Subchondral Region Research Articles

Bone marrow lesions in osteoarthritis: biomarker or treatment target? A narrative review.

Osteoarthritis (OA) is a leading cause of pain, functional impairment, and disability in older adults. However, there are no effective treatments to delay and reverse OA. Magnetic resonance imaging (MRI) can assess structural abnormalities of OA by directly visualizing damage and inflammatory reactions within the tissues and detecting abnormal signals in the subchondral bone marrow region. While some studies have shown that bone marrow lesions (BMLs) are one of the early signs of the development of OA and predict structural and symptomatic progression of OA, others claimed that BMLs are prevalent in the general population and have no role in the progression of OA. In this narrative review, we screened and summarized studies with different designs that evaluated the association of BMLs with joint symptoms and structural abnormalities of OA. We also discussed whether BMLs may serve as an imaging biomarker and a treatment target for OA based on existing clinical trials.

Alterations in compositional and cellular properties of the subchondral bone are linked to cartilage degeneration in hip osteoarthritis

ObjectiveThe subchondral bone is an emerging regulator of osteoarthritis (OA). However, knowledge of how specific subchondral alterations relate to cartilage degeneration remains incomplete. MethodFemoral heads were obtained from 44 patients with primary OA during total hip arthroplasty and from 30 non-OA controls during autopsy. A multiscale assessment of the central subchondral bone region comprising histomorphometry, quantitative backscattered electron imaging, nanoindentation, and osteocyte lacunocanalicular network characterization was employed. ResultsIn hip OA, thickening of the subchondral bone coincided with a higher number of osteoblasts (controls: 3.7±4.5 mm-1, OA: 16.4±10.2 mm-1, age-adjusted mean difference 10.5 mm-1 [95% CI 4.7 to 16.4], p<0.001) but a similar number of osteoclasts compared to controls (p=0.150). Furthermore, higher matrix mineralization heterogeneity (CaWidth, controls: 2.8±0.2 wt%, OA: 3.1±0.3 wt%, age-adjusted mean difference 0.2 wt% [95% CI 0.1 to 0.4], p=0.011) and lower tissue hardness (controls: 0.69±0.06 GPa, OA: 0.67±0.06 GPa, age-adjusted mean difference -0.05 GPa [95% CI -0.09 to -0.01], p=0.032) were detected. While no evidence of altered osteocytic perilacunar/canalicular remodeling in terms of fewer osteocyte canaliculi was found in OA, specimens with advanced cartilage degeneration showed a higher number of osteocyte canaliculi and larger lacunocanalicular network area compared to those with low-grade cartilage degeneration. Multiple linear regression models indicated that several subchondral bone properties, especially osteoblast and osteocyte parameters, were closely related to cartilage degeneration (R2 adjusted=0.561, p<0.001). ConclusionSubchondral bone properties in OA are affected at the compositional, mechanical, and cellular levels. Based on their strong interaction with cartilage degeneration, targeting osteoblasts/osteocytes may be a promising therapeutic OA approach. Data and materials availabilityAll data are available in the main text or the supplementary materials.

Effectiveness of Bilayer Scaffold Containing Chitosan/Gelatin/Diclofenac and Bovine Hydroxyapatite on Cartilage/Subchondral Regeneration in Rabbit Joint Defect Models.

Subchondral defects are often caused by trauma involving cartilage damage, leading to subsequent damage to the underlying bone, specifically the subchondral region. Bilayer scaffolds made from biomaterials, such as bovine hydroxyapatite, possess biocompatible and biodegradable properties that mimic the natural environmental conditions of target tissues so that they can support the formation of new tissues. On the other side, diclofenac as an anti-inflammatory drug potentiates to inhibit the inflammatory excess regarding the damage. This study aims to study the effectiveness of diclofenac scaffold to rabbit joint defect model. The scaffold was implanted in the rabbit femoral trochlear bone hole, which had a diameter of 5 mm and a depth of 4 mm. After 28 days of intervention, the animals were examined using macroscopic evaluation, hematoxylin-eosin (HE) staining, and immunohistochemistry (IHC) for type I collagen and type II collagen. Subsequently, the cartilage was evaluated using the International Cartilage Repair Society (ICRS) scoring system. The macroscopic ICRS scores were significantly higher (p < 0.05) in the bilayer scaffold implantation group compared to the monolayer scaffold and control groups. Histological ICRS scores were also significantly higher (p < 0.05) in the bilayer scaffold group compared to the control group. Type II collagen expression was higher (p < 0.05) in the bilayer scaffold group compared to the monolayer scaffold and control groups, although type I collagen expression was lower in comparison. In conclusion, this research suggests that the diclofenac-loaded bilayer scaffold effectively enhances cartilage and subchondral bone regeneration.

The Role of Diffusion Weighted MRI in Diagnosis of Sacroiliitis

Background: The main aim of this study is to investigate the effectiveness of Apparent Diffusion Coefficient (ADC) and Diffusion Weighted Imaging (DWI) in identifying and detecting active sacro-iliitis. The study seeks to evaluate the potential of these imaging techniques as diagnostic tools for this particular condition. Materials and Methods: A total of 79 people underwent MRI examination for low back pain. Thirty-four of these individuals did not show any pathology in the sacroiliac joints and were included in the control group. 45 people diagnosed with sacroiliitis formed the patient group. All participants underwent spin echo, planar echo, diffusion-weighted MR imaging at a b=1000 s/mm². ADC values were determined by assessing the subchondral regions adjacent to both sacroiliac joints. Relative ADC values were obtained for both the patient and control groups. Results: The study found a significant difference (p&amp;lt;0.05) in mean ADC values between the pa-tient group (1202.4±268.2 mm²/s) and the control group (423.9±71.9 mm²/s). These results indicate distinct diffusion patterns between the two groups. Additionally, the relative ADC values were significantly different (p&amp;lt;0.05) with 0.434 in the patient group and 0.153 in the control group, further supporting the observed disparities in diffusion characteristics. Conclusions: Diffusion-weighted imaging has similar diagnostic efficacy to other MRI methods in detecting active sacroiliitis. In addition, it is thought that the relative ADC values may contribute more to the diagnosis of sacroiliitis.

Mechanical parameter assessment of fresh human cancellous bone of the femoral head in atraumatic femoral head necrosis and primary coxarthrosis

BackgroundAtraumatic femoral head necrosis is a rare pathological change of the femoral head. It is characterized by local necrosis of the cancellous bone as a result of reduced blood supply to the bone. Even today it remains unclear how to assess the hardness of the necrosis, whether it is soft tissue that is easily removed, or hard tissue that is difficult to resect. MethodsFemoral heads with primary coxarthrosis were selected as a comparison group. For this purpose, 49 femoral heads obtained during total hip arthroplasty surgery with either condition (23 femoral head necrosis, 26 coxarthrosis) were transferred to the testing laboratory in fresh condition. Cylindrical specimens were obtained using a tenon cutter along the main trabecular load direction in the subchondral region of the femoral head. Additionally, thin bone slices were extracted proximal and distal to the specimens for density measurements. Brass plates were glued to the circular surfaces of the specimens. After curing of the adhesive, the specimens were mounted in the testing machine and destructive uniaxial compression tests were conducted. FindingsThe recorded mean compressive strengths and elastic moduli were almost identical for both groups, but the necrosis group showed significantly higher data scattering and range regarding the elastic modulus. The mean density of the coxarthrosis specimens was significantly higher than that of the necrotic specimens. InterpretationThe mechanical properties of cancellous bone vary considerably in the presence of femoral head necrosis. The existence of hard necrosis implies a potential challenge regarding the clinical resection of these tissues.

Ultra-high field magnetic resonance imaging of the quadriceps tendon enthesis in healthy subjects.

Although enthesitis is a hallmark of several rheumatologic conditions, current imaging methods are still unable to characterize entheses changes because of the corresponding short transverse relaxation times (T2). A growing number of MR studies have used Ultra-High Field (UHF) MRI in order to assess low-T2 tissues e.g., tendon but never in humans. The purpose of the present study was to assess in vivo the enthesis of the quadriceps tendon in healthy subjects using UHF MRI. Eleven healthy subjects volunteered in an osteoarthritis imaging study. The inclusion criteria were: no knee trauma, Lequesne index = 0, less than 3h of sport activities per week, and Kellgren and Lawrence grade = 0. 3D MR images were acquired at 7T using GRE sequences and a T2* mapping. Regions of interest i.e., trabecular bone, subchondral bone, enthesis, and tendon body were identified, and T2* values were quantified and compared. Quadriceps tendon enthesis was visible as a hyper-intense signal. The largest and the lowest T2* values were quantified in the subchondral bone region and the tendon body respectively. T2* value within subchondral bone was significantly higher than T2* value within the enthesis. T2* in subchondral bone region was significantly higher than the whole tendon body T2*. A T2* gradient was observed along the axis from the enthesis toward the tendon body. It illustrates different water biophysical properties. These results provide normative values which could be used in the field of inflammatory rheumatologic diseases and mechanical disorders affecting the tendon.

Osteochondral lesion of the talus: presentation and management - A case report

Osteochondral lesions of the talus (OLT) involve the chondral and subchondral region typically. Most are secondary to trauma. The patients present with pain, stiffness, swelling. Diagnosis is made typically by clinical and radiological correlation. Treatment strategies employed can be conservative or surgical. This case report is of a 24-year-old male, who presented with pain on the right ankle ,for a chronic period following trauma. The patient was diagnosed with OLT and underwent surgical treatment (Right medial malleolus osteotomy +curettage of right talus + bone grafting + reconstruction of the medial malleolus). This case study is aimed at understanding the various treatment strategies for OLT, both surgical and non-surgical and thus arriving at a conclusion. Treatment of osteochondral lesions is mainly by early screening in high-risk patients (trauma). Although outcomes are favorable in most of the cases, treatment should be individualized to every patient with adequate counseling of outcomes and complications.

EFFICACY OF CORE DECOMPRESSION WITH AUTOLOGOUS CANCELLOUS BONE GRAFTING ON HEALING IN AVN OF THE FEMORAL HEAD

Introduction:- Avascular necrosis (AVN) of the hip is a condition caused by interruption in the blood supply to the subchondral region of the head of the femur leading to death of the osteoblasts and osteocytes. the term osteonecrosis is now preferred. To study the efcacy of core decompression wi Aims And Objectives th autologous cancellous bone grafting on healing in AVN of the femoral head This study was conducted Material and methods:- in the Department of Orthopaedics, Jhalawar Medical College, Jhalawar (Raj.). 21 patients were admitted in the department of orthopaedics with avascular necrosis of femoral head and treated with core decompression autologous cancellous bone grafting from September 2019 to August 2020. Present study consisted of 21 Results:- patients of AVN femoral head , between age 20 to 60 years treated with core decompression and autologus bone grafting excellent results were obtained in 23.8% , good in 47.6%, fair in 19% while 9.5% patients had poor outcome Core decompression wi Conclusion:- th autologous cancellous bone grafting in early stages of AVN of femoral head is an effective modality to delay the progression of the disease, postpone the femoral head collapse and eventual arthritis, and also helps in revascularization of the femoral head.

Osteochondral junction leakage and cartilage joint lubrication

Background and ObjectivesPrevious studies have shown that there is potentially interstitial fluid exchange between cartilage tissue and the subarticular spongiosa region in the case of injury or disease (e.g., osteoarthritis and osteoporosis). Interstitial flow is also required for cartilage lubrication under joint load. A key question then is how cartilage lubrication is modified by increased interstitial fluid leakage across the osteochondral junction. Thus, the purpose of this study is to develop a numerical model to investigate changes in cartilage lubrication with changes in osteochondral junction leakage. MethodsThe multi-phase coupled model includes domains corresponding to the contact gap, cartilage tissue and subchondral bone plate region (ScBP). Each of these domains are treated as poroelastic systems, with their coupling implemented through mass and pressure continuity. The effects of osteochondral junction leakage on lubrication were investigated with a parametric study on the relative permeability between the ScBP and cartilage tissue. ResultsSignificant effects of ScBP permeability were predicted, especially during the early stage of the junction leakage development (early stage of the disease). There is a significant reduction in mixed-mode lubrication duration under the effect of increased junction leakage (the cartilage tissue mixed-mode lubrication duration is about 33% decrease for a relative permeability ratio of 0.1 between ScBP and cartilage tissue, and about 52% decrease under the osteoarthritis condition). In addition, the time for cartilage to reach steady-state consolidation is significantly reduced when ScBP permeability increases (the consolidation time reduces from roughly 2 h to 1.2 h when the relative permeability ratio increases from 0.001 to 0.1, and it reduces to 0.8 h for an advanced osteoarthritis condition). It is predicted that the initial friction coefficient could increase by over 60% when the ScBP permeability is consistent with an advanced osteoarthritis (OA) condition. ConclusionIncreased osteochondral junction leakage induced by joint injury and disease could result in increased cartilage surface wear rates due to more rapid interstitial fluid depressurization within articular cartilage.

Osteochondral regenerative engineering: challenges, state-of-the-art and translational perspectives.

Despite quantum leaps, the biomimetic regeneration of cartilage and osteochondral regeneration remains a major challenge, owing to the complex and hierarchical nature of compositional, structural and functional properties. In this review, an account of the prevailing challenges in biomimicking the gradients in porous microstructure, cells and extracellular matrix (ECM) orientation is presented. Further, the spatial arrangement of the cues in inducing vascularization in the subchondral bone region while maintaining the avascular nature of the adjacent cartilage layer is highlighted. With rapid advancement in biomaterials science, biofabrication tools and strategies, the state-of-the-art in osteochondral regeneration since the last decade has expansively elaborated. This includes conventional and additive manufacturing of synthetic/natural/ECM-based biomaterials, tissue-specific/mesenchymal/progenitor cells, growth factors and/or signaling biomolecules. Beyond the laboratory-based research and development, the underlying challenges in translational research are also provided in a dedicated section. A new generation of biomaterial-based acellular scaffold systems with uncompromised biocompatibility and osteochondral regenerative capability is necessary to bridge the clinical demand and commercial supply. Encompassing the basic elements of osteochondral research, this review is believed to serve as a standalone guide for early career researchers, in expanding the research horizon to improve the quality of life of osteoarthritic patients affordably.

Anti-Osteoarthritic Effects of Prunella Vulgaris and Gentiana Lutea In Vitro and In Vivo.

Osteoarthritis (OA) is the progressive destruction of articular cartilage with severe symptoms, including pain and stiffness. We investigated the anti-osteoarthritic effects of Prunella vulgaris (PV) and Gentiana lutea (GL) extract in primary cultured chondrocytes RAW 264.7 cells in vitro and destabilization of the medial meniscus (DMM)-induced OA mice in vivo. Primary chondrocytes were induced with IL-1β, and RAW 264.7 cells were treated with LPS and co-incubated with either individual extracts of PV and GL or different ratios of PV and GL mixture. For the OA animal model, the medial meniscus (DMM) was destabilized in 9-week-old male C57BL/6 mice. Treatment of individual PV and GL and combination of PV and GL extracts inhibited the mRNA expression level of COX2 in chondrocytes and RAW 264.7 cells. The optimized inhibitory effect was attained with a PV and GL combination at an 8:2 ratio (PG) without cytotoxic effects. PG extracts prevented the expression of catabolic factors (COX2, Mmp3, Mmp9, and Mmp13) and inflammatory mediator levels (PGE2 and collagenase). In addition, PG decreased subchondral sclerosis and increased BMD in the subchondral region of DMM-induced OA mice with protection of articular cartilage destruction by inhibiting inflammatory processes. This study suggests that PG may be an alternative medicinal herb for treatment of OA.

Using Radiomics to Detect Subtle Architecture Changes of Cartilage and Subchondral Bone in Chronic Lateral Ankle Instability Patients Based on MRI PD-FS Images

To use radiomics to detect the subtle changes of cartilage and subchondral bone in chronic lateral ankle instability (CLAI) patients based on MRI PD-FS images. A total of 215 CLAI patients and 186 healthy controls were included and randomly split into a training set (n=281, patients/controls=151/130) and an independent test set (n=120, patients/controls=64/56). They underwent ankle MRI examinations. On sagittal PD-FS images, eight cartilage regions and their corresponding subchondral bone regions were drawn. Radiomics models of cartilage, subchondral bone and combined cartilage and subchondral bone were built to differentiate CLAI patients from controls. A receiver operating characteristic curve (ROC) was used to assess the model's performance. In the test dataset, the cartilage model yielded an area under the curve (AUC) of 0.0.912 (95% confidence interval (CI): 0.858-0.965, p<0.001), a sensitivity of 0.859, a specificity of 0.893, a negative predictive value (NPV) of 0.848, and a positive predictive value (PPV) of 0.902. The subchondral bone model yielded an AUC of 0.837 (95% CI: 0.766-0.907, p<0.001), a sensitivity of 0.875, a specificity of 0.714, an NPV of 0.833, and a PPV of 0.778. For the combined model, the AUC was 0.921 (95% CI: 0.863-0.972, p<0.001), sensitivity was 0.844, specificity was 0.911, NPV was 0.836, and PPV was 0.915, whose AUC was higher than those of both the cartilage model and the subchondral bone model. The combined radiomics model achieved satisfying performance in detecting potential early architectural changes in cartilage and subchondral bone for CLAI patients.

Efficacy of Intra-articular, intra-osseous Injections of Platelet-Rich Plasma in Osteoarthritis Knee: A Randomized Clinical Trial

<h3>Research Objectives</h3> To evaluate the efficacy of intra-articular, intra-osseous Injections of platelet-rich plasma (PRP) and compare its efficacy with intra-articular injection of PRP in OA Knee. <h3>Design</h3> A parallel 2 group, prospective randomized clinical trial. <h3>Setting</h3> A tertiary care teaching hospital in India. <h3>Participants</h3> A total of 64 persons with OA knee with a Kellgren-Lawrence score of 3 were randomized into two groups. <h3>Interventions</h3> Persons in Group-I received 8ml of single intra-articular PRP injection, and persons in Group II received 18 ml of PRP (two-intra-osseous injections (5ml each in femoral-condyle and tibia plateau) and one intra-articular injection (8ml) of PRP (total 18 ml of PRP, for single joint)) the in the target knee joint under fluoroscopic guidance. All persons (n=64) were followed up at 3 and 6 months. <h3>Main Outcome Measures</h3> Clinical outcomes were evaluated using the visual analog (VAS) pain intensity scores and knee injury and osteoarthritis outcome score (KOOS) questionnaire. <h3>Results</h3> There was no disparity between the two groups in baseline demographic and clinical parameters. Both groups demonstrated statistically significant improvement in VAS pain scores and KOOS scores (pain, symptoms, ADL, sport/recreation, and quality of life) at baseline, 3- and 6 months. However, comparing the two groups revealed no significant difference in VAS scores and KOOS scores at six months. Persons in Group-II reported increased injection-associated pain following interventions. Except for injection-associated pain, no other adverse events were reported in any person. <h3>Conclusions</h3> Though both groups showed significant improvement following PRP injections, additional injections of PRP in the subchondral region did not provide additional benefits (pain-relief and KOOS scores) than intra-articular-PRP injections at 6 months. <h3>Author(s) Disclosures</h3> The institutional intramural research grant supported the study.

Transient spontaneous osteonecrosis of the knee (SONK) shortly after SARS-CoV-2 infection: A report of 2 cases

This article describes 2 cases of post-coronavirus disease 2019 (COVID-19) transient spontaneous osteonecrosis of the knee (PCT-SONK) observed in patients who had previously recovered from COVID-19 without corticosteroid administration. The possible pathomechanisms by which a recent SARS-CoV-2 infection may contribute as a causative factor for osteonecrosis are reviewed, and the differential diagnosis and treatment are discussed. Two patients (males, 45- and 47-year-old) presented with sudden onset knee pain with no trauma history. The pain persisted during rest and at night. On magnetic resonance imaging (MRI), no subchondral bone thickening was observed; bone edema was diffusely distributed in the whole femoral condyle, in contrast to the more focal edema that is typically concentrated mainly around the subchondral region in classic SONK. Both patients were treated nonoperatively with no weight bearing and pharmacological agents, and complete resolution of symptoms was achieved. A follow-up MRI 10 weeks after presentation revealed a near-complete loss of signal in the medial femoral condyle in both patients. Orthopedic surgeons should be cautious when sudden knee pain without concurrent trauma or a history of injury occurs shortly after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, even with mild COVID-19 illness. While some studies report the development of post-COVID-19 osteonecrosis after lower doses of corticosteroids and sooner after their administration than in comparable non-COVID-19 cases, our study is the first to report 2 cases with no corticosteroid administration at all. Therefore, the authors believe it adds to the body of knowledge on the potential connections between COVID-19 and PCT-SONK. The transient nature of symptoms and radiological findings suggest that aggressive surgical treatment of non-injury local bone edema occurring shortly after SARS-CoV-2 infection should be avoided.

Proximal sesamoid bone microdamage is localized to articular subchondral regions in Thoroughbred racehorses, with similar fracture toughness between fracture and controls.

To determine whether proximal sesamoid bone (PSB) microdamage and fracture toughness differ between Thoroughbred racehorses sustaining PSB fracture and controls. Cadaveric case-control. Twenty-four Thoroughbred racehorses (n=12 PSB fracture, n=12 control). Proximal sesamoid bones were dissected, and gross pathological changes and morphological measurements were documented. High-speed exercise history data were evaluated. Microdamage was assessed in fracture, fracture-contralateral limb (FXCL) and control PSBs using whole bone lead uranyl acetate (LUA) staining with micro-CT imaging or basic fuchsin histological analysis. Fracture toughness mechanical testing was carried out in 3-point-bending of microbeams created from PSB flexor cortices. Data were analyzed using ordinal logistic and linear regression models. Microdamage was detected most commonly in the articular subchondral region of PSBs via LUA micro-CT and basic fuchsin histology. There were no differences in microdamage between FXCL and control PSBs. Fracture toughness values were similar for FXCL (1.31 MPa√m) and control (1.35 MPa√m) PSBs. Exercise histories were similar except that horses sustaining fracture spent a greater percentage of their careers in rest weeks. Microdamage was detected in the articular region of PSBs but was not greater in horses sustaining catastrophic PSB fracture. Fracture toughness of PSB flexor cortices did not differ between FXCL and control PSBs. Although uncommon, microdamage is localized to the articular region of Thoroughbred racehorse PSBs. Catastrophic PSB failure is not associated with lower PSB flexor cortex fracture toughness.

Changes in Bone Mineral Density of the Femur and Tibia Before Injury to 2 Years After Anterior Cruciate Ligament Reconstruction in Division I Collegiate Athletes

Background: Osteoarthritis (OA) is a significant long term concern after anterior cruciate ligament (ACL) reconstruction (ACLR). A low bone mineral density (BMD), particularly in the subchondral region, has been associated with the development of OA and is evident at the knee in patients long after ACLR. It is unknown if persistent BMD deficits are present in high level collegiate athletes. Purpose/Hypothesis: The purpose of this study was to evaluate bilateral changes in the BMD of the femur and tibia from before the injury to 24 months after ACLR in collegiate athletes. We hypothesized that the BMD of both the distal femur and the proximal tibia would be significantly reduced within the surgical limb initially postoperatively but return to preinjury levels by 24 months after ACLR. Study Design: Cohort study; Level of evidence, 2. Methods: A total of 33 Division I collegiate athletes were identified between 2010 and 2021 (13 female) who underwent total body dual-energy X-ray absorptiometry (DXA) before sustaining an ACL injury. DXA was repeated at 6, 12, and 24 months after ACLR. Linear mixed effects models assessed differences in the BMD at 5%, 15%, and 50% of the femur's length (F5, F15, F50) and at 5%, 15%, and 50% of the tibia's length (T5, T15, T50) within each limb from before the injury to 24 months after ACLR, reported as Tukey-adjusted P values. Results: Compared with before the injury, the BMD at F5 of the surgical limb was reduced by 0.15 g/cm2 (SE, 0.02 g/cm2) at 6 months (P < .001). The BMD at F15 of the surgical limb was reduced by 0.06 g/cm2 (SE, 0.01 g/cm2), 0.09 g/cm2 (SE, 0.01 g/cm2), and 0.09 g/cm2 (SE, 0.01 g/cm2) at 6, 12, and 24 months, respectively (all P < .001). The BMD at T5 of the nonsurgical limb was reduced by 0.07 g/cm2 (SE, 0.02 g/cm2) at 12 months (P = .02) and 0.10 g/cm2 (SE, 0.02 g/cm2) at 24 months (P = .001). The BMD at T15 of the surgical limb was reduced by 0.07 g/cm2 (SE, 0.01 g/cm2) at 6 months and 0.08 g/cm2 (SE, 0.02 g/cm2) at 12 months (P < .001). Conclusion: BMD deficits at F15 of the surgical limb persisted out to 24 months (–7.1%) after ACLR compared with before the injury in collegiate athletes. The BMD at F5 and T15 of the surgical limb was reduced at 6 and 12 months but not at 24 months compared with preinjury levels. For the nonsurgical limb, no significant differences were detected, except for the T5 region at 12 months (–5.1%) and 24 months (–7.2%). The BMD at F50 and T50 of both limbs was not significantly different than preinjury levels at any time after ACLR.

3-D DISTRIBUTION OF BONE PARAMETERS ACROSS THE DISTAL FEMUR FROM WEIGHT BEARING CT FOLLOWS PATTERNS ACCORDING TO JOINT SPACE NARROWING PHENOTYPE: A MULTICENTER OSTEOARTHRITIS STUDY INVESTIGATION

Weight bearing CT (WBCT) technology has been increasingly used in imaging of knee osteoarthritis in recent years because of its ability to assess the weight bearing joint space. However, relatively little is known regarding the extent to which this cone beam technology can provide useful information on peri-articular bone beyond the subchondral regions. To explore relationships between WBCT-derived 3-D cortical bone thickness and trabecular bone attenuation at the distal femur with concurrent joint space narrowing phenotypes. WBCT imaging was obtained ancillary to the Multicenter Osteoarthritis Study at the 144-month visit. After semi-automatic segmentation, femoral cortical thickness (fCT) and trabecular attenuation (fTA) maps were created for each of 663 available distal femurs using cortical bone mapping. A template was registered to each individual distal femur and a 3-D statistical shape model created, followed by transfer of fCT and fTA distribution maps onto the template. A statistical parametric mapping (SPM) general linear model adjusted for age, sex, BMI, and the first 5 shape modes (controlling for effects of systematic misregistration) was used to test the dependence of fCT and fTA in turn on the experimental variables of concurrent radiographic medial and lateral OARSI joint space narrowing (JSN) grade. One knee from each participant was selected for inclusion, taking the side with worse compartmental baseline JSN grade or randomly if equal. 16 knees were excluded due to unachievable registration, with a final study set of a single knee from 386 individuals. 219 were female, mean ± SD age was 63.6 ± 9.6 yrs, mass 82.3 ± 17.7 kg, height 169 ± 9 cm, and BMI 28.5 ± 5.0 kg/m 2 . SPM significance ROIs according to baseline medial (left, figs 1 & 2) and lateral (right, figs 3 & 4) JSN phenotypes are shown for fCT (top row, figs 1 & 3) and fTA (bottom row, figs 2 & 4). SPM revealed significantly greater fCT by up to ∼0.1mm and fTA by up to ∼40 attenuation units (AU) for each increment in baseline JSN grade along the outer margin of the respective compartments (unmasked blue zones in each figure). Significantly greater fCT by up to ∼0.1mm for each increment in medial JSN grade also spread across the anterior aspect of the medial femoral condyle suggesting a wider regional relationship. 3-D distribution of fCT and fTA follow distinct patterns according to OARSI JSN phenotype, relating to recognised distributions of marginal osteophytosis and subchondral sclerosis. These results indicate that cone beam WBCT can quantify cardinal bony structural features of osteoarthritis and that their distribution is related to specific osteoarthritis OARSI JSN phenotypes. National Institutes of Health, University of Kansas (R01AR071648), University of Iowa. (U01AG18832), University of California-San Francisco (U01AG19069), Boston University (U01AG018820). NS is a consultant for Integra BioLife, Trice Medical and Pacira Biosciences. The authors would like to thank participants and staff of the MOST study. CORRESPONDENCE ADDRESS: tom@turmezei.com

Insight into the potential pathogenesis of human osteoarthritis via single-cell RNA sequencing data on osteoblasts.

Osteoarthritis (OA) is the most common degenerative joint disease caused by osteoblastic lineage cells. However, a comprehensive molecular program for osteoblasts in human OA remains underdeveloped. The single-cell gene expression of osteoblasts and microRNA array data were from human. After processing the single-cell RNA sequencing (scRNA-seq) data, it was subjected to principal component analysis (PCA) and T-Stochastic neighbor embedding analysis (TSNE). Differential expression analysis was aimed to find marker genes. Gene-ontology (GO) enrichment, Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis and Gene set enrichment analysis (GSEA) were applied to characterize the molecular function of osteoblasts with marker genes. Protein-protein interaction (PPI) networks and core module were established for marker genes by using the STRING database and Cytoscape software. All nodes in the core module were considered to be hub genes. Subsequently, we predicted the potential miRNA of hub genes through the miRWalk, miRDB and TargetScan database and experimentally verified the miRNA by GSE105027. Finally, miRNA-mRNA regulatory network was constructed using the Cytoscape software. We characterized the single-cell expression profiling of 4387 osteoblasts from normal and OA sample. The proportion of osteoblasts subpopulations changed dramatically in the OA, with 70.42% of the pre-osteoblasts. 117 marker genes were included and the results of GO analysis show that up-regulated marker genes enriched in collagen-containing extracellular matrix were highly expressed in the pre-osteoblasts cluster. Both KEGG and GSEA analyses results indicated that IL-17 and NOD-like receptor signaling pathways were enriched in down-regulated marker genes. We visualize the weight of marker genes and constructed the core module in PPI network. In potential mRNA-miRNA regulatory network, hsa-miR-449a and hsa-miR-218-5p may be involved in the development of OA. Our study found that alterations in osteoblasts state and cellular molecular function in the subchondral bone region may be involved in the pathogenesis of osteoarthritis.

Ultrastructural characteristics of the rats laryngeal mucosa and cartilage on the 7 and 14 days of the experimental opioid effect

Background and objective. Our main task was to study the ultrastructural organization of the laryngeal mucosa and cartilage on the seventh and fourteenth day of opioid exposure. Methods. The material for the study were mature, outbred male rats in the number of 32 animals, weighing 80g, aged 4.5 months. Animals were injected intramuscularly with Nalbuphine once a day at the same time (10-11 hours in the morning) for 14 days. The initial dose of Nalbuphine was 8 mg / kg during the first week, 15 mg / kg during the second week of the experimental study. Thus, we created the conditions for chronic opioid exposure. Animals were divided into 3 experimental groups: 1 – control group; 2 - animals that received the drug for 7 days; 3 - animals that received the drug for 14 days). All animals were kept in a vivarium. Animal care, labeling and all other manipulations were carried out taking into account the issues of bioethical norms. Before collecting necropsy material, the animal was removed from the experiment with diethyl ether. The the larynx mucosa and rats cartilage were used as the material for ultrastructural examination. Ultrastructural capsule was prepared according to conventional methods. Results. As a result of experimental opioid exposure at the end of 7 days we found alternative changes in the epithelial cells of different parts of the larynx, dyscirculatory changes in blood vessels of lamina propria and submucosa, as well as the destruction of chondrocytes of hyaline and elastic cartilages. The hemocapillaries of lamina propria and submucosa, especially in the ventricles of the larynx and in the subchondral region, were dilated, overflowing with erythrocytes. In the laryngeal mucosa and submucosal base of the laryngeal ventricles, in addition to the overflow of hemocapillaries with erythrocytes, a moderate accumulation of perivascular transudate was noted. At the end of the 14th day of the experimental opioid effect, a pronounced hemocapillaries injury was found, which was accompanied by an increase in the permeability of the vascular wall. In addition to blood plasma, erythrocytes were visualized in the enlarged lumens of hemocapillaries. The development of degenerative changes of endothelial cells, which were accompanied by inhomogeneous dilation of the tubules of the smooth and granular endoplasmic reticulum, was noted. The main substance of the connective tissue of the mucous membrane and submucosal base, especially around the vessels was impregnated with transudate.

Radiomics Feature Analysis of Cartilage and Subchondral Bone in Differentiating Knees Predisposed to Posttraumatic Osteoarthritis after Anterior Cruciate Ligament Reconstruction from Healthy Knees.

Objectives To introduce a new implementation of radiomics analysis for cartilage and subchondral bone of the knee and to compare the performance of the proposed models to classic T2 relaxation time in distinguishing knees predisposed to posttraumatic osteoarthritis (PTOA) after anterior cruciate ligament reconstruction (ACLR) and healthy controls. Methods 114 patients following ACLR after at least 2 years and 43 healthy controls were reviewed and allocated to training (n = 110) and testing (n = 47) cohorts. Radiomics models are built for cartilage and subchondral bone regions of different compartments: lateral femur (LF), lateral tibia (LT), medial femur (MF), and medial tibia (MT) and combined models of four compartments on T2 mapping images. The model performance of discrimination between patients and controls was illustrated with the receiver operating characteristic curve and compared with a classic T2 value-based model. Results The T2 value model of cartilage yielded moderate predictive performance in discerning patients and controls, with an AUC of 0.731 (95% confidence interval, 0.556–0.875) in the testing cohort, while the radiomics signature of cartilage and subchondral bone of different compartments demonstrated excellent performance, with AUCs of 0.864–0.979. Furthermore, the combined model reported an even better performance, with AUCs of 0.977 (95% confidence interval, 0.919–1.000) for the cartilage and 0.934 (95% confidence interval, 0.865–0.994) for the subchondral bone in the testing cohort. Conclusion The radiomics features of the cartilage and subchondral bone may be able to provide powerful tools with more sensitive detection than T2 values in differentiating knees at risk for PTOA after ACLR from healthy knees.