Tibial Load Research Articles

Molecular Identification of Spatially Distinct Anabolic Responses to Mechanical Loading in Murine Cortical Bone.

Osteoporosis affects over 200 million women worldwide, one-third of whom are predicted to suffer from an osteoporotic fracture in their lifetime. The most promising anabolic drugs involve administration of expensive antibodies. Because mechanical loading stimulates bone formation, our current data, using a mouse model, replicates the anabolic effects of loading in humans and may identify novel pathways amenable to oral treatment. Murine tibial compression produces axially varying deformations along the cortical bone, inducing highest strains at the mid-diaphysis and lowest at the metaphyseal shell. To test the hypothesis that load-induced transcriptomic responses at different axial locations of cortical bone would vary as a function of strain magnitude, we loaded the left tibias of 10-week-old female C57Bl/6 mice in vivo in compression, with contralateral limbs as controls. Animals were euthanized at 1, 3, or 24 hours post-loading or loaded for 1 week (n=4-5/group). Bone marrow and cancellous bone were removed, cortical bone was segmented into the metaphyseal shell, proximal diaphysis, and mid-diaphysis, and load-induced differential gene expression and enriched biological processes were examined for the three segments. At each time point, the mid-diaphysis (highest strain) had the greatest transcriptomic response. Similarly, biological processes regulating bone formation and turnover increased earlier and to the greatest extent at the mid-diaphysis. Higher strain induced greater levels of osteoblast and osteocyte genes, whereas expression was lower in osteoclasts. Among the top differentially expressed genes at 24-hours post-loading, 17 had known functions in bone biology, of which 12 were present only in osteoblasts, 3 exclusively in osteoclasts, and 2 were present in both cell types. Based on these results, we conclude that murine tibial loading induces spatially unique transcriptomic responses correlating with strain magnitude in cortical bone. © 2022 American Society for Bone and Mineral Research (ASBMR).

Activating EGFR Signaling Attenuates Osteoarthritis Development Following Loading Injury in Mice.

Posttraumatic osteoarthritis (PTOA) results in joint pain, loss of joint function, and impaired quality of daily life in patients with limited treatment options. We previously demonstrated that epidermal growth factor receptor (EGFR) signaling is essential for maintaining chondroprogenitors during articular cartilage development and homeostasis. Here, we used a nonsurgical, loading-induced PTOA mouse model to investigate the protective action of EGFR signaling. A single bout of cyclic tibial loading at a peak force of 6N injured cartilage at the posterior aspect of lateral femoral condyle. Similar loading at a peak force of 9 N ruptured the anterior cruciate ligament, causing additional cartilage damage at the medial compartment and ectopic cartilage formation in meniscus and synovium. Constitutively overexpression of an EGFR ligand, heparin binding EGF-like growth factor (HBEGF), in chondrocytes significantly reduced cartilage injury length, synovitis, and pain after 6N loading and mitigated medial side cartilage damage and ectopic cartilage formation after 9N loading. Mechanistically, overactivation of EGFR signaling protected chondrocytes from loading-induced apoptosis and loss of proliferative ability and lubricant synthesis. Overexpressing HBEGF in adult cartilage starting right before 6N loading had similar beneficial effects. In contrast, inactivating EGFR in adult cartilage led to accelerated PTOA progression with elevated cartilage Mankin score and synovitis score and increased ectopic cartilage formation. As a therapeutic approach, we constructed a nanoparticle conjugated with the EGFR ligand TGFα. Intra-articular injections of this nanoconstruct once every 3 weeks for 12 weeks partially mitigated PTOA symptoms in cartilage and synovium after 6N loading. Our findings demonstrate the anabolic actions of EGFR signaling in maintaining articular cartilage during PTOA development and shed light on developing a novel nanomedicine for PTOA. © 2022 American Society for Bone and Mineral Research (ASBMR).

Loss of Adenylyl Cyclase 6 in Leptin Receptor-Expressing Stromal Cells Attenuates Loading-Induced Endosteal Bone Formation.

ABSTRACTBone marrow stromal/stem cells represent a quiescent cell population that replenish the osteoblast bone‐forming cell pool with age and in response to injury, maintaining bone mass and repair. A potent mediator of stromal/stem cell differentiation in vitro and bone formation in vivo is physical loading, yet it still remains unclear whether loading‐induced bone formation requires the osteogenic differentiation of these resident stromal/stem cells. Therefore, in this study, we utilized the leptin receptor (LepR) to identify and trace the contribution of bone marrow stromal cells to mechanoadaptation of bone in vivo. Twelve‐week‐old Lepr‐cre;tdTomato mice were subjected to compressive tibia loading with an 11 N peak load for 40 cycles, every other day for 2 weeks. Histological analysis revealed that Lepr‐cre;tdTomato+ cells arise perinatally around blood vessels and populate bone surfaces as lining cells or osteoblasts before a percentage undergo osteocytogenesis. Lepr‐cre;tdTomato+ stromal cells within the marrow increase in abundance with age, but not following the application of tibial compressive loading. Mechanical loading induces an increase in bone mass and bone formation parameters, yet does not evoke an increase in Lepr‐cre;tdTomato+ osteoblasts or osteocytes. To investigate whether adenylyl cyclase‐6 (AC6) in LepR cells contributes to this mechanoadaptive response, Lepr‐cre;tdTomato mice were further crossed with AC6fl/fl mice to generate a LepR+ cell‐specific knockout of AC6. These Lepr‐cre;tdTomato;AC6 fl/fl animals have an attenuated response to compressive tibia loading, characterized by a deficient load‐induced osteogenic response on the endosteal bone surface. This, therefore, shows that Lepr‐cre;tdTomato+ cells contribute to short‐term bone mechanoadaptation. © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

A Biomechanical Study of Pivot-Shift and Lachman Translations in Anterior Cruciate Ligament-Sectioned Knees, Anterior Cruciate Ligament-Reconstructed Knees, and Knees With Partial Anterior Cruciate Ligament Graft Slackening: Instrumented Lachman Tests Statistically Correlate and Supplement Subjective Pivot-Shift Tests

To determine the statistical and predictive correlation between instrumented Lachman and pivot-shift tests with progressive loss of anterior cruciate ligament (ACL) function. The kinematic correlations between pivot-shift and Lachman anterior tibial translations (ATTs) in ACL-deficient and ACL-reconstructed states and in partially lax ACL grafts were determined with precise robotic testing in cadaveric knees. The Lachman test (100-N anteroposterior) and 2 pivot-shift loadings were conducted: anterior tibial loading (100 N), valgus rotation (7 Nm), and internal rotation (5 Nm and 1 Nm). The tibia was digitized to study the resulting medial, central, and lateral tibiofemoral compartment translations. In group 1 knees, 15 bone-patellar tendon-bone reconstructions were first tested, followed by ACL graft loosening with 3- and 5-mm increases in Lachman ATT. In group 2, 43 knees underwent robotic testing before and after ACL sectioning and underwent analysis of the effect of 3- and 5-mm increases in Lachman ATT and complete ACL sectioning on pivot-shift compartment translations. In group 1 knees, ACL graft loosening allowing a 3-mm increase in Lachman ATT resulted in increases in pivot-shift lateral compartment translation (lateral compartment ATT) of only 1.6±0.3 mm and 2.2 ± 1.0 mm (internal rotation of 5 Nm and 1 Nm, respectively) that were one-half of those required for a positive pivot-shift test finding. In group 2, for a 3-mm increased Lachman test, there were no positive pivot-shift values. In both groups, a Lachman test with an increase in ATT of 3 mm or less (100 N) had a 100% predictive value for a negative pivot-shift test finding. With ACL graft loosening and a 5-mm increase in the Lachman ATT, group 1 still had no positive pivot-shift values, and in group 2, a positive pivot-shift test finding occurred in 3 of 43 knees (7%, pivot shift 1-Nm internal rotation). After ACL sectioning, a highly predictive correlation was found between abnormal increases in Lachman and pivot-shift translations (P < .001). ACL graft slackening and an instrumented Lachman test with an increase in ATT of 3 mm or less were 100% predictive of a negative pivot-shift subluxation finding and retained ACL stability. Further graft slackening and a 5-mm increase in the Lachman ATT produced pivot-shift lateral compartment ATT increases still less than the values in the ACL-deficient state; however, 7% of the knees (3 of 43) were converted to a positive pivot-shift test finding indicative of ACL graft failure. Instrumented Lachman tests provide objective data on ACL function and graft failure to supplement subjective pivot-shift tests and are highly recommended for single-center and multicenter ACL studies. In the past decade, a near majority of published ACL studies no longer reported on instrumented Lachman tests, relying solely on highly subjective pivot-shift grading by multiple examiners.

Partial meniscectomy does not affect the biomechanics of anterior cruciate ligament reconstructed knee with a lateral posterior meniscal root tear.

The purpose of this study was to determine the effects of a lateral meniscus posterior root tear, partial meniscectomy, and total meniscectomy on knee biomechanics in the setting of anterior cruciate ligament (ACL) reconstruction. Thirteen fresh-frozen cadaver knees were tested with a robotic testing system under an 89.0-N anterior tibial load at full extension (FE), 15°, 30°, 60° and 90° of knee flexion and a simulated pivot-shift loading (7.0 Nm valgus and 5.0 Nm internal tibial rotation) at FE, 15° and 30° of knee flexion. Anterior tibial translation (ATT) and the in-situ force of ACL graft under the different loadings were measured in four knee states: (1) ACL reconstruction with intact lateral meniscus (Intact meniscus), (2) ACL reconstruction with lateral meniscal posterior root tear (Root tear), (3) ACL reconstruction with lateral posterior partial meniscectomy (Partial meniscectomy) and (4) ACL reconstruction with total lateral meniscectomy (Total meniscectomy). Under anterior tibial loading, compared with an intact meniscus, root tear significantly increased ATT at 15° and 30° of knee flexion (p < 0.05) and partial meniscectomy had almost same increased ATT as with root tear at any knee flexion between FE and 90°. Under simulated pivot-shift loading, total meniscectomy increased ATT compared with intact meniscus, root tear, partial meniscectomy at FE (p < 0.05). Under anterior tibial and simulated pivot-shift loading, partial meniscectomy has no significant effect on the stability of ACL-reconstructed knee with lateral meniscal posterior root tear, while total meniscectomy increased laxity at less than 30° of knee flexion. Clinically, in cases of irreparable meniscal root tears or persistent pain a partial meniscectomy can be considered in the setting of ACL reconstruction.

BIOMECHANICAL EFFECTS OF DIFFERENT LENGTHS OF CROSS-PINS IN ANTERIOR CRUCIATE LIGAMENT RECONSTRUCTION: A FINITE ELEMENT ANALYSIS

Complication rates of anterior cruciate ligament reconstruction (ACL-R) were reported to be around 15%. Although it is a very common arthroscopic surgery with good outcomes, breakage and migration of fixators are still possible to occur due to stability issue. One of the factors that affects the mechanical stability of fixators is its length. Therefore, the aim of this paper is to analyze the biomechanical effects of different lengths of fixators (cross-pin technique) towards the stabilities of the knee joint after ACL-R. Finite element analyses of knee joint with DST grafts and fixators were carried out. Mimics and 3-Matic were used in the development of knee joint models, while the grafts and fixators were designed by using SolidWorks software. All models were remeshed in the 3-Matic and numerical analysis was performed via MSC.Marc Mentat software. A 100 N anterior tibial load was applied onto the tibia to simulate the anterior drawer test after the surgery and proximal femur was fixed at all degrees of freedom. Based on the findings, cross-pin with 40[Formula: see text]mm in length provided the most favorable option for better treatment of ACL-R, where it could promote osseointegration and preventing fracture.

Abstract 3481: Continuous load bearing exercise inhibits the development of prostate cancer bone metastasis

Abstract Background: Prostate cancer (PCa) preferentially metastasizes to bone, causing considerable mortality and morbidity. Exercise is a widely accepted intervention for improving bone health and can benefit overall health in patients with PCa. However, there are no direct studies defining the impact of various exercise regimens on the development of PCa bone metastasis. Hypothesis: Exercise regimens that induce osteogenic responses inhibit the growth of PCa cells in bone. Methods: Human PCa cells (PC3, 1x105 cells per injection) were intracardiacally injected into 8-week-old male BALB/c nude mice which were then subjected to right tibial dynamic mechanical loading (mimicking load bearing exercise, 9N peak force, 40 cycles with 10 second intervals, three times a week) or treadmill exercise (12 meters/minute, 30 minutes/day, 5 days/week) for 3 weeks. Another cohort of mice were firstly subjected to one week of mechanical loading before the inoculation of PC3 cells and then withdrawn from exercise regimen. The growth of skeletal tumours was tracked by bioluminescence for 3 weeks post-injection and bone structure was examined by micro-CT ex vivo. For mechanical loading experiments, comparison was made between loaded and contra-lateral non-loaded tibias, while treadmill exercise group was compared to sedentary controls in the treadmill study. Results: In the continuous mechanical loading group, tumours were detected in non-loaded tibias in all 12 mice (100%), whilst 8 out of 12 mice showed reduced skeletal tumours in the loaded tibias (67%), with 4 having no tumour in the loaded leg (33%). Tumour burden (Flux: photon/second) in the non-loaded tibias was 134% higher than that in the loaded tibias. Micro-CT analysis suggested that loaded tibias had significantly increased trabecular (BV/TV) and cortical bone volume and trabecular thickness (Tb.Th) (p&amp;lt;0.001). Surprisingly, treadmill exercised mice had higher tumour burden (~91%) in the hind limbs compared to the sedentary controls (P&amp;lt;0.05), with no statistically significant improvement in bone mass examined by micro-CT. In the loading withdrawal group, 6 out of 8 mice (75%) showed larger tumour size in the loading withdrawal tibias than in the non-loaded tibias, while only two mice (25%) had smaller or no tumour in the loading withdrawal tibias. Tumor burden were ~90% higher in the loading withdrawal tibias (p&amp;lt;0.05, t-test). This is associated with fast diminishing osteogenic response within a week after ceasing the loading stimulus, confirmed using micro-CT analysis by comparing percentage changes of BV/TV and Tb.Th among baseline, 1-week loading, and loading withdrawn groups. Conclusion: The continuity of high-intensity load bearing exercise is critical to prevent PCa growth in bone, possibly via maintaining the balance of bone remodelling towards osteoblastic bone formation. Mild aerobic exercise evaluated here was unable to significantly improve bone mass or achieve the benefits in inhibiting PCa bone metastases observed with high intensity loading. Citation Format: Ning Wang, Hector M. Arredondo, Alexandria R. Sprules, Colby L. Eaton. Continuous load bearing exercise inhibits the development of prostate cancer bone metastasis [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3481.

Obesity and load-induced posttraumatic osteoarthritis in the absence of fracture or surgical trauma.

Osteoarthritis is increasingly viewed as a heterogeneous disease with multiple phenotypic subgroups. Obesity enhances joint degeneration in mouse models of posttraumatic osteoarthritis (PTOA). Most models of PTOA involve damage to surrounding tissues caused by surgery/fracture; it is unclear if obesity enhances cartilage degeneration in the absence of surgery/fracture. We used a nonsurgical animal model of load-induced PTOA to determine the effect of obesity on cartilage degeneration 2 weeks after loading. Cartilage degeneration was caused by a single bout of cyclic tibial loading at either a high or moderate load magnitude in adult male mice with severe obesity (C57Bl6/J + high-fat diet), mild obesity (toll-like receptor 5 deficient mouse [TLR5KO]), or normal adiposity (C57Bl6/J mice + normal diet and TLR5KO mice in which obesity was prevented by manipulation of the gut microbiome). Two weeks after loading, cartilage degeneration occurred in limbs loaded at a high magnitude, as determined by OARSI scores (P < .001). However, the severity of cartilage damage did not differ among groups. Osteophyte width and synovitis of loaded limbs did not differ among groups. Furthermore, obesity did not enhance cartilage damage in limbs evaluated 6 weeks after loading. Constituents of the gut microbiota differed among groups. Our findings suggest that, in the absence of surgery/fracture, obesity may not influence cartilage loss after a single mechanical insult, suggesting that either damage to surrounding tissues or repeated mechanical insult is necessary for obesity to influence cartilage degeneration. These findings further illustrate heterogeneity in PTOA phenotypes and complex interactions between mechanical/metabolic factors in cartilage loss.

Design and validation of a foot-ankle dynamic simulator with a 6-degree-of-freedom parallel mechanism.

An in vitro simulation test using a designed well-targeted test rig has been regarded as an effective way to understand the kinematics and dynamics of the foot and ankle complex in the dynamic stance phase, and it also allows alterations in both internal and external control compared to in vivo tests. However, current simulators are limited by some assumptions. In this study, a novel foot and ankle bionic dynamic simulator was developed and validated. A movable 6-degree-of-freedom parallel mechanism, known as Steward platform, was used as the core structure to drive the tibia, with a tibial force actuator applied with different loads. Four major muscle groups were actuated by four sensored pulling cables connected to muscle tendons. Simulation processes were controlled using a software developed based on a proportional-integral-derivative control loop, with tension-compression sensors mounted on tendon pulling cables and used as real-time monitor signals. An iterative learning module for tibial force control was integrated into the control software. Six specimens of the cadaveric foot-ankle were used to validate the simulator. The stance phase was successfully simulated within 5 s, and the tibia loads were applied based on the body weight of the cadaveric specimen donors. Typical three-dimensional ground reaction forces were successfully reproduced. The coefficient of multiple correlation analysis demonstrated good repeatability of the dynamic simulator for the ground reaction force (coefficient of multiple correlation > 0.89) and the range of ankle motion (coefficient of multiple correlation > 0.87 with only one exception). The simulated ranges of the foot-ankle joint rotation in stance were consistent with in vivo measurements, indicating the success of the dynamic simulation process. The proposed dynamic simulator can enhance the understanding of the mechanism of the foot-ankle movement, related injury prevention, and surgical intervention.

A Comparison of Central Anatomic Single-Bundle Reconstruction and Anatomic Double-Bundle Reconstruction in Anteroposterior and Rotational Knee Stability: Intraoperative Biomechanical Evaluation.

Postoperative anterior and rotational stability are still controversial when compared with single-bundle (SB) and double-bundle (DB) anterior cruciate ligament (ACL) reconstruction. This study aimed to compare the central anatomical SB and anatomical DB ACL reconstruction in intraoperative knee kinematics during continuous knee flexion-extension. A total of 34 patients who underwent ACL reconstruction using the hamstring tendon were evaluated intraoperatively before and immediately after ACL reconstruction using OrthoPilot ACL Navigation System Version 3.0. The patients were prospectively randomized into the central anatomical SB (17 knees) and the anatomical DB reconstruction (17 knees) groups. The tibial translation and rotation were continuously measured during knee flexion-extension under conventional knee motion, anterior tibial load (100N), and internal-external torque (3 N·m). The anterior tibial translation and total range of tibial rotation were calculated from the measurement values from 20 to 50 degrees at each 5-degree point. The anterior tibial translation (p = 0.59; two-factor repeated measures analysis of variance; η 2G = 0.0077) and total range of tibial rotation (p = 0.95; η 2G = 0.0001) at each knee flexion angle showed no significant difference between the central anatomical SB and anatomical DB reconstruction groups. It is suggested that the central anatomical SB reconstruction is comparable with the anatomical DB reconstruction in biomechanical anteroposterior and rotational knee stability at time 0.

A novel protection liner to improve graft-tunnel interaction following anterior cruciate ligament reconstruction: a finite element analysis

BackgroundDeteriorated bone-graft interaction at the tunnel entrance following ACL reconstruction (ACLR) is considered one of the primary causes of long-term tunnel enlargement and graft wear. Methods have been introduced to improve the long-term outcome, such as novel graft materials or alternative fixation methods, but have been met with varying degrees of success. This study aims to design a protection liner to improve the bone-graft interaction at the tunnel entrances.MethodsA finite element model of a human cadaveric knee was used to simulate traditional ACLR and ACLR using the protection liner. Stress distribution around the tunnel entrances and on the ACL graft were calculated under a combined loading of 103 N anterior tibial load, 7.5 Nm internal tibial moment, and 6.9 Nm valgus tibial moment at a joint flexion angle of 20°. Results were compared between the traditional ACLR and ACLR using a double liner (femoral and tibial) setup, as well as between the ACLR using a double liner setup and a single liner (femoral side) setup. Different materials (PEEK, Ti-6Al-4V, CoCrMo) for the liner were also evaluated.ResultsThe traditional ACLR resulted in concentrated stress on the graft where it contacted the tunnel entrance. Correspondingly, there were stress concentrations at the distal posterior zone of the femoral tunnel entrance and medial posterior zone of the tibial tunnel entrance, while the other zones suffered from a stress reduction. Use of the protection liner reduced the stress concentration around the tunnel entrances by up to 89% and increased the stress at the unloaded zones by up to 106%. Also, stress concentration on the graft was slightly decreased (15.4 vs 15.1 MPa) after using the liner. The single liner setup increased the stress concentration around the tibial tunnel entrance. Stiffer materials improved the stress distribution around tunnel entrances but had little effect on the stress on the graft.ConclusionsThe novel protection liner can improve the stress distribution on the graft and at the tunnel entrances, which may be beneficial for improving the clinical outcome of ACLR.

The mTORC2 Component Rictor Is Required for Load-Induced Bone Formation in Late-Stage Skeletal Cells.

ABSTRACTBone relies on mechanical cues to build and maintain tissue composition and architecture. Our understanding of bone cell mechanotransduction continues to evolve, with a few key signaling pathways emerging as vital. Wnt/β‐catenin, for example, is essential for proper anabolic response to mechanical stimulation. One key complex that regulates β‐catenin activity is the mammalian target of rapamycin complex 2 (mTORc2). mTORc2 is critical for actin cytoskeletal reorganization, an indispensable component in mechanotransduction in certain cell types. In this study, we probed the impact of the mTORc2 signaling pathway in osteocyte mechanotransduction by conditionally deleting the mTORc2 subunit Rictor in Dmp1‐expressing cells of C57BL/6 mice. Conditional deletion of the Rictor was achieved using the Dmp1–Cre driver to recombine Rictor floxed alleles. Rictor mutants exhibited a decrease in skeletal properties, as measured by DXA, μCT, and mechanical testing, compared with Cre‐negative floxed littermate controls. in vivo axial tibia loading conducted in adult mice revealed a deficiency in the osteogenic response to loading among Rictor mutants. Histological measurements of osteocyte morphology indicated fewer, shorter cell processes in Rictor mutants, which might explain the compromised response to mechanical stimulation. In summary, inhibition of the mTORc2 pathway in late osteoblasts/osteocytes leads to decreased bone mass and mechanically induced bone formation. © 2020 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

PTH(1\u201334) treatment and/or mechanical loading have different osteogenic effects on the trabecular and cortical bone in the ovariectomized C57BL/6 mouse

In preclinical mouse models, a synergistic anabolic response to PTH(1–34) and tibia loading was shown. Whether combined treatment improves bone properties with oestrogen deficiency, a cardinal feature of osteoporosis, remains unknown. This study quantified the individual and combined longitudinal effects of PTH(1–34) and loading on the bone morphometric and densitometric properties in ovariectomised mice. C57BL/6 mice were ovariectomised at 14-weeks-old and treated either with injections of PTH(1–34); compressive loading of the right tibia; both interventions concurrently; or both interventions on alternating weeks. Right tibiae were microCT-scanned from 14 until 24-weeks-old. Trabecular metaphyseal and cortical midshaft morphometric properties, and bone mineral content (BMC) in 40 different regions of the tibia were measured. Mice treated only with loading showed the highest trabecular bone volume fraction at week 22. Cortical thickness was higher with co-treatment than in the mice treated with PTH alone. In the mid-diaphysis, increases in BMC were significantly higher with loading than PTH. In ovariectomised mice, the osteogenic benefits of co-treatment on the trabecular bone were lower than loading alone. However, combined interventions had increased, albeit regionally-dependent, benefits to cortical bone. Increased benefits were largest in the mid-diaphysis and postero-laterally, regions subjected to higher strains under compressive loads.

Single-bundle MCL reconstruction with anatomic single-bundle ACL reconstruction does not restore knee kinematics.

The purpose of this study was to evaluate and compare knee kinematics and kinetics following either single bundle, modified triangular or double-bundle reconstruction of the superficial medial collateral ligament (sMCL) with single bundle anatomic ACL reconstruction. Using a cadaveric model (n = 10), the knee kinematics and kinetics following three MCL reconstructions (single-bundle(SB), double-bundle(DB), modified triangular) with single bundle anatomic ACL reconstruction were compared with the intact and deficient knee state. The knees were tested under (1) an 89-N anterior tibial load, (2) 5 N-m internal and external rotational tibial torques, and (3) a 7 N-m valgus torque. Anatomic ACL reconstruction with SB MCL reconstruction was able to restore anterior tibial translation and external rotation to intact knee values but failed to the internal and valgus rotatory stability. Anatomical DB MCL reconstruction (with SB ACL reconstruction) and the modified triangular MCL reconstruction (with SB ACL reconstruction) restored allknee kinematics to the intact value. This study shows that clinical presentation with combined ACL and severe sMCL injury, single-bundle MCL with single-bundle ACL reconstruction does not restore knee kinematics. Anatomical double-bundle MCL reconstruction may produce slightly better biomechanical stability than the modified triangular MCL reconstruction, but the modified triangular reconstruction might be more clinically practical with the advantages of being less invasive and technically simpler while at the same time can restore a nearly normal knee joint.

Partial Lateral Meniscectomy Affects Knee Stability Even in Anterior Cruciate Ligament-Intact Knees.

The effects of a partial lateral meniscectomy on knee kinematics and forces in the lateral meniscus are critical to understand. The purpose of this study was to quantify the effects of varying sizes of partial lateral meniscectomies of the posterior horn and a total lateral meniscectomy on knee kinematics and resultant forces in the lateral meniscus. Using a robotic testing system, loads (134-N anterior tibial load + 200-N axial compression, 5-Nm internal tibial torque + 5-Nm valgus torque, and 5-Nm external tibial torque + 5-Nm valgus torque) were applied to 10 fresh-frozen cadaveric knees. The resulting joint motion and resultant forces in the lateral meniscus were determined for 4 knee states: intact, one-third and two-thirds partial lateral meniscectomies of the posterior horn, and total lateral meniscectomy. A decrease in lateral translation of the tibia (up to 166.7%) was observed after one-third partial lateral meniscectomies of the posterior horn compared with the intact knee, in response to an anterior load at all knee flexion angles tested (p < 0.05). One-third partial lateral meniscectomies of the posterior horn decreased the resultant forces in the lateral meniscus compared with the intact knee at all knee flexion angles tested in response to an anterior load (p < 0.05) and to an internal tibial torque (p < 0.05). The results of two-thirds partial lateral meniscectomies of the posterior horn were similar to those of one-third partial meniscectomies (p > 0.05). Total lateral meniscectomies further decreased the lateral translation of the tibia (up to 316.6%) compared with the intact knee in response to an anterior load (p < 0.05). The changes in joint motion and meniscal forces observed in this study after even small partial lateral meniscectomies may predispose knees to further injury. Surgeons should always consider repairing and minimizing the resection of even small lateral meniscal tears to prevent the potential deleterious effects of partial meniscectomy reported in this cadaveric study.

Anatomic, All-Arthroscopic Reconstruction of Posterolateral Corner of the Knee: A Cadaveric Biomechanical Study

To assess the role of anatomic reconstruction of the posterolateral corner (PLC) of the knee arthroscopically in cadaveric knees with simulated isolated grade III posterolateral instability. A total of 12 nonpaired, fresh-frozen cadaveric knees were biomechanically subjected to a 10-Nm varus moment, 5-Nm external and internal rotation torques, and 134-N posterior tibial load at 0°, 15°, 30°, 60°, and 90° of knee flexion (0° for varus loading only). Testing was performed with an intact and sectioned PLC and after anatomic reconstruction of the PLC by an arthroscopic technique. Kinematics of each knee under various loading conditions was determined with a robotic universal force/moment sensor testing system. After sectioning, significant increases were found in varus rotation at 0°, 15°, 30°, 60°, and 90° of knee flexion; in external rotation at 15°, 30°, 60°, and 90° of knee flexion; in internal rotation at 60° of knee flexion only; and in posterior translation at 15° and 30° of knee flexion. After reconstruction, full recovery of knee stability was observed in varus rotation, external rotation, internal rotation, and posterior translation at all selected flexion angles without any overconstraint of knee kinematics. Anatomic reconstruction of the PLC can be performed arthroscopically with isolated grade III posterolateral instability of the knee, and nearly normal stability of the knee can be restored. PLC reconstruction by an anatomic, all-arthroscopic technique achieves optimal stability control and kinematics of the knee.

Joint laxity varies in response to partial and complete anterior cruciate ligament injuries throughout skeletal growth

Anterior cruciate ligament (ACL) injuries are increasingly common in the skeletally immature population. As such there is a need to increase our understanding of the biomechanical function of the joint following partial and complete ACL injury during skeletal growth. In this work, we aimed to assess changes in knee kinematics and loading of the remaining soft tissues following both partial and complete ACL injury in a porcine model. To do so, we applied anterior-posterior tibial loads and varus-valgus moments to stifle joints of female pigs ranging from early juvenile to late adolescent ages and assessed both kinematics and in-situ loads carried in the bundles of the ACL and other soft tissues including the collateral ligaments and the menisci. Partial ACL injury led to increased anterior tibial translation only in late adolescence and small increases in varus-valgus rotation at all ages. Complete ACL injury led to substantial increases in translation and rotation at all ages. At all ages, the medial collateral ligament and the medial meniscus combined to resist the majority of applied anterior tibial load following complete ACL transection. Across all ages and flexion angles, the contribution of the MCL ranged from 45 to 90% of the anterior load and the contribution of the medial meniscus ranged from 14 to 35% of the anterior load. These findings add to our current understanding of age-specific functional properties of both healthy and injured knees during skeletal growth.

Mechanosensitive Ca2+ signaling and coordination is diminished in osteocytes of aged mice during ex vivo tibial loading

ABSTRACTPurpose: The osteocyte is considered the major mechanosensor in bone, capable of detecting forces at a cellular level to coordinate bone formation and resorption. The pathology of age-related bone loss, a hallmark of osteoporosis, is attributed in part to impaired osteocyte mechanosensing. However, real-time evidence of the effect of aging on osteocyte responses to mechanical load is lacking. Intracellular calcium (Ca2+) oscillations have been characterized as an early mechanosensitive response in osteocytes in systems of multiple scales and thus can serve as a real-time measure of osteocyte mechanosensitivity. Our objective was to utilize an ex vivo model to investigate potentially altered mechanosensing in the osteocyte network with aging.Methods: Tibiae were explanted from young-adult (5 mo) and aged (22 mo) female mice and incubated with Fluo-8 AM to visualize osteocyte intracellular Ca2+. Whole tibiae were cyclically loaded while in situ osteocyte Ca2+ dynamics were simultaneously imaged with confocal microscopy. Responsive osteocyte percentage and Ca2+ peak characteristics were quantified, as well as signaling synchrony between paired cells in the field of view.Results: Fewer osteocytes responded to mechanical loading in aged mice compared to young-adult and did so in a delayed manner. Osteocytes from aged mice also lacked the well-correlated relationship between Ca2+ signaling synchrony and cell-cell distance exhibited by young-adult osteocytes.Conclusions: We have demonstrated, for the first time, real-time evidence of the diminished mechanosensing and lack of signaling coordination in aged osteocyte networks in tibial explants, which may contribute to pathology of age-induced bone loss.

Effects of the tibial tunnel position on knee joint stability and meniscal contact pressure after double-bundle anterior cruciate ligament reconstruction

BackgroundTo investigate the effect of the tibial tunnel position on knee stability and the maximum contact area and peak contact pressure on the menisci after double-bundle anterior cruciate ligament (ACL) reconstruction. MethodsTen human knee specimens (mean age: 74.1 ± 15.8 years) were used in this study. The anterior tibial loading test was conducted using a material testing machine at 30°, 60°, and 90° of knee flexion, with the anterior tibial translation (ATT) and the maximum contact area and peak contact pressure on the menisci measured. Outcome measures were compared between the following groups: 1) intact ACL (intact group); 2) anatomical tibial tunnel position (anatomical group) and 3) posterior tibial tunnel position (posterior group) with double-bundle reconstruction, and 4) ACL-deficient (deficient group). ResultsIn response to a 100 N anterior tibial load, the ATT was greater for the posterior and ACL-deficient groups compared to that in the intact group. The normalized maximum contact area of the medial meniscus significantly decreased for the posterior group compared to that in the intact group. The normalized peak contact pressure on the medial meniscus increased in all groups compared to that in the intact group, but with no between-group differences in pressure applied to the lateral meniscus. ConclusionsATT and contact pressure on the medial meniscus increased, concomitant with a decrease in contact area of the medial meniscus, as the position of the tibial tunnel position moved towards a posterior position.

Protective Effects of Controlled Mechanical Loading of Bone in C57BL6/J Mice Subject to Disuse.

ABSTRACTProlonged reduction in weightbearing causes bone loss. Disuse of bone is associated with recovery from common musculoskeletal injury and trauma, bed rest resulting from various medical conditions, and spaceflight. The hindlimb‐suspension rodent model is popular for simulating unloading and disuse. We hypothesized that controlled mechanical loading of the tibia would protect against bone loss occurring from concurrent disuse. Additionally, we hypothesized that areas of high mechanical peak strains (midshaft) would provide more protection than areas of lower strain (distal shaft). Adult C57BL6/J mice were suspended for 3 weeks, with one limb subjected to tibial compression four times per week. μCT imaging was completed at days 0, 11, and 21, in addition to serum analysis. Significant bone loss caused by hindlimb suspension was detected in trabecular bone by day 11 and worsened by day 21 (p < 0.05). Bone loss was also detected in cortical thickness and area fraction by day 21. However, four short bouts per week of compressive loading protected the loaded limb from much of this bone loss. At day 21, we observed a 50% loss in trabecular bone volume/total volume and a 6% loss in midshaft cortical thickness in unloaded limbs, but only 15% and 2% corresponding losses in contralateral loaded limbs (p = 0.001 and p = 0.02). Many bone geometry parameters of the loaded limbs of suspended animals did not significantly differ from non‐suspended control limbs. Conversely, this protective effect of loading was not detected in cortical bone at the lower‐strained distal shaft. Analysis of bone metabolism markers suggested that the benefits of loading occurred through increased formation instead of decreased resorption. This study uniquely isolates the role of externally applied mechanical loading of the mouse tibia, in the absence of muscle stimulation, in protecting bone from concurrent disuse‐related loss, and demonstrates that limited bouts of loading may be highly effective during prolonged disuse. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.