Subchondral Marrow Research Articles

Histological Evaluation of Arthritis in Mice

Arthritis is one the almost commonly prevalent painful diseases which cause limit the movement of joints. This study conducts to investigate histological alterations resulted in rheumatoid arthritis (RA)-induced in mice and estimating the levels of some serum biomarkers including serum IL-6, CRP and RF. Totally, 30 were purchased, acclimated, and divided into two groups; control that injected distilled water, and arthritis that injected adjuvant (CFA). Post the 25th day of experiment, all study mice of both groups were subjected for collection of blood and right ankle joints. Serologically, the findings of IL-6, CRP and RF of arthritis group were elevated significantly when compare to control mice. Histologically, the findings observed in mice of control group were included the proliferation of chondrocytes of articular cartilage with moderate cellular and subchondral marrow space, infiltration few inflammatory cells in dermis, proliferation of chondrocytes in articular cartilage with absence of inflammatory reaction in synovial cavity, moderate infiltration of inflammatory cells in subcutaneous tissue, nearly normal articular cartilage with regular tidemark and absence of sclerosis in marrow spaces, regenerative articular cartilage and regular tidemark line with presence of very narrow distance between articular cartilage and marrow bone, and existence of normal bone trabeculae. In arthritis mice, there were an infiltration of inflammatory cells in subcutaneous tissues and dermis, marked increases in numbers of osteoclasts, sclerosis, regular tidemark and proliferation of chondrocytes, low amonunt of abscesses in subcutaneous tissue, thickness of bone trabeculae, fragments of bone, subchondral sclerosis, moderate distance between bone and articular cartilage. In conclussion, RA causes severe impacts on tissues of affected joints. Studying the mechanism of inhibition during different inflammatory process appear needed.

An in vitro comparison of three nucleus pulposus removal techniques for partial intervertebral disc replacement: An ultra-high resolution MRI study.

Nuclectomy, also known as nucleotomy, is a percutaneous surgical procedure performed to remove nucleus material from the center of the disc. Multiple techniques have been considered to perform a nuclectomy, however, the advantages and disadvantages of each are not well understood. This in vitro biomechanical investigation on human cadaveric specimens aimed to quantitatively compare three nuclectomy techniques performed using an automated shaver, rongeurs, and laser. Comparisons were made in terms of mass, volume and location of material removal, changes in disc height, and stiffness. Fifteen vertebra-disc-vertebra lumbar specimens were acquired from six donors (40 ± 13 years) and split into three groups. Before and after nucleotomy axial mechanical tests were performed and T2-weighted 9.4T MRIs were acquired for each specimen. When using the automated shaver and rongeurs similar volumes of disc material were removed (2.51 ± 1.10% and 2.76 ± 1.39% of the total disc volume, respectively), while considerably less material was removed using the laser (0.12 ± 0.07%). Nuclectomy using the automated shaver and rongeurs significantly reduced the toe-region stiffness (p = 0.036), while the reduction in the linear region stiffness was significant only for the rongeurs group (p = 0.011). Post-nuclectomy, 60% of the rongeurs group specimens showed changes in the endplate profile while 40% from the laser group showed subchondral marrow changes. From the MRIs, homogeneous cavities were seen in the center of the disc when using the automated shaver. When using rongeurs, material was removed non-homogeneously both from the nucleus and annulus regions. Laser ablation formed small and localized cavities suggesting that the technique is not suitable to remove large volumes of material unless it is developed and optimized for this application. The results demonstrate that both rongeurs and automated shavers can be used to remove large volumes of NP material but the reduced risk of collateral damage to surrounding tissues suggests that the automated shaver may be more suitable.

Mechanisms and clinical implications of intervertebral disc calcification.

Low back pain is a leading cause of disability worldwide. Intervertebral disc (IVD) degeneration is often associated with low back pain but is sometimes asymptomatic. IVD calcification is an often overlooked disc phenotype that might have considerable clinical impact. IVD calcification is not a rare finding in ageing or in degenerative and scoliotic spinal conditions, but is often ignored and under-reported. IVD calcification may lead to stiffer IVDs and altered segmental biomechanics, more severe IVD degeneration, inflammation and low back pain. Calcification is not restricted to the IVD but is also observed in the degeneration of other cartilaginous tissues, such as joint cartilage, and is involved in the tissue inflammatory process. Furthermore, IVD calcification may also affect the vertebral endplate, leading to Modic changes (non-neoplastic subchondral vertebral bone marrow lesions) and the generation of pain. Such effects in the spine might develop in similar ways to the development of subchondral marrow lesions of the knee, which are associated with osteoarthritis-related pain. We propose that IVD calcification is a phenotypic biomarker of clinically relevant disc degeneration and endplate changes. As IVD calcification has implications for the management and prognosis of degenerative spinal changes and could affect targeted therapeutics and regenerative approaches for the spine, awareness of IVD calcification should be raised in the spine community.

Focal Chondral and Subchondral Bone Lesions of the Knee: Current Evidence for the Use of Biologic Treatment

Abstract Focal chondral and subchondral injuries of the knee are increasingly recognized and treated pathologies. Many operative approaches to these injuries have been established, including both reparative and reconstructive procedures. More recently, biologic approaches such as platelet rich plasma, bone marrow aspirate concentrate, and stem cells have been studied as potential adjuncts following joint preserving procedures. However, outcomes of biologic injections are mixed and evolving, which may partially be due to the underappreciated role of the subchondral bone in regulating the physiologic response of cartilage to stresses. The current review provides a comprehensive synopsis of the current literature with regards to the use of intra-articular biologics following cartilage preservation surgery as well as the use of biologics in treating subchondral and bone marrow lesions.

MRI of the Sacroiliac Joint in Healthy Children.

To listen to the podcast associated with this article, please select one of the following: iTunes, Google Play, or direct download. OBJECTIVE. Increasing reliance on MRI for the evaluation of sacroiliitis requires that radiologists be familiar with the normal appearance of the developing sacroiliac joint. We describe age-related MRI features of the sacroiliac joints in healthy children. SUBJECTS AND METHODS. Seventy healthy children from three age groups-prepubertal (8-10 years), peripubertal (11-13 years), and approaching skeletal maturity (14-17 years)-completed questionnaires and underwent sacroiliac joint MRI. Imaging studies were evaluated by three experienced pediatric radiologists. Metaphyseal-equivalent signal intensity, nonperiarticular osteitis, cartilage volume, joint fluid, enthesitis, and surface cortex irregularities were evaluated. Metaphyseal-equivalent signal intensity was evaluated using an ordinal grading system (types I-IV). Intraclass correlation coefficients were calculated to assess interrater reliability. RESULTS. Increased metaphyseal-equivalent signal intensity (types I and II) was present in most prepubertal children and in less than 10% of the group approaching skeletal maturity. More prepubertal girls had type I signal than boys, but signal progressed to type IV signal faster in girls than in boys. None of the subjects had subchondral marrow edema, but four subjects had nonperiarticular osteitis. Cartilage volumes decreased with advancing age in girls and, on average, were lower in girls than in boys of the same age. One subject had measurable joint fluid. Cortex irregularities were common (57.1%), most frequently seen along the iliac bone (51.4% ilium vs 11.4% sacrum, p < 0.01) and in the upper quadrants (42.8% upper vs 27.1% lower, p = 0.01). CONCLUSION. We provide valuable reference MRI descriptions of the healthy pediatric sacroiliac joint that should improve our ability to distinguish between normal and pathologic findings.

Diagnostic issue on spontaneous osteonecrosis of medial tibial plateau.

To the Editor: I read with great interest the recent report of Yang et al[1], “Clinical Characteristics and Treatment of Spontaneous Osteonecrosis of Medial Tibial Plateau: A retrospective case study” (published on November 5, 2018, Chin Med J, page 2544–2550), because there have been very few reports on isolated spontaneous medial tibial plateau osteonecrosis and little is known about osteonecrosis of the tibial plateau. I would like to comment on diagnostic issues in this letter. Osteonecrosis of the knee can be a devastating disease that leads to end-stage arthritis of the knee. The knee is the second most commonly affected site after the hip.[2] Spontaneous osteonecrosis of the knee (SPONK) involving medial femoral condyle was described as a distinct entity by Ahlback et al in 1968[3] and is also called idiopathic or primary osteonecrosis to distinguish it from secondary osteonecrosis, which is associated with corticosteroid therapy, blood dyscrasias, Gaucher disease, caisson disease,[4] and other rare conditions, for example, laser-assisted arthroscopic chondroplasty.[5] The condition usually involves a single condyle, most often the medial femoral condyle, affected in 94% of the cases and can also occur in the lateral femoral condyle or in the tibial plateaus.[6] Involvement of the tibial plateau, which was first reported in the French literature by d’Angelijan et al[7] in 1967 and was described in the English literature by Houpt et al[8] is less common. Only 2% of osteonecrosis around the knee may affect the tibial plateau. The medial tibial plateau is more frequently affected than the lateral.[9] Therefore, to our knowledge, it remains a rare cause of knee pain. In the article, the case group contains 22 patients in 15 months (from March 2015 to June 2016), it means real prevalence may be underestimated. Magnetic resonance imaging (MRI) is both sensitive and specific for recognizing SPONK of both medial femoral condyle and tibial plateau and recommended for detection of the disease, due to its high sensitivity in detecting bone marrow edema.[10] MRI characteristics include a diffuse area of hyperintensity widespread into the metaphysics on T2-weighted images, the focal subchondral area of low signal intensity adjacent to the subchondral bone plate on T1-weighted images and focal epiphyseal contour depressions. But the MRI-detected subchondral bone marrow lesion, comprised of fibrosis, necrosis, edema, and bleeding into fatty marrow in different proportions as well as abnormal trabeculae, is also a common finding in patients with OA.[11] In the article, the MRI images showed in Figures 2 and 5 have no typical MRI signs of spontaneous medial tibial plateau osteonecrosis, MRI T1 and T2 images show cartilage degeneration, narrow of joint space, focal bone marrow edema and formation of subchondral cysts in medial knee compartment. We think it is more likely anteromedial osteoarthritis of knee, not a typical SPONK of medial tibial plateau. Although medial unicompartmental knee arthroplasty is also appropriate surgical indication. We also noted that in the series, there are 17 patients (77%) with a Level III medial meniscus posterior root tears (MMPRT) and the lesions of 68% patients involved the central tibial plateau. Subchondral marrow edema deep to the MMPRT was described as a harbinger of meniscal root failure. Ipsilateral tibiofemoral compartment bone marrow edema and insufficiency fractures are commonly noted in the presence of posterior meniscal tears.[12] Therefore, differential diagnosis is important and the condition has not been clearly discussed. Funding This work was supported by a grant from Ministry of Science and Technology of China (No. 2017YFC0108003). Conflicts of interest None.

Unilateral sacroiliitis: differentiating infective and inflammatory etiology by magnetic resonance imaging and tissue studies.

Unilateral sacroiliitis (US) is an uncommon disease with varied etiology. The differentiation between infective and inflammatory causes for US based on MRI alone is often difficult. We studied the efficacy of MRI findings in comparison with tissue studies in the diagnosis of US. A retrospective analysis of patients who presented with US and evaluated with MRI, biopsy for histopathology and tissue cultures was performed. Patients with bilateral sacroiliitis, traumatic and postpartum sacroiliitis were excluded. Based on defined MRI criteria, the patients were divided into two groups-infective (group A) and inflammation (group B). In total, 33 patients (mean age-33.4 ± 17.2years) with MRI features of US had presented with unilateral gluteal pain (100%) and positive Patrick's test (91.9%). Based on the MRI features of severe subchondral marrow edema, widening of joint space, intra-articular abscess and periarticular muscle abscess, infective sacroiliitis (A) was diagnosed in 20/33 (60.6% cases). A total of 13/33 (39.3%) patients had features of inflammation (B), based on the following MRI criteria-subchondral sclerosis with minimal edema, erosions, maintained joint space without abscess/destruction. Tissue evidence of infection was positive in 13/20 (65%) patients in group A while it was negative in all group B patients. MRI had high sensitivity (71%) and 100% specificity in diagnosing inflammatory sacroiliitis while it had low specificity, but 100% sensitivity for diagnosing infective sacroiliitis. Hence, patients diagnosed as inflammatory sacroiliitis in MRI are unlikely to benefit from further tissue studies while percutaneous biopsy is recommended in patients diagnosed in MRI as infective sacroiliitis.

Osteochondral Lesions of the Knee: Differentiating the Most Common Entities at MRI.

Several pathologic conditions may manifest as an osteochondral lesion of the knee that consists of a localized abnormality involving subchondral marrow, subchondral bone, and articular cartilage. Although understanding of these conditions has evolved substantially with the use of high-spatial-resolution MRI and histologic correlation, it is impeded by inconsistent terminology and ambiguous abbreviations. Common entities include acute traumatic osteochondral injuries, subchondral insufficiency fracture, so-called spontaneous osteonecrosis of the knee, avascular necrosis, osteochondritis dissecans, and localized osteochondral abnormalities in osteoarthritis. Patient demographics, the clinical presentation, and the role of trauma are critical for differential diagnosis. A localized osteochondral defect can be created acutely or can develop as an end result of several chronic conditions. MRI features that aid in diagnosis include the location and extent of bone marrow edema, the presence of a fracture line, a hypointense area immediately subjacent to the subchondral bone plate, and deformity of the subchondral bone plate. These findings are essential in diagnosis of acute traumatic injuries, subchondral insufficiency fracture, and its potentially irreversible form, spontaneous osteonecrosis of the knee. If the lesion consists of a subchondral region demarcated from the surrounding bone, the demarcation should be examined for completeness and the presence of a "double-line sign" that is seen in avascular necrosis or findings of instability, which are important for proper evaluation of osteochondritis dissecans. Subchondral bone plate collapse, demonstrated by the presence of a depression or a fluid-filled cleft, can be seen in advanced stages of both avascular necrosis and subchondral insufficiency fracture, indicating irreversibility. Once the diagnosis is established, it is important to report pertinent MRI findings that may guide treatment of each condition. ©RSNA, 2018 An earlier incorrect version of this article appeared online. This article was corrected on August 23, 2018.

Bone Marrow Concentrate Does Not Improve Osseous Integration of Osteochondral Allograft Transplants in the Knee: A Comparative Magnetic Resonance Imaging Analysis

Objectives:Fresh osteochondral allograft transplantation (OCA), which transfers viable, mature hyaline cartilage and subchondral bone into full-thickness chondral defects, has demonstrated good long-term results in the knee. However, incomplete osseous trabecular integration of allograft bone with the host bone is correlated with inferior patient-reported outcomes (Williams et al, JBJS, 2007) and can lead to graft failure. As a result, augmentation of OCA with bone marrow aspirate concentrate (BMAC) has been hypothesized to improve osseous incorporation of the allograft compared to OCA alone. The purpose of this study was to compare the appearance of osseous integration at the host-graft junction on magnetic resonance imaging (MRI) in patients treated with BMAC+OCA versus patients treated with OCA alone.Methods:Between February 2013 and June 2016, 29 patients with full-thickness cartilage defects were treated with BMAC+OCA (n = 10) or OCA alone (n = 19) and followed prospectively with an MRI at approximately 12 months after surgery. Intraoperatively, bone marrow aspirate was harvested from the ipsilateral iliac crest (Magellan, Arteriocyte), and the allograft plug was soaked in BMAC prior to implantation. No patients received a concomitant meniscus allograft transplantation, realignment osteotomy, or anterior ligament reconstruction. Bone, cartilage, and ancillary features on postoperative MRI were assessed and graded using the Osteochondral Allograft MRI Scoring System (OCAMRISS) by a blinded musculoskeletal radiologist. This is a system that scores subchondral bone plate congruity, bone marrow signal intensity, osseous integration, and cystic changes of the graft and host-graft junction as part of the bone features assessment (Meric et al, Cartilage, 2015) (Table 1). Comparisons of demographic characteristics and OCAMRISS scores between groups were performed with the Mann-Whitney test.Results:The mean ages of the BMAC and control groups were 32.9 and 33.4 years, respectively (p = 0.95). Males comprised 60% of the BMAC group and 68% of the control group (p = 0.70). MRIs for the BMAC and control groups were obtained at a mean of 11.2 (range, 9-14) and 11.3 (range, 8-15) months after surgery, respectively (p = 0.87). Mean total OCAMRISS scores were not significantly different between groups (BMAC - 7.8, control - 8.0; p = 0.93). Furthermore, mean bone (BMAC - 2.3, control - 2.8; p = 0.22), cartilage (BMAC - 3.3, control - 3.0; p = 0.55), and ancillary (BMAC - 2.2, control - 2.3; p = 0.92) feature scores were not significantly different between groups. Imaging for 5 patients (50%) in the BMAC and 11 patients (59%) in the control groups (p = 0.71) demonstrated a persistent discernible cleft without crossing trabeculae at the host-graft junction (Figure 1). Almost all grafts (over 90%) demonstrated persistent subchondral marrow edema relative to the epiphyseal bone.Conclusion:The addition of autogenous BMAC to OCA did not enhance osseous integration and bony features at the host-graft junction compared to OCA alone at 12 months. Although more MRI follow-up of patients treated with BMAC+OCA is needed to confirm this finding, these results suggest that any augmentative biologic effect of BMAC for OCA, if one exists, is likely to be small.Table 1.Osteochondral Allograft Magnetic Reponance Imaging Scoring System (OCAMRISS) (adapted from Metric et al) MRI Feature MRI Score Bone Features1. Subchondral bone plate congruity of graft and host-graft junction0: Intract and flush; 1: Disrupted or not flush by >1 subchondral thickness 2. Subchondral bone marrow signal intensity of graft relative to epiphyseal bone0: Normal; 1: Abnormal (bone marrow edema pattern or hypointensity on all sequences) 3. Osseous integration at host-graft junction0: Crossing trabeculae; 1: Discernible cleft 4. Presence of cystic changes of graft and host-graft junction0: Absent; 1: PresentCartilage Features5. Cartilage signal of graft0: Normal; 1: Altered intensity (either hypointense of hyperintense, but not fluid); 2: Fluid signal intensity on all sequences 6. Cartilage “fill” of graft (percentage of volume)0: 76-100%; 1: 51-75% or >100%; 2: <50% 7. Cartilage edge integration at host-graft junction0: No discernible boundary; 1: Discernible boundary; 2: Discernible fissure >1 mm 8. Cartilage surface congruity of graft and host-graft junction0: Flush; 1: <50% offset of host cartilage; 2: >50% offset of host cartilage 9. Calcified cartilage integrity of graft0: Intract, thin, and smooth; 1: Altered (disrupted, thickened or blurred)Ancillary Features10. Opposing cartilage0: Normal; 1: Abnormal (bone marrow edema pattern or hypointensity on all sequences) 11. Meniscal tears0: Absent; 1: Present 12. Synovitis0: Absent; 1: Present 13. Fad pad scarring0: Absent; 1: PresentFigure 1.Representative 12-month coronal and sagittal MRI sections in a (A,B) 20-year-old male, demonstrating crossing trabeculae and minimal subchondral marrow edema, and (C,D) 16-year-old-male, demonstrating discernible clefts at the host-graft junction and significant subchondral marrow edema. Both were treated with BMAC+OCA

The Effects of Hyperacute Serum on the Elements of the Human Subchondral Bone Marrow Niche.

Mesenchymal stem cells (MSCs) are widely used in laboratory experiments as well as in human cell therapy. Their culture requires animal sera like fetal calf serum (FCS) as essential supplementation; however, animal sera pose a risk for clinical applications. Human blood derivatives, for example, platelet-rich plasma (PRP) releasates, are potential replacements of FCS; however, it is unclear which serum variant has the best effect on the given cell or tissue type. Additionally, blood derivatives are commonly used in musculoskeletal diseases like osteoarthritis (OA) or osteonecrosis as “proliferative agents” for the topical MSC pool. Hyperacute serum (HAS), a new serum derivative, has been designed to approximate the natural coagulation cascade with a single-step, additive-free preparation method. We investigated the effects of HAS on monolayer MSC cultures and in their natural niche, in 3D subchondral bone and marrow explants. Viability measurements, RT-qPCR evaluation for gene expression and flow cytometry for cell surface marker analysis were performed to compare the effects of FCS-, PRP-, or HAS-supplemented culture media. Monolayer MSCs showed significantly higher metabolic activity following 5 days' incubation in HAS, and osteoblast-specific mRNA expression was markedly increased, while cells also retained their MSC-specific cell surface markers. A similar effect was observed on bone and marrow explants, which was further confirmed with confocal microscopy analysis. Moreover, markedly higher bone marrow preservation was observed with histology in case of HAS supplementation compared to FCS. These findings indicate possible application of HAS in regenerative solutions of skeletal diseases like OA or osteonecrosis.

How to Manage a Failed Cartilage Repair: A Systematic Literature Review.

Purpose The aims of this paper are to report the rate and risk factors for the failure of the most common cartilage repair technique, and analyze the most important factors that could influence the choice of a specific surgical treatment to revise a failed cartilage repair. Methods A review of the literature was performed focusing on failed cartilage repair and related treatments. Two of the authors independently screened articles. Conflicts about the inclusion of a paper was resolved by further evaluation by the senior author. Review articles, articles written in languages different from/other than English, case reports, and papers that did not evaluate the outcomes of interest were excluded. Full-text version of each included paper was obtained and relevant data were extracted and collected in a database. Results At the end of the screening process, 31 articles were included. Microfractures and mosaicplasty showed a nonnegligible failure rate at short- and midterm. Better results, especially in terms of time to failure or revision, were reported with the use of autologous chondrocyte implantation (ACI) and osteochondral allograft (OCA) transplantation. Regarding the treatment of failed cartilage repair, the use of OCA transplantation in patients with previous failed cartilage repair may be a safe option. The revision of failed OCA transplantation with further OCA seems to have a greater failure rate. Patients with previous failed ACI or matrix-induced autologous chondrocyte implantation (MACI) who underwent further MACI or ACI reported acceptable results. Otherwise, ACI in patients with history of previous subchondral marrow stimulation (SMS) demonstrated a greater failure rate. Conclusion From the analysis of the literature, OCA transplantation seems to be the most reliable treatment of a failed SMS. ACI or MACI showed acceptable results in patients with previously failed MACI or ACI. Level of Evidence Level IV, systematic review of level I-IV studies.

Effect of a Rapidly Degrading Presolidified 10 kDa Chitosan/Blood Implant and Subchondral Marrow Stimulation Surgical Approach on Cartilage Resurfacing in a Sheep Model.

Objective This study tested the hypothesis that presolidified chitosan-blood implants are retained in subchondral bone channels perforated in critical-size sheep cartilage defects, and promote bone repair and hyaline-like cartilage resurfacing versus blood implant. Design Cartilage defects (10 × 10 mm) with 3 bone channels (1 drill, 2 Jamshidi biopsy, 2 mm diameter), and 6 small microfracture holes were created bilaterally in n = 11 sheep knee medial condyles. In one knee, 10 kDa chitosan-NaCl/blood implant (presolidified using recombinant factor VIIa or tissue factor), was inserted into each drill and Jamshidi hole. Contralateral knee defects received presolidified whole blood clot. Repair tissues were assessed histologically, biochemically, biomechanically, and by micro-computed tomography after 1 day ( n = 1) and 6 months ( n = 10). Results Day 1 defects showed a 60% loss of subchondral bone plate volume fraction along with extensive subchondral hematoma. Chitosan implant was resident at day 1, but had no effect on any subsequent repair parameter compared with blood implant controls. At 6 months, bone defects exhibited remodeling and hypomineralized bone repair and were partly resurfaced with tissues containing collagen type II and scant collagen type I, 2-fold lower glycosaminoglycan and fibril modulus, and 4.5-fold higher permeability compared with intact cartilage. Microdrill holes elicited higher histological ICRS-II overall assessment scores than Jamshidi holes (50% vs. 30%, P = 0.041). Jamshidi biopsy holes provoked sporadic osteonecrosis in n = 3 debrided condyles. Conclusions Ten kilodalton chitosan was insufficient to improve repair. Microdrilling is a feasible subchondral marrow stimulation surgical approach with the potential to elicit poroelastic tissues with at least half the compressive modulus as intact articular cartilage.

Characterization of subchondral bone histopathology of facet joint osteoarthritis in lumbar spinal stenosis.

Facet joint osteoarthritis may be a cause of low back pain in degenerative spine diseases including lumbar spinal stenosis. Subchondral bone is regarded as a potential therapeutic target for osteoarthritis treatment. The goal of this study was to characterize subchondral bone histopathology in osteoarthritic facet joints from lumbar spinal stenosis patients. Fifteen patients with degenerative spinal stenosis scheduled for transforaminal lumbar interbody fusion surgery were recruited for this study. Osteoarthritis severity was graded on T1- and T2-weighted MRI images using Weishaupt scoring system. Dissected osteoarthritic facet joints were subjected to histological and immunohistochemistry analyses to study relative abundance of osteoblast, osteoclasts, and macrophages using van Gieson's, tartrate-resistant acid phosphatase and CD68-antibody staining, respectively. Presence of nerve fibers was evaluated by PGP9.5-antibody staining. Differential bone histopathology, independent from radiological osteoarthritis grade, was observed in facet joints. Extensive de novo bone formation was found in subchondral bone tissues of eight of fifteen specimens. Regions of bone formation showed high abundance of blood vessels and CD68-positive macrophages, but were devoid of multinucleated osteoclasts. Additional pathological changes in subchondral marrow spaces, including inflammatory infiltration and enhanced osteoclast activity, were characterized by macrophage-rich tissues. PGP9.5-positive nerve fibers were detected near arterioles, but not in regions displaying bone pathology. Individual histopathological parameters did not associate with clinical features or radiological osteoarthritis severity. Subchondral bone histopathology of facet joint osteoarthritis in lumbar spinal stenosis is characterized by marrow infiltration by macrophage-rich tissues and enhanced de novo bone formation. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1475-1480, 2016.

Back Pain In A Junior Olympian - Running

HISTORY: 15 year old female member of the Uruguay Youth Olympic National Track Team with 1 year of back pain and 8 months of constant, worsening pain. Pain was located in the low lumbar region and worsened when she ran. Running hills and weighted exercises increased the intensity. Also worsened with prolonged sitting or standing. Improved with walking, stretching, and lying supine with knees in flexion. Outside MRI reported signs of degenerative disc pathology at L4-5 and Schmorl nodule of L5. MRI otherwise normal. After the PanAm games she stopped running completely to try to allow for healing; however, pain remained. Gained no benefit from physical therapy at home. Grew 7 cm in the last year. Questionably regular menses. Resting pain a 6/10. PHYSICAL EXAMINATION: Slender young female. Normal alignment of the pelvis. Tender from L3 to the sacrum in the midline and paraspinal region. Tenderness both SI joints. Pain with flexion and extension. Flexion slightly limited with a Schober’s of 20 cm. Extension -1. Lateral bend normal bilaterally without pain. Hip ROM normal. Straight leg raise negative. Popliteal angle of 70 degrees on the right, 40 degrees on the left. Strength and reflexes of upper and lower extremities are normal. DIFFERENTIAL DIAGNOSIS: 1. Sacroiliitis 2. Pars fracture/spondylolisthesis 3. Quadratus lumborum strain 4. Referred pain from hamstring strain 5. Pelvic/sacral stress fracture in the setting of possible female athlete triad 6. Discogenic low back pain 7. Facetogenic back pain TEST AND RESULTS: Sed Rate - 3 CRP - <3 MRI pelvis - Superior margins of both SI joints show significant subchondral marrow edema on both the sacral and iliac sides. Left greater than right subchondral fatty change. Mild disc degeneration at the L4-5 level. Normal gluteal and hamstring tendons. FINAL WORKING DIAGNOSIS: Bilateral acute on chronic sacroiliitis - likely autoimmune. TREATMENT AND OUTCOMES: 1. Core strengthening program. Encouraged to remain as active as possible. 2. Running evaluation. 3. Gradual return to run. 4. Decided not to get HLA-B27 because diagnosis already made. 5. Started on indomethacin 75mg BID. Consideration for TNF blockers in the future. 6. Rheumatology follow-up recommended. Expected to develop characteristic findings of spondyloarthropathy as she gets older. 7. Consider nutrition evaluation.

Histopathological Features of Facet Osteoarthritis in Patients with Lumbar Spinal Stenosis

Introduction Lumbar spinal stenosis (LSS) is a degenerative, age-related narrowing of the lower spinal canal that causes pressure on the nerves, leading to pain and reduced mobility. Hypertrophy of ligament flava and facet joints combined with disc protrusions are a causative for LSS. Osteoarthritic changes to the facet joint, including joint space narrowing, subchondral cysts and osteophyte formation are commonly detected using magnetic resonance imaging (MRI) and computed tomography (CT) scanning. However, the pathomechanisms of facet joint osteoarthritis (OA) at a cellular and molecular level are poorly understood and have been scarcely studied. In this study we sought to investigate the histological features and to uncover cellular pathomechanisms of facet joint OA. Material and Methods Fifteen patients undergoing surgical decompression due to degenerative LSS were included in this study (9 female/6 male, median age 66, range 49–85). Routine preoperative X-ray and MRI scanning of the lumbar spine was performed in all subjects. Severity of facet joint OA was assessed in MRI images using the Weishaupt grading system for the lumbar spine. The medial portion of facet joints was collected during surgical decompression of the spinal canal and processed for tissue histology. Tissue morphology was evaluated using haematoxylin and eosin (HE), Safranin-O and van Gieson's stains. The presence of macrophages, blood vessels and nerve fibers was investigated using immunohistological staining for their respective markers CD68, CD34 and PGP9.5. Functional osteoclasts were visualized using tartrate-resistant acid phosphatase (TRAP) staining. Subchondral bone area fraction (B.Ar/T.Ar) was determined using the ImageJ-plugin BoneJ. Results OA was evident in MRI images characterized by joint space narrowing, bone edema and cysts and hypertrophy of articular processes. The severe OA phenotype in facet joints from LSS patients was confirmed at a histological level by complete loss of proteoglycan staining, CD34+ vessel penetration, and fissuring of cartilage tissue. Subchondral B.Ar/T.Ar ranged between 0.6 and 0.8. In all samples, subchondral marrow spaces contained CD34+ blood vessels and CD68+ mononuclear macrophages. CD68+ multinucleated osteoclasts were detected in resorption pits at the bone surface in 80 percent of the patients. Functionality of osteoclasts was confirmed by positive staining of multinucleated bone cells for TRAP in serial sections. Osteoblast activity was demonstrated in 60 percent of the patients and predominantly characterized by large areas of intramembranous bone formation near the osteochondral junction. Formation of an osteoclast-rich pannus-like tissue was seen in one sample. Innervation of subchondral marrow spaces by PGP9.5-positive nerve fibers was scarce and exclusively found in the vicinity of arterioles. Conclusion Facet joints in LSS patients display radiological and histopathological features of OA. Two major OA phenotypes can be distinguished based upon cellular pathomechanisms in subchondral bone tissue: 1) osteoblast-rich intramembranous bone formation and 2) osteoclast/macrophage rich remodeling. Osteoimmunological mechanisms, specifically the interaction of CD68+ macrophages with bone-resident cells, play a – previously unknown – role in regulating subchondral bone sclerosis in progressive osteoarthritis. Targeting osteoimmunology might hold potential as a disease-modifying treatment for osteoarthritis.

Elevated marrow inflammatory cells and osteoclasts in subchondral osteosclerosis in human knee osteoarthritis.

Subchondral osteosclerosis, characterized by an increase of hypomineralized bone material, is a pathological hallmark of osteoarthritis. The cellular components in the subchondral marrow compartment that participate in this aberrant bone remodeling process remain to be elucidated. This study assessed the presence of marrow inflammatory cells and their relative abundance between nonsclerotic and sclerotic tissues in knee osteoarthritis. Bone samples from osteoarthritic knee tibial plateaus were stratified for histological analyses using computed tomography osteoabsorptiometry. Immunohistological analysis revealed the presence of CD20 (B-lymphocyte) and CD68 (macrophage), but not CD3 (T-lymphocyte) immunoreactive mononuclear cells in subchondral marrow tissues and their relative abundance was significantly increased in sclerotic compared with nonsclerotic bone samples. Multinucleated osteoclasts that stained positive for CD68 and tartrate-resistant acid phosphatase, predominantly associated with CD34-positive blood vessels and their abundance was strongly increased in sclerotic samples. Bone-specific alkaline phosphatase activity in outgrowth osteoblasts was induced by conditioned medium from nonsclerotic, but not sclerotic, bone pieces. These results suggest that an interaction between bone-resident cells and marrow inflammatory cells might play a role in aberrant bone remodeling leading to subchondral osteosclerosis. Elevated osteoclast activity in sclerotic bone suggests that bone formation and resorption activities are increased, yet uncoupled, in human knee osteoarthritis.

Chronic Ankle Instability and Progressing Pain - Wrestling

HISTORY: 53 year old male active former D1 wrestler presented with right ankle pain located anteriorly and anterior lateral. He has an unstable right ankle with multiple episodes of giving away for the past 15 years. Patient had a previous right ankle surgery with bone fragment removed 15 years ago, but no ligament repairs. His activities are restricted, although his goal is to be able to snow board. PHYSICAL EXAMINATION: Examination revealed restricted ROM with PF to 25 deg and DF to 10 deg. Inversion and Eversion were found to be 15 and 10 degrees.He has more soft tissue thickening and swelling over the lateral gutter. No indication of infection. Patient was tender at the lateral gutter, the talofibular ligament, calcaneofibular and mild tenderness over the peroneal’s and sinus tarsi. Anterior drawer was positive. Patient had no pain on the Achilles, negative Thompson. No pain over anterior tib/posterior tib/flex hall longus tendons. Sensations were equal and intact with good pulses present DIFFERENTIAL DIAGNOSIS: 1. Tendonitis of multiple tendon 2. DJD of ankle 3. CPPD 4. Heterotrophic calcification 5. Synovial chondromatosis TEST AND RESULTS: Right ankle AP, oblique and lateral radiographs -DJD of ankle. Unstable with varus stress bilaterally. -Severe osteochondromatosis -Anterior bone spurs MRI of right ankle/hindfoot -Moderately severe to severe degenerative OA in the tibiotalar joint -Chronic instability from ATFL rupture and chronic sprain of deltoid ligament complex -Extensive osteochondromatosis present within the ankle joint, most concentrated in the dilation of the flexor halluces longus tendon sheath -Tenosynovitis of the PT, FD, PL and FHL tendon sheaths -Mild to moderate tendinitis of PL with minimal abnormal grade 2 signal centrally within the peroneus longus tendon -Full-thickness articular cartilage loss and subchondral reactive marrow changes in the tibial plafond and talar dome. FINAL WORKING DIAGNOSIS: Extensive osteochondramatosis within the flexor halluces tendon with tenosynovitis of multiple tendons secondary to chronic ankle instability and DJD TREATMENT AND OUTCOMES: 1. Stability shoe with inserts 2. Physical therapy 3. Ankle scope with bone marrow aspiration, LCL repair, varus hind foot osteotomy, removal of loose fragments and bone spurs schedule for Dec 2014

Fresh Osteochondral Allografts in the Knee

Background: In most treatment algorithms, osteochondral allograft (OCA) transplantation is regarded as an alternative salvage procedure when other, previous reparative treatments have failed. Purpose: To compare the outcomes of a retrospective matched-pair cohort of (1) primary OCA transplantation and (2) OCA transplantation after failure of previous subchondral marrow stimulation. Study Design: Cohort study; Level of evidence, 3. Methods: An OCA database was used to identify 46 knees that had OCA transplantation performed as a primary treatment (group 1) and 46 knees that underwent OCA transplantation after failure of previous subchondral marrow stimulation (group 2). All patients had a minimum of 2 years’ follow-up. Patients in each group were matched for age (±5 years), diagnosis (osteochondral lesion, degenerative chondral lesion, traumatic chondral injury), and graft size (small, <5 cm2; medium, 5-10 cm2; large, >10 cm2). The groups had similar body mass indexes, sex distributions, and graft locations (femoral condyle, patella, and trochlea. The number and type of further surgeries after the OCA transplantation were assessed; failure was defined as any reoperation resulting in removal of the graft. Functional outcomes were evaluated by use of the modified Merle d’Aubigné-Postel (18-point) scale, International Knee Documentation Committee (IKDC) subjective knee evaluation form, Knee injury and Osteoarthritis Outcomes Score (KOOS), and the Knee Society function (KS-F) scale. Patient satisfaction, according to a 5-point scale from “extremely satisfied” to “dissatisfied,” was recorded at the latest follow-up. Results: Eleven of 46 knees (24%) in group 1 had reoperations, compared with 20 of 46 knees (44%) in group 2 (P = .04). The OCA was classified as a failure in 5 knees (11%) in group 1 and 7 knees (15%) in group 2 (P = .53). At 10 years of follow-up, survivorship of the graft was 87.4% and 86% in groups 1 and 2, respectively. Both groups showed improvement in pain and function on all subjective scores from preoperatively to the latest follow-up (all P < .001). Results showed that 87% of patients in group 1 and 97% in group 2 were “satisfied” or “extremely satisfied” with the OCA transplantation. Conclusion: Favorable results were shown in both groups with significant improvement of functional scores and excellent survivorship. Despite the higher reoperation rate in the previously treated group, previous subchondral marrow stimulation did not adversely affect the survivorship and functional outcome of OCA transplantation.

Osteochondral Allograft Transplantation for Knee Lesions after Failure of Cartilage Repair Surgery.

Objective:The objective of this study was to assess the outcome of osteochondral allograft (OCA) transplantation as a salvage procedure after various cartilage repair surgeries.Design:One hundred sixty-four knees in 163 patients (mean age = 32.6 years; range = 11-59 years; 55% males) were treated with OCA transplantation after subchondral marrow stimulation (SMS), osteochondral autograft transplantation (OAT), and autologous chondrocyte implantation (ACI). The majority of previous procedures were isolated SMS in 145 knees (88.4%). Mean allograft size was 8.5 ± 7.9 cm2. The most common location was in femoral condyle. The number and type of reoperations on the operative knee were assessed. Failure of the OCA transplantation was defined as any reoperation resulting in removal of the allograft. Functional outcomes were evaluated.Results:Sixty-eight knees had reoperations after OCA transplantation. Thirty-one knees (18.9%) were classified as allograft failures. The median time to failure was 2.6 ± 6.8 years (range = 0.7-23.4 years). Survivorship of the graft was 82% at 10 years and 74.9% at 15 years. Patients whose grafts were still in situ had a mean of 8.5 ± 5.6 years of follow-up. Scores on all functional outcomes scales improved significantly from preoperatively to latest follow-up. Eighty-nine percent of OCA transplantation patients reported being “extremely satisfied” or “satisfied.”Conclusion:Despite the high reoperation rate, OCA transplantation is a successful salvage surgical treatment after cartilage repair procedures. This cohort showed improved survivorship and functional outcomes of OCA transplantation after SMS, ACI, and OAT.

Role of magnetic resonance imaging in the evaluation of articular cartilage in painful knee joint

<b>Aim:</b> The aim of this study was to determine the role of the magnetic resonance imaging (MRI) in patients with atraumatic knee pain. <b>Background and Objectives:</b> Knee pain is one of the most common problems faced by people from time immemorial. There is a wide range of disease ranging from traumatic to degenerative causing knee pain in which articular cartilage is involved. Over the past 15 years, MRI has become the premier, first-line imaging study that should be performed in the evaluation of the painful knee in particular in tears of menisci, cruciate and collateral ligaments, osteochondral abnormalities (chondromalacia, osteoarthritis and osteochondral defects), synovial cysts and bone bruises. MRI, by virtue of its superior soft-tissue contrast, lack of ionizing radiation and multiplanar capabilities, is superior to more conventional techniques for the evaluation of articular cartilage. <b>Materials and Methods:</b> A prospective study was carried out on 150 patients in the Department of Radio-diagnosis, Padmashree Dr. D. Y. Patil Medical College, Hospital and Research Centre, Pimpri, Pune over a period of 2 years from June 2011 to May 2013. Patients having fracture or dislocations of the knee joint were also excluded from the study. Detailed clinical history, physical and systemic examination findings of all patients were noted in addition to the laboratory investigations. All patients were subjected to radiograph of knee anterior-posterior and lateral view. MRI was performed with Siemens 1.5 Tesla MAGNETOM Avanto machine. <b>Results:</b> In our study of 150 patients with knee pain, articular cartilage defect was found in 90 patients (60%). Out of 90 patients with articular cartilage defect, 30 patients (20%) had full thickness cartilage defects. Subchondral marrow edema was seen beneath 30 patients (20%) with articular cartilage defects. 32 patients (21.1%) had a complex or macerated meniscal tear. Complete anterior cruciate ligament tear was found in seven patients. Joint effusions were detected in 70% (105) of the knees. Large Baker cysts were observed in 6.1% of the knees. <b>Conclusion:</b> In conclusion, individual with acute or chronic knee pain without any definite history of trauma should be subjected to MRI study of the knee provided radiographs are non-informative or non-diagnostic. The study not only outlines the tendons, ligament and cartilage status, but also demonstrates subtle underlying bony pathologies causative for patient complaints.