Involvement of Siglec-15 in regulating RAP1/RAC signaling in cytoskeletal remodeling in osteoclasts mediated by macrophage colony-stimulating factor.

DNAX-associated protein 12 kD size (DAP12) is a dominant immunoreceptor tyrosine-based activation motif (ITAM)-signaling adaptor that activates costimulatory signals essential for osteoclastogenesis. Although several DAP12-associated receptors (DARs) have been identified in osteoclasts, including triggering receptor expressed on myeloid cells 2 (TREM-2), C-type lectin member 5 A (CLEC5A), and sialic acid-binding Ig-like lectin (Siglec)-15, their precise role in the development of osteoclasts and bone remodeling remain poorly understood. In this study, mice deficient in Trem-2, Clec5a, Siglec-15 were generated. In addition, mice double deficient in these DAR genes and FcεRI gamma chain (FcR)γ, an alternative ITAM adaptor to DAP12, were generated. Bone mass analysis was conducted on all mice. Notably, Siglec-15 deficient mice and Siglec-15/FcRγ double deficient mice exhibited mild and severe osteopetrosis respectively. In contrast, other DAR deficient mice showed normal bone phenotype. Likewise, osteoclasts from Siglec-15 deficient mice failed to form an actin ring, suggesting that Siglec-15 promotes bone resorption principally by modulating the cytoskeletal organization of osteoclasts. Furthermore, biochemical analysis revealed that Sigelc-15 activates macrophage colony-stimulating factor (M-CSF)-induced Ras-associated protein-1 (RAP1)/Ras-related C3 botulinum toxin substrate 1 (Rac1) pathway through formation of a complex with p130CAS and CrkII, leading to cytoskeletal remodeling of osteoclasts. Our data provide genetic and biochemical evidence that Siglec-15 facilitates M-CSF-induced cytoskeletal remodeling of the osteoclasts.

Elucidation of the association between additional distal femoral resection and extension angle improvement following the actual surgical steps with the Robot-TKA system.

BACKGROUND: This study investigates the association between additional distal femoral resection and improved flexion contracture in total knee arthroplasty (TKA) with a robot-assisted system. Flexion contracture is a common issue in patients with knee osteoarthritis, which causes postoperative complications and functional limitations. This study aims to evaluate the effectiveness of additional bone resection in flexion contracture correction and knee extension angle improvement after the actual surgical steps. METHODS: The study included 11 patients who underwent posterior-stabilized (PS)-type TKA with a robot-assisted system. The surgical technique consisted of precise bone resection and range of motion evaluation using a navigation system. A precut technique was used to facilitate posterior access and remove osteophytes that cause the contracture. The amount of additional distal femoral resection was determined based on the thickness of the insert trial required for achieving full extension. RESULTS: The flexion contracture correction angle and the amount of additional distal femoral resection demonstrated a linear relationship. An average of 2.0° with the standard error (SE) of 0.6° improvement in flexion contracture was observed per 1.0 mm of additional bone resection. The postoperative evaluation demonstrated a significant improvement in knee extension angle, thereby reducing the contracture degree. CONCLUSION: This study was the first to perform the additional distal femoral resection on the living knee, which closely replicates the actual surgical steps. The current study revealed that an additional 1.0 mm of distal femoral resection in PS-type TKA improves knee extension angle by 2.0° (SE 0.6°) within an additional resection range of 1.0 mm to 3.3 mm.

Improvement of absorbability, osteoconductivity, and strength of a ß-tricalcium phosphate spacer for opening wedge high tibial osteotomy: clinical evaluations with 106 patients.

BACKGROUND: An ideal synthetic spacer for medial opening wedge high tibial osteotomy (MOWHTO) has not yet been developed. The authors have developed a new ß-tricalcium phosphate (ß-TCP) spacer with 60% porosity (N-CP60) by modifying the micro- and macro-pore structures of a conventional ß-TCP spacer (CP60) that is widely used in clinical practice. The purpose of this study was to compare the absorbability, osteoconductivity, and in vivo strength of the N-CP60 spacer with those of the CP60 spacer, when used in MOWHTO. METHODS: First, the porosity, diameter distribution of macro- and micropores, and compressive strength of each ß-TCP block were examined using methodology of biomaterial science. Secondly, a clinical study was performed using a total of 106 patients (106 knees) with MOWHTO, who were followed up for 18 months after surgery. In these knees, the N-CP60 and CP-60 spacers were implanted into 49 tibias and 57 tibias, respectively. The absorbability and osteoconductivity were radiologically evaluated by measuring the area of the implanted spacer remaining unabsorbed and assessing with the Hemert's score, respectively. The incidence of cracking in the implanted spacers was determined using computed radiography. Statistical comparisons were made with non-parametric tests. The significance level was set at p = 0.05. RESULTS: The N-CP60 and CP60 blocks had almost the same porosity (mean, 61.0% and 58.7%, respectively). The diameter of macropores was significantly larger (p < 0.0001) in the N-CP60 block than in the CP60 block, while the diameter of micropores was significantly smaller (p = 0.019) in the N-CP60 block. The ultimate strength of the N-CP60 block (median, 36.8 MPa) was significantly greater (p < 0.01) than that of the CP60 block (31.6 MPa). As for the clinical evaluations, the absorption rate of the N-CP60 spacer at 18 months after implantation (mean, 48.0%) was significantly greater (p < 0.001) than that of the CP60 spacer (29.0%). The osteoconductivity of the N-CP60 spacer was slightly but significantly higher (p = 0.0408) than that of the CP60 spacer only in zone 1. The incidence of in vivo cracking of the posteriorly located N-CP60 spacer at one month (mean, 75.5%) was significantly lower (p = 0.0035) than that of the CP60 spacer (91.2%). CONCLUSIONS: The absorbability, osteoconductivity, and compressive strength of the new N-CP60 spacer were significantly improved by modifying the macro- and micro-pore structures, compared with the conventional CP60 spacer. The N-CP60 spacer is more clinically useful than the CP60 spacer. TRIAL REGISTRATION NUMBER: H29-0002.

Analysis of foot-originating malignant bone tumors: Epidemiology, characteristics, and survival outcomes.

BACKGROUND: The study examines the characteristics and outcomes of foot-originating malignant bone tumors via Surveillance Epidemiology and End Results (SEER) database analysis. METHODS: A retrospective review of 14,695 malignant bone tumor cases from 2000 to 2019 was conducted. RESULTS: Of the eligible cases, 147 (2.3 %) were foot-origin tumors, typically smaller and more commonly treated with surgery than those in other locations. These tumors were more frequently treated with surgical resection, with a higher proportion undergoing amputation. In contrast, foot-origin tumors were less often managed with chemotherapy and radiation. Foot-origin tumors exhibited higher survival rates compared to non-foot-origin tumors as shown in univariate analysis, although multivariate analysis did not reflect significant differences. CONCLUSION: Foot-originating malignant bone tumors tend to be smaller and are frequently surgically treated, correlating with favorable survival outcomes. These findings point to early detection as a potential factor in the improved survival rates, not necessarily the tumor's origin.

Ossification of the posterior longitudinal ligament is linked to heterotopic ossification of the ankle/foot tendons.

INTRODUCTION: Systemic osteogenesis has been speculated to be involved in the pathogenesis of ossification of the posterior longitudinal ligament (OPLL). Our purpose was to compare the radiologic prevalence and severity of heterotopic ossification in foot tendons of Japanese patients with OPLL and to determine their association with systemic heterotopic ossification. MATERIALS AND METHODS: Clinical and radiographic data of 114 patients with OPLL were collected from 2020 to 2022. Control data were extracted from a medical database of 362 patients with ankle radiographs. Achilles and plantar tendon ossification were classified as grades 0-4, and the presence of osteophytes at five sites in the foot/ankle joint was assessed by radiography. Factors associated with the presence and severity of each ossification were evaluated by multivariable logistic regression and linear regression analysis. RESULTS: The prevalence of Achilles and plantar tendon ossification (grade ≥ 2) was 4.0-5.5 times higher in patients with OPLL (40-56%) than in the controls (10-11%). The presence of Achilles tendon ossification was associated with OPLL, age, and coexisting plantar tendon ossification, and was most strongly associated with OPLL (standardized regression coefficient, 0.79; 95% confidence interval, 1.34-2.38). The severity of Achilles and plantar tendon ossification was associated with the severity of ossification of the entire spinal ligament. CONCLUSIONS: The strong association of foot tendon ossification with OPLL suggests that patients with OPLL have a systemic osteogenesis background. These findings will provide a basis for exploring new treatment strategies for OPLL, including control of metabolic abnormalities.

Glycosphingolipids in Osteoarthritis and Cartilage-Regeneration Therapy: Mechanisms and Therapeutic Prospects Based on a Narrative Review of the Literature.

Glycosphingolipids (GSLs), a subtype of glycolipids containing sphingosine, are critical components of vertebrate plasma membranes, playing a pivotal role in cellular signaling and interactions. In human articular cartilage in osteoarthritis (OA), GSL expression is known notably to decrease. This review focuses on the roles of gangliosides, a specific type of GSL, in cartilage degeneration and regeneration, emphasizing their regulatory function in signal transduction. The expression of gangliosides, whether endogenous or augmented exogenously, is regulated at the enzymatic level, targeting specific glycosyltransferases. This regulation has significant implications for the composition of cell-surface gangliosides and their impact on signal transduction in chondrocytes and progenitor cells. Different levels of ganglioside expression can influence signaling pathways in various ways, potentially affecting cell properties, including malignancy. Moreover, gene manipulations against gangliosides have been shown to regulate cartilage metabolisms and chondrocyte differentiation in vivo and in vitro. This review highlights the potential of targeting gangliosides in the development of therapeutic strategies for osteoarthritis and cartilage injury and addresses promising directions for future research and treatment.

A patient and public involvement study to explore patient perspectives on the efficacy of treatments for pain and numbness derived from ossification of posterior longitudinal ligament of the spine.

BACKGROUND: Chronic pain and numbness are common complaints in patients with ossification of the posterior longitudinal ligament of the spine (OPLL). However, it is unclear whether the current treatments are effective in patients with OPLL in terms of improving pain and numbness. METHODS: A cross-sectional survey of patients with OPLL was conducted to determine patient satisfaction with surgery and drug therapy for pain and numbness, and its association with health-related quality of life. The survey was conducted by a patient association and its members, and anonymized data were analyzed by physicians. Comparisons between groups were made using T-tests or Kruskal-Wallis and Steel-Dwass tests, chi-square tests, and Fisher's exact tests. RESULTS: Data from 121 patients with OPLL (age 69 ± 11 years, 69 males; 43 females; and 7 unknown) who completed a mailed questionnaire were analyzed. Of the 93 patients with a history of surgery for OPLL, 24% and 18% reported much improvement in pain and numbness, respectively. After surgery, 42% and 48% reported some improvement, and 34% and 34% reported no improvement, respectively. Patients whose numbness did not improve with surgery had a significantly poorer health-related quality of life than those who did. Of the 78 patients who received medication, only 2% reported "much improvement," 64% reported "some improvement," and 31% reported "no improvement at all." Compared to patients with OPLL only in the cervical spine, those with diffuse-type OPLL showed poorer improvement in numbness after surgery and poorer quality of life. CONCLUSIONS: The majority of patients with OPLL belonging to the association were unsatisfied with surgery and pharmacotherapy in terms of pain and numbness improvement, indicating that there is an unmet medical need for more effective treatment for chronic pain and numbness in patients with OPLL.

Itaconate reduces proliferation and migration of fibroblast-like synoviocytes and ameliorates arthritis models.

Fibroblast-like synoviocytes (FLS) play critical roles in rheumatoid arthritis (RA). Itaconate (ITA), an endogenous metabolite derived from the tricarboxylic acid (TCA) cycle, has attracted attention because of its anti-inflammatory, antiviral, and antimicrobial effects. This study evaluated the effect of ITA on FLS and its potential to treat RA. ITA significantly decreased FLS proliferation and migration in vitro, as well as mitochondrial oxidative phosphorylation and glycolysis measured by an extracellular flux analyzer. ITA accumulates metabolites including succinate and citrate in the TCA cycle. In rats with type II collagen-induced arthritis (CIA), intra-articular injection of ITA reduced arthritis and bone erosion. Irg1-deficient mice lacking the ability to produce ITA had more severe arthritis than control mice in the collagen antibody-induced arthritis. ITA ameliorated CIA by inhibiting FLS proliferation and migration. Thus, ITA may be a novel therapeutic agent for RA.

Simultaneous medial closing wedge distal femoral varus osteotomy and double-bundle anterior cruciate ligament reconstruction in the symptomatic femoral valgus deformity: A case report.

Distal femoral varus osteotomy (DFVO) is a widely recognized surgical procedure used to address valgus malalignment in patients with knee joint disorders. However, it still remains unclear whether anterior cruciate ligament (ACL) reconstruction can be performed in a single procedure along with DFVO. Herein, we present a 73-year-old female patient who developed lateral osteoarthritis of the knee with valgus alignment due to chronic ACL deficiency following a twisting injury during skiing. She was physiologically very active, and strongly demanded to return to sports. We performed a combined procedure involving a medial closing wedge DFVO using an anatomical locking plate, along with double-bundle ACL reconstruction. The postoperative radiograph confirmed successful correction of knee alignment, specifically achieving varus alignment with precise conformance of the anatomical plate to the medial contour of the distal femur following the osteotomy. The patient resumed her previous sports activities without experiencing knee pain. The operated knee demonstrated restored anterior stability, as indicated by negative Lachman test results, and regained full range of motion. Both the Knee Injury and Osteoarthritis Outcome Score and the 2011 Knee Society score demonstrated continuous postoperative improvements over the three-year follow-up period, indicating positive functional outcomes and joint preservation. To the best of our knowledge, this is the first case of medial closing wedge DFVO with anatomic double-bundle ACL reconstruction in the symptomatic femoral valgus deformity with chronic ACL deficiency in the literature.

Amputation surgery associated with shortened survival in patients with localized extremity bone sarcoma.

Background: This study assesses survival rates among patients with localized extremity bone sarcoma who have undergone amputation, pinpointing subpopulations that are disproportionately affected by amputation-related survival disparities. Methods: Examination of data was conducted using the Surveillance, Epidemiology, and End Results (SEER) program, analyzing records of 3765 patients diagnosed with localized extremity bone sarcoma between 2000 and 2019. Of these, 857 received amputations (Amputation cohort), and 2908 underwent limb-sparing surgeries. Propensity score matching, considering demographic and clinical features, was utilized to ensure a fair comparison. Results: Following propensity score matching, the study focused on 1714 cases. The Amputation cohort was observed to have significantly poorer survival rates (Cancer-Specific Survival [CSS]: Hazard Ratio [HR] = 1.28, 95% Confidence Interval [CI]: 1.05-1.55; Overall Survival [OS]: HR = 1.37, 95% CI: 1.15-1.63). Subsequent subgroup analysis indicated that individuals with tumors exceeding 8 cm in size or those located in the lower limbs were notably at a higher risk of shortened survival (for tumors >8 cm - CSS: HR = 1.32, 95% CI: 1.02-1.71; OS: HR = 1.39, 95% CI: 1.09-1.76; for lower limb tumors - CSS: HR = 1.25, 95% CI: 1.01-1.54; OS: HR = 1.33, 95% CI: 1.11-1.61). Conclusions: Our findings demonstrate that patients diagnosed with localized extremity bone sarcoma undergoing amputation exhibit lower survival rates, especially in cases involving tumors of greater size or those situated in the lower limbs. In patient groups where amputation is inevitable, careful follow-up is required after surgical intervention.

The alterations in nerve growth factor concentration in plasma and synovial fluid before and after total knee arthroplasty.

Total knee arthroplasty (TKA) is an effective procedure for pain relief; however, the emergence of postsurgical pain remains a concern. In this study, we investigated the production of nerve growth factor (NGF) and mediators that affect NGF production and their function in the synovial fluid and plasma after TKA. This study included 19 patients (20 knees) who had rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and knee osteoarthritis (OA) who underwent TKA, categorized into OA and non-OA groups. The levels of NGF, inflammatory cytokines, and lipid mediators were analyzed before and after surgery. The intraoperative synovial fluid NGF concentration was more than seven times higher in the non-OA group than in the OA group. The intra-articular NGF levels increased significantly by more than threefold postoperatively in the OA group but not in the non-OA group. Moreover, the levels of inflammatory cytokines and lipid mediators were increased in the synovial fluid of both groups. The intra-articular cytokines or NGF concentrations positively correlated with postoperative pain. Targeted NGF control has the potential to alleviate postsurgical pain in TKA, especially in patients with OA, emphasizing the importance of understanding NGF dynamics under different knee conditions.

Clinical outcomes of perforator-based propeller flaps versus free flaps in soft tissue reconstruction for lower leg and foot trauma: a retrospective single-centre comparative study.

BACKGROUND: The efficacy and safety of perforator-based propeller flaps (PPF) versus free flaps (FF) in traumatic lower leg and foot reconstructions are debated. PPFs are perceived as simpler due to advantages like avoiding microsurgery, but concerns about complications, such as flap congestion and necrosis, persist. This study aimed to compare outcomes of PPF and FF in trauma-related distal lower extremity soft tissue reconstruction. METHODS: We retrospectively studied 38 flaps in 33 patients who underwent lower leg and foot soft tissue reconstruction due to trauma at our hospital from 2015 until 2022. Flap-related outcomes and complications were compared between the PPF group (18 flaps in 15 patients) and the FF group (20 flaps in 18 patients). These included complete and partial flap necrosis, venous congestion, delayed osteomyelitis, and the coverage failure rate, defined as the need for secondary flaps due to flap necrosis. RESULTS: The coverage failure rate was 22% in the PPF group and 5% in the FF group, with complete necrosis observed in 11% of the PPF group and 5% of the FF group, and partial necrosis in 39% of the PPF group and 10% of the FF group, indicating no significant difference between the two groups. However, venous congestion was significantly higher in 72% of the PPF group compared to 10% of the FF group. Four PPFs and one FF required FF reconstruction due to implant/fracture exposure from necrosis. Additionally, four PPFs developed delayed osteomyelitis post-healing, requiring reconstruction using free vascularized bone graft in three out of four cases. CONCLUSIONS: Flap necrosis in traumatic lower-leg defects can lead to reconstructive failure, exposing implants or fractures and potentially causing catastrophic outcomes like osteomyelitis, jeopardizing limb salvage. Surgeons should be cautious about deeming PPFs as straightforward and microsurgery-free procedures, given the increased complication rates compared to FFs in traumatic reconstruction. DATA ACCESS STATEMENT: The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Bone Density Distribution Pattern in the Lateral Wall of the Femoral Intercondylar Notch: Implications for the Direct Insertion of the Femoral ACL Attachment.

Background: The ideal position of the femoral bone tunnel in the anterior cruciate ligament (ACL) is controversial. The functional importance of the ACL fiber varies depending on where it is attached to the femur. Functionally important fibers can cause high mechanical stress on the bone, and the Wolff law predicts that bone mineral density will increase at high mechanical stress sites. Purpose/Hypothesis: The purpose of this study was to use computed tomography imaging to determine the distribution pattern of bone density in the lateral intercondylar wall. It was hypothesized that the high-density area (HDA) of the lateral intercondylar wall would reflect the functional insertion of the ACL as reported in previous anatomic studies. Study Design: Descriptive epidemiology study. Methods: Data from 39 knees without ACL injuries were retrospectively collected. The HDA of the lateral intercondylar wall was defined as the region containing the top 10% of the radiodensity values. The shape of the HDA was approximated as an ellipse, and the quadrant method was used to determine the center of the ellipse. The association between the ratio of the minor axis to the major axis of the ellipse and background characteristics was investigated. Results: According to the quadrant method, the center of the HDA ellipse was 33.6% in the deep-shallow direction and 23.4% in the high-low direction. The center of the ellipse was comparable to the anatomic center of the ACL footprint, as previously reported. The ratio of the minor axis to the major axis of the ellipse was 0.58 (95% CI, 0.54-0.62). There was a significant negative correlation between the ratio of the minor axis to the major axis of the HDA ellipse and the posterior tibial slope (r = -0.38, P = .02). Conclusion: The center of the HDA ellipse was found to be similar to the anatomic center of the ACL footprint. Considering the mechanical stress responses in bone, the HDA of the lateral intercondylar wall has the potential to represent the ACL insertion, especially functional insertion.

Clinical Outcomes of Total Wrist Arthroplasty in Patients With Rheumatoid Arthritis: Minimum 10-Year Follow-Up Study.

PURPOSE: We developed a semiconstrained total wrist prosthesis that was used in a series of patients with rheumatoid arthritis. We previously reported favorable clinical outcomes for up to 5 years after surgery; however, the longer-term outcomes remain unclear. The objective of this study was to evaluate the clinical outcomes of this wrist prosthesis for the treatment of severe wrist rheumatoid arthritis during a minimum 10 years of follow-up. METHODS: From 2010 through 2012, total wrist arthroplasty using the semiconstrained total wrist arthroplasty device was performed in 20 wrists in 20 patients with rheumatoid arthritis (five men and 15 women). The mean patient age was 64 years (range, 50-84 years). Preoperative radiographs showed Larsen grade IV changes in 16 wrists and grade V changes in four wrists. Patients were evaluated clinically and radiologically before surgery, 5 years after surgery, and 10 years or more after surgery. Evaluated parameters were the visual analog scale for pain, range of motion, Figgie score, and Disabilities of the Arm, Shoulder, and Hand score. RESULTS: The minimum 10-year follow-up clinical results (mean, 11.3 years) were available for all 14 surviving patients (three men and 11 women). Significant improvements in the mean visual analog scale for pain, Figgie score, and Disabilities of the Arm, Shoulder, and Hand score, compared with those before surgery, were maintained from 5 years after surgery to the final follow-up. The mean wrist flexion angle tended to slightly decrease at 5 years after surgery compared with that before surgery but remained similar from 5 years after surgery to the final follow-up. The increase in the mean wrist extension angle, compared with that before surgery, was maintained from 5 years after surgery to the final follow-up. Radiographic evaluation had already revealed implant loosening in five of the 19 wrists at 5 years after surgery, but there were no new cases of component loosening identified at the final follow-up. CONCLUSIONS: Total wrist arthroplasty using the semiconstrained arthroplasty system achieves favorable clinical outcomes with no serious complications requiring revision for 10 years after surgery. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Osteoporosis, Osteoarthritis, and Subchondral Insufficiency Fracture: Recent Insights.

The increased incidence of osteoarthritis (OA), particularly knee and hip OA, and osteoporosis (OP), owing to population aging, have escalated the medical expense burden. Osteoarthritis is more prevalent in older women, and the involvement of subchondral bone fragility spotlights its association with OP. Notably, subchondral insufficiency fracture (SIF) may represent a more pronounced condition of OA pathophysiology. This review summarizes the relationship between OA and OP, incorporating recent insights into SIF. Progressive SIF leads to joint collapse and secondary OA and is associated with OP. Furthermore, the thinning and fragility of subchondral bone in early-stage OA suggest that SIF may be a subtype of OA (osteoporosis-related OA, OPOA) characterized by significant subchondral bone damage. The high bone mineral density observed in OA may be overestimated due to osteophytes and sclerosis and can potentially contribute to OPOA. The incidence of OPOA is expected to increase along with population aging. Therefore, prioritizing OP screening, early interventions for patients with early-stage OA, and fracture prevention measures such as rehabilitation, fracture liaison services, nutritional management, and medication guidance are essential.

Surgical Resection of Primary Tumor for Bone Metastatic Breast Cancer Patients at Initial Presentation.

BACKGROUND/AIM: The purpose of this study was to investigate whether primary tumor resection in patients with bone metastatic breast cancer has an impact on survival using the Surveillance, Epidemiology, and End Results database, considering subtype classification. PATIENTS AND METHODS: We included all female patients with bone metastatic breast cancer at initial presentation between 2010 and 2016 with known hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) statuses. Cases showing unknown cause of death or unknown HR/HER2 status were excluded. Survival analysis was performed using Cox proportional hazards modeling to calculate hazard ratios (HZR). RESULTS: Of the 13,450 patients included in this study, 2,073 patients were HR+/HER2+, 8,597 patients were HR+/HER2-, 797 patients were HR-/HER2+, and 1,182 patients were HR-/HER2- (triple-negative). Five-year overall survival (OS) rate was 34.5% in HR+/HER2+, 26.0% in HR+/HER2-, 29.2% in HR-/HER2+ and 8.0% in triple-negative. Triple-negative patients showed the worsen OS [HR+/HER2+: HZR=2.1, 95% confidence interval (CI)=1.9-2.3; HR+/HER2-: HZR= 2.4, 95%CI=2.2-2.6; HR-/HER2+: HZR=1.5, 95%CI=1.3-1.6]. After excluding patients who died within six months, primary tumor resection prolonged survival in each subtype classification except HR-/HER2+. CONCLUSION: Patients with triple-negative bone metastatic breast cancer showed unfavorable survival. Primary tumor resection prolonged survival in each subtype except for HR-/HER2+.

Articular cartilage corefucosylation regulates tissue resilience in osteoarthritis.

This study aimed to investigate the glycan structural changes that occur before histological degeneration in osteoarthritis (OA) and to determine the mechanism by which these glycan conformational changes affect cartilage degeneration. An OA model was established in rabbits using mannosidase injection, which reduced high-mannose type N-glycans and led to cartilage degeneration. Further analysis of glycome in human OA cartilage identified specific corefucosylated N-glycan expression patterns. Inhibition of N-glycan corefucosylation in mice resulted in unrecoverable cartilage degeneration, while cartilage-specific blocking of corefucosylation led to accelerated development of aging-associated and instability-induced OA models. We conclude that α1,6 fucosyltransferase is required postnatally to prevent preosteoarthritic deterioration of articular cartilage. These findings provide a novel definition of early OA and identify glyco-phenotypes of OA cartilage, which may distinguish individuals at higher risk of progression.

Secondary fracture and mortality risk with very high fracture risk osteoporosis and proximal femoral fracture.

INTRODUCTION: We aimed to investigate secondary fracture and mortality rates, and risk factors in patients with proximal femoral fractures. MATERIALS AND METHODS: We conducted a multicenter prospective cohort study on female patients with proximal femoral fractures who underwent surgical treatment between April 2020 and March 2021. Postoperative follow-ups were performed at 6-, 12-, 18-, and 24-month intervals to determine the secondary fracture and mortality rates, and the risk factors and its influence were examined. RESULTS: Of the 279 registered patients, 144 patients (51.6%) were diagnosed with very high fracture risk osteoporosis. The postoperative osteoporosis rate exceeded 96%; however, osteoanabolic agents were used sparingly. The risk factor of both secondary fracture and mortality was very high fracture risk osteoporosis, and secondary fractures within 12 months were markedly occurred. Secondary fracture rates increased as the number of matched very high fracture risk osteoporosis criteria increased. Notably, secondary fractures and mortality were recorded in 21.4% and 23.5% of the patients who met all criteria, respectively. CONCLUSION: Over half of the female patients with proximal femoral fractures had very high fracture risk osteoporosis. Although, very high fracture risk osteoporosis demonstrated a notably increased risk of secondary fractures, particularly at 12 months post-surgery, the use of osteoanabolic agents was substantially low. Collectively, our findings highlight the need to consider the risk of very high fracture risk osteoporosis, expand the use of medications to include osteoanabolic agents, and reconsider the current healthcare approach for proximal femoral fractures.