Fibronectin-LILRB4/gp49B interaction negatively regulates osteoclastogenesis through inhibition of RANKL-induced TRAF6/TAK1/NF-kB/MAPK signaling.

Dysregulation of osteoclasts, the multinucleated cells responsible for bone resorption, contributes to several degenerative bone disorders. Previously, we showed that blocking the leukocyte immunoglobulin (Ig)-like receptor B4 (LILRB4), a kind of inhibitory receptor that plays an important role in immune regulation, promotes osteoclast differentiation in vitro. Here, we explored whether gp49B, the murine ortholog of LILRB4, regulates osteoclastogenesis in vivo, and whether fibronectin (FN), a ligand of LILRB4/gp49B, certainly contributes to LILRB4/gp49B-mediated osteoclastogenesis. In comparison with wild-type mice, gp49B deficiency mice exhibited a loss of trabecular bone number and an increase in osteoclast formation. Gp49B knockout improved the bone resorptive capacity of osteoclasts derived from murine Raw264.7 cells by increasing osteoclast formation. We further revealed that gp49B deficiency increased the receptor activator of nuclear factor (NF)-κB ligand (RANKL)-induced signaling transduction by increasing the phosphorylation of transforming growth factor (TGF)-activated kinase 1 (TAK1), NF-κB and mitogen-activated protein kinases (MAPKs). Furthermore, the N-terminal 30 kDa proteolytic fragments of FN promoted gp49B-mediated inhibition of osteoclastogenesis by increasing Src homology-2-containing tyrosine phosphatase 1 (SHP-1) phosphorylation and tumor necrosis factor receptor-associated factor 6 (TRAF6)-SHP-1 association. In summary, the FN-LILRB4/gp49B interaction negatively regulates RANKL-induced TRAF6/TAK1/NF-κB/MAPK signaling in osteoclastogenesis.

Does total hip arthroplasty in elderly patients with femoral neck fractures reduce complications?: A Japanese DPC study.

BACKGROUND: The global increase in femoral neck fractures due to aging and osteoporosis is a major clinical challenge. The debate on the optimal surgical intervention for femoral neck fractures remains unresolved. This large-scale study explores femoral neck fractures among the elderly, focusing on the comparative outcomes of Total Hip Arthroplasty (THA) versus Bipolar Hemiarthroplasty (BHA) in Japanese patients. METHODS: Using the Japanese National Administrative Diagnosis Procedure Combination (DPC) database, we studied cases of femoral neck fracture from April 2016 to March 2023, and after propensity score matching by age, sex, and comorbidities, we examined the association between THA, complications, and clinical outcomes, and the usefulness of THA for elderly patients with femoral neck fracture. RESULTS: One-to-one propensity score matching identified 7741 pairs of THA and BHA cases. There was no difference in length of stay between the THA and BHA groups. Significantly more blood transfusions were required in the THA group. There was no significant difference in mortality between the THA and BHA groups, but there was a reduced risk of pneumonia in the THA group, with a ratio of 0.547 (95% CI: 0.418-0.715). On the other hand, the THA group had a higher risk of pulmonary embolism, with a ratio of 1.607 (95% CI: 1.379-1.874). The THA group shows improved discharge rates directly home from the facility where the operation was performed, with a ratio of 1.798 (95% CI: 1.675-1.929). CONCLUSION: The findings of this research indicate that THA is more effective than BHA in enabling elderly Japanese patients with femoral neck fractures to be discharged directly home and in preventing pneumonia, despite concerns about pulmonary embolism. These findings suggest that THA may improve functional prognosis in elderly patients with femoral neck fractures, although there is a trade-off with an increased risk of pulmonary embolism.

Acetabular coverage exerts minimal influence on femoral head collapse and the necessity for surgical intervention in patients with osteonecrosis of femoral head.

PURPOSE: The acetabular coverage in osteonecrosis of the femoral head (ONFH) affects the need for surgical intervention, and the collapse of the femoral head remains unclear. This study aimed to evaluate the relation between the acetabular coverage and the need for surgical treatment and femoral head collapse. METHODS: The study included 158 patients with 252 hips with glucocorticoid administration and idiopathic ONHF without osteoarthritis changes. The mean age at the first visit was 45.2 years, and the mean follow-up period was 92.2 months. All ONFH hips were subsequently divided into two groups: those needing surgical intervention and those without surgery. Additionally, it divided 167 initially non-collapsed hips into those that either later collapsed or not. Radiographic parameters with the centre-edge angle, acetabular roof obliquity, sharp angle, and necrotic location, following the guidelines of the Japanese Investigation Committee, were evaluated. RESULTS: There were no significant differences in radiographic parameters between the 106 hips that underwent surgery and the 146 hips without surgery. Among the 167 hips without initial collapse, 91 eventually collapsed while 76 did not; their radiographic findings have no significant differences. The necrotic locations were significantly larger in hips requiring surgical intervention or femoral head collapse. Furthermore, 21.8% (55 out of 252 hips) had acetabular dysplasia, which did not significantly correlate with the necessity for surgical treatment or the incidence of femoral head collapse. CONCLUSIONS: Acetabular coverage has little effect on the necessity for surgical treatment and femoral head collapse in ONFH patients over a long-term follow-up.

Clinical Outcomes of Bipolar Hemiarthroplasty with a Conjoined Tendon-Preserving Posterior Approach for Femoral Neck Fractures.

Background and Objectives: The conventional posterior approach in the lateral decubitus position is widely used for femoral neck fractures in femoral hemiarthroplasty. Postoperative dislocation is the major problem with this approach. The conjoined tendon-preserving posterior (CPP) approach is a less invasive surgical approach than the conventional posterior approach to the hip, maintains posterior stability, and preserves short external rotators and joint capsules. However, the mention was required to avoid muscle damage and whether muscle damage affects postoperative dislocation or not. The current study aimed to evaluate the clinical results of the CPP approach in hemiarthroplasty for femoral neck fractures and identify muscle damage risk factors. Materials and Methods: This study was a retrospective cohort study and included 170 hips in 168 patients. The mean age at the operation was 81.2 years. The preservation rate of the internal obturator muscle and gemellus inferior muscle and factors related to intraoperative short rotator muscle injury were investigated retrospectively. The postoperative complications and the relation between muscle damage and postoperative dislocation were investigated. Results: In the four hips (2.3%) with the obturator internus muscle damage, thirty-eight hips (22.4%) with gemellus inferior muscle damage were detected; in the muscle-damaged cases, the high body mass index (BMI) was significantly higher. The complication occurred in four hips (2.3%), including postoperative posterior dislocation in one hip without muscle damage (0.6%). Postoperative infection occurred in one hip (0.6%), and peroneal or sciatic nerve paralysis was suspected in two hips (1.1%). Conclusions: Compared to the conventional posterior approach in previous reports, the CPP approach reduces postoperative dislocation. A higher BMI is a risk factor for muscle damage, and the gemellus inferior muscle damage has no effect on postoperative dislocation. The CPP approach for BHA appeared to be an effective treatment method.

Impact of Octacalcium Phosphate/Gelatin (OCP/Gel) Composite on Bone Repair in Refractory Bone Defects.

In clinical settings, bone grafting is frequently used to treat bone defects. Therefore, the development of bone graft substitutes with superior bone formation ability is expected, instead of autogenous bone grafting. Octacalcium phosphate (OCP) has been developed as a bone graft substitute, and preclinical studies using OCP have reported superior bone formation ability compared with ß-tricalcium phosphate. Furthermore, OCP has been used in composite forms with natural polymers such as collagen and gelatin to improve the usability of OCP, and OCP/collagen composite forms have been clinically applied in the dental field because of their excellent usability and osteogenic potential. This review describes the development and preclinical results of OCP and OCP/gelatin (OCP/Gel) composites and prospects for future applications in orthopedics. The development of bone graft substitutes that achieve a high degree of biodegradability and strength will be needed for the clinical application of OCP composites in orthopedics in the future.

Low Young's Modulus TiNbSn Alloy Locking Plates Accelerate Osteosynthesis in Rabbit Tibiae.

A new beta TiNbSn alloy with a low Young's modulus of approximately 40 GPa has been developed to resolve the stress shielding by Young's modulus divergence. In this study, the efficacy of TiNbSn alloy locking plates on bone repair is compared to that of commercially pure titanium (CP-Ti). The TiNbSn alloy and CP-Ti, which have Young's moduli of 49.1 GPa and 107 GPa, respectively, were compared. Male Japanese white rabbits were anesthetized, and osteotomy and osteosynthesis with locking plates were performed on the right tibia. The bone repair was assessed using micro-computed tomography (CT), histomorphometry, immunohistochemistry, and mechanical testing. Micro-CT, histomorphometry, immunohistochemistry, and mechanical testing were performed four weeks after osteotomy. Six weeks after surgery, micro-CT and mechanical testing were performed. Micro-CT analysis at four weeks after surgery showed that the intramedullary fracture callus in the TiNbSn alloy group had more bone volume and numerous bridging structures compared to the CP-Ti group (CP-Ti vs. TiNbSn alloy, 34.3 ± 13.1 mm3 vs. 61.3 ± 19.6 mm3, p = 0.02; mean ± standard deviation). At four weeks post-osteotomy, the healed tibia showed significantly higher strength in the TiNbSn alloy group compared with CP-Ti (CP-Ti vs. TiNbSn alloy, 81.3 ± 31.2 N vs. 133.7 ± 46.6 N, p = 0.04). TiNbSn alloy locking plates had a more positive impact on bone formation and bone strength restoration than the CP-Ti locking plates during the early phase of bone healing.

How much force is acting on the shoulder joint to create a Hill-Sachs Lesion or reverse Hill-Sachs Lesion?

BACKGROUND: It has not been clarified yet how much force is acting on the shoulder joint to create Hill-Sachs/reverse Hill-Sachs lesions which are commonly observed in patients with anterior or posterior shoulder instability. The purpose of this study was to determine the magnitude of force to create these bony lesions using cadaveric shoulders. METHODS: Fourteen fresh-frozen cadaveric shoulders were used. Compression tests were performed using the universal testing machine. The specimens were randomly divided into two groups. In group A, the posterior humeral head (the bare area and articular cartilage) was first compressed against the anterior glenoid rim to simulate a Hill-Sachs lesion, followed by the anterior humeral head being compressed against the posterior glenoid rim. In group B, the same procedure was repeated in the reverse order. X-ray microcomputed tomography (microCT) was also performed. RESULTS: The maximum compression force to create a Hill-Sachs lesion was 771 ± 214 N (mean ± SD) on the articular cartilage of the posterior humeral head, which was significantly greater than the force of 447 ± 215 N to create it on the bare area (P = 0.0086). Regarding the reverse Hill-Sachs lesions, the maximum compression force was 840 ± 198 N when it was created on the articular cartilage of the anterior humeral head, which was significantly greater than the force of 471 ± 100 N when it was created at the footprint of the subscapularis tendon (P = 0.0238). MicroCT showed multiple breakage of the trabecular bone. CONCLUSION: A force to create a Hill-Sachs lesion or a reverse Hill-Sachs lesion was significantly greater when it was created on the humeral articular cartilage than at the non-cartilage area. Also, the force to create a reverse Hill-Sachs lesion was significantly greater than the one to create a Hill-Sachs lesion.

Long-term results of Chiari pelvic osteotomy on the preservation of hip function with mean follow-up of more than 30 years and its prognostic factors.

BACKGROUND: Clinical outcomes of Chiari pelvic osteotomy for acetabular dysplasia, including conversion to total hip arthroplasty (THA), have not been adequately explored. The purpose of this study was to examine the long-term results and clinical outcomes of Chiari pelvic osteotomy as the primary outcome and to analyze its prognostic factors as the second outcome. METHODS: This study was a multicenter, retrospective cohort study. Ninety-seven patients underwent Chiari pelvic osteotomy at three hospitals between March 1975 and October 1997. The long-term clinical outcomes of Chiari pelvic osteotomy, including conversion to THA and hip pain, were analyzed using the Kaplan-Meier method. In addition, the prognostic factors for conversion to THA after Chiari pelvic osteotomy were evaluated with clinical variables and radiographic parameters. RESULTS: The study included 51 hips in 45 patients (4 men and 41 women) with long-term follow-up. The survival rates assessed by Kaplan-Meier analysis with conversion to THA as an endpoint, were 90.2% (95% confidence interval (CI) 82.0-98.4%) at 20 years and 73.5% (95% CI 61.1-86.0%) at 30 years. In contrast, the Kaplan-Meier survival rates with the Japanese Orthopaedic Association hip score for pain ≤20 as an endpoint, were 86.3% (95% CI 76.8-95.7%) at 20 years and 65.6% (95% CI 52.3-79.0%) at 30 years. Only older age at osteotomy was the significantly poor prognostic factor for conversion to THA, with a hazard ratio of 1.11/year, 95% CI 1.06 to 1.18, (p < 0.01). CONCLUSION: Chiari pelvic osteotomy may still be a good alternative to bony reconstructive surgery for acetabular dysplasia especially in young patients. Only older age at the osteotomy was related to the poor prognosis of preserving hip function.

Genome-Wide Association Study and Transcriptome of Japanese Patients with Developmental Dysplasia of the Hip Demonstrates an Association with the Ferroptosis Signaling Pathway.

This study examined the association between developmental dysplasia of the hip (DDH) and disease-associated loci in a Japanese cohort. A genome-wide association study (GWAS) of 238 Japanese patients with DDH and 2044 healthy individuals was performed. As a replicate, GWAS was also conducted on the UK Biobank data with 3315 cases and matched 74,038 controls. Gene set enrichment analyses (GSEAs) of both the genetics and transcriptome of DDH were performed. Transcriptome analysis of cartilage specimens from DDH-associated osteoarthritis and femoral neck fractures was performed as a control. Most of the lead variants were very low-frequency ones in the UK, and variants in the Japanese GWAS could not be replicated with the UK GWAS. We assigned DDH-related candidate variants to 42 and 81 genes from the Japanese and UK GWASs, respectively, using functional mapping and annotation. GSEA of gene ontology, disease ontology, and canonical pathways identified the most enriched pathway to be the ferroptosis signaling pathway, both in the Japanese gene set as well as the Japanese and UK merged set. Transcriptome GSEA also identified significant downregulation of genes in the ferroptosis signaling pathway. Thus, the ferroptosis signaling pathway may be associated with the pathogenic mechanism of DDH.

Large language model may assist diagnosis of SAPHO syndrome by bone scintigraphy.

OBJECTIVE: In this study, we employed a large language model to evaluate the diagnostic efficacy of radiology reports of bone scintigraphy in the context of identifying SAPHO syndrome, and further examined the potential of such a model to augment the diagnostic procedure. METHODS: Imaging data and clinical information of 151 patients (105/46 women/men, mean age: 53.5 years) who underwent bone scintigraphy for suspected SAPHO syndrome between January 2007 and December 2022 were retrospectively reviewed. ChatGPT-4.0 was used as the large language model. The diagnostic performance of the large language model was verified by comparing the cases judged to have SAPHO syndrome that fulfilled Kahn's classification criteria based on a combination of concise radiology reports and skin lesions such as palmoplantar pustulosis, with cases diagnosed with SAPHO syndrome by rheumatologists based on all clinical information. The diagnostic performance of the large language model was verified. RESULTS: The diagnostic accuracy of a large language model for analyzing bone scintigraphy radiology reports in conjunction with information about skin symptoms, such as palmoplantar pustulosis, achieved a sensitivity of 83.5%, specificity of 69.4%, and an overall accuracy of 76.8%. DISCUSSION: While this research is an initial endeavor dedicated to the utilization of a substantial language model in the creation of a database for imaging diagnostics of rheumatic conditions, it exhibits commendable diagnostic accuracy, particularly for diseases with a wide range of symptoms like SAPHO syndrome, indicating a positive outlook for subsequent studies. CONCLUSION: This research indicates the prospective value of extensive language models in scrutinizing radiology accounts from bone scintigraphy for the diagnosis of SAPHO syndrome.

Assessment of clinical and radiological characteristics of Japanese patients with SAPHO syndrome.

OBJECTIVE: This study aimed to analyse the radiological characteristics and clinical diversity of Japanese patients with synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome, a heterogeneous disorder. METHODS: Radiographs and clinical information from 115 Japanese patients (female/male: 81/34, mean age at onset: 48.7 years) diagnosed with SAPHO syndrome between January 2007 and December 2020 were retrospectively reviewed. Additionally, the treatment for SAPHO syndrome was explored. RESULTS: Among the 115 patients, 70 patients had complications, including palmoplantar pustulosis, acne, or psoriasis. Imaging studies included bone scintigraphy, magnetic resonance imaging, computed tomography, and positron emission tomography in 71, 58, 70, and 23 patients, respectively. The most frequent lesions were arthritis and hyperostosis of the sternoclavicular joints in 96 patients; spinal lesions, including sacroiliac arthritis were observed in 85 patients. Peripheral aseptic osteitis was observed in 22 patients, and the tibia was involved in 12. The treatments consisted of analgesics, bisphosphonates, conventional synthetic disease-modifying anti-rheumatic drugs, and biologics (tumour necrosis factor inhibitors and interleukin-23p19 inhibitors) in 85, 15, 23, and 10 patients (8 and 2 patients), respectively. CONCLUSION: Sternoclavicular hyperostosis and pustulosis are frequently observed in patients with SAPHO syndrome. Biological agents were more frequently used in patients with peripheral osteitis and arthritis.

LPL/AQP7/GPD2 promotes glycerol metabolism under hypoxia and prevents cardiac dysfunction during ischemia.

In the heart, fatty acid is a major energy substrate to fuel contraction under aerobic conditions. Ischemia downregulates fatty acid metabolism to adapt to the limited oxygen supply, making glucose the preferred substrate. However, the mechanism underlying the myocardial metabolic shift during ischemia remains unknown. Here, we show that lipoprotein lipase (LPL) expression in cardiomyocytes, a principal enzyme that converts triglycerides to free fatty acids and glycerol, increases during myocardial infarction (MI). Cardiomyocyte-specific LPL deficiency enhanced cardiac dysfunction and apoptosis following MI. Deficiency of aquaporin 7 (AQP7), a glycerol channel in cardiomyocytes, increased the myocardial infarct size and apoptosis in response to ischemia. Ischemic conditions activated glycerol-3-phosphate dehydrogenase 2 (GPD2), which converts glycerol-3-phosphate into dihydroxyacetone phosphate to facilitate adenosine triphosphate (ATP) synthesis from glycerol. Conversely, GPD2 deficiency exacerbated cardiac dysfunction after acute MI. Moreover, cardiomyocyte-specific LPL deficiency suppressed the effectiveness of peroxisome proliferator-activated receptor alpha (PPARα) agonist treatment for MI-induced cardiac dysfunction. These results suggest that LPL/AQP7/GPD2-mediated glycerol metabolism plays an important role in preventing myocardial ischemia-related damage.

Numerous spindle-shaped lymphoma cells in lymphomatosis cerebri: An autopsy case report.

Lymphomatosis cerebri (LC) is a rare variant of primary central nervous system lymphoma (PCNSL). It is characterized by diffuse infiltration of atypical lymphoid cells with no mass formation and little or no contrast enhancement on magnetic resonance imaging (MRI). Interestingly, some lymphoma cells form characteristic spindle shapes; these cells are found in some variants of malignant lymphoma, such as primary cutaneous follicle center lymphoma, but they have not been reported in PCNSL or LC. Here, we provide an autopsy case report of LC in a 69-year-old immunocompetent man who developed rapidly progressive cognitive decline and died on day 68 after the episode despite treatment with intravenous methylprednisolone administration. MRI revealed high signal intensities on T2-weighted images of the cerebral hemispheres, cerebellum, brainstem, and spinal cord without gadolinium enhancement on T1-weighted images. On autopsy, diffuse infiltrative atypical cells were seen; these cells were positive for CD20 and CD79a and negative for GFAP, CD3, and CD5 on immunohistochemistry, resulting in a diagnosis of diffuse large B-cell lymphoma, specifically LC. We found characteristic spindle-shaped cells, especially in the cerebral cortex. This is the first report showing that lymphoma cells in PCNSL can take on a spindle-shaped form. It is difficult to recognize these spindle-shaped cells as lymphoma cells on hematoxylin and eosin staining and diagnose them correctly with small biopsy specimens without immunohistochemistry. This case suggests that we should add atypical, spindle-shaped cells to the differential diagnosis of PCNSL.

Octacalcium Phosphate/Gelatin Composite (OCP/Gel) Enhances Bone Repair in a Critical-sized Transcortical Femoral Defect Rat Model.

BACKGROUND: Bone grafting is widely used to treat large bone defects. A porous composite of a bioactive octacalcium phosphate material with gelatin sponge (OCP/Gel) has been shown to biodegrade promptly and be replaced with new bone both in animal models of a membranous bone defect and a long bone defect. However, it is unclear whether OCP/Gel can regenerate bone in more severe bone defects, such as a critical-size transcortical defect. QUESTIONS/PURPOSES: Using an in vivo rat femur model of a standardized, transcortical, critical-size bone defect, we asked: Compared with a Gel control, does OCP/Gel result in more newly formed bone as determined by (1) micro-CT evaluation, (2) histologic and histomorphometric measures, and (3) osteocalcin staining and tartrate-resistant acid phosphatase staining? METHODS: Thirty-four 12-week-old male Sprague-Dawley rats (weight 356 ± 25.6 g) were used. Gel and OCP/Gel composites were prepared in our laboratory. Porous cylinders 3 mm in diameter and 4 mm in height were manufactured from both materials. The OCP/Gel and Gel cylinders were implanted into a 3-mm-diameter transcortical critical-size bone defect model in the left rat femur. The OCP/Gel and Gel were randomly assigned, and the cylinders were implanted. The biological responses of the defect regions were evaluated radiologically and histologically. At 4 and 8 weeks after implantation, CT evaluation, histological examination of decalcified samples, and immunostaining were quantitatively performed to evaluate new bone formation and remaining bone graft substitutes and activity of osteoblasts and osteoclast-like cells (n = 24). Qualitative histological evaluation was performed on undecalcified samples at 3 weeks postimplantation (n = 10). CT and decalcified tissue analysis was not performed blinded, but an analysis of undecalcified specimens was performed under blinded conditions. RESULTS: Radiologic analysis revealed that the OCP/Gel group showed radiopaque regions around the OCP granules and at the edge of the defect margin 4 weeks after implantation, suggesting that new bone formation occurred in two ways. In contrast, the rat femurs in the Gel group had a limited radiopaque zone at the edge of the defect region. The amount of new bone volume analyzed by micro-CT was higher in the OCP/Gel group than in the Gel group at 4 and 8 weeks after implantation (​​4 weeks after implantation: OCP/Gel versus Gel: 6.1 ± 1.6 mm 3 versus 3.4 ± 0.7 mm 3 , mean difference 2.7 [95% confidence interval (CI) 0.9 to 4.5]; p = 0.002; intraclass correlation coefficient [ICC] 0.72 [95% CI 0.29 to 0.91]; 8 weeks after implantation: OCP/Gel versus Gel: 3.9 ± 0.7 mm 3 versus 1.4 ± 1.1 mm 3 , mean difference 2.5 [95% CI 0.8 to 4.3]; p = 0.004; ICC 0.81 [95% CI 0.47 to 0.94]). Histologic evaluation also showed there was a higher percentage of new bone formation in the OCP/Gel group at 4 and 8 weeks after implantation (​​4 weeks after implantation: OCP/Gel versus Gel: 31.2% ± 5.3% versus 13.6% ± 4.0%, mean difference 17.6% [95% CI 14.2% to 29.2%]; p < 0.001; ICC 0.83 [95% CI 0.53 to 0.95]; 8 weeks after implantation: OCP/Gel versus Gel: 28.3% ± 6.2% versus 9.5% ± 1.9%, mean difference 18.8% [95% CI 11.3% to 26.3%]; p < 0.001; ICC 0.90 [95% CI 0.69 to 0.97]). Bridging of the defect area started earlier in the OCP/Gel group than in the Gel group at 4 weeks after implantation. Osteocalcin immunostaining showed that the number of mature osteoblasts was higher in the OCP/Gel group than in the Gel group at 4 weeks (OCP/Gel versus Gel: 42.1 ± 6.5/mm 2 versus 17.4 ± 5.4/mm 2 , mean difference 24.7 [95% CI 16.2 to 33.2]; p < 0.001; ICC 0.99 [95% CI 0.97 to 0.99]). At 4 weeks, the number of osteoclast-like cells was higher in the OCP/Gel composite group than in the Gel group (OCP/Gel versus Gel: 3.2 ± 0.6/mm 2 versus 0.9 ± 0.4/mm 2 , mean difference 2.3 [95% CI 1.3 to 3.5]; p < 0.001; ICC 0.79 [95% CI 0.35 to 0.94]). CONCLUSION: OCP/Gel composites induced early bone remodeling and cortical bone repair in less time than did the Gel control in a rat critical-size, transcortical femoral defect, suggesting that OCP/Gel could be used as a bone replacement material to treat severe bone defects. CLINICAL RELEVANCE: In a transcortical bone defect model of critical size in the rat femur, the OCP/Gel composite demonstrated successful bone regeneration. Several future studies are needed to evaluate the clinical application of this interesting bone graft substitute, including bone formation capacity in refractory fracture and spinal fusion models and the comparison of bone strength after repair with OCP/Gel composite to that of autologous bone.

ß-type TiNbSn Alloy Plates With Low Young Modulus Accelerates Osteosynthesis in Rabbit Tibiae.

BACKGROUND: Ti6Al4V alloy, which is commonly used for biomedical applications, has a Young modulus (110 GPa) that is higher than that of human cortical bone (11 to 20 GPa). Using an implant with a material with a low Young modulus that enhances load sharing by the bone even more than those made of Ti6Al4V could be beneficial for bone healing and further reduce the potential for stress shielding. A new ß-type TiNbSn alloy has a low Young modulus of approximately 40 to 49 GPa. However, whether the new titanium alloy with a lower Young modulus is advantageous in terms of fracture healing has not been assessed, and a small-animal model seems a reasonable first step in its assessment. QUESTIONS/PURPOSES: To assess the impact of a TiNbSn alloy plate with a lower Young modulus compared with a Ti6Al4V alloy plate on fracture healing, we evaluated: (1) bony bridging and callus volume, (2) new bone formation and remaining cartilage tissue, (3) osteoblast activity in the callus, and (4) mechanical strength and stiffness of the callus in bending. METHODS: Fracture plates manufactured from TiNbSn and Ti6Al4V alloys, which have Young moduli of 49 GPa and 110 GPa, respectively, were compared. The main reason for using rabbits was the high reliability of the three-point bending mechanical test of the rabbit tibia. Forty-two male Japanese white rabbits weighing 2.8 to 3.4 kg were anesthetized. A 5-cm skin incision was made on the medial side in the mid-diaphysis of the right tibia. Eight-hole plates were used, which were 42 mm long, 5 mm wide, and 1.2 mm thick. Plate fixation was performed using three proximal and three distal screws. After the plate was installed, an osteotomy was performed using a 1-mm-wide wire saw to create a standardized tibial transverse osteotomy model with a 1-mm gap. Bone healing was quantitatively assessed by two nonblinded observers using micro-CT (bony bridging and callus volume), histomorphometry (new bone formation and remaining cartilage tissue), immunohistochemistry (osteoblast activity), and mechanical testing (mechanical strength and stiffness in bending). Measurements on nondemineralized specimens were descriptive statistics due to their small number. Four weeks after osteotomy and fixation, 30 rabbits were euthanized to undergo micro-CT and subsequent mechanical testing (n = 12), histomorphometry and immunohistochemistry with demineralized specimens (n = 12), and histomorphometry with a nondemineralized specimen (n = 6). Eight weeks postoperatively, 12 rabbits were euthanized for micro-CT and subsequent mechanical testing. RESULTS: Intramedullary fracture calluses treated with TiNbSn alloy plates had larger bone volumes and more numerous bridging structures than those treated with Ti6Al4V alloy plates at 4 weeks after osteotomy (Ti6Al4V alloy versus TiNbSn alloy: 30 ± 7 mm 3 versus 52 ± 14 mm 3 , mean difference 22 [95% CI 9 to 37]; p = 0.005; ICC 0.98 [95% CI 0.95 to 0.99]). Histologic assessments demonstrated there was greater new bone formation (total callus: Ti6Al4V versus TiNbSn: 16 ± 4 mm 2 versus 24 ± 7 mm 2 , mean difference 8 [95% CI 1 to 16]; p = 0.04; ICC 0.98 [95% CI 0.93 to 0.99]; intramedullary callus: Ti6Al4V versus TiNbSn: 6 ± 4 mm 2 versus 13 ± 5 mm 2 , mean difference 7 [95% CI 1 to 13]; p = 0.02; ICC 0.98 [95% CI 0.95 to 0.99]) and a higher number of osteocalcin-positive cells (Ti6Al4V alloy versus TiNbSn alloy: 1397 ± 197 cells/mm 2 versus 2044 ± 183 cells/mm 2 , mean difference 647 [95% CI 402 to 892]; p < 0.001; ICC 0.98 [95% CI 0.95 to 0.99]) in the TiNbSn alloy group than in the Ti6Al4V alloy group. At 4 weeks after osteotomy, both bone strength and stiffness of the healed bone in the TiNbSn alloy group were higher than those in the Ti6Al4V alloy group (maximum load: Ti6Al4V alloy versus TiNbSn alloy: 83 ± 30 N versus 127 ± 26 N; mean difference 44 [95% CI 8 to 80]; p = 0.02; stiffness: Ti6Al4V alloy versus TiNbSn alloy: 92 ± 43 N/mm versus 165 ± 63 N/mm; mean difference 73 [95% CI 4 to 143]; p = 0.047). Eight weeks after osteotomy, no between-group differences were observed in the strength and stiffness of the healed bone. CONCLUSION: The results of this study indicate that TiNbSn alloy plate with a lower Young modulus resulted in improved bone formation and stiffer callus during the early phase (4 weeks after surgery) but not the later phase (8 weeks after surgery) of bone healing. CLINICAL RELEVANCE: An overly stiff plate may impair callus formation and bone healing. The TiNbSn alloy plate with a low Young modulus improves the early formation of new bone and stiff callus at the osteotomy site compared with the Ti6Al4V alloy plate in the healing process, which may promote bone repair. TiNbSn alloy may be a promising biomaterial for fracture treatment devices. Further research to address concerns about the strength of TiNbSn alloy plates, such as fatigue life and plate fracture, will be necessary for clinical applications, including mechanical tests to verify fatigue life and validation in larger animals with greater body weight.

Mediastinal and Hilar Lymph Node Metastases from Renal Cell Carcinoma with Concomitant Lung Carcinoma: A Rare Case with Unique Diagnostic Challenges.

A 75-year-old man presented to our hospital 1 year after partial renal resection for clear cell carcinoma. A right lower lobe lung nodule noted at the time of surgery had increased to 3.0 cm in diameter and was confirmed as squamous cell lung carcinoma by bronchoscopic cytology. Computed tomography had also revealed paratracheal lymph node swelling. He underwent right lower lobectomy with lymph node dissection by video-assisted thoracic surgery. Pathological examination confirmed squamous cell carcinoma of the lung but diagnosed the right hilar and mediastinal lymph node metastases as clear cell carcinoma.

Different types of hip fragility fractures have different values of 25-hydroxyvitamin D and parathyroid hormone.

BACKGROUND: Vitamin D insufficiency/deficiency is related to fragility fracture. In most previous studies, there was no assessment of vitamin D deficiency status separately for hip fracture types. The first aim is to evaluate vitamin D and parathyroid hormone (PTH) status in patients with hip fracture. The second objective is to determine whether there are differences in vitamin D and PTH between the femoral neck fracture and the femoral metaphyseal fracture group. METHODS: 62 men and 248 women with fragility hip fractures were enrolled. 25-hydroxyviamin D [25(OH)D] and intact PTH (iPTH) values were evaluated, and femoral neck bone mineral density (BMD) was measured on the uninjured side. Vertebral fractures (VFs) were assessed using radiographs of the thoracic and lumbar spine. We examined the relationships of 25(OH)D value with the number of prevalent VFs, T-score of femoral neck, and iPTH level. These analyses were also performed, neck fracture and trochanteric fracture separately. RESULTS: Mean age was 85 years. The mean 25(OH)D was 11.2 (range, 4.0-26.1) ng/ml, whereas the mean iPTH value was 48.9 pg/ml (range, 9-429 pg/ml). The mean number of VFs was 1.5 (range, 0-11), and the mean T-score was -3.3 (range, -5.2 to -0.5). There was a weak correlation between the 25(OH)D value and the number of VFs. There was a weak but significant correlation between 25(OH)D and iPTH values. In the patients with trochanteric fractures, 25(OH)D value was significantly lower and iPTH value was significantly higher than those with neck fractures. There was a significant correlation between the 25(OH)D value and number of the VFs, 25(OH)D, and iPTH values only in trochanteric fractures. CONCLUSIONS: Vitamin D deficiency was severe and PTH levels were higher in the trochanteric fractures. Both vitamin D deficiency and high PTH levels were suggested to have association with bone fragility.

The intraoperative hip range of motion in total hip arthroplasty predicts postoperative patient's satisfaction for cutting toenails and putting on sock.

BACKGROUND: Restricted hip range of motion (ROM) has been proposed as a useful diagnostic tool for osteoarthritis. The relations between the intraoperative hip ROM under anesthesia in total hip arthroplasty (THA) and recovery of clinical mobility outcomes were unclear. This study evaluated the association between the intraoperative hip ROM under anesthesia in THA and the postoperative recovery of clinical mobility, including cutting toenails and putting on socks after THA. METHODS: The study was performed as a prospective cohort study and included 93 hips in 85 patients who underwent primary anterior-based muscle-sparing THA in the supine position. The hip ROM was evaluated under anesthesia before skin incision and intraoperative stability test. The Japanese Orthopaedic Association Hip-Disease Evaluation Questionnaire (JHEQ) was evaluated. A questionnaire on whether and how patients could cut toenails and putting on socks was assessed. The relationship between hip ROM at intraoperative stability tests and JHEQ moving score, cutting toenails, and putting on socks scores were evaluated statistically. RESULTS: We observed a week positive correlation between intraoperative hip ROM and the total of JHEQ mobility score. A moderate positive correlation was observed between external rotation angle with flexion 90°and cutting toenails and putting on socks score oh JHEQ. 94.6% and 96.8% of the patients could cut their toenails and putting on socks by themselves after surgery. The optimum cutoff range for high patient satisfaction for putting on socks and cutting toenails was 110° for flexion and 35°-40° for the external rotation angle in the intraoperative stability test. CONCLUSION: Hip ROM during intraoperative stability testing, especially the external rotation angle can predict postoperative outcomes and patient satisfaction for cutting toenails and putting on socks. We suggested that the capsule or capsular ligament release around the hip was increased to provide sufficient ROM without compromising stability.

Cytoskeletal Protein 4.1G Is Essential for the Primary Ciliogenesis and Osteoblast Differentiation in Bone Formation.

The primary cilium is a hair-like immotile organelle with specific membrane receptors, including the receptor of Hedgehog signaling, smoothened. The cilium organized in preosteoblasts promotes differentiation of the cells into osteoblasts (osteoblast differentiation) by mediating Hedgehog signaling to achieve bone formation. Notably, 4.1G is a plasma membrane-associated cytoskeletal protein that plays essential roles in various tissues, including the peripheral nervous system, testis, and retina. However, its function in the bone remains unexplored. In this study, we identified 4.1G expression in the bone. We found that, in the 4.1G-knockout mice, calcium deposits and primary cilium formation were suppressed in the trabecular bone, which is preosteoblast-rich region of the newborn tibia, indicating that 4.1G is a prerequisite for osteoblast differentiation by organizing the primary cilia in preosteoblasts. Next, we found that the primary cilium was elongated in the differentiating mouse preosteoblast cell line MC3T3-E1, whereas the knockdown of 4.1G suppressed its elongation. Moreover, 4.1G-knockdown suppressed the induction of the cilia-mediated Hedgehog signaling and subsequent osteoblast differentiation. These results demonstrate a new regulatory mechanism of 4.1G in bone formation that promotes the primary ciliogenesis in the differentiating preosteoblasts and induction of cilia-mediated osteoblast differentiation, resulting in bone formation at the newborn stage.

Association between Hip Center Position and Isokinetic Hip Muscle Performance after Anterolateral Muscle-Sparing Total Hip Arthroplasty.

Background and objectives: The superior placement of the acetabular cup induced the delayed recovery of abductor muscle moment after total hip arthroplasty (THA) with a conventional posterior approach. The anterior-based muscle-sparing (ABMS) THA effectively reduces soft tissue damage, including muscles. The influence of hip center position on anterior-based muscle-sparing (ABMS) total hip arthroplasty (THA) for post-operative hip muscle strength was unclear. We evaluate whether the hip center position affects the recovery of hip muscle strength after ABMS THA. Materials and Methods: The study was performed as a retrospective cohort study, and included 38 hips in 38 patients that underwent primary ABMS THA. Muscle strength was measured using isokinetic dynamometry before the operation, and at 6 and 12 months after surgery. The horizontal and vertical centers of rotation (H-COR and V-COR), vertical shift (V-shift), leg length, and global femoral offset were determined radiographically in reference to a previous report. Results: A weak negative correlation was observed between abduction muscle strength at 6 months and V-shift; a V-shift more than 15 mm demonstrated significantly decreased abductor muscle strength at 6 months. Conclusions: The superior placement of the hip center caused delayed recovery of abductor muscle strength in hips with anterolateral minimally invasive THA. There seems to exist no biomechanical reason why the same should not also be the case for the muscle-sparing approach.