Subchondral Zone Research Articles

SUCCINATE-RECEPTOR SYSTEM OF BONE AND CARTILAGE TISSUE IN PATIENTS WITH METABOLIC PHENOTYPE OF OSTEOARTHRITIS

Introduction. Currently, osteoarthritis (OA) has been identified as a polyetiological disease, where several phenotypes have been identified based on the leading frequency. Obviously, each clinical phenotype corresponds only to its fundamental changes on the part of various organs and systems. Un-til recently, special attention was paid to the study of metabolic processes in osteoarthritis (OA) and was paid to the state of the cartilage, but more and more interest was focused on the biochemistry of the subchondral bone, its microarchitectonics and signal function. Aid. To study the features of the manifestation of the succinate-receptor system of bone and cartilage tissue in patients with the metabolic phenotype of osteoarthritis. Material and methods. 42 patients took part in the study and were divided into 2 groups: 1 group – patients without articular disease, normal body mass index; 2 group – patients with metabolic phenotype of OA. The subjects were collected complaints, anamnesis, as well as general clinical and orthopedic examination. The levels of succinate, succinate receptor (SUCNR1) and succinate dehydrogenase (SDH) are measured in bone and cartilage tissue homogenates. Results. In the 2 group, an increase in SUCNR1 expression was detected in all studied areas of the joint in comparison with the 1 group. In the 2 group, the differences were tissue-specific in the distribution of SUCNR1 with a predominant increase in the amount of the receptor in the subchondral bone compared to the loaded (p=0.031) and non-loaded zone of cartilage (p=0.001). In the 1 group, the studied areas of cartilage and bone did not dif-fer in the amount of SUCNR1 from each other. In the group of patients with the metabolic phenotype of OA, an increase in mitochondrial succinate was found both in the subchondral bone tissue and in different zones of cartilage compared to the 1 group. The final indicators of SDH activity in the mito-chondria of the studied joint zones that we obtained turned out to be low in both groups, however, relatively high enzyme activity was observed in the subchondral zone of the bone of the group of metabolic phenotype of OA. Conclusion. In patients with the metabolic phenotype of OA, high expression of SUCNR1 in joint tissues is observed, which is tissue-specific with a predominant increase in the amount of SUCNR1 in the subchondral bone. We found higher levels of succinate in the subchondral bone and cartilaginous areas of joints in patients with the metabolic phenotype of OA and suggest that the succinate-SUCNR1 interaction in affected joints in OA is adaptive in nature.

Hypobaric hypoxia aggravates osteoarthritis via the alteration of the oxygen environment and bone remodeling in the subchondral zone.

A high prevalence of osteoarthritis (OA) has been observed among individuals living at high altitudes, and hypobaric hypoxia (HH) can cause bone mass and strength deterioration. However, the effect of HH on OA remains unclear. In this study, we aimed to explore the impact of HH on OA and its potential mechanisms. A rat knee OA model was established by surgery, and the rats were bred in an HH chamber simulating a high-altitude environment. Micro-computed tomography (Micro-CT), histological analysis, and RNA sequencing were performed to evaluate the effects of HH on OA invivo. A hypoxic co-culture model of osteoclasts and osteoblasts was also established to determine their effects on chondrogenesis invitro. Cartilage degeneration significantly worsened in the HH-OA group compared to that in the normoxia-OA (N-OA) group, 4 weeks after surgery. Micro-CT analysis revealed more deteriorated bone mass in the HH-OA group than in the N-OA group. Decreased hypoxia levels in the cartilage and enhanced hypoxia levels in the subchondral bone were observed in the HH-OA group. Furthermore, chondrocytes cultured in a conditioned medium from the hypoxic co-culture model showed decreased anabolism and extracellular matrix compared to those in the normoxic model. RNA sequencing analysis of the subchondral bone indicated that the glycolytic signaling pathway was highly activated in the HH-OA group. HH-related OA progression was associated with alterations in the oxygen environment and bone remodeling in the subchondral zone, which provided new insights into the pathogenesis of OA.

OUR EXPERIENCE IN THE USE OF BONE-CARTILAGE AUTOPLASTY IN THE TREATMENT OF PATIENTS WITH OSTEOCHONDRAL PATELLAR DEFECTS

Objective: to evaluate the effectiveness of bone-cartilage autoplasty in the treatment of patients with osteochondral patellar defects. Materials and methods. The study analyzed the results of surgical treatment of 7 patients for the period from 2012 to 2023 inclusive. All patients underwent inpatient treatment at the Department of Traumatology and Orthopedics No. 2 Clinics of Samara State Medical University (SamSMU). All patients had a defect of patellar cartilage on the background of osteoarthritis of the knee joint with a predominant lesion of the patellofemoral joint (patellofemoral arthrosis). Bone-cartilaginous autoplasty of the articular surface of the patella was used as an operation. Clinical evaluation of treatment results was carried out on the basis of the methods recommended by OARSI (Osteoarthritis Research Society International) before surgery and at 3, 6 and 12 months after surgery: VAS (Visual Analog Scale), WOMAC Index (Western Ontario and McMaster University Osteoarthritis Index) and M. Lequesne algofunctional index were determined. The condition of bone-cartilage tissue in the defect area before surgery and after bone-cartilage autoplasty was assessed using radiography and magnetic resonance imaging. Results and discussion. We noted that according to the studied indices and scales, the greatest positive dynamics was observed in the early postoperative period (3 months), the peak reached by 6 months, and full functional recovery occurred by 12 months (return to sports, high-intensity work). The most complete restructuring as a result of the examination of 7 patients according to radiography and MRI, we noted at the time of 6 months, when we see a complete restructuring of the patellar cartilage tissue, as well as the greatest signs of autograft integration in the subchondral zone. Conclusions. The use of bone-cartilage autoplasty as a method of surgical treatment in patients with osteochondral injuries of the patella in clinical practice is effective, expedient and its use in clinical practice is recommended from the standpoint of restoring the function of the knee joint, which leads to an improvement in the quality of life of patients. Nevertheless, its application requires taking into account all anatomical and functional features of the patellofemoral articulation.

Can we safely place the distal volar locking plate screws into the subchondral zone of a distal radius fracture using a 45° supination oblique view under fluoroscopic guidance?

Careful distal locking screw insertion into the subchondral zone is necessary to obtain proper mechanical strength of unstable distal radius fractures using volar locking plating. However, subchondral zone screw insertion increases the risk of intra-articular screw penetration, which may remain unrecognized during surgery due to complex distal radial anatomy. The purpose of this study was to evaluate the role of fluoroscopic guidance with a 45° supination oblique view technique for placing distal screws into the subchondral zone during volar locking plating for unstable distal radius fractures and to explore the factors associated with poor screw placement. We retrospectively analyzed 171 wrists of 169 patients treated with variable-angle volar locking plates for unstable radius fractures. The subchondral zone was defined as the metaphyseal area within 4mm of the articular margin of the distal radius. The location of the distal locking screws and radiographic parameters, including the teardrop angle, were measured using computed tomography scans and X-rays. Clinical and radiographic factors were examined to determine their possible associations with screw placement failure. Of 581 distal screws inserted, 559 screws (96.2%) were inserted into the subchondral zone and 17 screws into the metaphyseal zone (2.9%). Five screws (0.7%) in three wrists showed intra-articular placement: four screws were placed into the lunate fossa and one into the scaphoid fossa. These three wrists also exhibited significantly reduced teardrop angles. The distal screws were significantly closer to the joint line in the lunate fossa than the scaphoid fossa (1.9±0.9mm vs. 2.8±1mm, P < 0.000). The 45° supination oblique view technique is a useful fluoroscopic guiding technique for accurate and safe distal screw placement in the subchondral zone in volar locking plate fixation for distal radial fractures. However, a decreased teardrop angle or extended lunate fossa should be corrected before distal screw insertion to avoid intra-articular screw placement.

Особенности структурных изменений дистального суставного конца бедренной кости при экспериментальном моделировании остеомиелита

Features of structural changes in the joint components (synovial membrane, articular cartilage, subchondral bone) under the conditions of adjacent limb segment osteomyelitis are poorly understood and require thorough histological studies. Purpose Сomparative assessment of the structural reorganization of the main components of the distal articular end of the femur in experimental modeling of osteomyelitis. Material and methods Objects: distal metaphyses of the femur of intact rats (n = 5) and experimental ones (n = 16) in the conditions of modeled osteomyelitis of the femur. The culture of S. aureus was injected into the medullary canal in the experimental animals (n = 8) while saline was injected in the control group (n = 8). The animals were taken out of the experiment on the 21st day. Methods: histological, morphometric, and statistical methods were used. Results In the control group, the articular cartilage, subchondral bone plate, and subchondral zone retained their normal structure. Synovitis was not revealed. The values of the morphometric parameters were comparable with the intact norm. In the experimental group, bone microsequesters, osteoclastic resorption of the subchondral bone plate, inflammatory infiltration with the content of plasma cells and neutrophils were detected in the subchondral zone. Histological changes in the articular cartilage according to the classification of the International Society OARSI (2006) corresponded to grades 1 to 3 and were accompanied by synovitis. There was a significant (р &lt; 0.05) decrease in the thickness of non-calcified cartilage, a significant twofold decrease in the thickness of the subchondral bone plate, while the values of the thickness of the calcified cartilage exceeded those in the control group and the intact norm. Conclusion Under the conditions of an experimental model of chronic osteomyelitis of the femur, the revealed structural changes in the subchondral zone contribute to the progression of the destruction of the subchondral bone plate, articular cartilage and synovitis. This model of chronic osteomyelitis can be used to experimentally study various therapeutic strategies aimed at modifying subchondral bone remodeling and relieving synovitis.

Pathomorphological and pathochemical characteristic of the osteomyelitis focus in patients with diabetic osteoarthropathy (Charcot foot)

BACKGROUND: Osteomyelitis in diabetic osteoarthropathy occurs in 65 % of cases, and it is the main cause of non-traumatic amputations. The choice of optimal treatment technologies should be based on understanding the pathogenetic characteristics of this disease.AIM: To study the pathomorphological and pathochemical picture of osteomyelitic focus in patients with diabetic neuroosteoarthropathy.MATERIALS AND METHODS: Object — 20 patients (55.3±9.33 years) with Type 2 diabetes mellitus, diabetic neuroosteoarthropathy, chronic osteomyelitis of the foot bones. The treatment consisted in surgical debridement of the purulent focus with the material collection for pathomorphological and biochemical studies, and in reposition and alignment of bone fragments with the leg and foot fixation using the Ilizarov fixator in order to form bone ankylosis of the compromised joint.RESULTS: Subacute and acute course of chronic osteomyelitis was registered in 80 % of cases. As for the pathohistological changes in bone tissue, the following ones were the most significant: necrosis and the presence of an inflammatory infiltrate of varying severity depending on the phase of the inflammatory process. The articular cartilage structure was broken in all the cases. Activation of osteoclasts was observed in the osteomyelitis focus, especially in the subchondral zone. There was no subchondral bone plate in most cases, or only its fragments remained. Pathohistological examination of the soft tissues associated with the osteomyelitis focus indicated the presence of mirocirculatory and denervation disorders due to necrosis and hyalinosis of a significant part of microvessels against the background of compensatory hypervascularisation and chronic inflammation, narrowing and obliteration of the lumens of feeding arteries, almost complete absence of nerve elements in the tissues or their destructive changes. An increase in the activity of lytic enzymes was revealed in the interstitial environment of the tissues surrounding the osteomyelitis focus (138-fold increase in the activity of acid phosphatase, interstitial osteolytic index was 7.2-fold higher than blood serum index).CONCLUSION: The pathomorphological signs of chronic osteomyelitis subacute and acute processing were observed in most patients. Breaking the articular cartilage structure was accompanied by invasion of vessels, inflammatory infiltrate, and by activation of osteoclasts in the subchondral zone. Destructive changes of vessels and nerves in the soft tissues associated with the osteomyelitis focus can be etiopathogenetic factors of this disease development. The technologies for stopping this process should be based on obligatory debridement of the focus with sequestrnecrectomy, with regular monitoring of the operated segment condition.

Оценка синовита голеностопного сустава при диабетической нейроостеоартропатии в зависимости от воспалительной фазы хронического остеомиелита

Diabetic neuroosteoarthropathy complicated by osteomyelitis is one of the severe conditions of the ankle joint in patients with diabetes. The role of the synovium in the pathogenesis of this disease remains poorly understood. Purpose To identify structural changes in the synovium of the Charcot ankle depending on the inflammatory phase of chronic osteomyelitis. Material and methods The synovium and osteochondral fragments of the ankle were studied in 33 patients. Paraffin sections stained according to the three-color Masson method, hematoxylin and eosin, and semi-thin sections stained with methylene blue and basic fuchsin were studied using an AxioScope. A1 microscope with an AxioCam digital camera (Carl Zeiss MicroImaging GmbH, Germany) and Zenblue software (Carl Zeiss MicroImaging GmbH, Germany). The phase of the inflammatory process of chronic osteomyelitis was assessed according to the HOES of Tiemann et al (2014) and synovitis according to Krenn et al (2006). Results Full-thickness articular cartilage defects, synovial pannus, foci of osteonecrosis in the subchondral zone, bone microsequesters, osteoclastic resorption of the subchondral bone plate, replacement of bone marrow structures with granulation tissue, the severity which depended on the inflammatory stage of chronic osteomyelitis, were recorded in the process of studying osteochondral fragments. In 82 % of patients, the inflammatory phase of chronic osteomyelitis was characterized as active and subacute. In all the cases, hyperplasia, hypervascularization and hyperemia of the synovium with the presence of bone and cartilage fragments were observed, as well as inflammatory infiltrate, synovial pannus invading the articular cartilage. The vessels featured a pronounced narrowing of the lumens or their complete closure. The severity of synovitis correlated positively with the inflammatory phase of chronic osteomyelitis; Spearman's correlation coefficient of 0.76 indicated high relationship. Conclusions In diabetic osteoarthropathy of the ankle joint complicated by chronic osteomyelitis, the irreversible structural changes revealed in the synovium contribute to the formation of synovial pannus and the progression of destruction of the articular cartilage and subchondral bone. The severity of synovitis positively correlates with the inflammatory phase of chronic osteomyelitis.

High corrective osteotomy of the tibia using a pedicle graft for varus deformity of the knee joint

The method of valgus revascularizating tibia osteotomy using autoplasty of the clinoid defect by a pedicle graft is proposed for the treatment of patients with varus gonarthrosis. Nine patients with varus deforming arthrosis, decompensated form, stages 2 and 3, were operated on. Varus changes in the tibiofemoral angle ranged from 5 to 15. The mean consolidation term in the region of osteotomy was about 10 weeks. Follow up period was at least 2 years. The patients were clinically observed using screening monitoring system to control the disease severity and treatment efficacy. Draining effect and normalization of microcirculation were estimated by the measure of intraosseous pressure in subchondral zone. Dispersion analysis of the observation results has shown stable reduction of the average number ofpatient's condition severity from 27. 7 to 17 and the reduction of intraosseous pressure from 2.4 kPa to 0.9 kPa.

Integrated Osteochondral Microsphere Scaffolds with Biomimetic Architecture and Regional Vascularization for Joint Repair

Osteochondral lesion potentially causes a variety of joint degenerative diseases if it cannot be treated effectively and timely. Microfracture as the first line surgical choice achieves limited results for the larger defect whereas cartilage patches trigger integrated instability and cartilage fibrosis. To tackle aforementioned issues, here we explore to construct an integrated osteochondral scaffold for synergetic regeneration of cartilage and subchondral bone in one system. On the macro level, we fabricated three integrated scaffolds with distinct channel structure of Non-channel, Consecutive-channel and Inconsecutive-channel via Selective Laser Sintering (SLS). On the micro level, cartilage zone and subchondral bone zone of integrated scaffold consisted of small polycaprolactone (PCL) microspheres with the diameter of 50 μm and large PCL microspheres with the diameter of 150 μm, respectively. As a result, cartilage zone exhibited a dense phase for the inhibition of vessel invasion while subchondral zone generated a porous phase for the ingrowth of bone and vessel. Our findings showed that Inconsecutive-channel scaffolds possessed biomimetic hierarchical structure, adequate mechanical properties, gradient interconnected porosity in comparison with Non-channel and Consecutive-channel groups. Moreover, Inconsecutive-channel scaffolds obviously induced cartilage regeneration and subchondral bone remodeling. Consequently, this work not only achieves an effective and regeneratable microsphere scaffold for osteochondral reconstruction, but also provides a feasible methodology to recover injured joint through integrated design pattern. Funding Information: This work was financially supported by the National Key Research and Development Program of China (2017YFC1103900), the National Natural Science Foundation of China (32171323, 91939111), Key Research and Development Program of Hubei Province (2020BCB056), International Science and Technology Cooperation Projects of Shenzhen (GJHZ20200731095211035), Sanming Project of Medicine in Shenzhen (SZSM201812055), and the Fundamental Research Funds for the Central Universities (2019kfyRCPY103). Declaration of Interests: The authors declare no conflict of interest. Ethics Approval Statement: All procedures for animal experiments were approved by the Institutional Animal Care and Use Committee of Huazhong University of Science and Technology (SYXK20170094).

Microscopic Examination of Foot Joints Components in Charcot Arthropathy Complicated by Osteomyelitis

Background. Charcot arthropathy is a serious medical and social problem. Histological studies of foot joints components in Charcot arthropathy complicated by osteomyelitis are few. The purpose of this study was to assess structural changes in the articular cartilage and subchondral bone of the foot joints in Charcot arthropathy complicated by osteomyelitis. Materials and Methods. The bone-cartilage fragments of the ankle, subtalar and metatarsophalangeal joints with the surrounding soft tissues of 20 patients with Charcot arthropathy complicated by chronic osteomyelitis were examined. Part of the material was fixed in neutral formalin. All samples were subjected to standard histological processing. Paraffin sections were stained by Masson’s tricolor method, hematoxylin and eosin. Part of the material was embedded in epoxy resins. Then semi-thin sections were stained with methylene blue and basic fuchsin. Histological preparations were studied by digitizing images under the AxioScope A1 microscope (Carl Zeiss MicroImaging GmbH, Germany).The phase of chronic osteomyelitis inflammation was assessed semi-quantitatively using the histopathological scale by A. Tiemann et al. (2014). Results. In 80% of the patients, the inflammatory phase of chronic osteomyelitis was characterized as active and subacute. In all cases, the areas with full-layer of articular cartilage unweaving, up to the subchondral zone, with cartilaginous tissue fragments rejection into the joint cavity were revealed. Cytoarchitectonics was disrupted. The main part of chondrocytes was in a state of destruction. The articular surface was covered with pannus. There were no basophilic line and the zone of calcified cartilage. The hyaline cartilage was replaced by granulation and/or fibrous tissue. An inflammatory infiltrates was noted in the superficial and deep areas of the cartilage. The impairment of the structure and/or complete absence of the subchondral bone due to the high activity of osteoclasts in the subchondral zone were revealed. An excessive amount of osteoclasts at the border with the articular cartilage was noted, while the signs of reparative bone formation were poorly expressed. Edema and thickening of the vascular walls of the microvasculature were recorded. Conclusion. The microscopic examination of the foot joints in Charcot arthropathy complicated by osteomyelitis revealed structural impairment and/or complete absence of the subchondral bone due to the high activity of osteoclasts in the subchondral zone. Structural changes in the subchondral bone and synovial pannus led to irreversible destruction of articular cartilage and the penetration of infection. These should be taken into account in surgical planning.

Cryogenic 3D printing of heterogeneous scaffolds with gradient mechanical strengths and spatial delivery of osteogenic peptide/TGF-β1 for osteochondral tissue regeneration

Due to the increasing aging population and the high probability of sport injury among young people nowadays, it is of great demand to repair/regenerate diseased/defected osteochondral tissue. Given that osteochondral tissue mainly consists of a subchondral layer and a cartilage layer which are structurally heterogeneous and mechanically distinct, developing a biomimetic bi-phasic scaffold with excellent bonding strength to regenerate osteochondral tissue is highly desirable. Three-dimensional (3D) printing is advantageous in producing scaffolds with customized shape, designed structure/composition gradients and hence can be used to produce heterogeneous scaffolds for osteochondral tissue regeneration. In this study, bi-layered osteochondral scaffolds were developed through cryogenic 3D printing, in which osteogenic peptide/β-tricalcium phosphate/poly(lactic-co-glycolic acid) water-in-oil composite emulsions were printed into hierarchically porous subchondral layer while poly(D,L-lactic acid-co-trimethylene carbonate) water-in-oil emulsions were printed into thermal-responsive cartilage frame on top of the subchondral layer. The cartilage frame was further filled/dispensed with transforming growth factor-β1 loaded collagen I hydrogel to form the cartilage module. Although the continuously constructed osteochondral scaffolds had distinct microscopic morphologies and varied mechanical properties at the subchondral zone and cartilage zone at 37 °C, respectively, the two layers were closely bonded together, showing excellent shear strength and peeling strength. Rat bone marrow derived mesenchymal stem cells (rBMSCs) exhibited high viability and proliferation at both subchondral- and cartilage layer. Moreover, gradient rBMSC osteogenic/chondrogenic differentiation was obtained in the osteochondral scaffolds. This proof-of-concept study provides a facile way to produce integrated osteochondral scaffolds for concurrently directing rBMSC osteogenic/chondrogenic differentiation at different regions.

Arthroscopic tibiotalocalcaneal arthrodesis using an intramedullary locking nail

Arthroscopic tibiotalocalcaneal arthrodesis (TTCA) aims at reconstructing apain-free, orthograde, and functional limb with reduced invasiveness and lower complication rates compared to open arthrodesis. Combined osteoarthritis of the ankle and subtalar joint or hindfoot malalignment. Osteomyelitis/deep soft tissue infections, talus necrosis, severe deformity of hindfoot or distal tibia, pronounced boney defect, indication for combined total ankle replacement and subtalar fusion. Patient in supine position; arthroscopic debridement of the cartilage and subchondral zone, perforation of the subchondral bone marrow of the ankle and subtalar joint. Foot and hindfoot positioning. Special attention has to be paid to the calcaneus and talus inclination, hindfoot alignment and rotation. Temporary fixation, insertion of the guide wire, reaming and insertion of the retrograde, curved compression arthrodesis nail. If needed, autologous bone grafting. Proximal locking of the nail, application of compression, distal locking, wound closure. Lymphatic drainage, physical therapy, and restricted bed rest until wound healing. Non-weightbearing, immobilization for 8weeks, then step-wise increase of weightbearing. Fitting of custom-made shoes. Retrospectively included were 15patients treated by arthroscopic TTCA with an intramedullary nail (average age 56 ± 10years, 93% male, all had risk factors for postoperative complications). Due to apreoperative plantar ulceration, 4patients (27%) had 3 ± 1.8conditioning operations. Sufficient hindfoot correction was achieved in all patients. Major complications occurred in 33%(non-unions). In asubgroup analysis, the presence of aplantar ulceration significantly influenced the development of amajor complication. In acase-control study, major complications occurred in 63% and wound complications in 50% of patients for the open technique compared to 33% and 0%, respectively, for the arthroscopic technique. Although the current data do not prove superiority of arthroscopic TTCA compared to open TTCA, there appears to be astrong trend towards considerably lower complication rates following arthroscopic TTCA.

Effectiveness of intraosseous infiltration of autologous platelet-rich plasma in the area of the bone marrow edema in osteoarthritis of the knee joint

Osteoarthritis (OA) affects both elderly people, for whom it is one of the main causes of disability, and people of active working age and is an urgent clinical and social problem of resistance of pain syndrome to therapy. The disease is characterized by both destruction of intra-articular and paraarticular structures, such as subchondral bone. While OA is an important sign of pathological changes believe the bone marrow edema (BME). This work examines the effect of BME on development osteoarthritis, and therapeutic approaches to the management of patients with OA. The aim of the study was to develop a method of treatment of BME in OA of the knee joint by locally intraosseous injection of autologous thrombotic-rich plasma (PRP) into the edema zone. In this study 17 patients with the diagnosis: Osteoarthritis II-IV Grade. according to the classification of Kellgren–Lawrence, in which areas of local inflammation in the form of BME were detected on MRI in the subchondral zone in accordance with the international classification of WORMS (Whole Organ Magnetic Resonance Imaging Score). The mean age of patients was 41,7 ± 14,3 years, 10 of them were women and 7 men. Patients were treated with autological platelet-rich plasma under x-ray control injected from extra-articular intraosseous access in the area of BME. Evaluation of effectiveness of treatment performed by VAS, WOMAC and KOOS scales, before the introduction of autoplasma, after 1 and 3 months after the start of treatment. Three months after the manipulation, there was a statistically significant decrease in the intensity of inflammatory syndrome: for WOMAC by 17.5%, for KOOS by 19.4% and for VAS by 33,1% (p &lt; 0,01). Thus, the efficiency of intraosseous Infiltration of autologous platelet-rich plasma in the treatment of patients with OA, accompanied by edema of the bone marrow in the subchondral zone, was proved.

The intricate microchannel structure of the human femoral head

Purpose: The presence of a subchondral channel-like microstructure that provides a direct link between articular cartilage (AC) and deeper trabecular bone has been confirmed in a handful of classic literature. Referred to as "defects” or "breaks", they are not yet three-dimensionally visualized or characterized, despite their potential importance in understanding osteoarthritis (OA) progression/initiation. Here, we demonstrate the intricate 3D microstructure of the subchondral bone (SCB) channels in healthy human femoral head, and their region-dependent pattern. The microchannels are quantified in terms of average number (Ch.N), thickness (Ch.Th), as well as their correlation to the subchondral bone plate, and cartilage thicknesses. Methods: Human femurs from the anatomical gift program of the Medizinische Hochschule Hannover (MHH) were kindly provided to us. They were independently graded by three orthopaedic surgeons according to the Outerbridge classification system, and subsequently, five healthy female joints were selected. 44 measuring points were systematically defined on each sample. They were the intersections of two sets of geometrical features that were drawn on the femoral heads: 1) Twelve concentric lines, each separated by a 30°-angle interval, starting from the center (C) of the femoral head and ending on the neck junction. 2) four parallel parasagittal planes, which divided the arc between the C and the neck junctions into four equally-spaced regions. The location of each set of measuring points was standardized using a template grid, taking into account the normalized size of each femoral head. Cylindrical specimens (n=220, D=2.00 mm) were then drilled out from each sample and scanned using a high-definition micro-CT system (μCT 50, SCANCO Medical AG, Switzerland; voxel size=1.2 μm, source voltage=90 kVp, intensity=88 μA). The SCB channels were segmented and analyzed using appropriate evaluation scripts and threshold setting. 5-m thick sagittal sections of hip joint were cut and processed for toluidine blue and hematoxylin and eosin (H&E) staining. Sections were also incubated with primary antibodies against CD31 (ab28364, Abcam, 1:100), von Willebrand Factor (vWF, Dako, 1:200), calcitonin receptor (ab11042, Abcam, 1:75), and collagen type I (ab34710, Abcam, 1:200), and then processed for immunohistochemical staining using standard protocols. Statistical evaluation was carried out using SPSS package (IBM SPSS, version 25.0). Results: The data were categorized into three groups based on the contact area of the femoral head with the acetabulum: load-bearing region (LBR), non-load-bearing region (NLBR), and partial contact (PC). The microchannels showed a strong region-dependent architecture. They were abundant and small (Ch.N = 34.2 ± 11.3 1/mm; Ch.Th = 26 ± 16 μm) on the LBR, perpendicularly connecting SCB's surface to deeper trabecular spacing, while scarce and relatively thick (Ch.N = 3.7 ± 1.3 1/mm; Ch.Th = 168 ± 82 μm) on the NLBR of the femoral head. The area where the femoral head and acetabulum were only partially in contact (PC) showed a combination of thick and small channels (Ch.N = 19.6 ± 7.7 1/mm; Ch.Th = 75 ± 53 μm). The mean AC thickness was positively correlated (Pearson’s r = 0.43) with the number of microchannels (LBR: 696 ± 209 μm, PC: 575 ± 162 μm, NLBR: 315 ± 124 μm). H&E staining of the subchondral zone showed that articular cartilage was occasionally extended through the calcified cartilage and marrow spaces. Likewise, immunohistochemistry results demonstrated positive expression for vWF inside microchannels, a specific marker for endothelial cells. Conclusions: Our results demonstrate that an intricate microchannel structure exists in the subchondral bone of the human femoral head. The number, width, and distribution pattern of the channels is strongly region-dependent. The positive correlation of microchannel numbers with AC thickness in healthy femurs shows that they might play a dynamic role in the nutrition of AC.

Developmental Transformation and Reduction of Connective Cavities within the Subchondral Bone.

It is widely accepted that the subchondral bone (SCB) plays a crucial role in the physiopathology of osteoarthritis (OA), although its contribution is still debated. Much of the pre-clinical research on the role of SCB is concentrated on comparative evaluations of healthy vs. early OA or early OA vs. advanced OA cases, while neglecting how pure maturation could change the SCB’s microstructure. To assess the transformations of the healthy SCB from young age to early adulthood, we examined the microstructure and material composition of the medial condyle of the femur in calves (three months) and cattle (18 months) for the calcified cartilage (CC) and the subchondral bone plate (SCBP). The entire subchondral zone (SCZ) was significantly thicker in cattle compared to calves, although the proportion of the CC and SCBP thicknesses were relatively constant. The trabecular number (Tb.N.) and the connectivity density (Conn.D) were significantly higher in the deeper region of the SCZ, while the bone volume fraction (BV/TV), and the degree of anisotropy (DA) were more affected by age rather than the region. The mineralization increased within the first 250 µm of the SCZ irrespective of sample type, and became stable thereafter. Cattle exhibited higher mineralization than calves at all depths, with a mean Ca/P ratio of 1.59 and 1.64 for calves and cattle, respectively. Collectively, these results indicate that the SCZ is highly dynamic at early age, and CC is the most dynamic layer of the SCZ.

Bone block augmentation from the iliac crest for treatment of deep osteochondral defects of the knee resembles biomechanical properties of the subchondral bone.

Bone block augmentation from the iliac crest can be used for reconstruction of the osteochondral unit to restore the underlying subchondral bone upon restoration of the cartilaginous layer via matrix-induced chondrocyte transplantation. To critically understand the successful restoration of the defect, biomechanical and histological analysis of the implanted bone blocks is required. The aim of the study was to analyse the ability of the bone block technique to restore huge bone defects by mimicking the physiological subchondral zone. The experiments were performed using lateral femoral condyles and iliac crest bone grafts from the same cadavers (n = 6) preserved using the Thiel method. CT scans were made to evaluate bone pathology. Bone mineral density of all specimens was evaluated in the femoral head prior to testing. A series of tests were conducted for each pair of specimens. A static compression test was performed using an electro dynamic testing machine with maximal strength and failure behavior analyzed. Biomechanical tests were performed in the medial-lateral direction for iliac crest and for femoral condyles with and without removal of the cartilage layer. Histological analysis was performed on decalcified specimens for comparison of the condyle at lesion site and the graft. No significant difference in failure load could be found for iliac crest (53.3-180.5N) and femoral condyle samples upon cartilage removal (38.5-175.1N) (n.s.). The femoral condyles with an intact cartilage layer showed significantly higher loads (118.3-260.4N) compared to the other groups indicating that native or regenerated cartilage can further increase the failure load (p < 0.05). Bone mineral density significantly influenced failure load in all study groups (p < 0.05). Histological similarity of the cancellous bone in the femoral condyle and in the iliac crest was observed. However, within the subchondral zone, there was a higher density of sponge like organized trabeculae in the bone samples from the iliac crest. Tide mark was only detected at the osteochondral interface in femoral condyles. This study demonstrated that, bone blocks derived from the iliac crest allow a biomechanical appropriate and stable restoration of huge bony defects by resembling the subchondral zone of the femoral condyle. Therefore, bone augmentation from the iliac crest combined with matrix-induced autologous chondrocyte transplantation seems to be a reasonable method to treat these challenging injuries.

Schatzker II tibial plateau fractures: Anatomically precontoured 3.5 mm locking compression plates allow for improved patient outcome

Aims and Objectives: In the operative treatment of split depression factures to the lateral tibial plateau, the reconstruction of the depressed joint surface is eagerly sought after. The subchondral bony defect often requires bone grafting or bone graft substitutes. At least equally important is the achievement of an internal fixation that provides the greatest possible support for the fragile joint surface fragments. The design of the anatomically precontoured locking compression plates features a higher number of locking screws underneath the joint surface and permits the screw placement closer to the subchondral zone compared to conventional plates. Whether the altered design results in better patient outcome is analysed in this study. Materials and Methods: Our databank was searched for Schatzker II fractures from 2012 until 2015. Patients that underwent open reduction and internal fixation with anatomically precontoured 3.5 mm locking compression plates (A) or conventional 4,5 mm L-shaped locking compression plates and screws (B) were included and retrospectively evaluated. CT-scans, radiographs in two planes and in full length standing mode, if available, were analysed. Details of the operative procedures and secondary events were determined. Objective outcome parameters were collected from the patient records, subjective outcome parameters were assessed in a survey and WOMAC as well as Rasmussen functional knee scores were calculated. Results: A total of 36 patients were included (A=20, B=16). The mean patient age, the ratio male to female and the mean follow up were comparable. CT-scans revealed an equal mean size of the depressed joint surface (A: 23.7 x 25.3 mm; B: 23.9 x 24.0 mm) and maximal depression depth (11.2 and 11.8 mm). The duration of the operation, the frequency of utilizing bone grafts or bone graft substitutes and of lateral meniscus repair as well as the rate of subsequent implant removal were also comparable. In the early postoperative controls, the radiological assessment according to Rasmussen revealed a mean score of 9.1 (A) and of 8.5 (B). During follow up, the mean score decreased to 8.1 and 6.7 for A and B, respectively. This difference was statistically significant (p<0.05). A valgus deviation was more often observed in group B. Both, the WOMAC and the Rasmussen functional knee score revealed lower mean values for group B in the final evaluation. Conclusion: The progressive decrease of the Rasmussen radiological score for the conventional 4,5 mm L-shaped locking compression plates and screws was predominantly due to a secondary loss of reduction and an increasing valgus deviation. The altered design of the anatomically precontoured 3.5 mm locking compression plate seems to prevent more sufficiently the reduced joint surface fragments from sintering over time. The anatomically precontoured 3.5 mm locking compression plate allows for improved patient outcome and should closely be considered for internal fixation of split depression fractures to the lateral tibial plateau.

Gradient nano-engineered in situ forming composite hydrogel for osteochondral regeneration

Fabrication of anisotropic osteochondral-mimetic scaffold with mineralized subchondral zone and gradient interface remains challenging. We have developed an injectable semi-interpenetrating network hydrogel construct with chondroitin sulfate nanoparticles (ChS-NPs) and nanohydroxyapatite (nHA) (∼30–90 nm) in chondral and subchondral hydrogel zones respectively. Mineralized subchondral hydrogel exhibited significantly higher osteoblast proliferation and alkaline phosphatase activity (p < 0.05). Osteochondral hydrogel exhibited interconnected porous structure and spatial variation with gradient interface of nHA and ChS–NPs. Microcomputed tomography (μCT) demonstrated nHA gradation while rheology showed predominant elastic modulus (∼930 Pa) at the interface. Co–culture of osteoblasts and chondrocytes in gradient hydrogels showed layer–specific retention of cells and cell-cell interaction at the interface. In vivo osteochondral regeneration by biphasic (nHA or ChS) and gradient (nHA + ChS) hydrogels was compared with control using rabbit osteochondral defect after 3 and 8 weeks. Complete closure of defect was observed in gradient (8 weeks) while defect remained in other groups. Histology demonstrated collagen and glycosaminoglycan deposition in neo–matrix and presence of hyaline cartilage–characteristic matrix, chondrocytes and osteoblasts. μCT showed mineralized neo–tissue formation, which was confined within the defect with higher bone mineral density in gradient (chondral: 0.42 ± 0.07 g/cc, osteal: 0.64 ± 0.08 g/cc) group. Further, biomechanical push-out studies showed significantly higher load for gradient group (378 ± 56 N) compared to others. Thus, the developed nano-engineered gradient hydrogel enhanced hyaline cartilage regeneration with subchondral bone formation and lateral host-tissue integration.

Assessment of the zonal variation of perfusion parameters in the femoral head: a 3-T dynamic contrast-enhanced MRI pilot study.

The objective was to describe MR perfusion characteristics of the femoral head, with a focus on the subchondral bone. This prospective monocentric study was approved by our local Ethics Committee. Written informed consent was obtained from all subjects. Dynamic contrast-enhanced MRI of the right hip was performed in 59 adults with suspected spondyloarthritis (32 women, 28 men). Mean age was 37.5 (±12.5) years. Regions of interest were drawn in the femoral head epiphysis, in the subchondral areas the most exposed to mechanical load (superolateral, anterosuperior, and posterior zones) and in areas less exposed to mechanical load (inferior subchondral zone and center of the femoral head). Semi-quantitative and pharmacokinetic parameters were calculated using the Tofts model. Statistical analysis was performed with a linear mixed model to compare the perfusion parameters in the different femoral head zones. Extravascular extracellular volume and area under the curve were lower in the superolateral zone than in the inferior zone (p=0.0135 and p<0.0001 respectively) and the central zone (p=0.007 and p=0.0134 respectively). Extravascular extracellular volume and rate constant were lower in the anterosuperior zone than in the inferior zones (p=0.011 and p=0.029). In the anterosuperior zone, extravascular extracellular volume was lower, and time to peak was higher than in the central zones (p=0.0056 and p=0.0013 respectively). No significant differences were found for any values between other paired zones. The perfusion of femoral head subchondral bone assessed with dynamic contrast-enhanced magnetic resonance imaging is not homogeneous: the areas exposed to more mechanical loading are less perfused.

Biomechanical evaluation of straight antegrade nailing in proximal humeral fractures: the rationale of the \u201cproximal anchoring point\u201d

PurposeVarus failure is one of the most common failure modes following surgical treatment of proximal humeral fractures. Straight antegrade nails (SAN) theoretically provide increased stability by anchoring to the densest zone of the proximal humerus (subchondral zone) with the end of the nail. The aim of this study was to biomechanically investigate the characteristics of this “proximal anchoring point” (PAP). We hypothesized that the PAP would improve stability compared to the same construct without the PAP.MethodsStraight antegrade humeral nailing was performed in 20 matched pairs of human cadaveric humeri for a simulated unstable two-part fracture.ResultsBiomechanical testing, with stepwise increasing cyclic axial loading (50-N increments each 100 cycles) at an angle of 20° abduction revealed significantly higher median loads to failure for SAN constructs with the PAP (median, 450 N; range, 200–1.000 N) compared to those without the PAP (median, 325 N; range, 100–500 N; p = 0.009). SAN constructs with press-fit proximal extensions (endcaps) showed similar median loads to failure (median, 400 N; range, 200–650 N), when compared to the undersized, commercially available SAN endcaps (median, 450 N; range, 200–600 N; p = 0.240).ConclusionsThe PAP provided significantly increased stability in SAN constructs compared to the same setup without this additional proximal anchoring point. Varus-displacing forces to the humeral head were superiorly reduced in this setting. This study provides biomechanical evidence for the “proximal anchoring point’s” rationale. Straight antegrade humeral nailing may be beneficial for patients undergoing surgical treatment for unstable proximal humeral fractures to decrease secondary varus displacement and thus potentially reduce revision rates.