Background: The pathogenesis of human juvenile osteochondritis dissecans (JOCD) remains poorly understood, with multiple factors implicated, including ischemia, repetitive trauma, and genetic predisposition. Similarities in the predilection site and the diagnostic and clinical features of JOCD to the well-characterized veterinary counterpart, osteochondrosis dissecans, suggest that, similar to the animal disease, the pathogenesis JOCD may also be initiated in the first few years of life, when disruption of blood supply to the epiphyseal growth cartilage leads to failure of endochondral ossification. To gather data in support of the hypothesis that JOCD and osteochondrosis dissecans have a shared pathogenesis, biopsy specimens obtained from predilection sites of JOCD in juvenile human cadavers were histologically examined to determine whether they contained lesions similar to those found in animals diagnosed with subclinical osteochondrosis dissecans. Methods: In this descriptive laboratory study, 59 biopsy specimens (6 mm in diameter) were harvested from the central aspect (i.e., the notch side) of the femoral condyles of 26 human cadavers (1 month to 11 years old). Specimens were histologically evaluated for the presence of areas of cartilage necrosis and the morphology of cartilage canal blood vessels. Results: Locally extensive areas of necrotic epiphyseal cartilage were identified in 4 specimens obtained from 3 donors (ages 2 to 4 years). Areas of cartilage necrosis accompanied by focal failure of endochondral ossification or surrounded by subchondral bone were identified in biopsy specimens from 4 donors (ages 4 to 9 years). Conclusions: The identification of epiphyseal cartilage necrosis identical to that described in animals with subclinical osteochondrosis, found in biopsy specimens obtained from femoral predilection sites of JOCD in pediatric cadavers, suggests a shared pathogenesis of JOCD in humans and osteochondrosis dissecans in animals. Clinical Relevance: These findings imply that the pathogenesis of human JOCD likely starts 5 to 10 years prior to the development of clinical symptoms. Enhanced understanding of the temporal features of JOCD pathogenesis provides an opportunity for earlier diagnosis and treatment, likely resulting in improved outcomes for this condition in the future.

Background: Treatment of meniscal tears is necessary to maintain the long-term health of the knee joint. Morphological elements, particularly vascularity, that play an important role in meniscal healing are known to change during skeletal development. Purpose: To quantitatively evaluate meniscal vascularity, cellularity, collagen, and proteoglycan content by age and location during skeletal development. Study Design: Descriptive laboratory study. Methods: Medial and lateral menisci from 14 male and 7 female cadavers aged 1 month to 11 years were collected and evaluated. For each meniscus, histologic and immunohistologic techniques were used to establish the ratio of the area of proteoglycan (safranin O) positivity to the total area (proteoglycan ratio), collagen type I and type II immunostaining positivity, number of blood vessels, and cell density. These features were evaluated over the entire meniscus and also separately in 5 circumferential segments: anterior root, anterior horn, body, posterior horn, and posterior root. Additionally, cell density and number of blood vessels were examined in 3 radial regions: inner, middle, and periphery. Results: Age was associated with a decrease in meniscal vessel count and cell density, while the proteoglycan ratio increased with skeletal maturity. Differences in vessel counts, cellular density, and proteoglycan ratio in different anatomic segments as well as in the inner, middle, and peripheral regions of the developing menisci were also observed. Collagen immunostaining results were inconsistent and not analyzed. Conclusion: The cellularity and vascularity of the developing meniscus decrease with age and the proteoglycan content increases with age. All of these parameters are influenced by location within the meniscus. Clinical Relevance: Age and location differences in meniscal morphology, particularly in the number of blood vessels, are expected to influence meniscal healing.

Background: Osteochondritis dissecans (OCD) is a condition that oftentimes causes significant knee pain in pediatric patient populations. If left untreated, OCD significantly increases the risk of developing degenerative osteoarthritis along with its associated consequences and costs. Although a genetic component has been suggested to play a role in this disorder, few studies have been carried out in order to determine the underlying genetic etiology of this relatively common complex trait. The goal of our study was to perform an initial genome-wide association study (GWAS) to uncover candidate loci associated with the pathogenesis of OCD. Methods: Blood samples were acquired from 2 cohorts, aged 0 to 18 years old, consisting of 209 OCD cases and 1855 population-matched controls. Agencourt Genfind DNA isolation technology was used to isolate high-quality DNA from each sample. Genotype data was then generated utilizing the Illumina Infinium BeadChip array to examine single-nucleotide polymorphisms (SNPs). Results: In an initial GWAS analysis of our cohort, where a SNP was excluded if the Hardy-Weinberg Equilibrium test P<0.0001, the minor allele frequency<5%, and the genotyping call rate<90%, we obtained our first results for OCD. Although there was no SNP strictly reaching the threshold for genome-wide significance at this early stage, multiple SNPs (35) at several loci revealed evidence of suggestive association with OCD (P<5.0×10⁻⁵). Conclusions: The results from our preliminary study are encouraging. Herein we not only discuss the relevance and applicability of GWAS in studying a genetic basis for OCD, but have also identified top signals that may suggest loci involved in coordinated expression as well as a transcription factor involved in development that may be highly relevant to this trait. Clinical Relevance: If genetic predispositions for OCD are detected early enough in life, attempts at activity modification, counseling, and orthopaedic monitoring may successfully reduce progression of this condition, which may lead to progressive osteoarthritis in the third to fourth decade in at-risk patients.

Background: The quadriceps tendon (QT) is increasingly considered for primary and revision anterior cruciate ligament reconstruction in skeletally immature patients, as it may be harvested as a purely soft tissue graft with considerable tissue volume. Because of distinct rectus tendon (RT) separation from the QT complex, the potential for RT retraction exists and could lead to QT weakness after QT graft harvest. Purpose: To describe the anatomy of the pediatric QT and clarify decussation of the RT and QT to avoid the risk of delayed RT retraction and QT weakness after QT graft harvest. Study Design: Descriptive epidemiology study. Methods: Nine cadaveric knee specimens (aged 4-11 years) underwent gross dissection. Coronal-plane width and depth of the QT were measured at intervals proximal to the superior pole of the patella at distances of 0.0, 0.5, 1.0, and 1.5 times the length of the patella. The distance was measured from the superior patellar pole to the point of RT separation from the remainder of the deeper/posterior QT. Results: The median patellar length was 28 mm (interquartile range, 26-37 mm). The coronal-plane width of the QT was larger superficially/anteriorly when closest to the patella but wider when measured deeper/posteriorly as the tendon extended proximally. The median distance between the superior pole of the patella and RT separation from the QT was 0.95 times the patellar length. The distance to widening of the deeper/posterior aspect of the QT was 1.14 times the patellar length proximal to the patella. Conclusion: The RT begins a distinct separation from the QT above the superior pole of the patella at a median of 0.95 times the patellar length in skeletally immature specimens. The deeper/posterior aspect of the QT begins to increase in coronal-plane width proximally after a distance of 1.14 times the patellar length above the knee, while the superficial/anterior aspect of the tendon continues to narrow. Awareness of the separation of the RT from the QT, and the coronal-plane width variation aspects of the QT proximally, is important for surgeons utilizing the QT as a graft to avoid inadvertent release of the RT from the rest of the QT complex.

Background: We introduce a quantitative measure of epiphyseal cartilage vascularity and examine vessel networks during human skeletal maturation. Understanding early morphological changes in the distal femoral condyle is expected to provide information on the pathogenesis of developmental diseases such as juvenile osteochondritis dissecans. Methods: Twenty-two cadaveric knees from donors ranging from 1 month to 10 years of age were included in the study. Images of bone, cartilage, and vascularity were acquired simultaneously with a 3-dimensional gradient-recalled-echo magnetic resonance imaging (MRI) sequence. The secondary ossification center volume and total epiphysis cartilage volume ratio and articular-epiphyseal cartilage complex and epiphyseal cartilage widths were measured. Epiphyseal cartilage vascularity was visualized for 9 data sets with quantitative susceptibility mapping and vessel filtering, resulting in 3-dimensional data to inform vessel network segmentation and to calculate vascular density. Results: Three distinct, non-anastomosing vascular networks (2 peripheral and 1 central) supply the distal femoral epiphyseal cartilage. The central network begins regression as early as 3 months and is absent by 4 years. From 1 month to 3 years, the ratio of central to peripheral vascular area density decreased from 1.0 to 0.5, and the ratio of central to peripheral vascular skeletal density decreased from 0.9 to 0.6. A narrow, peripheral vascular rim was present at 8 years but had disappeared by 10 years. The secondary ossification center progressively acquires the shape of the articular-epiphyseal cartilage complex by 8 years of age, and the central areas of the medial and lateral femoral condyles are the last to ossify. Conclusions: Using cadaveric pediatric knees, we provide quantitative, 3-dimensional measures of epiphyseal cartilage vascular regression during skeletal development using vessel image features. Central areas with both early vascular regression and delayed ossification correspond to predilection sites of juvenile osteochondritis dissecans in this limited case series. Our findings highlight specific vascular vulnerabilities that may lead to improved understanding of the pathogenesis and better-informed clinical management decisions in developmental skeletal diseases. Clinical Relevance: This paradigm shift in understanding of juvenile osteochondritis dissecans etiology and disease progression may critically impact future patient management. Our findings highlight specific vascular vulnerabilities during skeletal maturation in a group of active young patients seen primarily by orthopaedic surgeons and sports medicine professionals.