Osteochondritis dissecans (OCD) is an increasingly common cause of knee pain and dysfunction among skeletally immature and young adult patients. An ideal treatment strategy with an optimal surgical technique to repair the osteochondral lesions in these patients is still controversial. The goal of this study is to evaluate and report the clinical and MRI findings for the treatment of OCD in the pediatric knee with bone marrow–derived cell transplantation by using a one-step surgical technique.
Osteochondritis dissecans (OCD) is a joint disorder with an increasingly common cause of knee pain and dysfunction among skeletally immature and young adult patients, especially those involved in competitive sports. Although the average age at presentation is between 10 and 20 years, OCD may occur in people of any age group. Men are more likely (two to three times) to develop OCD than women. In the knee joint, the posterolateral area of the medial femoral condyle is the most commonly involved site. OCD is characterized by an acquired, idiopathic lesion of subchondral bone with osseous reabsorption, collapse, and sequestrum formation that causes a spectrum of osteochondral lesions, from softening of the intact articular cartilage to a complete separation of osteochondral fragments and intra-articular loose bodies. An osteochondral fragment may be present in situ, partially or completely detached.
Although the origin of OCD remains controversial, plausible causes include endocrine disorders, familiar predisposition, vascular insufficiency, articular epiphyseal ossification aberrations, and repetitive trauma. Different classifications of OCD have been proposed basing on anatomic location, age of occurrence (juvenile and adult forms), joint pathology, and radiographic (scintigraphy and MRI) findings. Specifically, it is important to distinguish knee OCDs in skeletally immature patient from skeletally mature, because the natural history of cartilage growth, development, and repair varies in these two populations, with worse prognosis in patients with closed distal femoral physes.
Typically, the clinical signs and symptoms of OCD include pain, joint locking, decreased range of motion, swelling, tenderness, joint stiffness, and loose bodies (cartilage or osteochondral) in the joint. Treatment strategies of OCD are intended to restore the normal functioning of the affected joint and to alleviate pain. Early diagnosis and treatment of OCD, when most lesions are stable, is important in young patients to minimize the risk of long-term disability and provide the patient with more treatment options. If left untreated, OCD increases the risk of the patient eventually developing osteoarthritis in the affected knee. Although the ideal treatment strategy for OCD is still controversial, the osteochondral lesion of children whose bones are still growing may heal spontaneously with a period of rest and support. In a compliant patient with an immature epiphysis and a stable lesion, the likelihood is approximately 50% that the lesion will heal within 10 to 18 months with nonoperative treatment.
Failure of nonoperative treatment, usually after at least 3 to 6 months, is an indication for operative intervention. Drilling, open/arthroscopic fixation, fragment excision, microfractures, osteochondral grafting (autograft or allograft), and autologous chondrocyte implantation (ACI) have been described as viable surgical procedures. Among them, when fixation is not possible, osteochondral plug replacement procedures have the advantage of repairing osteochondral defects with viable autologous cartilage and bone, which have the capability to integrate with the adjacent native tissue. However, donor site pathology, discontinuity in the orientation of the cartilage plugs, and fibrocartilage in the gaps are disadvantages of autografts, whereas the idea of transplanting freshly obtained allograft provides the option of having a high-quality viable tissue. Cartilage regeneration using ACI instead provides a continuous cartilage repair with no or minimal donor site pathology. However, because ACI treatment requires two operative procedures with associated high costs, new methods of cartilage regeneration have been sought.
The ideal treatment strategy with an optimal surgical technique to repair the osteochondral lesions in patients with OCD is still controversial. Recently, a new one-step surgical procedure based on the transplantation of bone marrow–derived cells (BMDCs) was proposed for osteochondral repair in the ankle and knee, and subsequently, because of the satisfactory results obtained, has also been indicated for juvenile OCD. The rationale of BMDC transplantation is based on the capability of the multipotent cells along with their microenvironment to differentiate and regenerate both the cartilaginous and subchondral bone layer.
The goal of this study was to evaluate and report the clinical and MRI findings for the treatment of OCD lesion of the knee with BMDC transplantation using a one-step surgical technique in six juvenile patients with a 3-year follow-up.
Materials and methods
The study protocol was approved by an independent ethical committee, and signed informed consent for participation in this investigation was obtained from all included patients.
Patients
Six juvenile patients with OCD (four women and two men; mean age, 16 years; age range, 14–18 years) received osteochondral repair treatment in the affected knee with BMDC transplantation using a one-step surgical technique. Patients inclusion criteria were nonresponsiveness to conservative therapy and stage three to four osteochondral lesion, based on the International Cartilage Repair Society (ICRS) classification. The mean osteochondral defect size of these patients was 4.6 ± 1.5 cm 3 .
Patients
Six juvenile patients with OCD (four women and two men; mean age, 16 years; age range, 14–18 years) received osteochondral repair treatment in the affected knee with BMDC transplantation using a one-step surgical technique. Patients inclusion criteria were nonresponsiveness to conservative therapy and stage three to four osteochondral lesion, based on the International Cartilage Repair Society (ICRS) classification. The mean osteochondral defect size of these patients was 4.6 ± 1.5 cm 3 .
Clinical evaluation
To determine the clinical outcome, the knees were examined preoperatively and at 3 years’ follow-up and evaluated using International Knee Documentation Committee (IKDC) scores. This scoring system provides a measure of function so that higher the scores reflect higher level of function and lower level of symptoms. According to this system, the lowest possible score is 18 and the highest possible score is 100. Therefore, a score of 100 indicates no limitation with daily living or sports activities, along with absence of symptoms.
MRI evaluation
Based on the protocol suggested by the ICRS, MRI evaluation of the treated knee was performed at 3 years’ follow-up in all cases using a three-dimensional Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) scoring system. The MOCART criteria used to evaluate the cartilage repair were the (1) degree of filling of osteochondral defect (complete, hypertrophic, incomplete [inferior or superior to the 50% of the defect], exposure of subchondral bone); (2) integration of the regenerated tissue to the adjacent native tissue at the border zone (complete, incomplete); (3) surface of the regenerated tissue (intact, damaged inferior or superior to the 50% of the surface regenerated); (4) delayed-phase fast spin-echo (DPFSE) fat-saturated MR signal intensity of the regenerated tissue (isointense, moderately hyperintense, markedly hyperintense); (5) integrity of the lamina and subchondral bone; and (6) presence of joint effusion and subchondral edema. Both depth (mm) and volume of the regenerated defect (mm 3 ) were calculated with manual trace. The volume was calculated with the formula of the ellipsoid (A × B × C × 4/3π).
MR images were obtained using a 1.5T MR scanner (Signa HDxt, GE Healthcare, Buckinghamshire, UK) and a dedicated phased array coil. DPFSE MR pulse sequence was used to obtain coronal (with and without fat saturation) and sagittal (with fat saturation) high-resolution images. For all the patients, MRI acquisition protocol at 3 years’ follow-up was completed by coronal and sagittal T2 mapping high-resolution sequence with the following MR parameters: repetition time, 1000 ms; echo time range, 10 to 80 ms (for study of hyaline cartilage); matrix, 256 × 256; gap spacing 0; slice thickness 2 mm; and acquisition 1. T2 mapping was obtained using a multiecho (8 echoes train) and multislice (18 slices) sequence, with a total of 144 images acquired. Specific postprocessing T2 map software with final T2 grading-color maps had to be used for normal and regenerated cartilage. Coronal and sagittal MRI views were considered for T2 mapping evaluation. Measurement of the spatial distribution of the T2 map reveals areas with increased or decreased water content. These areas were measured with manual trace for single acquired slices.
In agreement with the study by Welsch and colleagues, the regions of interest (ROIs) covering a cartilage repair tissue were positioned within the identified cartilage repair sites. In all cases, cartilage repair sites were seen on three to five contiguous sagittal and coronal sections, and two to three ROIs were placed within the regenerated tissue per section. A region of morphologically normal-appearing cartilage within the same knee was selected as a reference (control), with three ROIs positioned along the control cartilage tissue. Anatomically, because all areas of cartilage repair were located within the weight-bearing zone of the femoral condyle, and therefore the reference cartilage sites were also selected from the weight-bearing area of the femoral articular surface. Cartilage was defined as normal when full thickness was preserved relative to the adjacent native cartilage and the articular surface was intact, and if no intraarticular MR signal intensity variations were visible.
Statistical analysis
All continuous data were expressed in terms of mean and standard deviation of the mean. A paired t -test was performed to test differences between basal and final measures, and MR T2 map value comparison between regenerated tissue and adjacent native cartilage (control). The Mann-Whitney test, evaluated using the Monte Carlo method for small samples, was performed to test differences between means of different groups. Spearman rank correlation was performed to investigate the relationships between continuous variables. For all tests, a P value less than 0.05 was considered significant. Because of the small sample, the authors decided to report all the Spearman correlations greater than 0.6. Statistical analysis was performed using the Statistical Package for the Social Sciences (SPSS) software version 15.0 (SPSS Inc., Chicago, Illinois, USA).
Surgical technique
Platelet Gel Production
A total of 120 mL of the patient’s venous blood was obtained and processed the day before surgery with the Vivostat System (Vivolution, Denmark, Birkeroed) to provide 6 mL of platelet-rich fibrin (PRF) gel.
Bone Marrow Aspiration
With the patient prone under spinal or general anesthesia, a total of 60 mL bone marrow aspirate was harvested from the posterior iliac crest with a marrow needle (size, 11 gauge × 100 mm) inserted 3 cm deep into the iliac bone. An aliquote of 5-mL bone marrow was aspirated from the iliac crest into a 20 mL plastic syringe internally coated with calcium–heparin solution. This procedure was repeated several times through the same skin opening until a total of 60 mL of bone marrow aspirate was collected. The marrow was aspirated in small fractions from different points to maximize the harvesting of the marrow stromal cells and to reduce dilution by peripheral blood.
Bone Marrow Concentration
The harvested bone marrow was processed directly in the operating room through removing most of the erythrocytes and plasma. A cell separator (Smart PReP, Harvest Technologies Corp., Plymouth, MA, USA) consisting of a centrifuge and a disposable double chamber device, provided 6 mL of concentrate containing nucleated cells after 15 minutes of multiple centrifugation cycles.
Arthroscopic BMDC Transplantation
After the bone marrow harvesting phase, a standard knee arthroscopy was performed, with the patient in the supine position. The OCD lesion was identified ( Fig. 1 ), and the detached fragment was removed and measured ( Fig. 2 ). A flipped cannula was inserted into the portal ipsilateral to the lesion to enable insertion of the surgical instrumentations and to retract the fat pad from the operative field. Using a specifically designed low-profile drill, the debridement of the osteochondral lesion was performed to create a circular biomaterial implantation site area with surrounding healthy native cartilage margins.
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Acute Traumatic and Sports-Related Osteochondral Injury of the Pediatric Knee
Epidemiology, Pathogenesis, and Imaging of Arthritis in Children
Articular Cartilage Development: A Molecular Perspective
Structural and Functional Maturation of Distal Femoral Cartilage and Bone During Postnatal Development and Growth in Humans and Mice
Clinical Relevance of Scaffolds for Cartilage Engineering
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