Subchondral Area Research Articles

CCR7 depletion alleviates bony growth imbalance following physeal injury in mice

Growth plates are the frequent sites of skeletal injury in children, leading to skeletal growth imbalances. Chemokines, including the receptor CCR7, play a crucial role in stem cell recruitment and cartilage homeostasis, with previous studies linking CCR7 to osteoarthritis progression. However, its role in growth plate cartilage remains unclear. We analyzed the role of CCR7 in the physeal cartilage repair process in mice model. Physeal injury was created in the proximal tibia in 3-week-old C57BL/6 mice (WT) and CCR7-knockout mice (CCR7−/−). Tibial length was measured macroscopically and sections of the physeal injury were analyzed histologically and immunohistochemically. Height and bone volume of the tibial growth plate and bone mineral density (BMD) of the subchondral area were measured by micro-CT. Mesenchymal stem cells (MSCs) were harvested and gene expression after osteogenic differentiation was analyzed using qRT-PCR. At 1, 3 and 5 weeks postoperatively, injured tibiae of CCR7−/− mice were less shortened than those of WT mice. Bone volume of the physeal bridge was significantly lower in CCR7−/− mice than in WT mice. In contrast, BMD of the subchondral area was comparable between CCR−/− and WT mice, and between sham and operated tibiae. In osteogenic differentiation, CCR7−/− mice showed significantly lowered expression of osteogenic markers such as Osterix, Runx2 and Type X collagen. We demonstrated CCR7 depletion in mice inhibited physeal bridge formation and ameliorated growth imbalances after physeal injury.

Our Experience with Surgical Treatment of Scaphoid Fractures with Headless Compression Screw

BACKGROUND: Fractures of the scaphoid bone are quite common, and they come with their own set of challenges due to the specific shape of the fractures and the delicate blood supply to the scaphoid bone. Failing to diagnose and treat acute scaphoid fractures promptly can result in failure of the bone to heal and subsequent development of wrist arthritis. Advances in diagnosis, surgery, and implant materials have led to a growing inclination towards early surgical fixation, even for non-displaced scaphoid fractures that could potentially be treated without surgery. AIM: The study's goal was to assess the effectiveness of headless compression screws for treating acute scaphoid fractures and, in two cases, nonunion following previous conservative therapy. METHODS: Between January 2022 and March 2024 ten patients with scaphoid fractures were surgically treated at the University Clinic of Traumatology Skopje, within twelve months follow-up. All of them were male with mean age of 27,3 years. All were diagnosed with X-rays and CT scans. Six of the fractures were on the right hand and four on the left. RESULTS: All the patients were surgically treated with open reduction and internal fixation with headless compression screw. Volar approach was used in 9 cases and dorsal approach in only one of them. Six of the patients were surgically treated within 4-14 days after injury and four of them were surgically treated due to non union after previous conservative treatment, two of them after three and two of them after seven months of injury. All fractures united after a mean time of 9,5 weeks, without secondary displacement. Throughout the follow-up period, there were no incidences of developing osteoarthritis of the wrist. CONCLUSIONS: It is crucial to understand that achieving a positive result is not guaranteed for every patient and relies on selecting the right patients and fractures. However, our study shows favorable results in sooner surgical treatment with the headless compression screw, rather than delayed treatment of scaphoid fractures. Surgical treatment with headless compression screw showed both functional and radiographic results. While it is beneficial for the screw to be positioned in the subchondral area, it is important to be cautious to avoid cortical penetration, as this will require the screw to be removed later.

İntertrokanterik Kırıkların Tedavisinde Subkondral Pençe Yerleştirme Gecikmeli Vidanın Yanal Kayma Mesafesine ve Kesmeye Etkisi

Introduction: The incidence of intertrochanteric fractures has increased in recent years due to the growing elderly population at risk of hip fractures, primarily attributed to osteoporosis. Among hip fractures, the prevalence of intertrochanteric fractures is progressively rising. Aim: To evaluate clinical and radiological results of the lag screw that deploys the claw in the subchondral area of the femoral head in the treatment of advanced age unstable intertrochanteric fractures. Methods: We retrospectively reviewed patients with intertrochanteric fractures treated with proximal femoral nails between 2019 and 2021. A total of 107 patients were examined under two groups according to the choice of the nail (Interclaw lag screw(n=52), Proximal femoral nail anti-rotation (n=55) used in the treatment. The radiological parameters in the post-operative 1st-day radiographs of the patients were evaluated. The changes in the first month, three, six months, and one-year control radiographs of the patients were evaluated. Changes in tip apex distance and lateral sliding of the lag screw were compared between the two groups. Result: There was no statistically significant difference between the two groups regarding operation time, post-operative femoral neck/shaft angle, post-operative Calcar gap (mm), and tip-apex distance (TAD) (mm). In the last clinical follow-up, the two groups had a statistically significant difference in the femoral neck/shaft angle and TAD change. There was a significant difference in sliding distance between the two groups at the last follow-up. Conclusion: Using a subchondral claw-deploying lag screw is a reliable implant choice in the surgical treatment of geriatric intertrochanteric fractures. The claw mechanism increases fixation strength and restricts the movements of the lag screw in the femoral head.

Effects of bone mineral density at the lateral sclerotic boundary on the femoral head collapse onset in osteonecrosis of the femoral head: A preliminary study

BackgroundIn the natural course of osteonecrosis of the femoral head, sclerotic changes at the boundary of necrotic lesion gradually occur until femoral head collapse. This study aims to examine the effects of bone mineral density at the lateral boundary of necrotic lesion on a subsequent femoral head collapse. MethodsWe developed patient-specific finite element models of 9 hips with subsequent collapse and 10 hips without subsequent collapse. Cubic regions of interest were selected at both subchondral areas of the lateral boundary and the adjacent necrotic lesion. Bone mineral density values of the regions of interest were quantitatively measured, and a ratio of bone mineral density values (lateral boundary/necrotic lesion) was calculated. Stress values at the lateral boundary were also evaluated. FindingsThe ratio of bone mineral density values was significantly higher in hips with subsequent collapse than that without subsequent collapse (p = 0.0016). The median equivalent stress and shear stress were significantly higher in hips with subsequent collapse than that without subsequent collapse (p = 0.0071, and p = 0.0143, respectively). The ratio of bone mineral density values showed a promising value in predicting the occurrence of subsequent femoral head collapse (AUC = 0.97). InterpretationOur results indicated that bone mineral density value at the lateral boundary of necrotic lesion may be associated with the occurrence of subsequent femoral head collapse in pre-collapse stage osteonecrosis of the femoral head.

Using 3D MRI Bone Shape to Predict Pre-Osteoarthritis of the Knee 2 Years After Anterior Cruciate Ligament Reconstruction

Background: Anterior cruciate ligament (ACL) injury increases risks for osteoarthritis (OA), a poorly modifiable and disabling condition. Joint changes of potentially reversible pre-OA have been described just 2 years after ACL reconstruction (ACLR) when early bone shape changes have also been reported. Purpose: This study evaluates relationships between interlimb differences in tibiofemoral bone shape derived from statistical shape modeling (SSM) of magnetic resonance imaging (MRI) and participant factors on patient-reported outcomes 2 years after unilateral ACLR. Study Design: Cross-sectional study; Level of evidence, 3. Methods: SSM-derived tibiofemoral bone shape and subchondral bone area were assessed from bilateral knee MRI scans of 72 participants with unilateral ACLR (mean age, 34 ± 11 years; 32 women) and compared with a reference cohort of 398 older individuals without OA (mean age, 50 ± 3 years; 213 women). Multivariable logistic regression models examined relationships between participant and surgical factors with interlimb differences in bone shapes or subchondral bone areas. Relationships between patient-reported outcomes and the interlimb differences in bone shape and subchondral area were examined using similar models. Results: Bone shape scores and subchondral bone areas were greater (more OA-like) in ACLR knees than uninjured contralateral knees in every bone metric tested (P≤ .001). Interlimb differences in femur shape scores of participants with ACLR were 65% greater (P < .001) than those of the significantly older reference cohort. Taller height, medial meniscal tears, and decreasing age were associated with larger interlimb differences in shape scores and subchondral areas (P < .05). Bone–patellar tendon–bone (BPTB) autograft recipients demonstrated greater interlimb subchondral area differences compared with allograft recipients (P < .05). Interlimb differences for hamstring autograft recipients did not differ from those with BPTB or allograft. Greater interlimb differences in medial femur subchondral areas were associated with worse patient-reported Knee injury and Osteoarthritis Outcome Score Symptoms (R = 0.27; P = .040). Conclusion: Even in the absence of radiographic OA, just 2 years after unilateral ACLR patients showed greater bone shape scores and subchondral areas consistent with pre-OA in their ACLR knees. Furthermore, greater medial femur bone areas were weakly associated with worse symptoms. Patients who are younger, are taller, have meniscal tears, or have BPTB grafts may be at increased risk for bony asymmetries 2 years after ACLR.

Costal Cartilage Graft Repair Osteochondral Defect in a Mouse Model.

Osteochondral defects develop into osteoarthritis without intervention. Costal cartilage can be utilized as an alternative source for repairing osteochondral defect. Our previous clinical study has shown the successful osteochondral repair by costal cartilage graft with integration into host bone bed. In this study, we investigate how cartilaginous graft adapt to osteochondral environment and the mechanism of bone-cartilage interface formation. Costal cartilage grafting was performed in C57BL/6J mice and full-thickness osteochondral defect was made as control. 3D optical profiles and micro-CT were applied to evaluate the reconstruction of articular cartilage surface and subchondral bone as well as gait analysis to evaluate articular function. Histological staining was performed at 2, 4, and 8 weeks after surgery. Moreover, costal cartilage from transgenic mice with fluorescent markers were transplanted into wild-type mice to observe the in vivo changes of costal chondrocytes. At 8 weeks after surgery, 3D optical profiles and micro-CT showed that in the graft group, the articular surface and subchondral bone were well preserved. Gait analysis and International Cartilage Repair Society (ICRS) score evaluation showed a good recovery of joint function and histological repair in the graft group. Safranin O staining showed the gradual integration of graft and host tissue. Costal cartilage from transgenic mice with fluorescent markers showed that donor-derived costal chondrocytes turned into osteocytes in the subchondral area of host femur. Costal cartilage grafting shows both functional and histological repair of osteochondral defect in mice. Graft-derived costal chondrocytes differentiate into osteocytes and contribute to endochondral ossification.

Does A Single Osteotomy Technique for Frozen Autograft (Pedicled Freezing) in Patients With Malignant Bone Tumors of the Long Bones Achieve Union and Local Tumor Control?

Biological reconstruction by replanting the resected tumor-bearing segment is preferred by some surgeons when caring for a patient with a bone sarcoma. Frozen autografts are advantageous because they are cost-effective, provide an excellent fit, permit the maintenance of osteoinductive and osteoconductive properties, and are not associated with transmission of viral disease. The pedicle frozen autograft technique, in which only one osteotomy is made for the freezing procedure, keeping the affected segment in continuity with the host bone and soft tissue instead of two osteotomies, maintains the affected segment with the host bone and soft tissue. This could restore blood flow more rapidly in a frozen autograft than in a free-frozen autograft with two osteotomies. (1) In what proportion of patients was union achieved by 6 months using this technique of frozen autografting? (2) What complications were observed in a small series using this approach? (3) What was the function of these patients as determined by Musculoskeletal Tumor Society (MSTS) score? (4) What proportion of patients experienced local recurrence? Between 2014 and 2017, we treated 87 patients for primary sarcomas of the femur, tibia, or humerus. Of those, we considered patients who could undergo intercalary resection and showed a good response to neoadjuvant chemotherapy as potentially eligible for this technique. Based on these criteria, 49% (43 patients) were eligible; a further 9% (eight) were excluded because of inadequate bone quality (defined as cortical thickness less than 50% by CT assessment). We retrospectively studied 32 patients who were treated with a single metaphyseal osteotomy, the so-called pedicle freezing technique, which uses liquid nitrogen. There were 20 men and 12 women. The median age was 18 years (range 13 to 48 years). The median follow-up duration was 55 months (range 48 to 63 months). Patients were assessed clinically and radiologically regarding union (defined in this study as bony bridging of three of four cortices by 6 months), the proportion of patients experiencing local recurrence, the occurrence of nononcologic complications, and MSTS scores. Three percent (one of 32) of the patients had nonunion (no union by 9 months). The median MSTS score was 90%, with no evidence of metastases at the final follow-up interval. Nine percent (three of 32) of our patients died. The local recurrence rate was 3.1% (one of 32 patients). The mean restricted disease-free survival time at 60 months (5 years) was 58 months (95% CI 55 to 62 months). Twenty-five percent of patients (eight of 32) experienced nononcologic complications. This included superficial skin burns (two patients), superficial wound infection (two patients), deep venous thrombosis (one patient), transient nerve palsy (two patients), and permanent nerve palsy (one patient). This treatment was reasonably successful in patients with sarcomas of the femur, tibia, and humerus who could undergo an intercalary resection, and this treatment did not involve the epiphysis and upper metaphysis. It avoids a second osteotomy site as in prior reports of freezing techniques, and union was achieved in all but one patient. There were few complications or local recurrences, and the patients' function was shown to be good. This technique cannot be used in all long-bone sarcomas, but we believe this is a reasonable alternative treatment for patients who show a good response to neoadjuvant chemotherapy, those in whom intercalary resection is feasible while retaining at least 2 cm of the subchondral area, and in those who have adequate bone stock to withstand the freezing process. Experienced surgeons who are well trained on the recycling technique in specialized centers are crucial to perform the technique. Further study is necessary to see how this technique compares with other reconstruction options. Level IV, therapeutic study.

Core Decompression Combined with Intraosseous Autologous Conditioned Plasma Injections Decreases Pain and Improves Function in Patients with Symptomatic Knee Bone Marrow Lesions.

The purpose of this prospective case series was to determine the effectiveness of using a combination of the core decompression and injection of autologous conditioned plasma (ACP) for the treatment of symptomatic knee bone marrow lesions (BML), as well as to report on the preliminary clinical results based on magnetic resonance imaging (MRI) and patient-reported outcomes (PROMs). Patients with OA-related BML who failed to improve on conservative treatment for three months underwent an identical procedure consisting of arthroscopy, core decompression, and the intraosseous injection of ACP and were followed up for 12 months. A statistically significant reduction in pain and an improvement in function, as measured by the Numeric Pain Rating Scale (NPRS) and Knee Injury and Osteoarthritis Outcome Score (KOOS), was observed at one-week follow-up (8.3 ± 0.8 to 1.5 ± 1.0; p ≤ 0.001 and 33.4 ± 10.6 to 53.9 ± 13.6; p ≤ 0.001 respectively). After six weeks, weight-bearing was allowed, but the trend did not change-the NPRS continued to be low (average 1.4 on 12-month follow-up) and the total KOOS increased 44.6 points from the baseline (average 78.0 on 12-month follow-up). The Whole-Organ Magnetic Resonance Imaging Score improved from 66.1 ± 19.4 prior to surgery to 58.0 ± 15.9 (p < 0.001) after 3 months. In our study, there was no control group, randomisation was not performed, and the sample size was relatively small. A combination of core decompression and the intraosseous injection of ACP into the affected subchondral area proved to be a safe and effective procedure that provides rapid pain relief and a significant increase in joint function up to one year postoperatively.

Administration of necrostatin-1 ameliorates glucocorticoid-induced osteonecrosis of the femoral head in rats.

Glucocorticoid (GC)-induced osteonecrosis of the femoral head (ONFH) is a serious complication of glucocorticoid treatment and is characterized by dysfunctional bone reconstruction at necrotic sites. Our previous study confirmed the protective potential of necrostatin-1, a selective blocker of necroptosis, in glucocorticoid-induced osteoporosis. In this study, rat models of GC-induced ONFH were established to evaluate the effects of necrostatin-1 on osteonecrotic changes and repair processes. Osteonecrosis was verified by histopathological staining. An analysis of trabecular bone architecture was performed to evaluate osteogenesis in the osteonecrotic zone. Then, necroptotic signaling molecules such as RIP1 and RIP3 were examined by immunohistochemistry. Histopathological observations indicated that necrostatin-1 administration reduced the incidence of osteonecrosis and the osteogenic response in subchondral areas. Additionally, bone histomorphometry demonstrated that necrostatin-1 intervention could restore bone reconstruction in the necrotic zone. The protective mechanism of necrostatin-1 was related to the inhibition of RIP1 and RIP3. Necrostatin-1 administration alleviated GC-induced ONFH in rats by attenuating the formation of necrotic lesions, recovering the function of osteogenesis, and suppressing glucocorticoid-induced osteocytic necroptosis by inhibiting the expression of RIP1 and RIP3.

Development and evaluation of nomograms for predicting osteoarthritis progression based on MRI cartilage parameters: data from the FNIH OA biomarkers Consortium

BackgroundOsteoarthritis (OA) is a leading cause of disability worldwide. However, the existing methods for evaluating OA patients do not provide enough comprehensive information to make reliable predictions of OA progression. This retrospective study aimed to develop prediction nomograms based on MRI cartilage that can predict disease progression of OA.MethodsA total of 600 subjects with mild-to-moderate osteoarthritis from the Foundation for National Institute of Health (FNIH) project of osteoarthritis initiative (OAI). The MRI cartilage parameters of the knee at baseline were measured, and the changes in cartilage parameters at 12- and 24-month follow-up were calculated. The least absolute shrinkage and selection operator (LASSO) regression analysis was used to extract the valuable characteristic parameters at different time points including cartilage thickness, cartilage volume, subchondral bone exposure area and uniform cartilage thickness in different sub regions of the knee, and the MRI cartilage parameters score0, scoreΔ12, and scoreΔ24 at baseline, 12 months, and 24 months were constructed. ScoreΔ12, and scoreΔ24 represent changes between 12 M vs. baseline, and 24 M vs. baseline, respectively. Logistic regression analysis was used to construct the nomogram0, nomogramΔ12, and nomogramΔ24, including MRI-based score and risk factors. The area under curve (AUC) was used to evaluate the differentiation of nomograms in disease progression and subgroup analysis. The calibration curve and Hosmer-Lemeshow (H-L) test were used to verify the calibration of the nomograms. Clinical usefulness of each prediction nomogram was verified by decision curve analysis (DCA). The nomograms with predictive efficacy were analyzed by secondary analysis. Internal verification was assessed using bootstrapping validation.ResultsEach nomogram included cartilage score, KL grade, WOMAC pain score, WOMAC disability score, and minimum joint space width. The AUC of nomogram0, nomogramΔ12, and nomogramΔ24 in predicing the progression of radiology and pain were 0.69, 0.64, and 0.71, respectively. All three nomograms had good calibration. Analysis by DCA showed that the clinical effectiveness of nomogramΔ24 was higher than others. Secondary analysis showed that nomogram0 and nomogramΔ24 were more capable of predicting OA radiologic progression than pain progression.ConclusionNomograms based on MRI cartilage change were useful for predicting the progression of mild to moderate OA.

The role of torsional stress in the development of subchondral insufficiency fracture of the femoral head: A finite element model analysis

BackgroundSubchondral insufficiency fracture of the femoral head generally occurs without evidence of trauma or with a history of minor trauma. Insufficient bone quality is considered one cause; however, the detailed mechanism of fracture development at the subchondral area (SA) is not understood. The aim of this study was to clarify the directions of force that cause subchondral fracture using finite element model analysis. MethodsTwo types of finite element models were generated from the CT data of femurs obtained from three individuals without osteoporosis (normal models) and another three with osteoporosis (osteoporosis models). Three directions of force, including compressive, shearing, and torsional, were applied to the femoral head. The distribution of von Mises stress (Mises stress) was evaluated at the SA, principal compressive trabeculae (PC), and principal tensile trabeculae. ResultsUnder compressive force, the mean Mises stress value was greatest at the PC in both the normal and osteoporosis models. Under shearing force, the mean Mises stress value tended to be greatest at the SA in the normal model and at the PC in the osteoporosis model. Under torsional force, the mean Mises stress value was greatest at the SA in both types of models. ConclusionsThe torsional force showed the greatest Mises stress at the SA in both the normal and osteoporosis models, suggesting the importance of torsion as a possible force responsible for subchondral insufficiency fracture development.

Stress on the posteromedial region of the proximal tibia increased over time after anterior cruciate ligament injury.

Anterior cruciate ligament (ACL) injury induces anterior and rotatory instability of the knee. However, the effect of this instability on the stress distribution in the knee joint in living participants is not clear. The aim of this study was to compare the distribution pattern of subchondral bone density across the proximal tibia in the knees with and without ACL injury, and to investigate the correlation between the distribution patterns of the subchondral bone density and the duration of ACL-deficiency. Radiographic and computed tomography (CT) data pertaining to 20 patients with unilateral ACL injury without combined injury (ACL-deficient group) and 19 nontraumatic subjects (control group) were collected retrospectively. Subchondral bone density of the proximal tibia was assessed using CT-osteoabsorptiometry. Both the medial and lateral compartments of the proximal tibia were divided into three subregions of equal width in the sagittal direction. The percentage of high subchondral bone density areas (HDA%) in each subregion was quantitatively analyzed. HDA% of the posteromedial region was significantly higher in the ACL-deficient group (mean: 21.6%) than in the control group (14.7%) (p = 0.002). In contrast, HDA% of the anteromedial region was significantly lower in the ACL-deficient group (9.4%) than in the control group (15.3%) (p = 0.048). The logarithm of the time elapsed from ACL injury to CT examination showed a significant correlation with HDA% in the posteromedial region (p = 0.032). Subchondral bone density in the posteromedial region significantly increased after ACL injury and correlated with the duration of ACL-deficiency in semi-log manner in meniscus intact knees. The increase in stress on the posteromedial region after ACL injury, which induces a change in the subchondral bone density, justifies early ACL reconstruction after ACL injury.

Subchondral Bone Relative Area and Density in Human Osteoarthritic Femoral Heads Assessed with Micro-CT before and after Mechanical Embedding of the Innovative Multi-Spiked Connecting Scaffold for Resurfacing THA Endoprostheses: A Pilot Study.

The multi-spiked connecting scaffold (MSC-Scaffold) prototype is the essential innovation in the fixation of components of resurfacing total hip arthroplasty (THRA) endoprostheses in the subchondral trabecular bone. We conducted the computed micro-tomography (micro-CT) assessment of the subchondral trabecular bone microarchitecture before and after the MSC-Scaffold embedding in femoral heads removed during long-stem endoprosthesis total hip arthroplasty (THA) of different bone densities from 4 patients with hip osteoarthritis (OA). The embedding of the MSC-Scaffold in subchondral trabecular bone causes the change in its relative area (BA/TA, bone area/total area ratio) ranged from 18.2% to 24.7% (translating to the calculated density ρB relative change 11.1–14.4%, and the compressive strength S relative change 75.3–122.7%) regardless of its initial density (before the MSC-Scaffold embedding). The densification of the trabecular microarchitecture of subchondral trabecular bone due to the MSC-Scaffold initial embedding gradually decreases with the increasing distance from the apexes of the MSC-Scaffold’s spikes while the spatial extent of this subchondral trabecular bone densification ranged from 1.5 to 2.5 mm (which is about half the height of the MSC-Scaffold’s spikes). It may be suggested, despite the limited number of examined femoral heads, that: (1) the magnitude of the effect of the MSC-Scaffold embedding on subchondral trabecular bone densification may be a factor contributing to the maintenance of the MSC-Scaffold also for decreased initial bone density values, (2) the deeper this effect of the subchondral trabecular bone densification, the better strength of subchondral trabecular bone, and as consequence, the better post-operative embedding of the MSC-Scaffold in the bone should be expected.

Fully automated cartilage segmentation of late stage osteoarthritis (KLG4) knees using deep learning with U-net architectures - model specificity is important

Purpose: The agreement and accuracy of automated cartilage segmentation of knees with radiographic osteoarthritis (ROA) using deep learning (DL) and convolutional neural network (CNN)-based U-Net architectures has recently been reported. It was observed that when using a model trained with a set of Kellgren Lawrence grade (KLG) 2-4 knees for this purpose, automated cartilage segmentation slightly overestimated cartilage thickness vs. the manual reference segmentation. This overestimation was particularly strong in a subcohort of KLG4 knees with denuded subchondral bone areas.

3D printing of an integrated triphasic MBG-alginate scaffold with enhanced interface bonding for hard tissue applications.

Osteochondral defects affect both of cartilage and subchondral areas, thus it poses a significant challenge to simultaneously regenerate two parts in orthopedics. Tissue engineering strategy is currently regarded as the most promising way to repair osteochondral defects. This study focuses on developing a multilayered scaffold with enhanced interface bonding through 3D printing. One-shot printing process enables control over material composition, pore structure, and size in each region of the scaffold, while realizes seamlessly integrated construct as well. The scaffold was designed to be triphasic: a porous bone layer composed of alginate sodium (SA) and mesoporous bioactive glasses (MBG), an intermediate dense layer also composed of SA and MBG and a cartilaginous layer composed of SA. The mechanical strength including the interface adhesion strength between layers were characterized. The results indicated that SA crosslinking after 3D printing anchored different materials together and integrated all regions. Additional scaffold soaking in simulated body fluid (SBF) and cell culture medium induced apatite deposition and had weakened the compressive and tensile strengths, while no layer dislocation or delamination occurred.

Differences in the microarchitectural features of the lateral collapsed lesion between osteonecrosis and subchondral insufficiency fracture of the femoral head.

Like osteonecrosis of the femoral head (ONFH), subchondral insufficiency fracture of the femoral head (SIF) causes femoral head collapse. However, little is known about the differences between the two diseases regarding the morphological features of the collapsed lesion. We tested the hypothesis that the morphological features of the lateral collapsed lesion would differ between ONFH and SIF. Twenty femoral heads histopathologically diagnosed as ONFH (n=10) or SIF (n=10) were used in this study. In the lateral collapsed lesion of each femoral head, cubic regions of interest (ROIs) were selected within the collapsed subchondral area and the nearby non-collapsed subchondral area. Micro-CT-based microarchitectural parameters were compared between the ROIs in each disease. Additionally, correlations between histopathological and microarchitectural features were evaluated. In ONFH, bone volume fraction, trabecular thickness, and bone mineral density in the collapsed area were all significantly lower than those in the nearby non-collapsed area where thickened bone trabeculae accompanied by appositional bone formation were invariably seen. On the other hand, in SIF there were no significant differences between the ROIs in any of these microarchitectural parameters. Histopathologically, varying degrees of callus formation overlying the fracture of the subchondral plate were seen around the lateral collapsed lesion. The morphological features of the lateral collapsed lesion were inconsistent between ONFH and SIF, suggesting different pathomechanisms of femoral head collapse.

Inhibition of Axin1 in osteoblast precursor cells leads to defects in postnatal bone growth through suppressing osteoclast formation

Axin1 is a negative regulator of β-catenin signaling and its role in osteoblast precursor cells remains undefined. In the present studies, we determined changes in postnatal bone growth by deletion of Axin1 in osteoblast precursor cells and analyzed bone growth in newborn and postnatal Axin1Osx mice and found that hypertrophic cartilage area was largely expanded in Axin1Osx KO mice. A larger number of chondrocytes and unabsorbed cartilage matrix were found in the bone marrow cavity of Axin1Osx KO mice. Osteoclast formation in metaphyseal and subchondral bone areas was significantly decreased, demonstrated by decreased TRAP-positive cell numbers, associated with reduction of MMP9- and cathepsin K-positive cell numbers in Axin1Osx KO mice. OPG expression and the ratio of Opg to Rankl were significantly increased in osteoblasts of Axin1Osx KO mice. Osteoclast formation in primary bone marrow derived microphage (BMM) cells was significantly decreased when BMM cells were cultured with conditioned media (CM) collected from osteoblasts derived from Axin1Osx mice compared with BMM cells cultured with CM derived from WT mice. Thus, the loss of Axin1 in osteoblast precursor cells caused increased OPG and the decrease in osteoclast formation, leading to delayed bone growth in postnatal Axin1Osx KO mice.

Histopathological Findings of Failed Free Vascularized Fibular Grafting for Osteonecrosis of the Femoral Head after Long-Term Follow-Up.

Purpose The aim of this study was to report the histopathology of failed free vascularized fibular grafting (FVFG) for osteonecrosis of the femoral head (ONFH) after a mean follow-up of 11.5 years (ranged from 10.6 to 14.2 years). Methods Six hips of 5 patients with a history of steroid use, aged 34–67 years, were in stage II of ONFH as classified by the Ficat and Arlet classification at the time of FVFG treatment. Grafting failure led to osteoarthritis of the hip joint during a mean of 11.5 years of follow-up. Femoral head specimens were first evaluated macroscopically. Bone specimens were sectioned into long strips, divided into necrotic, transitional, and healthy zones, and then prepared for nondecalcified and decalcified histopathological examination using hematoxylin and eosin (HE) staining, Goldner's trichrome staining, and immunofluorescence (IF) staining. Results Femoral head articular cartilage surfaces appeared thin, opaque, and partially cartilaginous missing, with gradual collapse detected in weight-bearing areas. The interface with the fibular graft showed well union, with no obvious gaps between graft and host bone, as observed macroscopically. The necrotic area was filled with fibular graft, cancellous bone, and cartilaginous or soft tissue invasion. Histopathology results revealed well integration between fibular graft and host bone, with thickened trabecular bone. Gaps occurred in transitional and healthy zones. In the necrotic zone, cartilaginous or soft tissue invasion occurred, while thin or missing articular cartilage exposed subchondral bone to hip joint surfaces. By IF counterstaining with CD-31 and α-SMA, blood vessel transplanted during fibular grafting could be clearly observed along the graft from healthy to necrotic zones. In the necrotic zone, blood vessels presented obviously and spread into the surrounding area of the graft tip. Conclusion After FVFG procedure with a mean follow-up of 11.5 years, fibular grafts retained their integrity as viable, vascularized, cortical bone that fused well with host bone and formed thickened trabecular bone surrounding the surface of the graft. However, the revascularization of FVFG's blood vessels spreading from the tip of the fibular graft into subchondral area of necrotic lesion did not improve significantly in these failure cases. The local necrotic lesion failed to be repaired as healthy trabecular bone to buttress articular surface and was occupied by soft tissues.

Microstructural analysis of subchondral bone in knee osteoarthritis

SummaryThe results of this study show increased formation of bone in the subchondral areas in advanced stages of osteoarthritis of the knee. These changes seem to be influenced by mechanical factors.IntroductionSubchondral bone changes seem to contribute to the progression of knee osteoarthritis (OA). This study aimed to analyze subchondral bone microstructure in specimens of late-stage knee OA in respect to articular cartilage damage, meniscus integrity, and knee joint alignment.MethodsThirty proximal tibiae of 30 patients (20 female and 10 male) with late-stage OA retrieved during total knee arthroplasty were scanned using a high-resolution micro-computed tomography. The scans were semi-automatically segmented into five volumes of interest. The volumes of interest were then further analyzed using commercially available software. The degree of articular cartilage damage was assessed semi-quantitatively by magnetic resonance imaging before surgery.ResultsThe mean bone fraction volume (bone volume/total volume (BV/TV)) in all weight-bearing locations was significantly higher compared to the non-weight-bearing reference point below the anterior cruciate ligament (p = 0.000). The mean BV/TV in the medial compartment was significantly higher compared to the lateral compartment (p = 0.007). As for the BV/TV in intact menisci, there was a significantly lower subchondral bone fraction volume compared to subluxated or luxated menisci in the medial (p = 0.020) and lateral compartment (p = 0.005). Varus alignment had a significantly higher subchondral BV/TV in the medial compartment, whereas valgus alignment had a significantly higher subchondral BV/TV in the lateral compartment (p = 0.011).ConclusionsThe results show significant differences of subchondral bone microstructural parameters in respect to cartilage damage, meniscus’ structural integrity, and knee joint alignment. Therefore, subchondral bone changes seem to be a secondary process in the late-stage OA of the knee caused by mechanical changes.

Osteocyte TGFβ1‑Smad2/3 is positively associated with bone turnover parameters in subchondral bone of advanced osteoarthritis.

Subchondral sclerosis is considered the main characteristic of advanced osteoarthritis, in which bone remodeling mediated by transforming growth factor β (TGFβ) signaling plays an indispensable role in the metabolism. Osteocytes have been identified as pivotal regulators of bone metabolism, due to their mechanosensing and endocrine function. Therefore, the aim of the present study was to investigate the association between osteocyte TGFβ signal and subchondral sclerosis. Knee tibia plateau samples were collected from osteoarthritic patients and divided into three groups: The full cartilage, partial cartilage and full defect groups. Next, changes in osteocyte TGFβ signaling and subchondral bone structure underlying various types of cartilage erosion were detected. Bone mineral density (BMD) assay, histology [hematoxylin and eosin, Safranin-O/Fast green, and tartrate resistant acid phosphatase (TRAP) staining], and reverse transcription-quantitative PCR mainly detected structural alterations, osteogenic and osteo-clastic activity in the cartilage and subchondral bone. The activation of the TGFβ signaling pathway in the subchondral bone was detected by immunohistochemistry and western blotting. The association between osteocyte TGFβ and the regulation of bone metabolism was analyzed by correlation analysis, and further proven in vitro. It was confirmed that the BMD of the subchondral bone increased and underwent sclerosis in the partial cartilage and full defect groups. Additional observation included the thinning of the area of calcified cartilage, in which a bone island formed locally, with subchondral bone plate thickening and increased trabecular bone volume. TRAP staining suggested an increase in bone resorption in subchondral underlying areas of the partial cartilage and full defect groups. Immunohistochemistry results confirmed the activation of osteocyte TGFβ in subchondral underlying areas with severe cartilage erosion. Moreover, osteocyte phosphorylated-Smad2/3 was positively correlated with subchondral BMD, alkaline phosphatase and osteopontin mRNA expression, but it was negatively correlated with TRAP+ cells. Furthermore, it was confirmed in vitro that osteocyte TGFβ signaling could regulate the osteogenic and osteoclastic activity of the mesenchymal stem cells. This study illustrated that osteocyte TGFβ signaling is positively associated with the remodeling of subchondral bone in advanced osteoarthritis and provides a preliminary theoretical basis for further investigations of the role and mechanism of osteocyte TGFβ in subchondral of osteoarthritis.