Orthopaedic Research Society Research Articles

Influence of Ibuprofen on Bone Healing After Colles' Fracture: A Randomized Controlled Clinical Trial.

Non-steroidal anti-inflammatory drugs (NSAIDs) may delay bone healing. [Therefore, it is important to establish whether NSAID preparations delay bone healing and what correlations, if any, exist between different bone studies-DEXA-scanning, bone markers, roentgenology controls, and histological examination of newly formed bone]. The purpose of this prospective controlled study was to investigate whether ibuprofen affects bone mineral density, turnover biomarkers, and histomorphometric characteristics of the callus after a Colles' fracture. This study was a single-center, triple-blinded, randomized clinical trial. Ninety-five patients (80 females) with displaced Colles' fracture, median age 65 (range 40-85) years were included in the study and operated on by external fixation from June 2012 through to June 2015. Eighty-nine patients received interventional medicine and 83 completed the 1-year follow-up. The 7-day ibuprofen group received 600 mg of ibuprofen three times a day (N = 29), the 3-day ibuprofen group received ibuprofen for 3 days (N = 30) and a placebo for the following 4 days, and finally, the placebo group received a placebo for 7 days (N = 30). The primary outcome was the difference in bone mineral density between the ultra-distal region of the injured and non-injured radius at 3 months after surgery. The histomorphometric outcomes included the assessment of callus tissue volume and surface fractions at 6 weeks postoperatively. The biomarkers Osteocalcin and CrossLaps were measured at baseline, 1 week, 2 weeks, 6 weeks, 3 months, and 1 year. We included the results of the dropped-out patients in the intention to treat analysis. There was no difference between treatment groups in bone mineral density, histomorphometric estimations, and changes in bone biomarkers. These findings may offer an indication of ibuprofen as a bone-safe analgesic treatment in an acute fracture-phase. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:545-554, 2020.

BMSCs-Derived Exosomes Ameliorate Pain Via Abrogation of Aberrant Nerve Invasion in Subchondral Bone in Lumbar Facet Joint Osteoarthritis.

Lumbar facet joint osteoarthritis (LFJ OA) is regarded as one of the common causes of low back pain (LBP). The pathogenesis and underlying mechanism of this disease are largely unknown, there is still no effective disease-modifying therapy. This study aims to investigate the efficacy of exosomes derived from bone marrow mesenchymal stem cells (BMSCs) on the pathogenesis and behavioral signs of LBP in the LFJ OA mouse model. The pathogenetic change in cartilage and aberrant nerve invasion in the subchondral bone of LFJ in a mouse model after treatment with BMSC-exosomes was evaluated.BMSC-exosomes could relieve pain via abrogation of aberrant CGRP-positive nerve and abnormal H-type vessel formation in the subchondral bone of LFJ. Moreover, BMSC-exosomes attenuated cartilage degeneration and inhibited tartrate-resistant acid phosphatase expression and RANKL-RANK-TRAF6 signaling activation to facilitate subchondral bone remodeling. These results indicated that BMSC-exosomes could relive behavioral signs of LBP and pathological processes in LFJ OA. BMSC-exosomes have a prominent protective effect and might be a potential therapeutic option for the treatment of LFJ OA causing LBP. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:670-679, 2020.

Staphylococcus aureus Prosthetic Joint Infection Is Prevented by a Fluorine- and Phosphorus-Doped Nanostructured Ti-6Al-4V Alloy Loaded With Gentamicin and Vancomycin.

Prosthetic joint infection (PJI) is one of the most devastating complications in orthopedic surgery. One approach used to prevent PJI is local antibiotic therapy. This study evaluates the antibiotic release, in vitro cytocompatibility and in vivo effectiveness in preventing PJI caused by Staphylococcus aureus (S. aureus) of the fluorine- and phosphorus-doped, bottle-shaped, nanostructured (bNT) Ti-6Al-4V alloy loaded with a mixture of gentamicin and vancomycin (GV). We evaluated bNT Ti-6Al-4V loading with a mixture of GV, measuring the release of these antibiotics using high-performance liquid chromatography. Further, we describe bNT Ti-6Al-4V GV cytocompatibility and its efficacy against S. aureus using an in vivo rabbit model. GV was released from bNT Ti-6Al-4V following a Boltzmann non-linear model and maximum release values were obtained at 240 min for both antibiotics. The cell proliferation of MCT3T3-E1 osteoblastic cells significantly increased at 48 (28%) and 168 h (68%), as did the matrix mineralization (52%) of these cells and the gene expression of three of the most important markers related to bone differentiation (more than threefold for VEGF and BGLAP, and 65% for RunX) on bNT Ti-6Al-4V GV compared with control. In vivo study results show that bNT Ti-6Al-4V GV can prevent S. aureus PJI according to histopathological and microbiological results. According to our results, bNT Ti-6Al-4V loaded with a mixture of GV using the soaking method is a promising biomaterial with favorable cytocompatibility and osteointegration, demonstrating local bactericidal properties against S. aureus. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:588-597, 2020.

Collagen Coating Effects on Fe-Mn Bioresorbable Alloys.

Bioresorbable iron-manganese alloys (Fe-30%Mn) are considered as one of the next-generation resorbable materials for orthopedic applications. Previous in vitro study showed that Fe30Mn scaffolds with 10% porosity displayed strong mechanical properties and adequate degradation rate without severe cytotoxicity effect. However, the cellular compatibility of these alloys in terms of cell-to-cell and alloy-to-cell interactions is not ideal. Collagen is the most abundant protein in human bone, providing structural support beneficial to bone healing. We hypothesized that coating collagen on Fe30Mn can improve osteointegration or activities promoting cell adhesion, migration, and proliferation, as the alloy degrades. After preparing collagen coating on Fe-30Mn via spin coating, we conducted a corrosion test and a direct cytotoxicity test on four Fe30Mn groups: non-porous and 10% porosity, with and without collagen coating. Furthermore, we evaluated and compared the morphologies of cells over a period of 7 days. Results showed that there was no significant difference between the collagen-coated and non-coated groups in corrosion rates, yet a significant decrease from the porous non-coated group to the porous collagen-coated group in cytotoxicity level was found. Cell morphology on the porous non-coated group displayed round shape, whereas that on the porous collagen-coated group displayed flattened spreading. The study showed that the collagen coating significantly increased the initial cell viability and adhesion for both the porous and non-porous groups without impeding their degradation rates. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:523-535, 2020.

Effects of Sprifermin, IGF1, IGF2, BMP7, or CNP on Bovine Chondrocytes in Monolayer and 3D Culture.

ABSTRACTOne possible approach to treat osteoarthritis (OA) is to counteract cartilage degeneration with anabolic compounds that stimulate chondrocyte proliferation and/or extracellular matrix (ECM) production. Several molecules including sprifermin (recombinant human fibroblast growth factor [FGF18]), insulin‐like growth factor‐1 [IGF1] and ‐2 [IGF2], C‐type natriuretic peptide [CNP], and bone metamorphic protein 7 [BMP7] have been shown to have these characteristics both in vitro and in vivo. However, it is not known how these molecules compare each other regarding their effect on phenotype and stimulation of ECM production in primary chondrocytes. The effects of sprifermin, IGF1, IGF2, CNP, and BMP7 were evaluated on bovine articular chondrocytes, first in monolayer to determine their effective concentrations, and then in three‐dimensional (3D) culture at concentrations of 100 ng/ml for sprifermin; 300 ng/ml for IGF1, IGF2, and BMP7; and 10 nM for CNP. In 3D culture, the effects of a permanent exposure or a cyclic exposure consisting of 24 h incubation per week with the compounds were evaluated. All growth factors increased ECM production and cell proliferation to a similar extent but CNP had almost no effect on bovine chondrocytes. Sprifermin was more effective with cyclic exposure, IGF1, and IGF2 with permanent exposure, and BMP7 showed similar results with both exposures. Regarding the cell phenotype, sprifermin appeared to be the only compound favoring the chondrocyte phenotype; it decreased type I collagen expression and had no hypertrophic effect. Together, these results confirmed that sprifermin is a promising disease‐modifying OA drug. © 2019 The Authors. Journal of Orthopaedic Research ® published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society. J Orthop Res 38:653–662, 2020

Attenuation of Post-Traumatic Osteoarthritis After Anterior Cruciate Ligament Injury Via Inhibition of Hedgehog Signaling.

We aimed to investigate whether post-traumatic osteoarthritis (PTOA) progression is appropriately represented by a PTOA mouse model using a unique climbing cage to add mechanical loading after anterior cruciate ligament (ACL) transection and to determine how Hedgehog signaling inhibition prevents PTOA progression by observing time-dependent morphological changes. This controlled laboratory study histologically compared mice with surgically-induced ACL transection (ACLT) and those with voluntary increased activity in a climbing cage from 1 week postoperatively (ACLT + climbing). We generated conditional knockout (cKO) mice with a deleted Smoothened (Smo) gene. Time-dependent histopathological, immunohistochemical, and gene expression analyses were performed. The ACLT + climbing group showed more severe cartilage defects and massive osteophyte formation than the ACLT group. Smo deletion significantly suppressed PTOA progression. The time-dependent assessment revealed cartilaginous processes of equivalent size at the posterior tibial margin in the Smo cKO and control mice at 4 weeks postoperatively. However, at 8 weeks postoperatively, mature ossifying lesions were detected in the controls but not in Smo cKO mice. In the articular cartilage, ADAMTS5 and RUNX2 expression were observed in hypertrophic chondrocytes near the defective cartilage in controls but not in Smo cKO mice. Climbing exercise after ACLT accelerated PTOA progression more severely not only through increasing joint instability induced by ACLT but also through mechanical loading force induced by climbing exercise. Hedgehog signaling inhibition attenuated PTOA progression by suppressing chondrocyte hypertrophy induced by mechanical loads, to which ACL-deficient athletes are usually exposed. Thus, Hedgehog signaling inhibition may be a therapeutic option to prevent arthritic changes in athletes. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:609-619, 2020.

Somatosensory Function Influences Aberrant Gait Biomechanics Following Anterior Cruciate Ligament Reconstruction.

Osteoarthritis is common following anterior cruciate ligament reconstruction (ALCR), and aberrant gait biomechanics are considered a primary contributor. Somatosensory dysfunction potentially alters gait biomechanics, but this association is unclear. Therefore, the purposes of this investigation were to compare somatosensory function between limbs and evaluate associations between somatosensory function and gait biomechanics linked to osteoarthritis development in individuals with ALCR. Seventy-three volunteers with ALCR participated. Gait biomechanics (peak vertical ground reaction force magnitude and loading rate, peak internal knee extension and valgus moments, peak knee flexion and varus angles, and quadriceps/hamstrings co-activation) were assessed as subjects walked at their preferred speed. The somatosensory function was assessed via joint position sense error (knee flexion) and vibratory perception threshold (femoral epicondyles, malleoli, and first metatarsal). Though somatosensory function did not differ between the ACLR and contralateral limbs, poorer joint position sense in the ACLR limb was associated with lower loading rates and internal knee extension moments, and greater co-activation. Poorer vibratory perception at the medial and lateral malleoli and first metatarsal head in the ACLR limb was associated with lower loading rates, greater internal knee valgus moments and varus angles, and greater co-activation. Poorer vibratory perception at the medial malleolus and first metatarsal head in the contralateral limb was associated with greater peak knee varus angles and internal knee valgus moments. These results suggest that future research evaluating rehabilitation approaches for improving somatosensory function is warranted as a potential approach for restoring normal gait biomechanics and reducing osteoarthritis risk. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:620-628, 2020.

Murine Axial Compression Tibial Loading Model to Study Bone Mechanobiology: Implementing the Model and Reporting Results.

In vivo, tibial loading in mice is increasingly used to study bone adaptation and mechanotransduction. To achieve standardized and defined experimental conditions, loading parameters and animal-related factors must be considered when performing in vivo loading studies. In this review, we discuss these loading and animal-related experimental conditions, present methods to assess bone adaptation, and suggest reporting guidelines. This review originated from presentations by each of the authors at the workshop "Developing Best Practices for Mouse Models of In Vivo Loading" during the Preclinical Models Section at the Orthopaedic Research Society Annual Meeting, San Diego, CA, March 2017. Following the meeting, the authors engaged in detailed discussions with consideration of relevant literature. The guidelines and recommendations in this review are provided to help researchers perform in vivo loading experiments in mice, and thus further our knowledge of bone adaptation and the mechanisms involved in mechanotransduction. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:233-252, 2020.

Clinical Utility of Advanced Imaging of the Knee.

Advanced imaging modalities, including computed tomography, magnetic resonance imaging (MRI), and dynamic fluoroscopic imaging, allow for a comprehensive evaluation of the knee joint. Compositional sequences for MRI can allow for an evaluation of the biochemical properties of cartilage, meniscus, and ligament that offer further insight into pathology that may not be apparent on conventional clinical imaging. Advances in image processing, shape modeling, and dynamic studies also offer a novel way to evaluate common conditions and to monitor patients after treatment. The purpose of this article is to review advanced imaging modalities of the knee and their current and anticipated future applications to clinical practice. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:473-482, 2020.

Assessment of Cartilage Repair Quality With the International Cartilage Repair Society Score and the Oswestry Arthroscopy Score.

The International Cartilage Repair Society (ICRS) score and the Oswestry Arthroscopic Score (OAS) have been validated to evaluate repair tissue quality. However, the performance of these scores has not been studied in typical patients undergoing cartilage repair and who have lesions of varying sizes. In this study, we compared the performance of the ICRS and the OAS scores and analyzed the effect of lesion characteristics on the performance of these two scores. Cartilage repair quality was assessed in a total of 104 arthroscopic observations of cartilage repair sites of the knee in 62 patients after autologous chondrocyte implantation. Two observers scored the repair areas independently with the ICRS and the OAS scores. The performance of both scores was evaluated according to internal consistency and inter-rater reliability and correlation between the scores. The frequency and proportion of disagreements were analyzed according to the repair site area and the given score. The correlation between the scores was good (r = 0.91, 95% confidence interval [CI]: 0.87-0.94). Both scores showed moderate internal consistency and inter-rater reliability. Cronbach's α was 0.88 (95% CI: 0.80-0.92) for the ICRS score and 0.79 (95% CI: 0.70-0.86) for the OAS score. The intraclass correlation coefficient was 0.89 (95% CI: 0.84-0.92) for the ICRS and 0.81 (95% CI: 0.74-0.87) for the OAS scores. The frequency and proportion of disagreements were higher in larger repair sites. In arthroscopic use, both ICRS and OAS scores perform similarly, however, their reliability deteriorates as the lesion size increases. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:555-562, 2020.

Quadriceps Muscle Size Following ACL Injury and Reconstruction: A Systematic Review.

Image-based assessments of quadriceps muscle size facilitate examination of structural changes after anterior cruciate ligament (ACL) injury and reconstruction (ACLR). Understanding the effects of ACLR on muscle size measures may aid in clarifying the contribution of quadriceps atrophy toward quadriceps strength. The purpose of this study was to systematically review the literature examining the effects of ACLR on quadriceps muscle volume and cross-sectional area (CSA). An online database search was conducted using Web of Science, SportDISCUS, PubMed (Medline), CINHAL (EBSCO), and Cochrane Library limited to articles published after January 1, 1980. Means and standard deviations were extracted for the ACLR limb and the contralateral limb, and sample characteristics from relevant articles. Magnitude of between limb differences were assessed using pooled effect sizes (Hedge's g) and 95% confidence intervals. Eleven articles (five CSA, six muscle volume) were included in this systematic review. Included studies reported negative effective sizes, indicating that the ACLR limb was smaller in CSA or muscle volume compared with the contralateral limb; however, 36% of the included articles reported meaningful difference between the limbs. Quadriceps atrophy may occur following ACL injury and persist after rehabilitation, however, the magnitude of these reductions may not be clinically meaningful and may only partially explain the persistent quadriceps weakness that is ubiquitous among this patient population. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:598-608, 2020.

Aged Mice Demonstrate Greater Muscle Degeneration of Chronically Injured Rotator Cuff.

Massive tears of the rotator cuff (RC) are often associated with progressive and irreversible muscle degeneration due to fibrosis, fatty infiltration, and muscle atrophy. RC tears are common in individuals older than 60 years and the repair of these tears is amongst the most prevalent of orthopedic procedures. However, most current models of this injury are established in young animals, which may not accurately recapitulate the clinical condition. In this study, we used a murine model of massive RC tears to evaluate age-related muscle degeneration following chronic injury. The expression of the fibro-adipogenic genes encoding collagen type III and leptin was higher in aged RC compared with matched injured young tissue at 2 weeks post-injury, and development of fibrosis was accelerated in aged mice within 5 days post-injury. Furthermore, the synthesis of collagens type I and III and fat tissue accumulation were significantly higher in injured RCs of aged mice. Similar frequency of fibro-adipogenic PDGFRβ+ PDGFRα+ progenitor cells was measured in non-injured RC of aged and young mice, but PDGFRβ+ PDGFRα+ cells contributed to significantly larger fibrotic lesions in aged RCs within 2 weeks post-injury, implying a more robust fibrotic environment in the aged injured muscle. Altogether, these findings demonstrate age-dependent differences in RC response to chronic injury with a more profound fibro-adipogenic change in aged muscles. Clinically, cell therapies for muscular pathologies should not only consider the cell type being transplanted but also the recipient milieu into which these cells are seeded. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:320-328, 2020.

Elbow Biomechanics, Radiocapitellar Joint Pressure, and Interosseous Membrane Strain Before and After Radial Head Arthroplasty.

Complex radial head fracture and elbow instability can be treated with radial head arthroplasty. Good clinical results have been described after this surgical treatment. However, the revision and complication rate reported in the literature is concerning. This might be due to altered kinematics after radial head arthroplasty. Eight human native elbows were examined with dynamic radiostereometric analysis and compared with a radial head arthroplasty. Translations of the radial head in the x-, y-, and z-directions relative to the humerus and the ulna were measured. The radiocapitellar joint pressure was measured using a pressure sensor. The tension within the interosseous membrane was measured using a custom-made strain gauge. After radial head arthroplasty, the radial head was displaced approximately 1.8 mm medially and 1.4 mm distally at the starting point. During unloaded flexion motion the difference in all translations between the native radial head and the radial head arthroplasty was less than 1 mm (95% confidence interval [CI] ± 0.5 mm) (p = 0.001). With loading the difference was less than 1.5 mm (95% CI ± 1.5 mm) (p = 0.001). The mean difference in radiocapitellar joint contact pressure was less than 0.30 MPa (95% CI ± 0.40 MPa) (p = 0.001) during unloaded flexion motion. There were only submillimetre kinematic changes and small changes in joint pressure and interosseous membrane tension after the insertion of a radial head arthroplasty in an experimental setting. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:510-522, 2020.

Synchrotron MicroCT Reveals the Potential of the Dual Contrast Technique for Quantitative Assessment of Human Articular Cartilage Composition.

ABSTRACTDual contrast micro computed tomography (CT) shows potential for detecting articular cartilage degeneration. However, the performance of conventional CT systems is limited by beam hardening, low image resolution (full‐body CT), and long acquisition times (conventional microCT). Therefore, to reveal the full potential of the dual contrast technique for imaging cartilage composition we employ the technique using synchrotron microCT. We hypothesize that the above‐mentioned limitations are overcome with synchrotron microCT utilizing monochromatic X‐ray beam and fast image acquisition. Human osteochondral samples (n = 41, four cadavers) were immersed in a contrast agent solution containing two agents (cationic CA4+ and non‐ionic gadoteridol) and imaged with synchrotron microCT at an early diffusion time point (2 h) and at diffusion equilibrium (72 h) using two monochromatic X‐ray energies (32 and 34 keV). The dual contrast technique enabled simultaneous determination of CA4+ (i.e., proteoglycan content) and gadoteridol (i.e., water content) partitions within cartilage. Cartilage proteoglycan content and biomechanical properties correlated significantly (0.327 < r < 0.736, p < 0.05) with CA4+ partition in superficial and middle zones at both diffusion time points. Normalization of the CA4+ partition with gadoteridol partition within the cartilage significantly (p < 0.05) improved the detection sensitivity for human osteoarthritic cartilage proteoglycan content, biomechanical properties, and overall condition (Mankin, Osteoarthritis Research Society International, and International Cartilage Repair Society grading systems). The dual energy technique combined with the dual contrast agent enables assessment of human articular cartilage proteoglycan content and biomechanical properties based on CA4+ partition determined using synchrotron microCT. Additionally, the dual contrast technique is not limited by the beam hardening artifact of conventional CT systems. © 2019 The Authors. Journal of Orthopaedic Research® published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society. J Orthop Res 38:563–573, 2020

Length Matters: Short Base-Plate Angle Guides May Lead to Guide-Wire Mal-Positioning When Inserting a DHS. A Radiographic Modeling Study.

The dynamic hip screw (DHS) consists of a barrel-plate fixed to the relatively-straight proximal femoral shaft, and a screw which slides within the barrel at a fixed angle, usually 135°. The guide-wire is inserted using a guide at the set angle. Guide design varies between manufacturers, with some new guides being particularly short. We analysed the impact of guide design on the resulting trajectory of the guidewire, and its potential to cause a surgical error. Twenty AP hip radiographs were analysed. Trauma Cad (Brainlab, Munich, Germany) software was used to template a 4-hole 135° DHS onto the intact femur with the screw positioned in the center of the head. A template of a Stryker (Michigan, USA) 135° DHS guide (37 mm long) was then overlaid at the hip screw entry point, and the set trajectory marked. The divergence between the two trajectories was measured (α angle). The distance the guide would have to be moved inferiorly to attainthe correct position in the head was then noted. The median divergence (α angle) caused by the guide relative to the ideal position was 6° (range 2-12). This led to the guidewire placement being a median of 9.1 mm (range 3-23) superior in the head (β).To achieve the correct position of the wire in the head, the guide needed to be moved inferiorly a median of 8 mm (range 2-10). © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:574-577, 2020.

Posterior Pelvic Tilt From Supine to Standing in Patients With Symptomatic Developmental Dysplasia of the Hip.

Pelvic sagittal inclination (PSI) significantly affects the femoral head coverage by the acetabulum in patients with developmental dysplasia of the hip (DDH), while no reports have quantified PSI in DDH patients in the supine and standing positions. Furthermore, little is known about how PSI changes after periacetabular osteotomies. Herein, PSI in the supine and standing positions was quantified in DDH patients preoperatively and postoperatively. Twenty-five patients with DDH who had undergone periacetabular osteotomies were analyzed. The preoperative PSI and the PSI 2 years after surgery were measured in the supine and standing positions using the image registration technique between radiographs and computed tomographic images. The percentage of patients who showed PSI changes of more than 10° from the supine to the standing position was quantified. PSI changed 8.2 ± 5.0° posteriorly from the supine to the standing position during the preoperative period. Posterior pelvic tilt of more than 10° was found in nine cases (36%). Two years after periacetabular osteotomies, the postural PSI change was 7.1 ± 3.9° posteriorly. When the preoperative and postoperative PSI values were compared, PSI in the standing position did not differ (p = 0.20). Similarly, the amount of PSI change from the supine to standing position was not significantly different (p = 0.26). In conclusion, posterior pelvic tilt in the standing position was found preoperatively in symptomatic DDH patients, and it remained for 2 years after periacetabular osteotomies. This postural change in PSI does not seem to influence the outcome of periacetabular osteotomy. However, during preoperative planning, surgeons should recognize that acetabular anteversion or anterior acetabular coverage differs between the supine and standing positions in some patients with DDH. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:578-587, 2020.

Influence of Hamstrings on Knee Moments During Loading Response of Gait in Individuals Following ACL Reconstruction.

Biomechanical studies consistently report smaller knee extensor moments in the surgical limb during loading response (LR) of gait following ACL reconstruction (ACLr). However, this reduction in knee loading is quantified by net joint moments (NJM). As a result, in the presence of greater hamstring activity, the true contribution from the knee extensors may not be reduced. The purpose of this study is to compare hamstring activity and strength and knee joint moments between individuals post-ACLr and controls. Eighteen individuals 3 months post-ACLr and matched controls walked and net knee extensor moment peak and impulse and hamstring activity were identified during LR, as well as maximal hamstring strength. A hybrid musculoskeletal model estimated knee flexor moments from joint kinematics and hamstring electromyography. Flexor moments (SIMM) were scaled based on strength. Knee extensor moments were estimated from the sum of the net knee moment and estimated knee flexor moment; estimated extensor moment peaks and impulse were calculated during LR. Repeated measures analysis of variancecompared groups and limbs. Smaller net knee extensor moment and greater hamstring activity, as well as deficits in maximal hamstring strength, were observed in the surgical limb (all p < 0.05). When accounting for the torque-producing capabilities of the knee flexors, estimated knee extensor moment peak and impulse were smaller in the surgical limb. These findings suggest that net knee moments accurately reflect smaller knee extensor loading post-ACLr. Statement of Clinical Significance: Rehabilitation programs should target increasing knee extensor loading to restore gait mechanics during early rehabilitation. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:378-386, 2020.

Anteroposterior Translational Malalignment of Ankle Arthrodesis Alters Foot Biomechanics in Cadaveric Gait Simulation.

Tibiotalar arthrodesis is a common surgical treatment for end-stage ankle arthritis. Proper ankle alignment is important as malalignment can lead to complications that may require revision surgery. This study aimed to determine how anteroposterior (AP) translational malalignment of ankle arthrodesis affects distal foot joint kinematics and plantar pressure. Ankle arthrodesis was performed on 10 cadaveric foot specimens using a custom fixture that could fuse the ankle neutrally and induce discrete malalignments (3, 6, and 9 mm) anteriorly and posteriorly. Gait was simulated under each alignment with a robotic gait simulator, and foot bone motion and plantar pressure were quantified. AP translational malalignment did not substantially affect plantar pressure or joint range of motion, but there were several significant differences in joint position throughout stance phase. Differences were seen in five joints (talocalcaneal, talonavicular, calcaneocuboid, fifth tarsometatarsal, and first metatarsophalangeal) and in the position of the first metatarsal relative to the talus. The most extreme effects occurred when the talus was displaced 6 mm or more posteriorly. In vivo, this may lead to aberrant joint loading, which could negatively impact patient outcomes. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:450-458, 2020.

Rotator Cuff Tear Susceptibility Is Associated With Variants in Genes Involved in Tendon Extracellular Matrix Homeostasis.

Rotator cuff tears (RCT) is a multifactorial disease with genetic factors contributing for the disease etiology. We hypothesized that genetic variants in genes involved in extracellular matrix (ECM) homeostasis may alter susceptibility to RCT. We evaluated 20 polymorphisms of genes involved in ECM homeostasis in 211 cases of full-thickness tears of the supraspinatus (Nfemales = 130; Nmales = 81) and 567 age-matched controls (Nfemales = 317; Nmales = 250). Multivariate logistic regressions were carried out with age, gender, genetic ancestry (based on the analysis of 61 biallelic short insertion/deletion polymorphisms), and common co-morbidities (diabetes, dyslipidemia, and smoking habits) as covariates. We observed that carriers of the rare allele of both studied variants of TGFB1, as well as their G/A (rs1800470/rs1800469) haplotype,were less susceptible to RCT (p < 0.05). In contrast, carriers of the G allele of MMP9 rs17576 (p = 0.014) or G/G haplotype (rs17576/rs17577; p < 0.001) had an increased risk for tendon tears. The presence of the T allele of MMP2 rs2285053 (p = 0.033), the T allele of MMP3 rs679620 (p = 0.024), and the TT-genotype of TIMP2 rs2277698 (p = 0.01) was associated with susceptibility to tears, especially in females. In males, the A allele of COL5A1 rs3196378 (p = 0.032) and the G allele of TGFBR1 rs1590 (p = 0.039) were independent risk factors for RCT. The C/T COL5A1 (rs3196378/rs11103544) haplotype was associated with a reduced risk of tears in males (p = 0.03). In conclusion, we identified the genetic variants associated with RCT susceptibility, thereby reinforcing the role of genes involved in the structure and homeostasis of the ECM of tendons in disease development. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:192-201, 2020.

Neo-Angiogenesis, Transplant Viability, and Molecular Analyses of Vascularized Bone Allotransplantation Surgery in a Large Animal Model.

Vascularized composite allotransplantation of bone is a possible alternative treatment for large osseous defects but requires life-long immunosuppression. Surgical induction of autogenous neo-angiogenic circulation maintains transplant viability without this requirement, providing encouraging results in small animal models [1-3]. A preliminary feasibility study in a swine tibia model demonstrated similar findings [4, 5]. This study in swine tibial allotransplantation tests its applicability in a pre-clinical large animal model. Previously, we have demonstrated bone vascularized composite allotransplantation (VCA) survival was not the result of induction of tolerance nor an incompetent immune system [1]. Fourteen tibia vascularized bone allotransplants were microsurgically transplanted orthotopically to reconstruct size-matched tibial defects in Yucatan miniature swine. Two weeks of immunosuppression was used to maintain allotransplant pedicle patency during angiogenesis from a simultaneously implanted autogenous arteriovenous bundle. The implanted arteriovenous bundle was patent in group 1 and ligated in group 2 (a neo-angiogenesis control). At twenty weeks, we quantified the neo-angiogenesis and correlated it with transplant viability, bone remodeling, and gene expression. All patent arteriovenous bundles maintained patency throughout the survival period. Micro-angiographic, osteocyte cell count and bone remodeling parameters were significantly higher than controls due to the formation of a neo-angiogenic autogenous circulation. Analysis of gene expression found maintained osteoblastic and osteoclastic activity as well as a significant increase in expression of endothelial growth factor-like 6 (EGFL-6) in the patent arteriovenous bundle group. Vascularized composite allotransplants of swine tibia maintained viability and actively remodeled over 20 weeks when short-term immunosuppression is combined with simultaneous autogenous neo-angiogenesis. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:288-296, 2020.