Eventual Osteoarthritis Research Articles

Strategies for the Codelivery of Osteoclasts and Mesenchymal Stem Cells in 3D-Printable Osteochondral Scaffolds.

Osteochondral defects, characterized by structural compromises to articular cartilage and subchondral bone, can cause pain and lead to progressive cartilage damage and eventual osteoarthritis. Unfortunately, repairing these defects remains difficult because of the poor regenerative properties of cartilage and complex mechanical demands of the joint. As such, the field of tissue engineering aims to develop multiphasic implants that replace pathological cartilage and bone tissue and restore mechanical functionality to the joint. Recent bone physiology investigations have demonstrated that osteoclast (OC) lineage cells are inextricably involved in osteoblastic bone formation through an extensive network of anabolic signaling pathways, and so the codelivery OC and osteoblast (OB) lineage cells within scaffolds is being actively explored for bone tissue engineering purposes. However, it remains unclear how these cells can be incorporated into the design of multiphasic osteochondral scaffolds to potentially enhance subchondral bone formation and subsequent implant osseointegration. To explore this question, we examined direct surface seeding and hydrogel encapsulation as potential scaffold cellularization strategies. First, we examined how OC precursor cells and peripheral blood monocytes (PBMCs) influence early-stage bone matrix development and osteogenesis in 2D coculture. Then, we evaluated the osteogenic potential of mesenchymal stem cells (MSCs) and PBMCs cocultures encapsulated within a gelatin methacrylate (GelMA) hydrogel system. Our findings demonstrate that coculturing PBMCs with MSCs in 2D cultures significantly enhanced cell proliferation, early bone matrix deposition, and the formation of cell clusters by Day 28. However, we observed no significant difference in type I collagen deposition between GelMA hydrogel scaffolds cultured in basal and OC conditions during the same period. In addition, we found that the GelMA hydrogel system with MSC/PBMC cocultures in OC conditions exhibited decreased osteogenic activity by Day 28. Collectively, our findings support the osteogenic potential of OC-lineage cells in 2D culture conditions, and the potential benefits of surface-seeding for the codelivery of OC-lineage cells and MSCs in osteo-scaffolds for enhanced osteochondral regeneration and broader bone tissue engineering purposes.

The Effect of Neonatal, Juvenile, and Adult Donors on Rejuvenated Neocartilage Functional Properties.

Cartilage does not naturally heal, and cartilage lesions from trauma and wear-and-tear can lead to eventual osteoarthritis. To address long-term repair, tissue engineering of functional biologic implants to treat cartilage lesions is desirable, but the development of such implants is hindered by several limitations, including (1) donor tissue scarcity due to the presence of diseased tissues in joints, (2) dedifferentiation of chondrocytes during expansion, and (3) differences in functional output of cells dependent on donor age. Toward overcoming these challenges, (1) costal cartilage has been explored as a donor tissue, and (2) methods have been developed to rejuvenate the chondrogenic phenotype of passaged chondrocytes for generating self-assembled neocartilage. However, it remains unclear how the rejuvenation processes are influenced by donor age and, thus, how to develop strategies that specifically target age-related differences. Using histological, biochemical, proteomic, and mechanical assays, this study sought to determine the differences among neocartilage generated from neonatal, juvenile, and adult donors using the Yucatan minipig, a clinically relevant large animal model. Based on the literature, a relatively young adult population of animals was chosen due to a reduction in functional output of human articular chondrocytes after 40 years of age. After isolation, costal chondrocytes were expanded, rejuvenated, and self-assembled, and the neocartilages were assessed. The aggregate modulus values of neonatal constructs were at least 1.65-fold of those from the juvenile or adult constructs. Poisson's ratio also significantly differed among all groups, with neonatal constructs exhibiting values 49% higher than adult constructs. Surprisingly, other functional properties such as tensile modulus and glycosaminoglycan content did not significantly differ among groups. Total collagen content was slightly elevated in the adult constructs compared to neonatal and juvenile constructs. A more nuanced view using bottom-up mass spectrometry showed that Col2a1 protein was not significantly different among groups, but protein content of several other collagen subtypes (i.e., Col1a1, Col9a1, Col11a2, and Col12a1) was modulated by donor age. For example, Col12a1 protein content in adult constructs was found to be 102.9% higher than neonatal-derived constructs. Despite these differences, this study shows that different aged donors can be used to generate neocartilages of similar functional properties. Impact statement Tissue-engineered neocartilage can be generated with functional properties that mimic native cartilage tissue. However, cell sourcing challenges hinder clinical translation of tissue-engineered cartilage. Chondrocytes can be expanded and rejuvenated for the generation of functional self-assembled cartilage, making an allogeneic approach feasible. However, it is currently unclear if donor age impacts functional properties. In this study, using the Yucatan minipig as a clinically relevant large animal model, we demonstrate that functional properties of self-assembled neocartilage are relatively consistent regardless of donor age, suggesting that a wider range of donor ages may be used for cartilage tissue engineering than previously expected.

Degenerative Joint Disease After Meniscectomy.

The meniscus has an important role in stabilizing the knee joint and protecting the articular cartilage from shear forces. Meniscus tears are common injuries and can disrupt these protective properties, leading to an increased risk of articular cartilage damage and eventual osteoarthritis. Certain tear patterns are often treated with arthroscopic partial meniscectomy, which can effectively relieve symptoms. However, removal of meniscal tissue can also diminish the ability of the meniscus to dissipate hoop stresses, resulting in altered biomechanics of the knee joint including increased contact pressures. This makes meniscal repair an important treatment consideration whenever possible. Understanding the incidence and mechanism of osteoarthritis development after arthroscopic partial meniscectomy as it relates to different tear morphologies and other treatment alternatives (ie, meniscus repair) is important to appropriately treat meniscus tears.

Early knee loading asymmetries may be at the root of eventual osteoarthritis development after anterior cruciate ligament reconstruction

Purpose: Osteoarthritis (OA) development after anterior cruciate ligament (ACL) reconstruction (ACLR) is a well-documented phenomenon. Those who develop OA after ACLR display altered gait mechanics, such as reduced involved (IN) limb peak medial compartment force (pMCF, vs uninvolved [UN]) as early as 6 months after surgery. Recent advancements in magnetic resonance imaging (MRI) have allowed for the quantification of tissue degeneration via quantitative MRI (qMRI) techniques such as T2 mapping.

Short-Term Outcomes of Synovectomy and Total Knee Replacement in Patients with Diffuse-Type Pigmented Villonodular Synovitis.

Diffuse-type pigmented villonodular synovitis is a rare benign disease that causes disorders of the knee, including erosion of subchondral bone and cyst formation, with eventual osteoarthritis. The purpose of this study was to evaluate the short-term outcomes of synovectomy and total knee replacement in patients with the diffuse type of pigmented villonodular synovitis. From November 2011 to May 2015, we performed synovectomy and total knee replacement in 28 patients with diffuse pigmented villonodular synovitis diagnosed on the basis of histopathology of biopsy specimens. Clinical data were collected perioperatively and during follow-up for evaluation of surgical efficacy. No intraoperative complications were encountered. Mean operative duration was 73.4 minutes (range: 47-115 minutes); mean estimated blood loss was 223.9 mL (range: 50-600 mL). The mean duration of follow-up was 58.7 months (range: 36-84 months). Mean range of motion improved from 86.1 ± 11.3 degrees (range: 60-100 degrees) to 107 ± 11.4 degrees (range: 90-130 degrees). Average Knee Society clinical scores improved from 38.9 ± 9.5 (range: 17-54) to 84.4 ± 6.1 (range: 75-98); functional scores improved from 48.9 ± 13.1 (range: 25-80) to 84.6 ± 6.1 (range: 75-95; p < 0.05 for both). Postoperative radiographs showed no signs of prosthesis loosening, periprosthetic fractures, or dislocation. The short-term efficacy of synovectomy and total knee replacement in treating patients with diffuse pigmented villonodular synovitis was satisfactory.

Nanotherapy Targeting NF-κB Attenuates Acute Pain After Joint Injury.

Inflammation after joint injury leads to joint responses that result in eventual osteoarthritis development. Blockade of inflammation, by suppressing NF-κB expression, has been shown to reduce joint injury-induced chondrocyte apoptosis and reactive synovitis in vivo. Herein, we demonstrate that the suppression of NF-κB p65 expression also significantly mitigates the acute pain sensitivity induced by mechanical injury to the joint. These results suggest that early intervention with anti-NF-κB nanotherapy mitigates both structural and pain-related outcomes, which in turn may impact the progression of post-traumatic osteoarthritis.

Ptosis of the hip: a new radiographic finding in patients undergoing femoroacetabular osteoplasty.

ABSTRACTPtosis is a newly described phenomenon appearing on AP radiographs of patients undergoing femoroacetabular osteoplasty (FAO), and refers to a reverse break down in Shenton’s Line. Thorough characterization of this phenomenon is needed to better understand the hip morphology and pathologic ramifications. Our goal was to define the radiographic hip parameters accompanying a break down in Shenton’s Line and to determine how these values compare with standard values in normal hips. Using two independent readers, we retrospectively reviewed the medical records and preoperative supine radiographs of 630 patients (1260 hips) who underwent FAO by a single surgeon between 2003 and 2016. Prevalence of hip pathology and 28 radiographic parameters in ptosis hips was measured, as well as a comparison between unilateral ptosis hips and contralateral normal hips. Of the 53 patients (106 hips) who fulfilled the criteria for the study, 94 hips had a Shenton’s Line break down of at least 5 mm. Sixty-nine percent of ptosis hips had femoroacetabular impingement (FAI), 70.2% had coxa profunda, and 52.1% had partial joint space narrowing. Ptosis hips had 1.05 mm less lateral subluxation (P = 0.012), 2.28° larger Center-edge angle (P = 0.046), 2.59° smaller Sharp angle (P = 0.011) and 2.49% smaller extrusion index (P = 0.016) compared with contralateral normal hips. FAI is prevalent in patients with a positive ptosis sign. The high prevalence of partial joint space narrowing could suggest eventual osteoarthritis. We believe our results demonstrate the importance of further investigation of a positive ptosis sign on AP pelvic radiographs.

Early-stage osteonecrosis of the femoral head: where are we and where are we going in year 2018?

Osteonecrosis of the femoral head (ONFH) is a devastating condition affecting relatively young patients whereby the femoral head is necrotic, resulting in significant pain, articular surface collapse, and eventual osteoarthritis. This condition has been highly associated with chronic steroid use, alcoholism, and hip trauma, as well as other less common conditions. Without intervention, this condition has a high likelihood of progressing and developing into end-stage osteoarthritis. Unfortunately, ONFH is difficult to diagnose on plain radiographs in the early stages of the disease, and often requires more advanced imaging modalities such as MRI in order to fully assess for early degeneration. Providers, therefore, must have a high index of suspicion when a younger patient presents with hip pain and negative X-rays. Unfortunately, in patients whose femoral heads have already collapsed, joint-preserving procedures are not effective, and total hip arthroplasty remains the most reliable long-term treatment. Multiple treatments have been pursued to address osteonecrosis in patients whose femoral head have not yet collapsed, but the results of these treatments are mixed. The most promising of these interventions to date is core decompression with the use of concentrated bone marrow aspirate to improve the healing potential of the femoral head. Further studies including randomized clinical trials are necessary in order to assess the effectiveness of this therapy, the best possible source of cells and the best method of implantation in order to further improve results in those with pre-collapse ONFH.

Abnormal Gutter Geometry as a Risk Factor of Chronic Ankle Instability

Category: Ankle, Sports Introduction/Purpose: Abnormalities in the tibial plafond geometry, such as varus deformity or insufficient talar anterior coverage, have been recognized as the congenital risk factors of chronic ankle instability (CAI) and eventual osteoarthritis (OA) development. Given that the gutter articulations are playing a substantial role in ankle stability, presumably, geometrical abnormality of these articulations also increases such risks, though this concept has not been well addressed to date. Our recent study (2016 AOFAS Annual Summer Meeting) revealed that OA ankles are frequently (&gt;50%) marked by excessive anterior and/or inferior opening of the talar side-walls. The present study examined whether or not CAI cases share these geometrical characteristic, so as to identify a risk factor that predispose ankles to CAI and eventual OA development. Methods: Clinical multi-detector computed tomography (MDCT) images, from 29 symptomatic CAI cases who were indicated for surgical repair or reconstruction of the lateral ligaments, and from 54 asymptomatic non-degenerative (control) ankles, were selected for 3-D morphometric evaluation of the talar dome side-wall geometry. Using a DICOM viewer, a local coordinate system for each ankle was established using talar landmarks. Then, on a transverse section at 3-5 mm distal to the superior aspect of the talar trochlea, the angle between the medial and lateral side-wall tangential lines (regressed from five cortical surface reference points for each) was measured as the “anterior opening angle.” Similarly, the “inferior opening angle” was measured on a mid-coronal section. Differences between groups were statistically tested using a t-test. Results: The anterior opening angles in CAI cases (mean +/- SD: 11.9 +/- 4.4 degrees) were significantly larger (p &lt; 0.001) than in control cases (7.4 +/- 3.4). Defining the range of mean +/- 2SD in Control as “normal” (Figure 1), 9 out of 29 CAI cases (31%) had excessive anterior opening of the talar side-wall surfaces. Although the inferior opening angle did not exhibit significant difference between the groups (28.5 +/- 9.6 in CAI versus 25.5 +/- 5.9 in Control, p = 0.082). Defining the range of mean +/- 2SD in Control as “normal” (Figure 1), 4 CAI cases (14%) had excessive inferior opening. In total, 12 out of 29 CAI cases (41%) had abnormal talar side-wall geometry. Conclusion: These data suggest that a certain fraction of CAI ankles feature abnormal geometrical characteristics consistent with OA ankles, i.e. excessive anterior and/or inferior opening of the talar dome side-walls. Given that none of the CAI cases had remarkable degenerative or traumatic deformities, these characteristics are arguably congenital. Theoretically, the posteriorly narrower shape of the talar trochlea would reduce talocurural congruity in plantar flexion, while the inferiorly wider shape itself would reduce coronal plane stability. These geometrical abnormalities appear to predispose ankles to CAI. For such ankles, aggressive surgical stabilization may forestall OA development following lateral ligament injuries.

Reliability of Tönnis classification in early hip arthritis: a useless reference for hip-preserving surgery.

The Tönnis classification is widely accepted for grading hip arthritis, but its usefulness as a reference in hip-preserving surgery is yet to be demonstrated. We aimed to evaluate reproducibility of the Tönnis classification in early stages of hip osteoarthritis, and thus determine whether it is a reliable reference for hip-preserving surgery. Three orthopaedic surgeons with different levels of experience examined 117 hip X-rays that were randomly mixed of two groups: a group of 31 candidates for hip-preserving surgery and a control group of 30 patients that were asymptomatic with respect to the hip joint. The surgeons were asked to rate an eventual osteoarthritis according to the Tönnis classification. After 2 months, the surgeons were asked to re-evaluate the X-rays in a random order. Intra- and interobserver reliabilities were calculated by comparing the observers' two estimations using Kappa statistics. Kappa values for interobserver reliability were slight or fair (range 0.173-0.397). Kappa values for intraobserver reproducibility were fair (range 0.364-0.397). Variance in grading no and slight osteoarthritis was the most frequent cause for intra- and interobserver disagreements (76.3 and 73.01% of the non-concordant observations, respectively). The confidence interval analysis showed that the observers' experience did not affect reproducibility. The Tönnis classification is a poor method to assess early stages of hip osteoarthritis. These findings suggest that its routine use in therapeutic decision-making for conservative hip surgery should be reconsidered.

Ultrasonographic Assessment of the Distal Femoral Cartilage Thickness in Patients with Homozygous Sickle Cell Disease.

To compare the distal femoral cartilage thickness of patients with sickle cell disease (SCD) with those of healthy subjects using ultrasonography. The study comprised 30 patients with SCD (16 male, 14 female; mean age, 30.1 years) and 30 age- and sex-matched healthy subjects. Demographic features and medications of the patients were recorded. With the knees held in maximum flexion, the femoral cartilage thickness was measured bilaterally with a 7- to 12-MHz linear probe. Using ultrasonography, 3 midpoint measurements were taken from both knees: lateral femoral condyle (LFC), intercondylar area (ICA), and medial femoral condyle (MFC). Patients with SCD had thinner femoral cartilage thickness values at LFC (P = 0.004), at MFC (P = 0.000), and ICA (P = 0.002) when compared with those of the healthy subjects. Patients with SCD also had lower Hb levels (P = 0.000) levels. Weak positive correlations were determined between Hemoglobin (Hb) levels and ultrasonographic measurements in the SCD group at MFC (r = 0.331, P = 0.010), and ICA (r = 0.289 , P = 0.025 ). Low levels of Hb seem to affect the femoral cartilage thickness. These preliminary findings of decreased femoral cartilage thickness in SCD patients should be complemented with future studies. The possibility of early knee joint degeneration and eventual osteoarthritis in SCD should be kept in mind.

Femoroacetabular impingement: current concepts in diagnosis and treatment.

As a result of reading this article, physicians should be able to: 1. Identify the etiology of femoroacetabular impingement. 2. Assess femoroacetabular impingement on physical examination. 3. Recognize femoroacetabular impingement on imaging studies. 4. Discuss modern techniques to effectively treat femoroacetabular impingement, both open and arthroscopic. Femoroacetabular impingement (FAI) is a recently proposed concept describing abnormal anatomic relationships within the hip joint that may lead to articular damage. Impingement is caused by bony deformities or spatial malorientation of the femoral head-neck junction and/or the acetabulum. These abnormalities lead to pathologic contact and shearing forces at the acetabular labrum and cartilage during physiological hip motion. There is an increasing body of evidence that these forces lead to cartilage wear and eventual osteoarthritis. Treatment options for FAI are evolving rapidly. Although the gold standard remains open hip dislocation, arthroscopic techniques have shown significant promise. It is possible that early recognition and treatment of subtle deformity about the hip may reduce the rate of hip osteoarthritis in the future.

Osteonecrosis of the femoral head: An update in year 2012

Osteonecrosis is a phenomenon involving disruption to the vascular supply to the femoral head, resulting in articular surface collapse and eventual osteoarthritis. Although alcoholism, steroid use, and hip trauma remain the most common causes, several other etiologies for osteonecrosis have been identified. Basic science research utilizing animal models and stem cell applications continue to further elucidate the pathophysiology of osteonecrosis and promise novel treatment options in the future. Clinical studies evaluating modern joint-sparing procedures have demonstrated significant improvements in outcomes, but hip arthroplasty is still the most common procedure performed in these affected younger adults. Further advances in joint-preserving procedures are required and will be widely studied in the coming decade.

Current management of femoro-acetabular impingement

Summary Femoro-acetabular impingement (FAI) is a common cause of hip pain in young adults. The condition can result in labral tears, articular cartilage lesions and eventual osteoarthritis of the hip. FAI results from an abnormal bony shape of the femoral head / neck or the acetabular rim or both, which causes contact (impingement) between the neck and acetabular rim during movement of the hip joint. Two different mechanisms are described, although a combination of the two mechanisms is frequent. Cam impingement is caused by an abnormality of the femoral head and neck; principally a reduction in offset between the head and the neck. Pincer impingement is caused by an abnormality on the acetabular side, with either excessive retroversion of the acetabulum or an unduly prominent anterior wall. Either problem is associated with the development of chondral lesions (especially in the acetabulum) and labral pathology. Patients with FAI usually present with deep groin pain exacerbated by hip flexion. X-rays typically show an anterior impingement bump on the anterior femoral neck on a horizontal beam lateral, abnormalities of head/neck offset or an excessively prominent anterior acetabular wall. Surgery is the treatment of choice and this involves open or arthroscopic bony resection to improve femoral head-neck clearance with either resection or refixation of the damaged labrum. Both the femoral head/neck junction and the acetabular rim may require bony resection. Such surgery yields good symptomatic relief, but whether the surgery prevents the development of osteoarthritis in the hip in the long term is currently unknown.

The destructive capabilities of the synovium in the haemophilic joint.

The pathogenesis of chronic haemophilic synovitis and the destructive capabilities of the synovium are multifactorial. As a result of repeated haemarthroses, synovial hyperthrophy occurs, iron and cellular debris are phagocytized, and hydrolytic enzymes synthesized by the proliferating synovium are released into the joint. An inflammatory process develops, and the nutrition of the articular cartilage is affected by the abnormal synovial fluid, immobilization of the joint, and the presence of fibrous adhesions. Chronic hypertrophic synovitis is a progressive destructive condition in the joint and, unless it is treated, the joint is doomed. With the development of cartilaginous destruction, progressive chondrolysis and eventual osteoarthritis set in.