learning (DL) based model to segment femur and tibia. In case of MRIs, we utilized previously validated segmentations of femur, tibia, corresponding cartilage tissues, and menisci. Osteophyte detection was performed using DL models in four compartments: medial femur (FM), lateral femur (FL), medial tibia (TM), and lateral tibia (TL). To analyze the confounding effects of soft tissues, we investigated their morphology in combination with bones, including bones+cartilage, bones+menisci, and all the tissues. From X-ray-based 2D morphology, the models yielded balanced accuracy of 0.73, 0.69, 0.74, and 0.74 for FM, FL, TM, TL, respectively. Using 3D bone morphology from MRI, balanced accuracy was 0.80, 0.77, 0.71, and 0.76, respectively. The performance was higher than in 2D for all the compartments except for TM, with significant improvements observed for femoral compartments. Adding menisci or cartilage morphology consistently improved balanced accuracy in TM, with the greatest improvement seen for small osteophyte. Otherwise, the models performed similarly to bones-only. Our experiments demonstrated that MRI-based models show higher detection capability than X-ray based models for identifying knee osteophytes. This study highlighted the feasibility of automated osteophyte detection from X-ray and MRI data and suggested further need for development of osteophyte assessment criteria in addition to OARSI, particularly, for early osteophytic changes.

Piezo1 expression in chondrocytes controls endochondral ossification and osteoarthritis development.

Piezo proteins are mechanically activated ion channels, which are required for mechanosensing functions in a variety of cell types. While we and others have previously demonstrated that the expression of Piezo1 in osteoblast lineage cells is essential for bone-anabolic processes, there was only suggestive evidence indicating a role of Piezo1 and/or Piezo2 in cartilage. Here we addressed the question if and how chondrocyte expression of the mechanosensitive proteins Piezo1 or Piezo2 controls physiological endochondral ossification and pathological osteoarthritis (OA) development. Mice with chondrocyte-specific inactivation of Piezo1 (Piezo1Col2a1Cre), but not of Piezo2, developed a near absence of trabecular bone below the chondrogenic growth plate postnatally. Moreover, all Piezo1Col2a1Cre animals displayed multiple fractures of rib bones at 7 days of age, which were located close to the growth plates. While skeletal growth was only mildly affected in these mice, OA pathologies were markedly less pronounced compared to littermate controls at 60 weeks of age. Likewise, when OA was induced by anterior cruciate ligament transection, only the chondrocyte inactivation of Piezo1, not of Piezo2, resulted in attenuated articular cartilage degeneration. Importantly, osteophyte formation and maturation were also reduced in Piezo1Col2a1Cre mice. We further observed increased Piezo1 protein abundance in cartilaginous zones of human osteophytes. Finally, we identified Ptgs2 and Ccn2 as potentially relevant Piezo1 downstream genes in chondrocytes. Collectively, our data do not only demonstrate that Piezo1 is a critical regulator of physiological and pathological endochondral ossification processes, but also suggest that Piezo1 antagonists may be established as a novel approach to limit osteophyte formation in OA.

Transcript-dependent effects of the CALCA gene on the progression of post-traumatic osteoarthritis in mice.

Osteoarthritis represents a chronic degenerative joint disease with exceptional clinical relevance. Polymorphisms of the CALCA gene, giving rise to either a procalcitonin/calcitonin (PCT/CT) or a calcitonin gene-related peptide alpha (αCGRP) transcript by alternative splicing, were reported to be associated with the development of osteoarthritis. The objective of this study was to investigate the role of both PCT/CT and αCGRP transcripts in a mouse model of post-traumatic osteoarthritis (ptOA). WT, αCGRP-/- and CALCA-/- mice were subjected to anterior cruciate ligament transection (ACLT) to induce ptOA of the knee. Mice were sacrificed 4 and 8 weeks post-surgery, followed by micro-CT and histological evaluation. Here we show that the expression of both PCT/CT and αCGRP transcripts is induced in ptOA knees. CALCA-/- mice show increased cartilage degeneration and subchondral bone loss with elevated osteoclast numbers compared to αCGRP-/- and WT mice. Osteophyte formation is reduced to the same extent in CALCA-/- and αCGRP-/- mice compared to WT controls, while a reduced synovitis score is noticed exclusively in mice lacking CALCA. Our data show that expression of the PCT/CT transcript protects from the progression of ptOA, while αCGRP promotes osteophyte formation, suggesting that CALCA-encoded peptides may represent novel targets for the treatment of ptOA.

Tranexamic Acid Attenuates the Progression of Posttraumatic Osteoarthritis in Mice.

BACKGROUND: Posttraumatic osteoarthritis (OA) is a common disorder associated with a high socioeconomic burden, particularly in young, physically active, and working patients. Tranexamic acid (TXA) is commonly used in orthopaedic trauma surgery as an antifibrinolytic agent to control excessive bleeding. Previous studies have reported that TXA modulates inflammation and bone cell function, both of which are dysregulated during posttraumatic OA disease progression. PURPOSE: To evaluate the therapeutic effects of systemic and topical TXA treatment on the progression of posttraumatic OA in the knee of mice. STUDY DESIGN: Controlled laboratory study. METHODS: OA was induced via anterior cruciate ligament (ACL) transection on the right knee of female mice. Mice were treated with TXA or vehicle intraperitoneally daily or intra-articularly weekly for 4 weeks, starting on the day of surgery. Articular cartilage degeneration, synovitis, bone erosion, and osteophyte formation were scored histologically. Micro-computed tomography evaluation was conducted to measure the subchondral bone microstructure and osteophyte volume. Cartilage thickness and bone remodeling were assessed histomorphometrically. RESULTS: Both systemic and topical TXA treatment significantly reduced cartilage degeneration, synovitis, and bone erosion scores and increased the ratio of hyaline to calcified cartilage thickness in posttraumatic OA. Systemic TXA reversed ACL transection-induced subchondral bone loss and osteophyte formation, whereas topical treatment had no effect. Systemic TXA decreased the number and surface area of osteoclasts, whereas those of osteoblasts were not affected. No effect of topical TXA on osteoblast or osteoclast parameters was observed. CONCLUSION: Both systemic and topical TXA exerted protective effects on the progression of posttraumatic OA. Drug repurposing of TXA may, therefore, be useful for the prevention or treatment of posttraumatic OA, particularly after ACL surgery. CLINICAL RELEVANCE: TXA might be beneficial in patients with posttraumatic OA of the knee.

Vertebral artery stenosis from osteophyte: A systematic review and case series.

BACKGROUND: Rotational vertebral artery syndrome, also referred to as Bow Hunter's syndrome (BHS), manifests when the vertebral artery (VA) is compressed following head rotation. This compression is often caused by an osteophyte and may lead to symptoms of a posterior stroke. This systematic review aims to shed light on the current management strategies for BHS resulting from osteophytes. Additionally, we present two illustrative cases where the VA compression by an osteophyte was effectively resolved by complete resection of the problematic bone spur. METHODS: A literature search was conducted across Embase, PubMed and Medline in September 2023. Keywords related to vertebral artery [MESH], vertebrobasilar insufficiency [MESH] and osteophyte [MESH] were the focus of this review. Risk of bias in retained studies was assessed using the Joanna Briggs Institute Critical Appraisal tools for Qualitative Research. A narrative synthesis of our findings is presented. RESULTS: A total of 30 studies were included in this review. Vertigo was the most reported symptom by patients (n = 16). On imaging, the VA was often compressed at C4-5 (n = 10) and C5-6 (n = 10) with no evident side predominance observed. Anterior cervical discectomy and fusion (ACDF, n = 13) followed by anterior decompression without fusion (n = 8) were the most performed surgical procedures to manage BHS. CONCLUSION: Surgical decompression of the VA is a safe and effective intervention for patients experiencing symptomatic osteophytic compression during head rotation. This procedure restores normal vascular function and reduces the risk of ischemic events. This review highlights the importance of timely diagnosis and intervention in such cases.