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Allograft safety is a great concern owing to the risk of disease transmission from nonsterile tissues. Radiation sterilization is not used routinely because of deleterious effects on the mechanical integrity and stability of allograft collagen. We previously reported several individual cross-linking or free radical scavenging treatments provided some radioprotective effects for tendons. We therefore asked whether a combination of treatments would provide an improved protective effect after radiation exposure regarding mechanical properties and enzyme resistance. To address this question we treated 90 rabbit Achilles tendons with a combination of cross-linking (1-ethyl-3-[3-dimethyl aminopropyl] carbodiimide [EDC]) and one of three scavenging regimens (mannitol, ascorbate, or riboflavin). Tendons then were exposed to one of three radiation conditions (gamma or electron beam irradiation at 50 kGy or unsterilized). Combination-treated tendons (10 per group) had increases in mechanical properties and higher resistance to collagenase digestion compared with EDC-only and untreated tendons. Irradiated tendons treated with EDC-mannitol, -ascorbate, and -riboflavin combinations had comparable strength to native tendon and had averages of 26%, 39%, and 37% greater, respectively, than those treated with EDC-only. Optimization of a cross-linking protocol and free radical scavenging cocktail is ongoing with the goal of ensuring sterile allografts through irradiation while maintaining their structure and mechanical properties. [ABSTRACT FROM AUTHOR]

Ionizing radiation could supplement tissue bank screening to further reduce the probability of diseases transmitted by allografts if denaturation effects can be minimized. It is important, however, such sterilization procedures be nondetrimental to tissues. We compared crosslinking and free radical scavenging potential methods to accomplish this task in tendon tissue. In addition, two forms of ionizing irradiation, gamma and electron beam (e-beam), were also compared. Crosslinkers included 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) and glucose, which were used to add exogenous crosslinks to collagen. Free radical scavengers included mannitol, ascorbate, and riboflavin. Radioprotective effects were assessed through tensile testing and collagenase resistance testing after irradiation at 25 kGy and 50 kGy. Gamma and e-beam irradiation produced similar degenerative effects. Crosslinkers had the highest strength at 50 kGy, EDC treated tendons had 54% and 49% higher strength than untreated, for gamma and e-beam irradiation respectively. Free radical scavengers showed protective effects up to 25 kGy, especially for ascorbate and riboflavin. Crosslinked samples had higher resistance to collagenase and over a wider dose range than scavenger-treated. Of the options studied, the data suggest EDC precrosslinking or glucose treatment provides the best maintenance of native tendon properties after exposure to ionizing irradiation. [ABSTRACT FROM AUTHOR]

Background: It is difficult to diagnose and grade bony stress injury (BSI) in the athletic adolescent population without advanced imaging. Radiographs are recommended as a first imaging modality, but have limited sensitivity and, even when findings are present, advanced imaging is often recommended., Hypothesis: It was hypothesized that the significance of radiographs is underestimated for BSI in the adolescent with positive clinical examination and history findings., Study Design: Case series., Level of Evidence: Level 4., Methods: A total of 80 adolescent athletes with a history of shin pain underwent clinical examination by an orthopaedic surgeon. On the day of clinical examination, full-length bilateral tibial radiographs and magnetic resonance imaging (MRI) scans were obtained. MRI scans were reviewed using Fredericson grading for BSI. At the completion of the study, radiographic images were re-evaluated by 2 musculoskeletal (MSK) radiologists, blinded to MRI and clinical examination results, who reviewed the radiographs for evidence of BSI. Radiographic results were compared with clinical examination and MRI findings. Sensitivity, specificity, negative predictive value, and positive predictive value were calculated based on comparison with MRI., Results: All radiographs were originally read as normal. Of the tibia studied, 80% (127 of 160) showed evidence of BSI on MRI. None of the original radiographs demonstrated a fracture line on initial review by the orthopaedic surgeons. Retrospective review by 2 MSK radiologists identified 27% of radiographs (34 of 127) with evidence of abnormality, which correlated with clinical examination and significant findings on MRI. Review of radiographs found evidence of new bone on 0 of 28 Fredericson grade 0, 0 of 19 Fredericson grade I, 11 of 80 (13.7%) Fredericson grade II, 18 of 28 (64%) Fredericson grade III, and 5 of 5 (100%) Fredericson grade IV. Sensitivity of radiographs showed evidence of new bone on 27% (34 of 127) of initial radiographs, with presence more common with greater degree of BSI, as 23 of 33 (70%) were higher-grade injuries (III of IV) of BSI. Specificity and positive predictive value were 100%, while negative predictive value was 17%., Conclusion: These findings highlight the importance of initial radiographs in identifying high-grade BSI. As radiographs are readily available in most office settings of sports medicine physicians, this information can influence the management of adolescent athletic BSI without the need to delay treatment to obtain an MRI., Clinical Relevance: Adolescent athletes with radiographic evidence of BSI should be treated in a timely and more conservative manner, given the likelihood of higher-grade BSI. In addition, clinicians knowledgeable of the radiographic findings of high-grade BSI should feel more confident that a negative initial radiograph is not likely to be a high-grade BSI and can modify their treatment plans accordingly.

Background: Tibial bone stress injuries are common among the athletic adolescent population. A thorough patient history and clinical examination are essential to identify the location and extent of injury. However, there has been little description or any validation of clinical tests to help guide clinicians. Consequently, a formal diagnosis is usually dependent on results from proper imaging., Hypothesis: Clinical examinations will be both highly sensitive and specific determining the incidence, grade, and location of tibial bone stress injury as compared with magnetic resonance imaging (MRI)., Study Design: Case-control., Level of Evidence: Level 2., Methods: A total of 80 consecutive athletic adolescents, from various sports, with greater than 1-week history of shin pain were enrolled in this institutional review board-approved study. Exclusion criteria were age >19 years and history of traumatic injury. Patients underwent a standardized clinical examination, which included a fulcrum test (FT), tap/percussion test (TT), vibration test (VT) utilizing a 128-Hz tuning fork, weight bearing lunge test (WBLT) to determine degree of dorsiflexion range of motion (ROM), and vertical single leg hop test (VSLHT) for height, landing, and pain. Bilateral lower extremity MRI was completed on the same day as clinical evaluation and served as the injury reference. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated to evaluate each clinical examination for its ability to identify a bone stress injury., Results: A total of 159 tibiae in 80 patients were evaluated. No single test or combination of tests was both highly sensitive and specific. Individual clinical tests demonstrated sensitivity ranging from 0.11 to 0.72 and specificity ranging from 0.37 to 0.93. The VSLHT noting an increase in pain was the most sensitive test (0.72; 95% CI, 0.62-0.78); however, its specificity was only 0.37 (95% CI, 0.19-0.55), with a PPV of 0.84 (95% CI, 0.78-0.91) and NPV of 0.20 (95% CI, 0.089-0.31). The WBLT demonstrated a mean ROM of 8 cm, with side-to-side differences (range 0-4 cm) not influencing incidence of injury. Combinations of tests demonstrated low sensitivity (0.03-0.40), with better specificity (0.63-1.0). When considering ability to identify higher grades of injury (grade III/IV), all tests had a high NPV indicating that if clinical tests were negative, there was a high likelihood that the patient did not have a grade III or IV injury., Conclusion: No single test or combination of tests was both highly sensitive and specific. Clinicians cannot solely rely on clinical examination for determining extent or severity of bone stress injury in the athletic adolescent population, but when combinations of tests are negative, there is likely not a high-grade bone stress injury., Clinical Relevance: Clinical tests utilized in the evaluation of adolescent tibial bone stress injury may help indicate the presence or absence of higher grade tibial bone stress injury.

Background: The incidence of adolescent overuse injuries, including bone stress injuries (BSIs), is on the rise. The identification of a BSI in the early stages is key to successful treatment. The Shin Pain Scoring System (SPSS) was developed to aid clinicians in identifying patients with a BSI., Hypothesis: The SPSS will correlate with magnetic resonance imaging (MRI) grading of a BSI in an adolescent population., Study Design: Cohort study (diagnosis); Level of evidence, 2., Methods: Enrolled in this study were 80 adolescent high school athletes between the ages of 13 and 18 years participating in a variety of sports with more than 1 week of atraumatic shin pain. The SPSS questionnaire was completed for each participant, and physical examination findings were recorded. Each question and physical examination item was allotted a point value, which totaled 29 points. Radiographs and MRI scans of both lower legs were obtained for each participant. The SPSS score was statistically analyzed using logistic regression, a classification matrix, and a 2 × 2 contingency table to evaluate validity and predictability., Results: Logistic regression analysis of our data determined that 3 categories of SPSS scores provided the highest diagnostic value when compared with MRI grading based on the Fredericson classification (0-4). The SPSS correctly identified 43.5% of injuries for category 1 (MRI grades 0-1), 62.5% for category 2 (MRI grade 2), and 50.0% for category 3 (MRI grades 3-4). Overall, the SPSS correctly identified the degree of BSI in 54.4% of all tibias studied. Binary analysis for validity demonstrated a sensitivity of 96%, specificity of 26%, positive predictive value of 76%, and negative predictive value of 71% for the SPSS relative to the "gold standard" MRI results., Conclusion: The SPSS is a potentially valid method to identify tibial BSIs, given the sensitivity and negative and positive predictive values. It also provides helpful categorization to alert clinicians to the presence of a BSI and direct further diagnostics and/or interventions. The SPSS should be considered as an additional tool to use when evaluating adolescents with atraumatic tibial BSIs., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: University Orthopaedic Associates provided free use of their MRI equipment for some of the study participants. C.J.G. has received research support from the Musculoskeletal Transplant Foundation and educational support from Arthrex. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto., (© The Author(s) 2019.)

Background: Bony stress injuries (BSIs) are common among adolescents involved in high school sports. A better understanding of factors that contribute to adolescent BSI is needed to target preventative measures., Hypothesis: Individuals who suffer a BSI will demonstrate significant differences in training methods, sleep, diet, and history of injury compared with a healthy, noninjured control group., Study Design: Descriptive epidemiologic study., Methods: Data from the National High School Stress Fracture Registry (NHSSFR), an internet-based adolescent BSI survey, were used to identify variables reported with adolescent (13-18 years of age) BSI. These findings were compared with a survey of 100 (50 males, 50 females) healthy athletic controls to identify significant differences between healthy adolescents and those with BSI., Results: A total of 346 stress fractures were reported in 314 (206 females, 108 males) athletes within the NHSSFR. Comparison with healthy control participants demonstrated multiple significant findings. In particular, body mass index was significantly lower for patients with BSI injury compared with controls ( P < 0.001). Patients slept significantly less than the control group (7.2 vs 7.95 hours; F = 34.41; P < 0.001). Females also slept significantly less hours than males (7.2 vs 7.63 hours; F = 11.02; P < 0.001). Fifty-eight percent of those who reported a BSI did not engage in any weight training. Those with a BSI had significantly higher average stress ratings than control participants (1.67 vs 1.42; P < 0.001), and females also rated their stress levels significantly higher than males (1.8 vs 1.38; P < 0.001). A significant difference between patients with any BSI and control participants existed for history of "shin splints" (Pearson χ 2 = 28.31; P < 0.001), and females also expressed having shin pain lasting for longer than 4 weeks (Pearson χ 2 = 8.12; P < 0.001) and more often (Pearson χ 2 = 5.84; P = 0.02) than males. There was also a significant difference between patients with BSI and control subjects regarding dairy intake (2.25 vs 2.69; F = 6.43; P = 0.01)., Conclusion: Findings revealed significant differences between those who reported a BSI relative to healthy athletic adolescents. These differences included body mass index, prior history of shin splints, involvement in weight training, amount of sleep, daily stress, and dairy intake. Preventive measures should be developed to address these areas to reduce the incidence of BSIs in the adolescent population.

Objective: Collagenase-3, a matrix metalloproteinase (MMP-13) that can degrade collagen II and aggrecan, is produced by osteoarthritic (OA) chondrocytes and may contribute to matrix destruction in this disease. Our laboratory has previously identified a specific endocytotic receptor for collagenase-3 on osteoblastic and fibroblastic cells, which couples with the low-density lipoprotein receptor-related protein (LRP1) to mediate the internalization and degradation of this enzyme. We hypothesized that the activity of this receptor system is reduced in OA chondrocytes which may lead to increased local extracellular levels of collagenase-3 and increased destruction of the cartilage matrix at pericellular sites., Methods: Human chondrocytes and synoviocytes were obtained from OA knees at the time of joint replacement surgery and from non-arthritic control specimens following autopsy or surgery. Enzyme-linked immunosorbant assay (ELISA) was used to measure collagenase-3 secreted from primary cultures. Iodinated collagenase-3 was used to analyze the cell-surface binding, internalization and intracellular degradation of collagenase-3. Reverse-transcriptase polymerase chain reaction was used to confirm chondrocyte phenotype and the expression of collagenase-3 and LRP1 mRNAs., Results: OA chondrocytes and synoviocytes demonstrated significantly reduced (75-77%) binding of recombinant 125I collagenase-3. Internalization and degradation of the ligand was also significantly reduced (64-72%) in OA cells. Collagenase-3 removal was inhibited by the LRP1 receptor-associated protein (RAP)., Conclusion: These results suggest a mechanism whereby impaired receptor-mediated removal of collagenase-3 in OA chondrocytes may lead to enhanced local degradation of the cartilage matrix. This work also implicates an LRP family member in endocytotic receptor-mediated collagenase-3 processing and suggests a novel therapeutic target for OA.